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Hunter CJ, Marhoffer EA, Holleck JL, Ein Alshaeba S, Grimshaw AA, Chou A, Carey GB, Gunderson CG. Effect of empiric antibiotics against Pseudomonas aeruginosa on mortality in hospitalized patients: a systematic review and meta-analysis. J Antimicrob Chemother 2025; 80:322-333. [PMID: 39656468 DOI: 10.1093/jac/dkae422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 11/06/2024] [Indexed: 02/04/2025] Open
Abstract
BACKGROUND Empiric antibiotics active against Pseudomonas aeruginosa are recommended by professional societies for certain infections and are commonly prescribed for hospitalized patients. The effect of this practice on mortality is uncertain. METHODS A systematic literature search was conducted using Embase, Medline, PubMed, Web of Science, Cochrane, Scopus and Google Scholar from earliest entry through 9 October 2023. We included studies of patients hospitalized with P. aeruginosa infections that compared mortality rates depending on whether patients received active empiric antibiotics. RESULTS We found 27 studies of 12 522 patients that reported adjusted OR of active empiric antibiotics on mortality. The pooled adjusted OR was 0.40 (95% CI, 0.32-0.50), favouring active empiric antibiotics. In practice, the mortality effect of empiric antibiotics against P. aeruginosa depends on the prevalence of P. aeruginosa and baseline mortality. The estimated absolute mortality benefit was 0.02% (95% CI, 0.02-0.02) for soft tissue infections, 0.12% (95% CI, 0.10-0.13) for urinary tract infections and community-acquired pneumonia, 0.3% (0.25-0.34) for sepsis without shock, 1.1% (95% CI, 0.9-1.4) for septic shock and 2.4% (95% CI, 1.9-2.8) for nosocomial pneumonia. CONCLUSIONS The mortality effect for empiric antibiotics against P. aeruginosa depends crucially on the prevalence of P. aeruginosa and baseline mortality by type of infection. For soft tissue infections, urinary tract infections and community-acquired pneumonia, the mortality benefit is low. Meaningful benefit of empiric antibiotics against P. aeruginosa is limited to patients with approximately 30% mortality and 5% prevalence of P. aeruginosa, which is largely limited to patients in intensive care settings.
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Affiliation(s)
- Cameron J Hunter
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Elizabeth A Marhoffer
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Department of Medicine, Veteran Affairs Connecticut Healthcare System, West Haven, CT, USA
| | - Jürgen L Holleck
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Department of Medicine, Veteran Affairs Connecticut Healthcare System, West Haven, CT, USA
| | - Samer Ein Alshaeba
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Department of Medicine, Veteran Affairs Connecticut Healthcare System, West Haven, CT, USA
| | - Alyssa A Grimshaw
- Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT, USA
| | - Andrew Chou
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Department of Medicine, Veteran Affairs Connecticut Healthcare System, West Haven, CT, USA
- Department of Medicine, Division of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA
| | - George B Carey
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Department of Medicine, Veteran Affairs Connecticut Healthcare System, West Haven, CT, USA
| | - Craig G Gunderson
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Department of Medicine, Veteran Affairs Connecticut Healthcare System, West Haven, CT, USA
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Koutake Y, Nagasaki Y, Hirata R, Soejima K, Nishi H, Tsukada H, Hamasaki S, Hashimoto M. Effects of meropenem supply restriction: A multicenter retrospective study. J Infect Chemother 2025; 31:102475. [PMID: 39029622 DOI: 10.1016/j.jiac.2024.07.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 06/02/2024] [Accepted: 07/15/2024] [Indexed: 07/21/2024]
Abstract
BACKGROUND In Japan, the supply of one generic meropenem product was restricted from August 2022 to March 2023. OBJECTIVE To determine the effects of meropenem (MEPM) restriction. METHODS We conducted a multicenter retrospective study comparing antimicrobial use, bacteremia mortality, and drug-resistant bacteria detected before the restriction of MEPM (control period), from September 2021 to February 2022, and after the restriction of MEPM (MEPM supply restriction period), from September 2022 to February 2023, in five institutions. RESULTS The number of carbapenem days of therapy (DOTs) were decreased in all five institutions. Fourth-generation cephalosporin DOTs increased in all facilities, and piperacillin/tazobactam DOTs increased in four facilities. The 30-day and 90-day mortality rates were significantly higher during the MEPM supply restriction period than those during the control period. Moreover, survival time was significantly shorter during the MEPM supply restriction period than that during the control period. Multivariable analysis revealed that MEPM supply restriction, age >80 years, Pitt Bacteremia Score ≥4, platelet count <10 × 104/μL, serum albumin level <2.5 g/dL, and methicillin-resistant Staphylococcus aureus bloodstream infection were independent risk factors for 30-day mortality. The detection rates of carbapenem-resistant Pseudomonas aeruginosa and Enterobacteriaceae did not differ significantly between the two periods. CONCLUSIONS MEPM supply restriction decreased the use of carbapenems and increased the use of other broad-spectrum antimicrobial agents, which worsened the prognosis of bacteremia. Overall, carbapenems are important drugs for the treatment of infectious diseases and are difficult to replace in unforeseen situations such as drug supply outages.
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Affiliation(s)
- Yoshimichi Koutake
- Department of Pharmacy, Clinical Research Institute, NHO Kyushu Medical Center, 1-8-1 Jigyouhama, Chuo-ku, Fukuoka 810-8563, Japan.
| | - Yoji Nagasaki
- Department of Infectious Diseases, NHO Kyushu Medical Center, Fukuoka, Japan
| | - Ryosuke Hirata
- Department of Pharmacy, Clinical Research Institute, NHO Kyushu Medical Center, 1-8-1 Jigyouhama, Chuo-ku, Fukuoka 810-8563, Japan
| | - Keiji Soejima
- Department of Pharmacy, NHO Nagasaki Medical Center, Nagasaki, Japan
| | - Hiromi Nishi
- Department of Pharmacy, NHO Fukuoka Higashi Medical Center, Fukuoka, Japan
| | - Hiroko Tsukada
- Department of Pharmacy, NHO Beppu Medical Center, Oita, Japan
| | - Shohei Hamasaki
- Department of Pharmacy, NHO Kagoshima Medical Center, Kagoshima, Japan
| | - Masashi Hashimoto
- Department of Pharmacy, Clinical Research Institute, NHO Kyushu Medical Center, 1-8-1 Jigyouhama, Chuo-ku, Fukuoka 810-8563, Japan
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Falconer K, Hammond R, Parcell BJ, Gillespie SH. Investigating the time to blood culture positivity: why does it take so long? J Med Microbiol 2025; 74. [PMID: 39757997 DOI: 10.1099/jmm.0.001942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025] Open
Abstract
Introduction. Bloodstream infections (BSIs) are one of the most serious infections investigated by microbiologists. However, the time to detect a BSI fails to meet the rapidity required to inform clinical decisions in real time.Gap Statement. Blood culture (BC) is considered the gold standard for diagnosing bloodstream infections. However, the time to blood culture positivity can be lengthy. Underpinning this is the reliance on bacteria replicating to a high concentration, which is necessary for the detection using routine blood culture systems. To improve the diagnosis and management of patients with BSIs, more sensitive detection methods are required.Aim. The study aimed to answer key questions addressing the delay in BSI detection and whether the time to BSI detection could be expedited using a Scattered Light Integrated Collection (SLIC) device.Methodology. A proof-of-concept study was conducted to compare the time to positivity (TTP) of Gram-negative BCs flagging positive on BacT/ALERT with an SLIC device. An SLIC device was utilized to compare the TTP of the most prevalent BSI pathogens derived from nutrient broth and BC, the influence of bacterial load on TTP and the TTP directly from whole blood. Additionally, the overall turnaround time (TAT) of SLIC was compared with that of a standard hospital workflow.Results. Most pathogens tested took significantly longer to replicate when derived from BC than from nutrient medium. The median TTP of Gram-negative BC on BacT/ALERT was 13.56 h with a median bacterial load of 6.4×109 c.f.u. ml-1. All pathogens (7/7) derived from BC at a concentration of 105 c.f.u. ml-1 were detectable in under 70 min on SLIC. Decreasing Escherichia coli BC concentration from 105 to 102 c.f.u. ml-1 increased the TTP of SLIC from 15 to 85 min. Direct BSI detection from whole blood on SLIC demonstrated a 76% reduction in TAT when compared with the standard hospital workflow.Conclusion. An SLIC device significantly reduced the TTP of common BSI pathogens. The application of this technology could have a major impact on the detection and management of BSI.
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Affiliation(s)
- Kerry Falconer
- Division of Infection and Global Health, School of Medicine, University of St Andrews, St Andrews, UK
| | - Robert Hammond
- Division of Infection and Global Health, School of Medicine, University of St Andrews, St Andrews, UK
| | - Benjamin J Parcell
- Division of Infection and Global Health, School of Medicine, University of St Andrews, St Andrews, UK
- Ninewells Hospital and Medical School, Dundee, UK
| | - Stephen H Gillespie
- Division of Infection and Global Health, School of Medicine, University of St Andrews, St Andrews, UK
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Davis SC, Gil J, Solis M, Strong R, Cassagnol R. Efficacy of a Topical Nitric Oxide-Releasing Gel on Polymicrobial Wound Infections. Mil Med 2024:usae551. [PMID: 39671514 DOI: 10.1093/milmed/usae551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 10/02/2024] [Accepted: 12/03/2024] [Indexed: 12/15/2024] Open
Abstract
INTRODUCTION Wounds are colonized frequently by heterogeneous microflora. Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) are two of the most isolated bacterial species from wounds, and both typically form highly organized biofilms. Nitric oxide (NO) is a short-lived, diatomic, lipophilic gas with antimicrobial activity. Recently, NO and its derivatives have been shown to exhibit broad-spectrum antimicrobial activity against bacteria, viruses, and parasites. MATERIALS AND METHODS P. aeruginosa strain ATCC 27312 or military isolate PA09-010 were combined with methicillin-resistant S. aureus strain MRSA USA300 to demonstrate the ability of NO to reduce polymicrobial infections in a porcine wound infection model. Deep partial-thickness wounds (10 mm × 7 mm × 0.5 mm) were made on four animals using a specialized electrokeratome. Wounds were inoculated with MRSA USA300 combined with PA09-010 in three animals and MRSA USA300 combined with PA27312 in one animal, then wounds were covered with polyurethane film dressings. After 48 hours, three wounds were recovered for baseline enumeration. The remaining wounds were randomly assigned to treatment groups and treated once daily. The NO topical gels tested were combinations of two phases, ointment phases with various concentrations (2-20%) combined with hydrogels with fast or slow release kinetics. A 4-day study with microbiological recovery was conducted on day 4. A separate 7-day study was also conducted, with microbial burden assessed on day 7. RESULTS The largest efficacy against MRSA USA300 was observed for the NO formulation with 2% concentration and fast release kinetics. This treatment reduced the MRSA USA300 bacterial count by more than 99.97% and 99.95% from baseline in wounds co-infected with PA09-010 and PA 27312, respectively, at day 7. Treatments showed a minimal efficacy against PA27312 and PA09-010 strains in both assessment times. MRSA USA300 was reduced to a lesser extent when it was combined with PA27312 as compared to PA09-010. CONCLUSIONS These studies demonstrate that NO-releasing topical formulations effectively reduce the MRSA burden in established biofilms composed of multiple microorganisms. Minimal efficacy against PA was observed. It has been demonstrated that MRSA bioburden is significantly reduced when inoculated together with P. aeruginosa. A better understanding of mechanisms of host-bacteria interactions, in single or mixed species biofilms, may lead to the development of novel therapeutic approaches. Overall, NO offers a promising alternative treatment against MRSA in polymicrobial infections.
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Affiliation(s)
- Stephen C Davis
- Dr. Philip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Joel Gil
- Dr. Philip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Michael Solis
- Dr. Philip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Ryan Strong
- Dr. Philip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Roger Cassagnol
- Dr. Philip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
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Restrepo-Arbeláez N, García-Betancur JC, Pallares CJ, El Ayoubi LW, Kiratisin P, Kanj SS, Villegas MV. Can risk factors and risk scores help predict colonization and infection in multidrug-resistant gram-negative bacteria? ANTIMICROBIAL STEWARDSHIP & HEALTHCARE EPIDEMIOLOGY : ASHE 2024; 4:e196. [PMID: 39563931 PMCID: PMC11574599 DOI: 10.1017/ash.2024.455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 10/01/2024] [Accepted: 10/02/2024] [Indexed: 11/21/2024]
Abstract
Antimicrobial resistance (AMR) is positioning as one of the most relevant threats to global public health and threatens the effective treatment of an ever-growing number of bacterial infections in various healthcare settings, particularly in acute care and surgical units, as well as in the community. Among multidrug-resistant (MDR) gram-negative bacteria (MDRGNB), Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii require special attention, since they account for most of the mortality associated with bacterial infections and are often MDR. It is clear that there is an important global variation in antibiotic resistance profiles among MDRGNB species. Extended-spectrum β-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, DTR-P. aeruginosa, and MDR-A. baumannii are the focus of this review. Here, we summarize a series of relevant studies on risk factors associated with colonization and infection with these MDRGNB. Likewise, we offer a comparative overview of those studies providing scoring systems to predict the risk of infection with these MDR pathogens, and their pros and cons. Despite the variable accuracy of published risk factors for predicting colonization or infection with MDRGNB, these scores are valuable tools that may help anticipate colonization and infection among those colonized. More importantly, they may help reduce unnecessary use of broad-spectrum antimicrobials and guiding the selection of an optimal treatment.
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Affiliation(s)
- Natalia Restrepo-Arbeláez
- Grupo de investigación en Resistencia Antimicrobiana y Epidemiología Hospitalaria (RAEH), Universidad El Bosque, Bogotá D.C., Colombia
| | - Juan Carlos García-Betancur
- Grupo de investigación en Resistencia Antimicrobiana y Epidemiología Hospitalaria (RAEH), Universidad El Bosque, Bogotá D.C., Colombia
| | - Christian José Pallares
- Grupo de investigación en Resistencia Antimicrobiana y Epidemiología Hospitalaria (RAEH), Universidad El Bosque, Bogotá D.C., Colombia
- Clínica Imbanaco Grupo Quirónsalud, Cali, Colombia
| | - L'Emir Wassim El Ayoubi
- Division of Infectious Diseases, and Center for Infectious Diseases Research, American University of Beirut Medical Center, Beirut, Lebanon
| | - Pattarachai Kiratisin
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Souha S Kanj
- Division of Infectious Diseases, and Center for Infectious Diseases Research, American University of Beirut Medical Center, Beirut, Lebanon
| | - María Virginia Villegas
- Grupo de investigación en Resistencia Antimicrobiana y Epidemiología Hospitalaria (RAEH), Universidad El Bosque, Bogotá D.C., Colombia
- Clínica Imbanaco Grupo Quirónsalud, Cali, Colombia
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Lodise TP, Obi EN, Watanabe AH, Yucel E, Min J, Nathanson BH. Comparative evaluation of early treatment with ceftolozane/tazobactam versus ceftazidime/avibactam for non-COVID-19 patients with pneumonia due to multidrug-resistant Pseudomonas aeruginosa. J Antimicrob Chemother 2024; 79:2954-2964. [PMID: 39258877 PMCID: PMC11531822 DOI: 10.1093/jac/dkae313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 08/19/2024] [Indexed: 09/12/2024] Open
Abstract
BACKGROUND Ceftolozane/tazobactam and ceftazidime/avibactam are commonly used in patients with MDR-Pseudomonas aeruginosa (PSA) pneumonia (PNA). This study compared outcomes between non-COVID-19 hospitalized patients with MDR-PSA PNA who received ceftolozane/tazobactam or ceftazidime/avibactam. METHODS The study included non-COVID-19 adult hospitalized patients with MDR-PSA PNA in the PINC AI Healthcare Database (2016-22) who received ceftolozane/tazobactam or ceftazidime/avibactam within 3 days of index culture for ≥2 days. Outcomes were mortality, recurrent MDR-PSA PNA, discharge destination, post-index culture day length of stay (LOS) and costs (in US dollars, USD), and hospital readmission. RESULTS The final sample included 197 patients (117 ceftolozane/tazobactam, 80 ceftazidime/avibactam). No significant differences were observed in mortality and post-index culture LOS and costs between groups. In the multivariable analyses, patients who received ceftolozane/tazobactam versus ceftazidime/avibactam had lower recurrent MDR-PSA PNA (7.9% versus 18.0%, P = 0.03) and 60 day PNA-related readmissions (11.1% versus 28.5%, P = 0.03) and were more likely to be discharged home (25.8% versus 9.8%, P = 0.03). Compared with ceftazidime/avibactam patients, ceftolozane/tazobactam patients had lower adjusted median total antibiotic costs (5052 USD versus 8099 USD, P = 0.003) and lower adjusted median comparator (ceftolozane/tazobactam or ceftazidime/avibactam) antibiotic costs (3938 USD versus 6441 USD, P = 0.005). In the desirability of outcome ranking (DOOR) analysis, a ceftolozane/tazobactam-treated patient was more likely to have a more favourable outcome than a ceftazidime/avibactam-treated patient [DOOR probability: 59.6% (95% CI: 52.5%-66.8%)]. CONCLUSIONS Early treatment with ceftolozane/tazobactam may offer some clinical and cost benefits over ceftazidime/avibactam in patients with MDR-PSA PNA. Further large-scale studies are necessary to comprehensively understand the outcomes associated with these treatments for MDR-PSA PNA.
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Affiliation(s)
- Thomas P Lodise
- Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY, USA
| | - Engels N Obi
- Merck & Co., Inc., 2025 E Scott Ave, Rahway, NJ, USA
| | | | - Emre Yucel
- Merck & Co., Inc., 2025 E Scott Ave, Rahway, NJ, USA
| | - Jae Min
- Merck & Co., Inc., 2025 E Scott Ave, Rahway, NJ, USA
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Chaftari AM, Dagher H, Hachem R, Jiang Y, Lamie P, Wilson Dib R, John T, Haddad A, Philip A, Alii S, Mulanovich P, Yuan Y, Chaftari P, Raad I. A randomized non-inferiority study comparing imipenem/cilastatin/relebactam with standard-of-care Gram-negative coverage in cancer patients with febrile neutropenia. J Antimicrob Chemother 2024; 79:2543-2553. [PMID: 39092963 DOI: 10.1093/jac/dkae254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 07/06/2024] [Indexed: 08/04/2024] Open
Abstract
BACKGROUND Antibiotic overuse leads to the emergence of antibiotic resistance that threatens immunocompromised cancer patients. Infections caused by MDR Gram-negative pathogens are difficult to treat and associated with high mortality. Hence, empirical therapy with standard-of-care (SOC) antibiotics could be suboptimal in these vulnerable patients. New antibiotics covering potential resistant pathogens may be considered. METHODS We conducted a randomized non-inferiority study comparing safety and efficacy of imipenem/cilastatin/relebactam (IPM/REL), a β-lactam/β-lactamase inhibitor combination, with SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) in cancer patients with febrile neutropenia. Patients received at least 48 h of IV antibiotics and were assessed at end-of-IV (EOIV) therapy, test of cure (TOC; Days 21-28), and late follow-up (LFU; Days 35-42). RESULTS A total of 100 patients were enrolled (49 IPM/REL and 50 SOC). Demographics and rates of documented microbiological infections were similar in both groups. In the SOC arm, 86% of antibiotics consisted of cefepime. Patients on IPM/REL had a higher favourable clinical response at EOIV than those on SOC (90% versus 74%; P = 0.042); however, responses were similar at TOC and LFU. Microbiological eradication was comparable at all three timepoints. Study drug-related adverse events and adverse events leading to drug discontinuation were similar in both groups, with no study drug-related mortality. CONCLUSIONS Our results suggest that compared with SOC antibiotics, predominantly cefepime, IPM/REL for empirical coverage of febrile neutropenia in cancer patients is generally safe and could be associated with a better clinical outcome at EOIV. The current SOC consisting mainly of agents that do not cover for ESBL-producing and carbapenem-resistant Enterobacterales bacteria should be reconsidered.
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Affiliation(s)
- Anne-Marie Chaftari
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Hiba Dagher
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Ray Hachem
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Ying Jiang
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Peter Lamie
- Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rita Wilson Dib
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Teny John
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Andrea Haddad
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Ann Philip
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Shahnoor Alii
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Patricia Mulanovich
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Ying Yuan
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Patrick Chaftari
- Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Issam Raad
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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Hickson SM, Hoehensteiger JK, Mayer-Coverdale J, Torres VVL, Feng W, Monteith JN, Henderson IR, McCarthy KL, Wells TJ. Antibody-Mediated Serum Resistance Protects Pseudomonas aeruginosa During Bloodstream Infections. J Infect Dis 2024; 230:e221-e229. [PMID: 38235716 PMCID: PMC11326846 DOI: 10.1093/infdis/jiad457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 10/17/2023] [Indexed: 01/19/2024] Open
Abstract
BACKGROUND Pseudomonas aeruginosa is a frequent pathogen isolated from bacterial bloodstream infection (BSI) and is associated with high mortality. To survive in the blood, P aeruginosa must resist the bactericidal action of complement (ie, serum killing). Antibodies usually promote serum killing through the classical complement pathway; however, "cloaking antibodies" (cAbs) have been described, which paradoxically protect bacteria from serum killing. The relevance of cAbs in P aeruginosa BSI is unknown. METHODS Serum and P aeruginosa were collected from a cohort of 100 patients with BSI. Isolates were tested for sensitivity to healthy control serum (HCS). cAb prevalence was determined in sera. Patient sera were mixed with HCS to determine if killing of the matched isolate was inhibited. RESULTS Overall, 36 patients had elevated titers of cAbs, and 34 isolates were sensitive to HCS killing. Fifteen patients had cAbs and HCS-sensitive isolates; of these patients, 14 had serum that protected their matched bacteria from HCS killing. Patients with cAbs were less likely to be neutropenic or have comorbidities. CONCLUSIONS cAbs are prevalent in patients with P aeruginosa BSI and allow survival of otherwise serum-sensitive bacteria in the bloodstream. Generation of cAbs may be a risk factor for the development of BSI.
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Affiliation(s)
- Sarah M Hickson
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | | | - Johanna Mayer-Coverdale
- UQ Centre for Clinical Research, The University of Queensland, Herston, Australia
- Department of Microbiology, Pathology Queensland, Brisbane, Australia
| | - Von Vergel L Torres
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Wenkang Feng
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Joshua N Monteith
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Ian R Henderson
- Institute of Molecular Biosciences, The University of Queensland, Brisbane, Australia
| | - Kate L McCarthy
- Department of Microbiology, Pathology Queensland, Brisbane, Australia
- Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Timothy J Wells
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia
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Wangchinda W, Kaye KS, Patel TS, Albin OR, Saravolatz L, Petrie JG, Pogue JM. A comparison of strategies for identifying patients at risk for carbapenem-resistant or extended β-lactam-resistant Pseudomonas aeruginosa. J Antimicrob Chemother 2024; 79:1337-1345. [PMID: 38581308 DOI: 10.1093/jac/dkae104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 03/20/2024] [Indexed: 04/08/2024] Open
Abstract
OBJECTIVES To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-β-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures. METHODS This retrospective study analysed hospitalized patients with positive P. aeruginosa cultures between 2015 and 2021. Two case-control analyses were performed to identify risk factors and develop scoring tools for distinguishing patients with CR versus carbapenem-susceptible (CS) P. aeruginosa and EBR versus CS P. aeruginosa. The performance of institutionally derived scores, externally derived scores and the presence/absence of key risk factors to predict CR and EBR were then compared. RESULTS A total of 2379 patients were included. Of these, 8.3% had a positive culture for CR, 5.0% for EBR and 86.7% for CS P. aeruginosa. There was substantial overlap in risk factors for CR and EBR. Institutional risk scores demonstrated modestly higher area under the ROC curve values than external scores for predicting CR (0.67 versus 0.58) and EBR (0.76 versus 0.70). Assessing the presence/absence of ≥1 of the two strongest predictors (prior carbapenem use or CR isolation within 90 days) was slightly inferior to scoring tools for predicting CR, and comparable for predicting EBR. CONCLUSIONS Clinicians concerned about CR in P. aeruginosa should consider the likelihood of EBR when making treatment decisions. A simple approach of assessing recent history of CR isolation or carbapenem usage performed similarly to more complex scoring tools and offers a more pragmatic way of identifying patients who require coverage for resistant P. aeruginosa.
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Affiliation(s)
- Walaiporn Wangchinda
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Keith S Kaye
- Department of Medicine, Rutgers University, Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Twisha S Patel
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA
| | - Owen R Albin
- Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Louis Saravolatz
- Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Joshua G Petrie
- Center for Clinical Epidemiology and Population Health, Marshfield Clinic Research Institute, Marshfield, WI, USA
| | - Jason M Pogue
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA
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10
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Li Z, Yang W, Ye X, Yuan Q, Zhao J, Du Z, Yu J, Sun Y, Wu X, Hu J. Early Intraventricular Antibiotic Therapy Improved In-Hospital-Mortality in Neurocritical Patients with Multidrug-Resistant Bacterial Nosocomial Meningitis and Ventriculitis. Neurocrit Care 2024; 40:612-620. [PMID: 37498458 DOI: 10.1007/s12028-023-01781-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 06/09/2023] [Indexed: 07/28/2023]
Abstract
BACKGROUND Hospital-acquired multidrug-resistant (MDR) bacterial meningitis and/or ventriculitis (MEN) is a severe condition associated with high mortality. The risk factors related to in-hospital mortality of patients with MDR bacterial MEN are unknown. We aimed to examine factors related to in-hospital mortality and evaluate their prognostic value in patients with MDR bacterial MEN treated in the neurointensive care unit. METHODS This was a single-center retrospective cohort study of critically ill neurosurgical patients with MDR bacterial MEN admitted to our hospital between January 2003 and March 2021. Data on demographics, admission variables, treatment, time to start of intraventricular (IVT) therapy, and in-hospital mortality were analyzed. Both univariate and multivariable analyses were performed to identify determinants of in-hospital mortality. RESULTS All 142 included patients received systemic antibiotic therapy, and 102 of them received concomitant IVT treatment. The median time to start of IVT treatment was 2 days (interquartile range 1-5 days). The time to start of IVT treatment had an effect on in-hospital mortality (hazard ratio 1.17; 95% confidence interval 1.02-1.34; adjusted p = 0.030). The cutoff time to initiate IVT treatment was identified at 3 days: patients treated within 3 days had a higher cerebrospinal fluid (CSF) sterilization rate (81.5%) and a shorter median time to CSF sterilization (7 days) compared with patients who received delayed IVT treatment (> 3 days) (48.6% and 11.5 days, respectively) and those who received intravenous antibiotics alone (42.5% and 10 days, respectively). CONCLUSIONS Early IVT antibiotics were associated with superior outcomes in terms of the in-hospital mortality rate, time to CSF sterilization, and CSF sterilization rate compared with delayed IVT antibiotics and intravenous antibiotics alone.
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Affiliation(s)
- Zhiqi Li
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Middle Wulumuqi Road 12#, Jing'an District, Shanghai, 200040, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China
| | - Weijian Yang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Middle Wulumuqi Road 12#, Jing'an District, Shanghai, 200040, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China
| | - Xiangru Ye
- Neuro-intensive Care Unit, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qiang Yuan
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Middle Wulumuqi Road 12#, Jing'an District, Shanghai, 200040, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China
| | - Jianlan Zhao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Middle Wulumuqi Road 12#, Jing'an District, Shanghai, 200040, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China
| | - Zhuoying Du
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Middle Wulumuqi Road 12#, Jing'an District, Shanghai, 200040, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China
| | - Jian Yu
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Middle Wulumuqi Road 12#, Jing'an District, Shanghai, 200040, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China
| | - Yirui Sun
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Middle Wulumuqi Road 12#, Jing'an District, Shanghai, 200040, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China
| | - Xuehai Wu
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Middle Wulumuqi Road 12#, Jing'an District, Shanghai, 200040, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China
| | - Jin Hu
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Middle Wulumuqi Road 12#, Jing'an District, Shanghai, 200040, China.
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China.
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China.
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11
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Fukuma Y, Nomura T, Mikami T, Tanaka K, Taira N. Severe Pseudomonas aeruginosa Pneumonia in a Breast Cancer Patient Despite Pegfilgrastim Administration. Cureus 2024; 16:e57156. [PMID: 38686264 PMCID: PMC11057642 DOI: 10.7759/cureus.57156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2024] [Indexed: 05/02/2024] Open
Abstract
Pegfilgrastim dramatically reduces febrile neutropenia (FN) caused by high-risk chemotherapy. This report details the presentation of a 72-year-old female who developed a fatal infection of Pseudomonas aeruginosa pneumonia that occurred during preoperative chemotherapy despite pegfilgrastim administration. She was brought to the hospital with symptoms of high fever and general fatigue during chemotherapy, but her respiratory symptoms were minimal, and a chest computed tomography (CT) showed no obvious signs of pneumonia. She had FN. After she was hospitalized, her breathing and consciousness worsened rapidly, and the chest CT showed prominent lobar pneumonia. Her blood cultures suggested P. aeruginosa, so she was quickly switched to meropenem. She was diagnosed with septic shock and acute respiratory distress syndrome due to severe P. aeruginosa pneumonia, and she was started on noninvasive positive pressure ventilation with immunoglobulin preparations. P. aeruginosa developed drug resistance, so it was necessary to change antibiotics. She was discharged without complications of pulmonary fibrosis on chest CT. It is crucial to always be aware that severe infections can occur even with pegfilgrastim administration, promptly identify the causative pathogen, and intervene with early treatment.
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Affiliation(s)
- Yuna Fukuma
- Breast and Thyroid Surgery, Kawasaki Medical School, Okayama, JPN
| | - Tsunehisa Nomura
- Breast and Thyroid Surgery, Kawasaki Medical School, Okayama, JPN
| | - Tsuyoshi Mikami
- Breast and Thyroid Surgery, Kawasaki Medical School, Okayama, JPN
| | - Katsuhiro Tanaka
- Breast and Thyroid Surgery, Kawasaki Medical School, Okayama, JPN
| | - Naruto Taira
- Breast and Thyroid Surgery, Kawasaki Medical School, Okayama, JPN
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12
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Nakashima H, Miyazaki M, Kuwamura T, Oda K, Haga Y, Imakyure O. Relationship between Target Time above Minimum Inhibitory Concentration Achievement Rate of Meropenem Using Monte Carlo Simulation and In-Hospital Survival in Patients with Pseudomonas aeruginosa Bacteremia. Antibiotics (Basel) 2024; 13:219. [PMID: 38534654 DOI: 10.3390/antibiotics13030219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 02/16/2024] [Accepted: 02/26/2024] [Indexed: 03/28/2024] Open
Abstract
Pseudomonas aeruginosa bacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration (fT>MIC) of MEPM and its therapeutic efficacy in P. aeruginosa bacteremia has not been explored. This study aimed to investigate this relationship by defining the target % fT>MIC of MEPM as 75%. The retrospective study spanned 14 years and included hospitalized patients treated with MEPM for P. aeruginosa bacteremia. Monte Carlo simulation was used to calculate the probability of target attainment (PTA) for each patient, and the threshold for a PTA of 75% fT>MIC associated with in-hospital survival was determined using receiver operating characteristic (ROC) curves. The ROC curve-derived PTA associated with improved in-hospital survival was 65.0%, a significant finding in multivariate logistic regression analysis adjusted for patient background factors (odds ratio: 20.49, 95% confidence interval: 3.02-245.23, p = 0.005). This result suggests a dosing regimen that achieves a PTA of at least 65% when the target fT>MIC of MEPM for treating P. aeruginosa bacteremia is defined as 75%.
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Affiliation(s)
- Hajime Nakashima
- Department of Pharmacy, Japan Community Health Care Organization Kyushu Hospital, Fukuoka 806-0034, Japan
| | - Motoyasu Miyazaki
- Department of Pharmacy, Fukuoka University Chikushi Hospital, Fukuoka 818-8502, Japan
| | - Tsuneo Kuwamura
- Department of Pharmacy, Japan Community Health Care Organization Kurume General Hospital, Fukuoka 830-0013, Japan
| | - Kazutaka Oda
- Department of Pharmacy, Kumamoto University Hospital, Kumamoto 860-8556, Japan
| | - Yumi Haga
- Department of Clinical Laboratory, Japan Community Health Care Organization Kyushu Hospital, Fukuoka 806-0034, Japan
| | - Osamu Imakyure
- Department of Pharmacy, Fukuoka University Chikushi Hospital, Fukuoka 818-8502, Japan
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13
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El-Haffaf I, Laverdière J, Albert M, Marsot A, Williamson D. Potential benefits of therapeutic drug monitoring for beta-lactam antibiotics in augmented renal clearance patients: a case report. Can J Physiol Pharmacol 2024; 102:69-74. [PMID: 37713726 DOI: 10.1139/cjpp-2023-0109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2023]
Abstract
Augmented renal clearance (ARC) is commonly described in critically ill patients, making drug pharmacokinetics even harder to predict in this population. This case report displays the value of therapeutic drug monitoring (TDM) of piperacillin/tazobactam (PTZ) in this population. We identified two patients with ARC and intermittent administration of PTZ who took part in a prospective, descriptive study conducted at Hôpital du Sacré-Cœur de Montréal. Both had plasma samples drawn at peak, middle, and end of their dosing intervals of PTZ. Minimal inhibitory concentrations (MICs) of 4 and 8 mg/L were chosen to evaluate therapeutic target attainment at middle and end of dosing interval. The first patient was a 52-year-old male with a renal clearance rate estimated at 147 mL/min who received 3.375 g PTZ every 6 h. The second patient, a 49-year-old male, had an estimated renal clearance rate of 163 mL/min and received the same regimen. Both patients had piperacillin concentrations above the target MICs at middle of the dosing interval, but they failed to reach a trough concentration above 8 mg/L. The present case report showcases two patients with subtherapeutic PTZ concentrations despite strict following of local administration protocols. This suboptimal administration could not only lead to treatment failure, but also to the selection and growth of resistant pathogens. Implementing TDM would offer the possibility to adjust drug regimens in real-time and prevent situations like these from occurring.
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Affiliation(s)
- Ibrahim El-Haffaf
- Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada
- Laboratoire de Suivi Thérapeutique Pharmacologique et Pharmacocinétique, Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada
| | - Jean Laverdière
- Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada
| | - Martin Albert
- Hôpital du Sacré-Cœur de Montréal, CIUSSS NIM Research Center, Montreal, QC, Canada
- Faculty of Medicine, Université de Montréal, Montreal, QC, Canada
| | - Amélie Marsot
- Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada
- Laboratoire de Suivi Thérapeutique Pharmacologique et Pharmacocinétique, Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada
- Centre de recherche, CHU Sainte-Justine, Montréal, QC, Canada
| | - David Williamson
- Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada
- Hôpital du Sacré-Cœur de Montréal, CIUSSS NIM Research Center, Montreal, QC, Canada
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14
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Sophonsri A, Lou M, Ny P, Minejima E, Nieberg P, Wong-Beringer A. Machine learning to identify risk factors associated with the development of ventilated hospital-acquired pneumonia and mortality: implications for antibiotic therapy selection. Front Med (Lausanne) 2023; 10:1268488. [PMID: 38170135 PMCID: PMC10759933 DOI: 10.3389/fmed.2023.1268488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 11/28/2023] [Indexed: 01/05/2024] Open
Abstract
Background Among patients with nosocomial bacterial pneumonia, those who decompensated to requiring mechanical ventilation (vHABP) faced the highest mortality followed by ventilator-associated pneumonia (VABP) and non-ventilated hospital-acquired pneumonia (nvHABP). The objectives of this study were to identify risk factors associated with the development and mortality of vHABP and to evaluate antibiotic management. Methods A multicenter retrospective cohort study of adult inpatients with nosocomial pneumonia during 2014-2019 was performed. Groups were stratified by vHABP, nvHABP, and VABP and compared on demographics, clinical characteristics, treatment, and outcomes. Multivariable models were generated via machine learning to identify risk factors for progression to vHABP as well as pneumonia-associated mortality for each cohort. Results 457 patients (32% nvHABP, 37% vHABP, and 31% VABP) were evaluated. The vHABP and nvHABP groups were similar in age (median age 66.4 years) with 77% having multiple comorbidities but more vHABP patients had liver disease (18.2% vs. 7.7% p = 0.005), alcohol use disorder (27% vs. 7.1%, p < 0.0001), and were hospitalized within the past 30 days (30.4% vs. 19.5%, p = 0.02). An immediate need for ventilatory support occurred in 70% of vHABP patients on the day of diagnosis. Mortality was the highest in vHABP followed by VABP and nvHABP groups (44.6% vs. 36% vs. 14.3%, p < 0.0001). Nearly all (96%) vHABP patients had positive cultures, with Gram-negative pathogens accounting for 58.8% whereby 33.0% were resistant to extended-spectrum β-lactams (ESBLs), ceftriaxone (17.5%), fluoroquinolones (20.6%), and carbapenems (12.4%). Up to half of the vHABP patients with ESBL-Enterobacterales or P. aeruginosa did not receive an effective empiric regimen; over 50% increase in mortality rate was observed among patients whom effective therapy was initiated past the day of pneumonia diagnosis. Risk factors associated with vHABP development were alcohol use disorder, APACHE II score, vasopressor therapy prior to infection, and culture positive for ESBL-Enterobacterales whereas history of hospitalization in the past 30 days, active malignancy, isolation of ceftriaxone-resistant pathogens or Pseudomonas aeruginosa, and vasopressor therapy were risk factors for vHABP-associated mortality. Conclusion Patients with vHABP experienced an acute and severe decompensation upon diagnosis. The risk factors identified in this study could provide actionable data for clinicians to identify those at risk for vHABP at the onset of pneumonia and to target antimicrobial stewardship efforts to improve treatment success.
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Affiliation(s)
- Anthony Sophonsri
- Department of Clinical Pharmacy, University of Southern California, Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, United States
| | - Mimi Lou
- Department of Clinical Pharmacy, University of Southern California, Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, United States
| | - Pamela Ny
- Department of Pharmacy, Huntington Hospital, Pasadena, CA, United States
| | - Emi Minejima
- Department of Clinical Pharmacy, University of Southern California, Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, United States
- Department of Pharmacy, Los Angeles General Medical Center, Los Angeles, CA, United States
| | - Paul Nieberg
- Department of Medicine – Infectious Diseases, Huntington Hospital, Pasadena, CA, United States
| | - Annie Wong-Beringer
- Department of Clinical Pharmacy, University of Southern California, Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, United States
- Department of Pharmacy, Huntington Hospital, Pasadena, CA, United States
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15
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Hojat LS, Wilson BM, Perez F, Mojica MF, Singer ME, Bonomo RA, Epstein LH. Association of COVID-19 coinfection with increased mortality among patients with Pseudomonas aeruginosa bloodstream infection in the Veterans Health Administration system. ANTIMICROBIAL STEWARDSHIP & HEALTHCARE EPIDEMIOLOGY : ASHE 2023; 3:e237. [PMID: 38156202 PMCID: PMC10753479 DOI: 10.1017/ash.2023.455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 08/14/2023] [Accepted: 08/17/2023] [Indexed: 12/30/2023]
Abstract
Objective Pseudomonas aeruginosa bloodstream infection (PA-BSI) and COVID-19 are independently associated with high mortality. We sought to demonstrate the impact of COVID-19 coinfection on patients with PA-BSI. Design Retrospective cohort study. Setting Veterans Health Administration. Patients Hospitalized patients with PA-BSI in pre-COVID-19 (January 2009 to December 2019) and COVID-19 (January 2020 to June 2022) periods. Patients in the COVID-19 period were further stratified by the presence or absence of concomitant COVID-19 infection. Methods We characterized trends in resistance, treatment, and mortality over the study period. Multivariable logistic regression and modified Poisson analyses were used to determine the association between COVID-19 and mortality among patients with PA-BSI. Additional predictors included demographics, comorbidities, disease severity, antimicrobial susceptibility, and treatment. Results A total of 6,714 patients with PA-BSI were identified. Throughout the study period, PA resistance rates decreased. Mortality decreased during the pre-COVID-19 period and increased during the COVID-19 period. Mortality was not significantly different between pre-COVID-19 (24.5%, 95% confidence interval [CI] 23.3-28.6) and COVID-19 period/COVID-negative (26.0%, 95% CI 23.5-28.6) patients, but it was significantly higher in COVID-19 period/COVID-positive patients (47.2%, 35.3-59.3). In the modified Poisson analysis, COVID-19 coinfection was associated with higher mortality (relative risk 1.44, 95% CI 1.01-2.06). Higher Charlson Comorbidity Index, higher modified Acute Physiology and Chronic Health Evaluation score, and no targeted PA-BSI treatment within 48 h were also predictors of higher mortality. Conclusions Higher mortality was observed in patients with COVID-19 coinfection among patients with PA-BSI. Future studies should explore this relationship in other settings and investigate potential SARS-CoV-2 and PA synergy.
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Affiliation(s)
- Leila S. Hojat
- Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, Cleveland, OH, USA
- Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Brigid M. Wilson
- Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, Cleveland, OH, USA
- Geriatric Research Education and Clinical Center (GRECC), the VA Northeast Ohio Healthcare System, Cleveland, OH, USA
| | - Federico Perez
- Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, Cleveland, OH, USA
- Geriatric Research Education and Clinical Center (GRECC), the VA Northeast Ohio Healthcare System, Cleveland, OH, USA
- Case Western Reserve University, Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, OH, USA
| | - Maria F. Mojica
- Case Western Reserve University, Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, OH, USA
- Research Service, VA Northeast Ohio Healthcare System, Cleveland, OH, USA
- Grupo de Resistencia Antimicrobiana y Epidemiología Hospitalaria, Universidad El Bosque, Bogotá, Colombia
- Departments of Pathology, Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Mendel E. Singer
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA
| | - Robert A. Bonomo
- Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, Cleveland, OH, USA
- Geriatric Research Education and Clinical Center (GRECC), the VA Northeast Ohio Healthcare System, Cleveland, OH, USA
- Case Western Reserve University, Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, OH, USA
- Research Service, VA Northeast Ohio Healthcare System, Cleveland, OH, USA
- Departments of Pathology, Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Lauren H. Epstein
- Infectious Diseases, US Department of Veterans Affairs Medical Center, Decatur, GA, USA
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16
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Zou I, Abate D, Newman M, Heil EL, Leekha S, Claeys KC. Crossroads of Antimicrobial and Diagnostic Stewardship: Assessing Risks to Develop Clinical Decision Support to Combat Multidrug-Resistant Pseudomonas. Open Forum Infect Dis 2023; 10:ofad512. [PMID: 37901124 PMCID: PMC10603593 DOI: 10.1093/ofid/ofad512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/10/2023] [Indexed: 10/31/2023] Open
Abstract
Background Early detection of multidrug-resistant Pseudomonas aeruginosa (MDRP) remains challenging. Existing risk prediction tools are difficult to translate to bedside application. The goal of this study was to develop a simple electronic medical record (EMR)-integrated tool for prediction of MDRP infection. Methods This was a mixed-methods study. We conducted a split-sample cohort study of adult critical care patients with P aeruginosa infections. Two previously published tools were validated using c-statistic. A subset of variables based on strength of association and ease of EMR extraction was selected for further evaluation. A simplified tool was developed using multivariable logistic regression. Both c-statistic and theoretical trade-off of over- versus underprescribing of broad-spectrum MDRP therapy were assessed in the validation cohort. A qualitative survey of frontline clinicians assessed understanding of risks for MDRP and potential usability of an EMR-integrated tool to predict MDRP. Results The 2 previous risk prediction tools demonstrated similar accuracy in the derivation cohort (c-statistic of 0.76 [95% confidence interval {CI}, .69-.83] and 0.73 [95% CI, .66-.8]). A simplified tool based on 4 variables demonstrated reasonable accuracy (c-statistic of 0.71 [95% CI, .57-.85]) without significant overprescribing in the validation cohort. The risk factors were prior MDRP infection, ≥4 antibiotics prior to culture, infection >3 days after admission, and dialysis. Fourteen clinicians completed the survey. An alert providing context regarding individual patient risk factors for MDRP was preferred. Conclusions These results can be used to develop a local EMR-integrated tool to improve timeliness of effective therapy in those at risk of MDRP infections.
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Affiliation(s)
- Iris Zou
- Department of Nursing, University of Maryland Medical Center, Baltimore, Maryland, USA
| | - Daniel Abate
- Department of Pharmacy, Baltimore Washington Medical Center, Baltimore, Maryland, USA
| | - Michelle Newman
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Emily L Heil
- Department of Practice and Health Outcomes Research, University of Maryland School of Pharmacy, Baltimore, Maryland, USA
| | - Surbhi Leekha
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Kimberly C Claeys
- Department of Practice and Health Outcomes Research, University of Maryland School of Pharmacy, Baltimore, Maryland, USA
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Zhou M, Kang HZ, Gu CY, Liu YJ, Wang Y, Miao M, Fu JH, Tang XW, Qiu HY, Fu CC, Jin ZM, Li CX, Chen SN, Sun AN, Wu DP, Han Y. [Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2023; 44:484-489. [PMID: 37550204 PMCID: PMC10450549 DOI: 10.3760/cma.j.issn.0253-2727.2023.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Indexed: 08/09/2023]
Abstract
Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
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Affiliation(s)
- M Zhou
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - H Z Kang
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - C Y Gu
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - Y J Liu
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - Y Wang
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - M Miao
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - J H Fu
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - X W Tang
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - H Y Qiu
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - C C Fu
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - Z M Jin
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - C X Li
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - S N Chen
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - A N Sun
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - D P Wu
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
| | - Y Han
- The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, National Clinical Research Center for Hematologic Diseases, Suzhou 215006, China
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Xu S, Song Z, Han F, Zhang C. Effect of appropriate empirical antimicrobial therapy on mortality of patients with Gram-negative bloodstream infections: a retrospective cohort study. BMC Infect Dis 2023; 23:344. [PMID: 37221465 DOI: 10.1186/s12879-023-08329-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 05/14/2023] [Indexed: 05/25/2023] Open
Abstract
BACKGROUND Little evidence exists regarding the prevalence of pathogens in bloodstream infections (BSIs), the mortality risk, and the benefit of combination therapy over monotherapy. This study aims to describe patterns of empiric antimicrobial therapy, and the epidemiology of Gram-negative pathogens, and to investigate the effect of appropriate therapy and appropriate combination therapy on the mortality of patients with BSIs. METHODS This was a retrospective cohort study including all patients with BSIs of Gram-negative pathogens from January 2017 to December 2022 in a Chinese general hospital. The in-hospital mortality was compared between appropriate and inappropriate therapy, and between monotherapy and combination therapy for patients receiving appropriate therapy. We used Cox regression analysis to identify factors independently associated with in-hospital mortality. RESULTS We included 205 patients in the study, of whom 147 (71.71%) patients received appropriate therapy compared with 58 (28.29%) who received inappropriate therapy. The most common Gram-negative pathogen was Escherichia coli (37.56%). 131 (63.90%) patients received monotherapy and 74 (36.10%) patients received combination therapy. The in-hospital mortality was significantly lower in patients administered appropriate therapy than inappropriate therapy (16.33% vs. 48.28%, p = 0.004); adjusted hazard ratio [HR] 0.55 [95% CI 0.35-0.84], p = 0.006). In-hospital mortality was also not different in combination therapy and monotherapy in the multivariate Cox regression analyses (adjusted HR 0.42 [95% CI 0.15-1.17], p = 0.096). However, combination therapy was associated with lower mortality than monotherapy in patients with sepsis or septic shock (adjusted HR 0.94 [95% CI 0.86-1.02], p = 0.047). CONCLUSIONS Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to Gram-negative pathogens. Combination therapy was associated with improved survival in patients with sepsis or septic shock. Clinicians need to choose optical empirical antimicrobials to improve survival outcomes in patients with BSIs.
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Affiliation(s)
- Shanshan Xu
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Zhihui Song
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Furong Han
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Chao Zhang
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
- , No.1 Dongjiaomin Lane, Beijing, Dongcheng District, China.
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Cao Y, Jiang T, Lin Y, Fang X, Ding P, Song H, Li P, Li Y. Time-series prediction and detection of potential pathogens in bloodstream infection using mcfDNA sequencing. Front Cell Infect Microbiol 2023; 13:1144625. [PMID: 37249984 PMCID: PMC10213887 DOI: 10.3389/fcimb.2023.1144625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 04/18/2023] [Indexed: 05/31/2023] Open
Abstract
Introduction Next-generation sequencing of microbial cell free DNA (mcfDNA-seq) has emerged as a promising diagnostic method for blood stream infection (BSI) and offers the potential to detect pathogens before blood culture. However, its application is limited by a lack of clinical validation. Methods We conducted sequential mcfDNA-seq on blood samples from ICU participants at high risk of BSI due to pneumonia, or intravascular catheterization; and explored whether mcfDNA-seq could diagnose and detect pathogens in advance of blood culture positivity. Blood culture results were used as evaluation criteria. Results A total of 111 blood samples were collected during the seven days preceding and on the day of onset of 16 BSI episodes from 13 participants. The diagnostic and total predictive sensitivity of mcfDNA-seq were 90% and 87.5%, respectively. The proportion of pathogenic bacteria was relatively high in terms of both diagnosis and prediction. The reads per million of etiologic agents trended upwards in the days approaching the onset of BSI. Discussion Our work found that mcfDNA-seq has high diagnostic sensitivity and could be used to identify pathogens before the onset of BSI, which could help expand the clinical application of mcfDNA-seq.
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Affiliation(s)
- Yinghao Cao
- Department of Clinical Laboratory Medicine, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Clinical Laboratory Medicine, The Sixth Medical Center of People's Liberation Army (PLA) General Hospital of Beijing, Beijing, China
| | - Tingting Jiang
- Department of Epidemiology and Biostatistics, School of Public Health, An Hui Medical University, Hefei, China
- Biosecurity Department, Chinese People's Liberation Army (PLA) Center for Disease Control and Prevention, Beijing, China
| | - Yanfeng Lin
- Biosecurity Department, Chinese People's Liberation Army (PLA) Center for Disease Control and Prevention, Beijing, China
| | - Xiaofeng Fang
- Department of Clinical Laboratory Medicine, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Clinical Laboratory Medicine, The Sixth Medical Center of People's Liberation Army (PLA) General Hospital of Beijing, Beijing, China
| | - Peipei Ding
- Department of Clinical Laboratory Medicine, The Sixth Medical Center of People's Liberation Army (PLA) General Hospital of Beijing, Beijing, China
| | - Hongbin Song
- Department of Epidemiology and Biostatistics, School of Public Health, An Hui Medical University, Hefei, China
- Biosecurity Department, Chinese People's Liberation Army (PLA) Center for Disease Control and Prevention, Beijing, China
| | - Peng Li
- Biosecurity Department, Chinese People's Liberation Army (PLA) Center for Disease Control and Prevention, Beijing, China
| | - Yanjun Li
- Department of Clinical Laboratory Medicine, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Clinical Laboratory Medicine, The Sixth Medical Center of People's Liberation Army (PLA) General Hospital of Beijing, Beijing, China
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
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Routray A, Mane A. Knowledge, Attitude, and Practice (KAP) Survey on the Management of Multidrug-Resistant Gram-Negative Infections With Innovative Antibiotics: Focus on Ceftazidime-Avibactam. Cureus 2023; 15:e39245. [PMID: 37378116 PMCID: PMC10292104 DOI: 10.7759/cureus.39245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/19/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Antimicrobial resistance (AMR) is a major public health dilemma and a chief health concern globally. The rising incidence of resistance against carbapenems, which are considered most effective against gram-negative bacteria, has added to the concern and has limited the number of available treatment options. Newer antibiotic options may be required to tackle the mounting concern of antibiotic resistance. However, only a few antimicrobials are in the pipeline for managing infections instigated by multidrug-resistant (MDR) gram-negative bacteria. This justifies the prudent application of already available antibiotics. Among newer antibiotics available to healthcare professionals (HCPs), ceftazidime-avibactam (CAZ-AVI) has shown good efficacy in the management of MDR gram-negative infections. METHOD A cross-sectional survey on the knowledge, attitude, and practices (KAP) among HCPs was carried out using a questionnaire comprising 21 parameters related to AMR patterns on the need for innovative antibiotics to manage MDR gram-negative infections and the usage of CAZ-AVI by HCPs while managing such infections. The KAP scores were calculated to rank respondents' KAP levels. RESULT Out of the 204 study respondents, the majority (~80%) (n=160) believed that renewed efforts should be made to seek antimicrobial agents that will add to the armamentarium of treatment options for MDR gram-negative infections. CAZ-AVI is an important treatment alternative for managing MDR gram-negative infections (n=90, 45%). Further, it can be the first choice of definitive therapy for oxacillinases (OXA)-48-producing carbapenem-resistant Enterobacterales (n=84, 42%). HCPs also believed that the use of CAZ-AVI in clinical practice will require high levels of antimicrobial stewardship (n=100, 49%). CONCLUSION Novel and innovative antibiotics are the need of the hour in the management of MDR gram-negative infections. CAZ-AVI has established its effectiveness in treating these infections; however, the molecule must be utilized prudently while keeping stewardship principles in mind.
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Stahl JP, Canouï E, Bleibtreu A, Dubée V, Ferry T, Gillet Y, Lemaignen A, Lesprit P, Lorrot M, Lourtet-Hascoët J, Manaquin R, Meyssonnier V, Pavese P, Pham TT, Varon E, Gauzit R. SPILF update on bacterial arthritis in adults and children. Infect Dis Now 2023; 53:104694. [PMID: 36948248 DOI: 10.1016/j.idnow.2023.104694] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 03/13/2023] [Indexed: 03/24/2023]
Abstract
In 2020 the French Society of Rhumatology (SFR) published an update of the 1990 recommendations for management of bacterial arthritis in adults. While we (French ID Society, SPILF) totally endorse this update, we wished to provide further information about specific antibiotic treatments. The present update focuses on antibiotics with good distribution in bone and joint. It is important to monitor their dosage, which should be maximized according to PK/PD parameters. Dosages proposed in this update are high, with the optimized mode of administration for intravenous betalactams (continuous or intermittent infusion). We give tools for the best dosage adaptation to conditions such as obesity or renal insufficiency. In case of enterobacter infection, with an antibiogram result "susceptible for high dosage", we recommend the requesting of specialized advice from an ID physician. More often than not, it is possible to prescribe antibiotics via the oral route as soon as blood cultures are sterile and clinical have symptoms shown improvement. Duration of antibiotic treatment is 6 weeks for Staphylococcus aureus, and 4 weeks for the other bacteria (except for Neisseria: 7 days).
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Affiliation(s)
- J P Stahl
- Université Grenoble Alpes, Maladies Infectieuses, 38700, France.
| | - E Canouï
- Equipe mobile d'infectiologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Centre de Référence des Infections Ostéo-Articulaires complexes (CRIOAc Cochin) APHP-CUP, Paris, France
| | - A Bleibtreu
- Maladies Infectieuseset Tropicales, Hôpital Pitié Salpêtrière, AP-HP Sorbonne Université, Paris France
| | - V Dubée
- Maladies Infectieuses et Tropicales, CHU d'Angers, Angers, France
| | - T Ferry
- Maladies Infectieuses et Tropicales, Centre de Référence des Infections Ostéo-Articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Hôpital de la Croix-Rousse, 69004, Hospices Civils de Lyon, Lyon, France. Service des Maladies Infectieuses, Département de médecine, Hôpitaux Universitaires de Genève, Suisse
| | - Y Gillet
- Urgences et Réanimation Pédiatrique, Hospices Civils de Lyon, Université Claude Bernard Lyon, France
| | - A Lemaignen
- Maladies Infectieuses, CHRU de Tours, Université de Tours, 37044, France
| | - P Lesprit
- Maladies Infectieuses, CHU Grenoble Alpes, 38043, France
| | - M Lorrot
- Pédiatrie Générale et Equipe Opérationnelle d'Infectiologie, Centre de Référence des Infections Ostéo-Articulaires complexes (CRIOAc Pitié), Hôpital Armand Trousseau AP-HP Sorbonne Université, Paris France
| | | | - R Manaquin
- Maladies Infectieuses et Tropicales, GHSR , CHU de La Réunion, CRAtb La Réunion, Saint-Pierre, 97410, FRANCE
| | - V Meyssonnier
- Centre de Référence des Infections Ostéo-articulaires, GH Diaconesses Croix Saint-Simon, 75020, Paris, France; Service de Médecine Interne Générale, Département de médecine, Hôpitaux Universitaires de Genève, Suisse
| | - P Pavese
- Maladies Infectieuses, CHU Grenoble Alpes, 38043, France
| | - T-T Pham
- Maladies Infectieuses et Tropicales, Centre de Référence des Infections Ostéo-Articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Hôpital de la Croix-Rousse, 69004, Hospices Civils de Lyon, Lyon, France. Service des Maladies Infectieuses, Département de médecine, Hôpitaux Universitaires de Genève, Suisse
| | - E Varon
- Centre National de Référence des Pneumocoques, CRC-CRB, Centre Hospitalier Intercommunal de Créteil, 94000, Créteil, France
| | - R Gauzit
- Equipe mobile d'infectiologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Centre de Référence des Infections Ostéo-Articulaires complexes (CRIOAc Cochin) APHP-CUP, Paris, France
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Alosaimy S, Lagnf AM, Hobbs ALV, Mubarez M, Kufel WD, Morrisette T, Polisetty RS, Li D, Veve MP, Simon SP, Truong J, Finch N, Venugopalan V, Rico M, Amaya L, Yost C, Cubillos A, Chandler E, Patch M, Smith IMK, Biagi M, Wrin J, Moore WJ, Molina KC, Rebold N, Holger D, Kunz Coyne AJ, Jorgensen SCJ, Witucki P, Tran NN, Davis SL, Sakoulas G, Rybak MJ. Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam. Clin Infect Dis 2023; 76:e1444-e1455. [PMID: 35982631 DOI: 10.1093/cid/ciac670] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 07/27/2022] [Accepted: 08/16/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). METHODS We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time to nephrotoxicity between the 2 groups. RESULTS We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560-6.993). Results of the stratified Kaplan-Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). CONCLUSIONS Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.
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Affiliation(s)
- Sara Alosaimy
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA
| | - Abdalhamid M Lagnf
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA
| | - Athena L V Hobbs
- Department of Pharmacy, Baptist Memorial Hospital-Memphis, Memphis, Tennessee, USA
| | - Musa Mubarez
- Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center College of Pharmacy, Memphis, Tennessee, USA
| | - Wesley D Kufel
- Department of Pharmacy Practice, Binghamton University School of Pharmacy and Pharmaceutical Sciences, Binghamton, New York, USA.,Department of Pharmacy, State University of New York Upstate Medical University, Syracuse, New York, USA
| | - Taylor Morrisette
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.,Department of Clinical Pharmacy and Outcomes Sciences, Medical University of South Carolina College of Pharmacy, Charleston, South Carolina, USA.,Department of Pharmacy Services, Medical University of South Carolina Shawn Jenkins Children's Hospital, Charleston, South Carolina, USA
| | - Radhika S Polisetty
- Department of Pharmacy Practice, Midwestern University College of Pharmacy Downers Grove Campus, Downers Grove, Illinois, USA.,Department of Pharmacy, Northwestern Medicine Central Dupage Hospital, Winfield, Illinois, USA
| | - David Li
- Department of Pharmacy, Northwestern Medicine Central Dupage Hospital, Winfield, Illinois, USA
| | - Michael P Veve
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.,Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center College of Pharmacy, Memphis, Tennessee, USA.,Department of Pharmacy, Henry Ford Hospital, Detroit, Michigan, USA
| | - Sam P Simon
- Maimonides Medical Center, Brooklyn, New York, USA
| | - James Truong
- Department of Pharmacy, Brooklyn Hospital, Brooklyn, New York, USA
| | - Natalie Finch
- Department of Pharmacy Services, Harris Health System, Bellaire, Texas, USA
| | - Veena Venugopalan
- Department of Pharmacotherapy & Translational Research, University of Florida, Gainesville, Florida, USA
| | - Matthew Rico
- Department of Pharmacy, Beaumont Hospital, Royal Oak, Michigan, USA
| | - Lee Amaya
- Department of Pharmacy, Beaumont Hospital, Royal Oak, Michigan, USA
| | - Christine Yost
- Department of Pharmacy, Beaumont Hospital, Royal Oak, Michigan, USA
| | - Ashley Cubillos
- Department of Pharmacy, Lee Memorial Health System, Fort Myers, Florida, USA
| | - Elisabeth Chandler
- Department of Pharmacy, Lee Memorial Health System, Fort Myers, Florida, USA
| | - Megan Patch
- Department of Pharmacy, Lee Memorial Health System, Fort Myers, Florida, USA
| | | | - Mark Biagi
- Department of Pharmacy, Swedish American Hospital, Rockford, Illinois, USA
| | - Justin Wrin
- Department of Pharmacy, Indiana University Health, Indianapolis, Indiana, USA
| | - W Justin Moore
- Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois, USA
| | - Kyle C Molina
- Department of Pharmacy-Infectious Disease, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA
| | - Nicholas Rebold
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA
| | - Dana Holger
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA
| | - Ashlan J Kunz Coyne
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA
| | - Sarah C J Jorgensen
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Paige Witucki
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA
| | - Nikki N Tran
- Department of Pharmacy, Henry Ford Hospital, Detroit, Michigan, USA.,Department of Pharmacy, Ohio State University Waxner Medical Center, Columbus, Ohio, USA
| | - Susan L Davis
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.,Department of Pharmacy, Henry Ford Hospital, Detroit, Michigan, USA
| | - George Sakoulas
- Division of Host-Microbe Systems and Therapeutics, University of California San Diego School of Medicine, San Diego, California, USA
| | - Michael J Rybak
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.,Department of Pharmacy, Detroit Receiving Hospital, Detroit, Michigan, USA.,Department of Medicine, Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, Michigan, USA
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23
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Frem JA, Doumat G, Kazma J, Gharamti A, Kanj SS, Abou Fayad AG, Matar GM, Kanafani ZA. Clinical predictors of mortality in patients with pseudomonas aeruginosa infection. PLoS One 2023; 18:e0282276. [PMID: 37115776 PMCID: PMC10146515 DOI: 10.1371/journal.pone.0282276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 02/10/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Infections caused by Pseudomonas aeruginosa are difficult to treat with a significant cost and burden. In Lebanon, P. aeruginosa is one of the most common organisms in ventilator-associated pneumonia (VAP). P. aeruginosa has developed widespread resistance to multiple antimicrobial agents such as fluoroquinolones and carbapenems. We aimed at identifying risk factors associated for P. aeruginosa infections as well as identifying independent risk factors for developing septic shock and in-hospital mortality. METHODS We used a cross-sectional study design where we included patients with documented P. aeruginosa cultures who developed an infection after obtaining written consent. Two multivariable regression models were used to determine independent predictors of septic shock and mortality. RESULTS During the observed period of 30 months 196 patients were recruited. The most common predisposing factor was antibiotic use for more than 48 hours within 30 days (55%). The prevalence of multi-drug resistant (MDR) P. aeruginosa was 10%. The strongest predictors of mortality were steroid use (aOR = 3.4), respiratory failure (aOR = 7.3), identified respiratory cultures (aOR = 6.0), malignancy (aOR = 9.8), septic shock (aOR = 18.6), and hemodialysis (aOR = 30.9). CONCLUSION Understanding resistance patterns and risk factors associated with mortality is crucial to personalize treatment based on risk level and to decrease the emerging threat of antimicrobial resistance.
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Affiliation(s)
- Jim Abi Frem
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
| | - George Doumat
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
| | - Jamil Kazma
- Department of Obstetrics & Gynecology, George Washington University School of Medicine, Washington, District of Columbia, United States of America
| | - Amal Gharamti
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
| | - Souha S Kanj
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
| | - Antoine G Abou Fayad
- Department of Experimental Pathology, Immunology, and Microbiology, American University of Beirut, Beirut, Lebanon
- WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Ghassan M Matar
- Department of Experimental Pathology, Immunology, and Microbiology, American University of Beirut, Beirut, Lebanon
- WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Zeina A Kanafani
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
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Reynolds D, Burnham JP, Vazquez Guillamet C, McCabe M, Yuenger V, Betthauser K, Micek ST, Kollef MH. The threat of multidrug-resistant/extensively drug-resistant Gram-negative respiratory infections: another pandemic. Eur Respir Rev 2022; 31:220068. [PMID: 36261159 PMCID: PMC9724833 DOI: 10.1183/16000617.0068-2022] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 06/09/2022] [Indexed: 12/22/2022] Open
Abstract
Antibiotic resistance is recognised as a global threat to human health by national healthcare agencies, governments and medical societies, as well as the World Health Organization. Increasing resistance to available antimicrobial agents is of concern for bacterial, fungal, viral and parasitic pathogens. One of the greatest concerns is the continuing escalation of antimicrobial resistance among Gram-negative bacteria resulting in the endemic presence of multidrug-resistant (MDR) and extremely drug-resistant (XDR) pathogens. This concern is heightened by the identification of such MDR/XDR Gram-negative bacteria in water and food sources, as colonisers of the intestine and other locations in both hospitalised patients and individuals in the community, and as agents of all types of infections. Pneumonia and other types of respiratory infections are among the most common infections caused by MDR/XDR Gram-negative bacteria and are associated with high rates of mortality. Future concerns are already heightened due to emergence of resistance to all existing antimicrobial agents developed in the past decade to treat MDR/XDR Gram-negative bacteria and a scarcity of novel agents in the developmental pipeline. This clinical scenario increases the likelihood of a future pandemic caused by MDR/XDR Gram-negative bacteria.
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Affiliation(s)
- Daniel Reynolds
- Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Jason P Burnham
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | | | - Mikaela McCabe
- Dept of Pharmacy Practice, University of Health Sciences and Pharmacy, St. Louis, MO, USA
| | - Valerie Yuenger
- Dept of Pharmacy Practice, University of Health Sciences and Pharmacy, St. Louis, MO, USA
| | - Kevin Betthauser
- Dept of Pharmacy Practice, University of Health Sciences and Pharmacy, St. Louis, MO, USA
| | - Scott T Micek
- Dept of Pharmacy Practice, University of Health Sciences and Pharmacy, St. Louis, MO, USA
| | - Marin H Kollef
- Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA
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Wibisono A, Harb G, Crotty M, Rahmanzadeh K, Alexander J, Hunter L, Dominguez E. Quantifying Gram-Negative Resistance to Empiric Treatment After Repeat ExpoSure To AntimicRobial Therapy (RESTART). Open Forum Infect Dis 2022; 9:ofac659. [PMID: 36582770 PMCID: PMC9795471 DOI: 10.1093/ofid/ofac659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 12/08/2022] [Indexed: 12/13/2022] Open
Abstract
Background Antibiotic exposure is a primary predictor of subsequent antibiotic resistance; however, development of cross-resistance between antibiotic classes is also observed. The impact of changing to a different antibiotic from that of previous exposure is not established. Methods This was a retrospective, single-center cohort study of hospitalized adult patients previously exposed to an antipseudomonal β-lactam (APBL) for at least 48 hours in the 90 days prior to the index infection with a gram-negative bloodstream or respiratory infection. Susceptibility rates to empiric therapy were compared between patients receiving the same (repeat group) versus a different antibiotic from prior exposure (change group). Results A total of 197 patients were included (n = 94 [repeat group] and n = 103 [change group]). Pathogen susceptibility to empiric therapy was higher in the repeat group compared to the change group (76.6% vs 60.2%; P = .014). After multivariable logistic regression, repeat APBL was associated with an increased likelihood of pathogen susceptibility (adjusted odds ratio, 2.513; P = .012). In contrast, there was no difference in susceptibility rates between the repeat group and the subgroup of change patients who received an empiric APBL (76.6% vs 78.5%; P = .900). Longer APBL exposure duration (P = .012) and chronic kidney disease (P = .002) were associated with higher nonsusceptibility to the exposure APBL. In-hospital mortality was not significantly different between the repeat and change groups (18.1% vs 23.3%; P = .368). Conclusions The common practice of changing to a different APBL from that of recent exposure may not be warranted.
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Affiliation(s)
- Arya Wibisono
- Department of Pharmacy, Methodist Dallas Medical Center, Dallas, Texas, USA
| | - Gaielle Harb
- Department of Pharmacy, Methodist Dallas Medical Center, Dallas, Texas, USA
| | - Matthew Crotty
- Correspondence: Matthew Crotty, PharmD, BCIDP, Department of Pharmacy, Methodist Dallas Medical Center, 1441 N Beckley Ave, Dallas, TX 75203 ()
| | | | - Julie Alexander
- Department of Internal Medicine, Methodist Dallas Medical Center, Dallas, Texas, USA
| | - Leigh Hunter
- Department of Internal Medicine, Methodist Dallas Medical Center, Dallas, Texas, USA
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Thomas CM, Peterson J, Ahiskali A, Hamid L, Butts J, Czachura J, Alpern JD. Hospital pharmacy acquisition of nonstocked antimicrobials-current processes and areas for improvement. J Am Pharm Assoc (2003) 2022; 62:1848-1854. [PMID: 36068143 PMCID: PMC9637775 DOI: 10.1016/j.japh.2022.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND The delivery of prompt and appropriate antimicrobial therapy for life-threatening infections is an important antimicrobial stewardship measure and a priority for hospitals. OBJECTIVES To better understand U.S. hospital pharmacy stocking processes and acquisition of nonstocked antimicrobials and to identify strategies for improving this process. METHODS This mixed-methods study recruited infectious diseases and antimicrobial stewardship pharmacists. Semistructured interviews with pharmacists in Minnesota were conducted via video conferencing software from January 21, 2021, to March 17, 2021. Audio recordings of the interviews guided survey development and were also transcribed, coded, and qualitatively analyzed. Surveys were distributed throughout the United States via an e-mail listserv, and responses were collected between August 5, 2021, and September 15, 2021. RESULTS Ten interviews and 78 surveys were included in the analysis. Formulary and stocking practices varied based on institution. Stocking decisions were most frequently based on the frequency of use, clinical utility, and cost of antimicrobials. Nonstocked antimicrobials were often ordered from the wholesale distributor but, if needed urgently, acquired from another local institution. Antibacterial agents were the most frequently needed nonstocked antimicrobials, especially those targeting multidrug-resistant gram-negative bacteria. When acquiring nonstocked antimicrobials, barriers include process inefficiencies, cost, availability, and safety concerns. Improved information sharing between local institutions may help improve this process. CONCLUSION In this exploratory study, antimicrobial stocking practices varied within U.S. hospitals. Acquisition of nonstocked, urgently needed antimicrobials from neighboring hospitals may be common; however, this process lacks guidance and is often inefficient. Establishing better mechanisms for information sharing may improve this process and should be explored.
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Affiliation(s)
- Christine M. Thomas
- Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN
| | | | | | - Lina Hamid
- M Health Fairview, University of Minnesota Medical Center, Minneapolis, MN
| | - Jessica Butts
- Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN
| | - Jennifer Czachura
- Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN
| | - Jonathan D. Alpern
- Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN; and Clinical Research Investigator, HealthPartners Institute, Bloomington, MN
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Comparative Analysis of Complicated Urinary Tract Infections Caused by Extensively Drug-Resistant Pseudomonas aeruginosa and Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae. Antibiotics (Basel) 2022; 11:antibiotics11111511. [PMID: 36358167 PMCID: PMC9686592 DOI: 10.3390/antibiotics11111511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 10/24/2022] [Accepted: 10/26/2022] [Indexed: 11/17/2022] Open
Abstract
The objective was to compare clinical characteristics, outcomes, and economic differences in complicated urinary tract infections (cUTI) caused by extensively drug-resistant Pseudomonas aeruginosa (XDR P. aeruginosa) and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-K. pneumoniae). A retrospective study was conducted at a tertiary care hospital. Patients with XDR P. aeruginosa and ESBL-K. pneumoniae cUTIs were compared. The primary outcome was clinical failure at day 7 and at the end of treatment (EOT). Secondary outcomes: 30- and 90-day mortality, microbiological eradication, and economic cost. Two-hundred and one episodes were included, of which 24.8% were bloodstream infections. Patients with XDR P. aeruginosa cUTI more frequently received inappropriate empirical therapy (p < 0.001). Nephrotoxicity due to antibiotics was only observed in the XDR P. aeruginosa group (26.7%). ESBL-K. pneumoniae cUTI was associated with worse eradication rates, higher recurrence, and higher infection-related readmission. In multivariate analysis, XDR P. aeruginosa was independently associated with clinical failure on day 7 of treatment (OR 4.34, 95% CI 1.71−11.04) but not at EOT, or with mortality. Regarding hospital resource consumption, no significant differences were observed between groups. XDR P. aeruginosa cUTI was associated with worse early clinical cures and more antibiotic side effects than ESBL-K. pneumoniae infections. However, no differences in mortality or in hospitalization costs were observed.
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Appaneal HJ, Caffrey AR, Lopes V, Piehl EC, Puzniak LA, LaPlante KL. Assessing Rates of Co-Resistance and Patient Outcomes in Multidrug-Resistant Pseudomonas aeruginosa. Microbiol Spectr 2022; 10:e0233622. [PMID: 36005836 PMCID: PMC9603501 DOI: 10.1128/spectrum.02336-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 08/04/2022] [Indexed: 01/04/2023] Open
Abstract
Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with poor patient outcomes due to complex co-resistance patterns. We described common co-resistance patterns, clinical characteristics, and associated outcomes in patients admitted with an MDR P. aeruginosa. This national, multicenter, retrospective cohort study within the Veterans Affairs included adults hospitalized with a MDR P. aeruginosa infection (January 2015-December 2020) per Centers for Disease Control definition. Clinical outcomes were compared among those with differing MDR P. aeruginosa co-resistance: resistant to carbapenems and extended-spectrum cephalosporins and piperacillin-tazobactam (CARB/ESC/PT) versus without CARB/ESC/PT resistance; resistant to carbapenems and extended-spectrum cephalosporins and fluoroquinolone (CARB/ESC/FQ) versus without CARB/ESC/FQ resistance. We included 3,763 hospitalized patients. Co-resistance to CARB/ESC/PT was observed in 42.7%, and to CARB/ESC/FQ in 40.7%. The lowest co-resistance rates were observed with ceftolozane-tazobactam (6.2%, n = 6/97; 12.5%, n = 10/80, respectively) and ceftazidime-avibactam (5.2%, n = 5/97; 12.5%, n = 10/80, respectively). Overall, 14.2% of patients died during hospitalization, 59.7% had an extended length of stay, and 14.9% had reinfection with hospitalization. Outcomes were similar between patients with MDR P. aeruginosa strains with and without co-resistance to CARB/ESC/PT and CARB/ESC/FQ. Among a national cohort of patients hospitalized with MDR P. aeruginosa infections, co-resistance to three classes of standard of care antibiotics, such as carbapenem, extended-spectrum cephalosporins, and piperacillin-tazobactam or fluoroquinolones, exceeded 40% in our study population, posing great concerns for selecting appropriate empirical therapy. Clinical outcomes were poor for all patients, regardless of different co-resistance patterns. New treatment options are needed for hospitalized patients with suspected or confirmed MDR P. aeruginosa infections. IMPORTANCE We studied antibiotic co-resistance patterns in a national group of hospitalized patients with infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa, a type of bacteria that resists treatment to at least three classes of antibiotics. Co-resistance to antibiotic classes most typically used for treatment was common, which makes selecting appropriate antibiotics to successfully treat the infections difficult. Outcomes, including death, were poor for all patients in our study, regardless of the different patterns of co-resistance to common antibiotic classes. New antibiotics are needed to help treat hospitalized patients with MDR P. aeruginosa infections.
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Affiliation(s)
- Haley J. Appaneal
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA
- College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA
- Center of Innovation in Long-Term Support Services, Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA
- School of Public Health, Brown University, Providence, Rhode Island, USA
| | - Aisling R. Caffrey
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA
- College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA
- Center of Innovation in Long-Term Support Services, Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA
- School of Public Health, Brown University, Providence, Rhode Island, USA
| | - Vrishali Lopes
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA
| | - Emily C. Piehl
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA
- College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA
| | | | - Kerry L. LaPlante
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA
- College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA
- Center of Innovation in Long-Term Support Services, Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA
- Warren Alpert Medical School of Brown University, Division of Infectious Diseases, Providence, Rhode Island, USA
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Activity of ceftolozane/tazobactam against clinical isolates of Pseudomonas aeruginosa from patients in the Middle East and Africa - Study for Monitoring Antimicrobial Resistance Trends (SMART) 2017-2020. Int J Infect Dis 2022; 125:250-257. [PMID: 36244599 DOI: 10.1016/j.ijid.2022.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 09/30/2022] [Accepted: 10/10/2022] [Indexed: 11/07/2022] Open
Abstract
OBJECTIVES We evaluated the activity of ceftolozane/tazobactam (C/T), and comparators against clinical Pseudomonas aeruginosa isolates collected for the global Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in ten countries in the Middle East and Africa to augment scarce standardized surveillance data in this region. METHODS Minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institute broth microdilution and interpreted with European Committee on Antimicrobial Susceptibility Testing breakpoints. P. aeruginosa isolates testing with C/T MIC >4 mg/l or imipenem MIC >2 mg/l were screened for β-lactamase genes. RESULTS C/T was active against 91.4% and 87.0% of P. aeruginosa isolates from the Middle East and Africa, respectively (14-21 and 7-16 percentage points higher than most β-lactam comparators, respectively). Considerable variation in susceptibility was seen across countries, which largely correlated with the observed prevalence of carbapenemases and/or extended-spectrum β-lactamases. Differences across countries were smaller for C/T than for the β-lactam comparators, ranging from 81% C/T-susceptible among isolates from Jordan to 95% for Qatar. Among subsets resistant to meropenem, ceftazidime, or piperacillin/tazobactam, C/T maintained activity against 51-73% of isolates from the Middle East and against 27-54% from Africa (where metallo-β-lactamase and GES carbapenemase rates were higher). CONCLUSION Given the desirability of β-lactam use among clinicians, C/T represents an important option in the treatment of infections caused by P. aeruginosa.
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Cheng J, Li Q, Zhang G, Xu H, Li Y, Tian X, Chen D, Luo Z. Time to appropriate antimicrobial therapy serves an independent prognostic indicator in children with nosocomial Klebsiella pneumoniae bloodstream infection. BMC Pediatr 2022; 22:568. [PMID: 36192715 PMCID: PMC9531447 DOI: 10.1186/s12887-022-03622-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 09/20/2022] [Indexed: 02/08/2023] Open
Abstract
We tend to investigate the connection between time to appropriate therapy (TTAT) and prognosis in pediatric patients with nosocomial Klebsiella pneumoniae (K. pneumoniae) bloodstream infection, and find the optimal cutoff point for the empirical administration of antimicrobials. This retrospective study was conducted in Children's Hospital of Chongqing Medical University, and inpatients with nosocomial K. pneumoniae bloodstream infection were finally enrolled. We applied the Classification and Regression Tree (CART) analysis to find the TTAT cutoff point and the Logistic Regression analysis to evaluate prognostic indicators. The incidence of septic shock and mortality was 17.91% (12/67) and 13.43% (9/67), respectively. The CART-derived TTAT cutoff point was 10.7 h. The multivariate logistic regression analysis indicated delayed therapy (TTAT ≥ 10.7 h), pediatric risk of mortality (PRISM) III scores ≥ 10, time to positivity (TTP) ≤ 13 h, and requiring for invasive mechanical ventilation were independently associated with the incidence of septic shock (Odds ratio [OR] 9.87, 95% Confidence interval [CI] 1.46-66.59, P = 0.019; OR 9.69, 95% CI 1.15-81.39, P = 0.036; OR 8.28, 95% CI 1.37-50.10, P = 0.021; OR 6.52, 95% CI 1.08-39.51, P = 0.042; respectively) and in-hospital mortality (OR 22.19, 95% CI 1.25-393.94, P = 0.035; OR 40.06, 95% CI 2.32-691.35, P = 0.011; OR 22.60, 95% CI 1.78-287.27, P = 0.016; OR 12.21, 95% CI 1.06-140.67, P = 0.045; respectively).Conclusions: TTAT is an independent predictor of poor outcomes in children with nosocomial K. pneumoniae bloodstream infection. Initial appropriate antimicrobial therapy should be administrated timely and within 10.7 h from the onset of bloodstream infection is recommended.
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Affiliation(s)
- Jie Cheng
- Department of Emergency, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorder, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 401122, China
| | - Qinyuan Li
- Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorder, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 401122, China
| | - Guangli Zhang
- Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorder, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 401122, China
| | - Huiting Xu
- Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorder, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 401122, China
| | - Yuanyuan Li
- Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorder, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 401122, China
| | - Xiaoyin Tian
- Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorder, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 401122, China
| | - Dapeng Chen
- Department of Clinical Laboratory Center, Children's Hospital of Chongqing Medical University, Chongqing, 401122, China
| | - Zhengxiu Luo
- Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorder, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 401122, China.
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Coppola N, Maraolo AE, Onorato L, Scotto R, Calò F, Atripaldi L, Borrelli A, Corcione A, De Cristofaro MG, Durante-Mangoni E, Filippelli A, Franci G, Galdo M, Guglielmi G, Pagliano P, Perrella A, Piazza O, Picardi M, Punzi R, Trama U, Gentile I. Epidemiology, Mechanisms of Resistance and Treatment Algorithm for Infections Due to Carbapenem-Resistant Gram-Negative Bacteria: An Expert Panel Opinion. Antibiotics (Basel) 2022; 11:1263. [PMID: 36140042 PMCID: PMC9495208 DOI: 10.3390/antibiotics11091263] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/05/2022] [Accepted: 09/13/2022] [Indexed: 11/17/2022] Open
Abstract
Antimicrobial resistance represents a serious threat for global health, causing an unacceptable burden in terms of morbidity, mortality and healthcare costs. In particular, in 2017, carbapenem-resistant organisms were listed by the WHO among the group of pathogens for which novel treatment strategies are urgently needed. Fortunately, several drugs and combinations have been introduced in recent years to treat multi-drug-resistant (MDR) bacteria. However, a correct use of these molecules is needed to preserve their efficacy. In the present paper, we will provide an overview on the epidemiology and mechanisms of resistance of the most common MDR Gram-negative bacteria, proposing a treatment algorithm for the management of infections due to carbapenem-resistant bacteria based on the most recent clinical evidence.
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Affiliation(s)
- Nicola Coppola
- Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Alberto Enrico Maraolo
- Emerging Infectious Disease with High Contagiousness Unit, Cotugno Hospital, AORN Dei Colli, 80131 Naples, Italy
| | - Lorenzo Onorato
- Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Riccardo Scotto
- Infectious Diseases Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80138 Naples, Italy
| | - Federica Calò
- Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Luigi Atripaldi
- Clinical Pathology Unit, Cotugno Hospital, AORN Dei Colli, 80131 Naples, Italy
| | - Anna Borrelli
- Direzione Sanitaria, “San Giovanni di Dio e Ruggi d’Aragona” University Hospital, 84125 Salerno, Italy
| | - Antonio Corcione
- Intensive Care Unit, Monaldi Hospital, AORN Dei Colli, 80131 Naples, Italy
| | | | - Emanuele Durante-Mangoni
- Department of Precision Medicine, University of Campania ‘L. Vanvitelli’ and Unit of Infectious and Transplant Medicine, Monaldi Hospital, AORN Ospedali dei Colli, 80131 Naples, Italy
| | - Amelia Filippelli
- Department of Medicine Surgery and Dentistry, University of Salerno and Clinical Pharmacology and Pharmacogenetics Unit, “San Giovanni di Dio e Ruggi d’Aragona” University Hospital, 84125 Salerno, Italy
| | - Gianluigi Franci
- Department of Medicine Surgery and Dentistry, University of Salerno and Clinical Pathology and Microbiology Unit, “San Giovanni di Dio e Ruggi D’Aragona” University Hospital, 84125 Salerno, Italy
| | - Maria Galdo
- Pharmacy Unit, AORN Dei Colli, 80131 Naples, Italy
| | | | - Pasquale Pagliano
- Department of Medicine Surgery and Dentistry, University of Salerno, Infectious Diseases Unit, 84125 Salerno, Italy
| | - Alessandro Perrella
- Emerging Infectious Disease with High Contagiousness Unit, Cotugno Hospital, AORN Dei Colli, 80131 Naples, Italy
| | - Ornella Piazza
- Department of Medicine, Surgery and Dentistry, University of Salerno, Unit of Anesthesiology, 84125 Salerno, Italy
| | - Marco Picardi
- Department of Clinical Medicine and Surgery, Hematology Unit, Federico II University, 80131 Naples, Italy
| | - Rodolfo Punzi
- Hepatic Infectious Disease Unit, Cotugno Hospital, AORN Dei Colli, 80131 Naples, Italy
| | - Ugo Trama
- UOSD Politica del Farmaco e Dispositivi, Campania region, 80143 Naples, Italy
| | - Ivan Gentile
- Infectious Diseases Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80138 Naples, Italy
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Rando E, Giovannenze F, Murri R, Sacco E. A review of recent advances in the treatment of adults with complicated urinary tract infection. Expert Rev Clin Pharmacol 2022; 15:1053-1066. [PMID: 36062485 DOI: 10.1080/17512433.2022.2121703] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Complicated urinary tract infections (cUTIs) entail diverse clinical conditions that could be managed differently and not necessarily with premature empiric therapy. Since multidrug-resistant organisms (MDROs) are widely spreading worldwide, the possibility of encountering these resistant bacteria is inevitably part of the daily life of physicians who manage cUTIs. AREAS COVERED The advances in the management of cUTIs are explored, illustrating: 1) a proposed therapeutical approach to cUTIs within the antimicrobial stewardship context; 2) evidence regarding novel antibiotics targeting MDROs. Evidence research has been performed through MEDLINE/PubMed using appropriate keywords and terms regarding cUTIs published before June 2022. EXPERT OPINION Novel antimicrobial drugs are available in the clinicians' armamentarium. Selecting the optimal therapy for suitable patients may be challenging given the multifaceted group of cUTIs. Carbapenems use is widely increasing, the role of old β-lactam/β-lactamase inhibitors is constantly revised, and novel drugs lack real-life studies. Understanding the different ranges of the complexity of patients affected by cUTIs may help select the most suitable antibiotic for every single case. More multicentric observational studies targeting cUTIs are needed to elucidate the appropriate drug based on patient characteristics and presentations, providing stronger recommendations for cases encountered in everyday clinical practice.
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Affiliation(s)
- Emanuele Rando
- Dipartimento di Sicurezza e Bioetica - Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesca Giovannenze
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Rita Murri
- Dipartimento di Sicurezza e Bioetica - Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy.,Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Emilio Sacco
- Urology Dept., Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
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Maseda E, Suárez de la Rica A. The role of cefiderocol in clinical practice. REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2022; 35 Suppl 2:39-44. [PMID: 36193984 PMCID: PMC9632056 DOI: 10.37201/req/s02.06.2022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/29/2023]
Abstract
Cefiderocol is a new antimicrobial with a chemical structure similar to ceftazidime and cefepime. In this review we will focus on the role of cefiderocol in different clinical scenarios produced by resistant Gram-negative microorganisms, especially to carbapenems. In infections caused by Gram-negative microorganisms, inappropriate antibiotic treatment increased the risk of mortality almost fourfold. In patients with hospital-acquired infection and septic shock; with sepsis and poor functional reserve due to fragility; in immunocompromised patients; and in those with local ecology, individual history of colonization or previous infection and risk factors for carbapenem-resistant Enterobacteriaceae (CRE) such as the presence of chronic multi-morbidities, the best option would be to start an active empirical treatment against gram-negative bacteria resistant to carbapenems and later in 24-36 h with the information obtained from the cultures we could decide on a definitive empirical or directed treatment and avoid unnecessary overuse of these antibiotics. Cefiderocol would be in these cases a good candidate due to its excellent in vitro activity against all classes of beta-lactamase-producing Gram-negatives (including carbapenemase class A, B and D producers), as well as against non-fermenting Gram-negatives such as P. aeruginosa, Acinetobacter spp. and S. maltophilia. It is necessary to optimize the use of new antibiotics such as cefiderocol, guaranteeing the best available treatment to patients while delaying the emergence and spread of resistance.
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Affiliation(s)
- E Maseda
- Emilio Maseda, Servicio de Anestesia y Reanimación. Hospital Valdecilla, Santander, Spain.
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Swaminathan S, Routray A, Mane A. Early and Appropriate Use of Ceftazidime-Avibactam in the Management of Multidrug-Resistant Gram-Negative Bacterial Infections in the Indian Scenario. Cureus 2022; 14:e28283. [PMID: 36072213 PMCID: PMC9440350 DOI: 10.7759/cureus.28283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/22/2022] [Indexed: 11/23/2022] Open
Abstract
The increasing prevalence of antibiotic-resistant pathogens exerts a substantial burden on the healthcare infrastructure worldwide. The World Health Organization (WHO) has declared that multidrug-resistant (MDR) Gram-negative pathogens, especially, carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii, and Pseudomonas aeruginosa as the topmost priority while developing newer antimicrobials. The increasing prevalence of infectious diseases caused by MDR Gram-negative bacteria also poses a challenge when choosing the empiric antimicrobial therapy for seriously ill hospitalized patients. The infections caused by MDR Gram-negative organisms ultimately result in increased mortality, morbidity, prolonged hospital stay, and increased cost of management. To tackle these challenges, newer antimicrobials like ceftazidime-avibactam were explored. The article also discusses the in vitro activity and therapeutic efficacy of ceftazidime-avibactam along with its pharmacokinetic properties and the role it will play in the management of MDR Gram-negative organisms in the Indian setting. Several studies have highlighted the role of early and appropriate antibiotic use in the reduction of mortality in patients with Gram-negative infections. Timely initiation of appropriate antibiotic therapy for serious infections leads to favorable clinical outcomes. Early and appropriate use of ceftazidime-avibactam while treating MDR Gram-negative infections has been associated with improved clinical outcomes. The aim of this review is to highlight the efficacy of ceftazidime-avibactam in the treatment of MDR Gram-negative infections. We have also summarized the information on outcomes achieved by early and appropriate use of ceftazidime-avibactam.
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Canton R, Doi Y, Simner PJ. Treatment of carbapenem-resistant Pseudomonas aeruginosa infections: a case for cefiderocol. Expert Rev Anti Infect Ther 2022; 20:1077-1094. [PMID: 35502603 DOI: 10.1080/14787210.2022.2071701] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 04/26/2022] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Carbapenem-resistant (CR) Pseudomonas aeruginosa infections constitute a serious clinical threat globally. Patients are often critically ill and/or immunocompromised. Antibiotic options are limited and are currently centered on beta-lactam-beta-lactamase inhibitor (BL-BLI) combinations and the siderophore cephalosporin cefiderocol. AREAS COVERED This article reviews the mechanisms of P. aeruginosa resistance and their potential impact on the activity of current treatment options, along with evidence for the clinical efficacy of BL-BLI combinations in P. aeruginosa infections, some of which specifically target infections due to CR organisms. The preclinical and clinical evidence supporting cefiderocol as a treatment option for P. aeruginosa involving infections is also reviewed. EXPERT OPINION Cefiderocol is active against most known P. aeruginosa mechanisms mediating carbapenem resistance. It is stable against different serine- and metallo-beta-lactamases, and, due to its iron channel-dependent uptake mechanism, is not impacted by porin channel loss. Furthermore, the periplasmic level of cefiderocol is not affected by upregulated efflux pumps. The potential for on-treatment resistance development currently appears to be low, although more clinical data are required. Information from surveillance programs, real-world compassionate use, and clinical studies demonstrate that cefiderocol is an important treatment option for CR P. aeruginosa infections.
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Affiliation(s)
- Rafael Canton
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
| | - Yohei Doi
- Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Patricia J Simner
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Goyal M, Pelegrin AC, Jaillard M, Saharman YR, Klaassen CHW, Verbrugh HA, Severin JA, van Belkum A. Whole Genome Multi-Locus Sequence Typing and Genomic Single Nucleotide Polymorphism Analysis for Epidemiological Typing of Pseudomonas aeruginosa From Indonesian Intensive Care Units. Front Microbiol 2022; 13:861222. [PMID: 35910643 PMCID: PMC9329958 DOI: 10.3389/fmicb.2022.861222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 06/17/2022] [Indexed: 11/13/2022] Open
Abstract
We have previously studied carbapenem non-susceptible Pseudomonas aeruginosa (CNPA) strains from intensive care units (ICUs) in a referral hospital in Jakarta, Indonesia (Pelegrin et al., 2019). We documented that CNPA transmissions and acquisitions among patients were variable over time and that these were not significantly reduced by a set of infection control measures. Three high risk international CNPA clones (sequence type (ST)235, ST823, ST357) dominated, and carbapenem resistance was due to carbapenemase-encoding genes and mutations in the porin OprD. Pelegrin et al. (2019) reported core genome analysis of these strains. We present a more refined and detailed whole genome-based analysis of major clones represented in the same dataset. As per our knowledge, this is the first study reporting Single Nucleotide Polymorphisms (wgSNP) analysis of Pseudomonas strains. With whole genome-based Multi Locus Sequence Typing (wgMLST) of the 3 CNPA clones (ST235, ST357 and ST823), three to eleven subgroups with up to 200 allelic variants were observed for each of the CNPA clones. Furthermore, we analyzed these CNPA clone clusters for the presence of wgSNP to redefine CNPA transmission events during hospitalization. A maximum number 35350 SNPs (including non-informative wgSNPs) and 398 SNPs (ST-specific_informative-wgSNPs) were found in ST235, 34,570 SNPs (including non-informative wgSNPs) and 111 SNPs (ST-specific_informative-wgSNPs) in ST357 and 26,443 SNPs (including non-informative SNPs) and 61 SNPs (ST-specific_informative-wgSNPs) in ST823. ST-specific_Informative-wgSNPs were commonly noticed in sensor-response regulator genes. However, the majority of non-informative wgSNPs was found in conserved hypothetical proteins or in uncharacterized proteins. Of note, antibiotic resistance and virulence genes segregated according to the wgSNP analyses. A total of 8 transmission chains for ST235 strains followed by 9 and 4 possible transmission chains for ST357 and ST823 were traceable on the basis of pairwise distances of informative-wgSNPs (0 to 4 SNPs) among the strains. The present study demonstrates the value of detailed whole genome sequence analysis for highly refined epidemiological analysis of P. aeruginosa.
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Affiliation(s)
- Manisha Goyal
- bioMérieux Open Innovation and Partnerships, Macry-LÉtoile, France
| | | | | | - Yulia Rosa Saharman
- Department of Clinical Microbiology, Faculty of Medicine, Dr. Cipto Mangunkusumo General Hospital, Universitas Indonesia, Jakarta, Indonesia
- Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Corné H. W. Klaassen
- Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Henri A. Verbrugh
- Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Juliëtte A. Severin
- Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Alex van Belkum
- bioMérieux Open Innovation and Partnerships, Macry-LÉtoile, France
- *Correspondence: Alex van Belkum,
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Avent ML, McCarthy KL, Sime FB, Naicker S, Heffernan AJ, Wallis SC, Paterson DL, Roberts JA. Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection Model. Microbiol Spectr 2022; 10:e0052522. [PMID: 35442072 PMCID: PMC9241727 DOI: 10.1128/spectrum.00525-22] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 03/28/2022] [Indexed: 12/02/2022] Open
Abstract
Debate continues as to the role of combination antibiotic therapy for the management of Pseudomonas aeruginosa infections. We studied the extent of bacterial killing by and the emergence of resistance to meropenem and amikacin as monotherapies and as a combination therapy against susceptible and resistant P. aeruginosa isolates from bacteremic patients using the dynamic in vitro hollow-fiber infection model. Three P. aeruginosa isolates (meropenem MICs of 0.125, 0.25, and 64 mg/L) were used, simulating bacteremia with an initial inoculum of ~1 × 105 CFU/mL and the expected pharmacokinetics of meropenem and amikacin in critically ill patients. For isolates susceptible to amikacin and meropenem (isolates 1 and 2), the extent of bacterial killing was increased with the combination regimen compared with the killing by monotherapy of either antibiotic. Both the combination and meropenem monotherapy were able to sustain bacterial killing throughout the 7-day treatment course, whereas regrowth of bacteria occurred with amikacin monotherapy after 12 h. For the meropenem-resistant P. aeruginosa isolate (isolate 3), only the combination regimen demonstrated bacterial killing. Given that tailored antibiotic regimens can maximize potential synergy against some isolates, future studies should explore the benefit of combination therapy against resistant P. aeruginosa. IMPORTANCE Current guidelines recommend that aminoglycosides should be used in combination with β-lactam antibiotics as initial empirical therapy for serious infections, and otherwise, patients should receive β-lactam antibiotic monotherapy. Given the challenges associated with studying the clinical effect of different antibiotic strategies on patient outcomes, useful data for subsequent informed clinical testing can be obtained from in vitro models like the hollow-fiber infection model (HFIM). Based on the findings of our HFIM, we propose that the initial use of combination therapy with meropenem and amikacin provides some bacterial killing against carbapenem-resistant P. aeruginosa isolates. For susceptible isolates, combination therapy may only be of benefit in specific patient populations, such as critically ill or immunocompromised patients. Therefore, clinicians may want to consider using the combination therapy for the initial management and ceasing the aminoglycosides once antibiotic susceptibility results have been obtained.
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Affiliation(s)
- Minyon L. Avent
- The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
- Queensland Statewide Antimicrobial Stewardship Program, Royal Brisbane and Women’s Hospital, Herston, Queensland, Australia
| | - Kate L. McCarthy
- The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
- Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, Australia
| | - Fekade B. Sime
- The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
| | - Saiyuri Naicker
- The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
| | - Aaron J. Heffernan
- The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
- School of Medicine, Griffith University, Southport, Queensland, Australia
- Department of Pharmacy, Royal Brisbane and Women’s Hospital, Brisbane, Australia
| | - Steven C. Wallis
- The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
| | - David L. Paterson
- The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
| | - Jason A. Roberts
- The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
- Department of Pharmacy, Royal Brisbane and Women’s Hospital, Brisbane, Australia
- Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Australia
- Division of Anaesthesiology, Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France
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Montrucchio G, Costamagna A, Pierani T, Petitti A, Sales G, Pivetta E, Corcione S, Curtoni A, Cavallo R, De Rosa FG, Brazzi L. Bloodstream Infections Caused by Carbapenem-Resistant Pathogens in Intensive Care Units: Risk Factors Analysis and Proposal of a Prognostic Score. Pathogens 2022; 11:pathogens11070718. [PMID: 35889963 PMCID: PMC9315650 DOI: 10.3390/pathogens11070718] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/20/2022] [Accepted: 06/22/2022] [Indexed: 02/06/2023] Open
Abstract
Considering the growing prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) bloodstream infection (BSI) in intensive care units (ICUs), the identification of specific risk factors and the development of a predictive model allowing for the early identification of patients at risk for CR-Klebsiella pneumoniae, Acinetobacter baumannii or Pseudomonas aeruginosa are essential. In this retrospective case–control study including all consecutive patients showing an episode of BSI in the ICUs of a university hospital in Italy in the period January–December 2016, patients with blood culture positive for CR-GNB pathogens and for any other bacteria were compared. A total of 106 patients and 158 episodes of BSI were identified. CR-GNBs induced BSI in 49 patients (46%) and 58 episodes (37%). Prognosis score and disease severity at admission, parenteral nutrition, cardiovascular surgery prior to admission to ICU, the presence of sepsis and septic shock, ventilation-associated pneumonia and colonization of the urinary or intestinal tract were statistically significant in the univariate analysis. The duration of ventilation and mortality at 28 days were significantly higher among CR-GNB cases. The prognostic model based on age, presence of sepsis, previous cardiovascular surgery, SAPS II, rectal colonization and invasive respiratory infection from the same pathogen showed a C-index of 89.6%. The identified risk factors are in line with the international literature. The proposal prognostic model seems easy to use and shows excellent performance but requires further studies to be validated.
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Affiliation(s)
- Giorgia Montrucchio
- Department of Surgical Sciences, University of Turin, 10126 Turin, Italy; (A.C.); (T.P.); (A.P.); (G.S.); (L.B.)
- Department of Anesthesia, Intensive Care and Emergency, Città Della Salute e Della Scienza di Torino University Hospital, 10126 Turin, Italy
- Correspondence:
| | - Andrea Costamagna
- Department of Surgical Sciences, University of Turin, 10126 Turin, Italy; (A.C.); (T.P.); (A.P.); (G.S.); (L.B.)
- Department of Anesthesia, Intensive Care and Emergency, Città Della Salute e Della Scienza di Torino University Hospital, 10126 Turin, Italy
| | - Tommaso Pierani
- Department of Surgical Sciences, University of Turin, 10126 Turin, Italy; (A.C.); (T.P.); (A.P.); (G.S.); (L.B.)
- Department of Anesthesia, Intensive Care and Emergency, Città Della Salute e Della Scienza di Torino University Hospital, 10126 Turin, Italy
| | - Alessandra Petitti
- Department of Surgical Sciences, University of Turin, 10126 Turin, Italy; (A.C.); (T.P.); (A.P.); (G.S.); (L.B.)
- Department of Anesthesia, Intensive Care and Emergency, Città Della Salute e Della Scienza di Torino University Hospital, 10126 Turin, Italy
| | - Gabriele Sales
- Department of Surgical Sciences, University of Turin, 10126 Turin, Italy; (A.C.); (T.P.); (A.P.); (G.S.); (L.B.)
- Department of Anesthesia, Intensive Care and Emergency, Città Della Salute e Della Scienza di Torino University Hospital, 10126 Turin, Italy
| | - Emanuele Pivetta
- Department of General and Specialized Medicine, Division of Emergency Medicine and High Dependency Unit, Città Della Salute e Della Scienza di Torino University Hospital, 10126 Turin, Italy;
| | - Silvia Corcione
- Department of Medical Sciences, Infectious Diseases, University of Turin, 10126 Turin, Italy; (S.C.); (F.G.D.R.)
- Division of Geographic Medicine, Tufts University School of Medicine, 145 Harrison Ave, Boston, MA 02111, USA
| | - Antonio Curtoni
- Microbiology and Virology Unit, Città Della Salute e Della Scienza di Torino University Hospital, 10126 Turin, Italy; (A.C.); (R.C.)
| | - Rossana Cavallo
- Microbiology and Virology Unit, Città Della Salute e Della Scienza di Torino University Hospital, 10126 Turin, Italy; (A.C.); (R.C.)
| | - Francesco Giuseppe De Rosa
- Department of Medical Sciences, Infectious Diseases, University of Turin, 10126 Turin, Italy; (S.C.); (F.G.D.R.)
| | - Luca Brazzi
- Department of Surgical Sciences, University of Turin, 10126 Turin, Italy; (A.C.); (T.P.); (A.P.); (G.S.); (L.B.)
- Department of Anesthesia, Intensive Care and Emergency, Città Della Salute e Della Scienza di Torino University Hospital, 10126 Turin, Italy
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Yoon CH, Bartlett S, Stoesser N, Pouwels KB, Jones N, Crook DW, Peto TEA, Walker AS, Eyre DW. Mortality risks associated with empirical antibiotic activity in Escherichia coli bacteraemia: an analysis of electronic health records. J Antimicrob Chemother 2022; 77:2536-2545. [PMID: 35723965 PMCID: PMC9410673 DOI: 10.1093/jac/dkac189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 05/17/2022] [Indexed: 11/14/2022] Open
Abstract
Background Reported bacteraemia outcomes following inactive empirical antibiotics (based on in vitro testing) are conflicting, potentially reflecting heterogeneity in causative species, MIC breakpoints defining resistance/susceptibility, and times to rescue therapy. Methods We investigated adult inpatients with Escherichia coli bacteraemia at Oxford University Hospitals, UK, from 4 February 2014 to 30 June 2021 who were receiving empirical amoxicillin/clavulanate with/without other antibiotics. We used Cox regression to analyse 30 day all-cause mortality by in vitro amoxicillin/clavulanate susceptibility (activity) using the EUCAST resistance breakpoint (>8/2 mg/L), categorical MIC, and a higher resistance breakpoint (>32/2 mg/L), adjusting for other antibiotic activity and confounders including comorbidities, vital signs and blood tests. Results A total of 1720 E. coli bacteraemias (1626 patients) were treated with empirical amoxicillin/clavulanate. Thirty-day mortality was 193/1400 (14%) for any active baseline therapy and 52/320 (16%) for inactive baseline therapy (P = 0.17). With EUCAST breakpoints, there was no evidence that mortality differed for inactive versus active amoxicillin/clavulanate [adjusted HR (aHR) = 1.27 (95% CI 0.83–1.93); P = 0.28], nor of an association with active aminoglycoside (P = 0.93) or other active antibiotics (P = 0.18). Considering categorical amoxicillin/clavulanate MIC, MICs > 32/2 mg/L were associated with mortality [aHR = 1.85 versus MIC = 2/2 mg/L (95% CI 0.99–3.73); P = 0.054]. A higher resistance breakpoint (>32/2 mg/L) was independently associated with higher mortality [aHR = 1.82 (95% CI 1.07–3.10); P = 0.027], as were MICs > 32/2 mg/L with active empirical aminoglycosides [aHR = 2.34 (95% CI 1.40–3.89); P = 0.001], but not MICs > 32/2 mg/L with active non-aminoglycoside antibiotic(s) [aHR = 0.87 (95% CI 0.40–1.89); P = 0.72]. Conclusions We found no evidence that EUCAST-defined amoxicillin/clavulanate resistance was associated with increased mortality, but a higher resistance breakpoint (MIC > 32/2 mg/L) was. Additional active baseline non-aminoglycoside antibiotics attenuated amoxicillin/clavulanate resistance-associated mortality, but aminoglycosides did not. Granular phenotyping and comparison with clinical outcomes may improve AMR breakpoints.
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Affiliation(s)
- Chang Ho Yoon
- Big Data Institute, Nuffield Department of Population Health, University of Oxford, UK.,Nuffield Department of Medicine, University of Oxford, UK
| | - Sean Bartlett
- Nuffield Department of Medicine, University of Oxford, UK
| | - Nicole Stoesser
- Nuffield Department of Medicine, University of Oxford, UK.,Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.,The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.,Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, UK
| | - Koen B Pouwels
- Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, UK.,Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Nicola Jones
- Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK
| | - Derrick W Crook
- Nuffield Department of Medicine, University of Oxford, UK.,Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.,The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.,Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, UK
| | - Tim E A Peto
- Nuffield Department of Medicine, University of Oxford, UK.,Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.,The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.,Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, UK
| | - A Sarah Walker
- Nuffield Department of Medicine, University of Oxford, UK.,The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.,Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, UK
| | - David W Eyre
- Big Data Institute, Nuffield Department of Population Health, University of Oxford, UK.,Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.,The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.,Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, UK
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Hung YP, Lee CC, Ko WC. Effects of Inappropriate Administration of Empirical Antibiotics on Mortality in Adults With Bacteraemia: Systematic Review and Meta-Analysis. Front Med (Lausanne) 2022; 9:869822. [PMID: 35712120 PMCID: PMC9197423 DOI: 10.3389/fmed.2022.869822] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 05/03/2022] [Indexed: 11/13/2022] Open
Abstract
Introduction Bloodstream infections are associated with high mortality rates and contribute substantially to healthcare costs, but a consensus on the prognostic benefits of appropriate empirical antimicrobial therapy (EAT) for bacteraemia is lacking. Methods We performed a systematic search of the PubMed, Cochrane Library, and Embase databases through July 2021. Studies comparing the mortality rates of patients receiving appropriate and inappropriate EAT were considered eligible. The quality of the included studies was assessed using Joanna Briggs Institute checklists. Results We ultimately assessed 198 studies of 89,962 total patients. The pooled odds ratio (OR) for the prognostic impacts of inappropriate EAT was 2.06 (P < 0.001), and the funnel plot was symmetrically distributed. Among subgroups without between-study heterogeneity (I2 = 0%), those of patients with severe sepsis and septic shock (OR, 2.14), Pitt bacteraemia scores of ≥4 (OR, 1.88), cirrhosis (OR, 2.56), older age (OR, 1.78), and community-onset/acquired Enterobacteriaceae bacteraemia infection (OR, 2.53) indicated a significant effect of inappropriate EAT on mortality. The pooled adjusted OR of 125 studies using multivariable analyses for the effects of inappropriate EAT on mortality was 2.02 (P < 0.001), and the subgroups with low heterogeneity (I2 < 25%) exhibiting significant effects of inappropriate EAT were those of patients with vascular catheter infections (adjusted OR, 2.40), pneumonia (adjusted OR, 2.72), or Enterobacteriaceae bacteraemia (adjusted OR, 4.35). Notably, the pooled univariable and multivariable analyses were consistent in revealing the negligible impacts of inappropriate EAT on the subgroups of patients with urinary tract infections and Enterobacter bacteraemia. Conclusion Although the current evidence is insufficient to demonstrate the benefits of prompt EAT in specific bacteraemic populations, we indicated that inappropriate EAT is associated with unfavorable mortality outcomes overall and in numerous subgroups. Prospective studies designed to test these specific populations are needed to ensure reliable conclusions. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier: CRD42021270274.
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Affiliation(s)
- Yuan-Pin Hung
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan City, Taiwan.,Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City, Taiwan.,Department of Medicine, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
| | - Ching-Chi Lee
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City, Taiwan.,Clinical Medicine Research Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City, Taiwan
| | - Wen-Chien Ko
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City, Taiwan.,Department of Medicine, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
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41
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Metabolic preference assay for rapid diagnosis of bloodstream infections. Nat Commun 2022; 13:2332. [PMID: 35484129 PMCID: PMC9050716 DOI: 10.1038/s41467-022-30048-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 04/14/2022] [Indexed: 12/13/2022] Open
Abstract
Bloodstream infections (BSIs) cause >500,000 infections and >80,000 deaths per year in North America. The length of time between the onset of symptoms and administration of appropriate antimicrobials is directly linked to mortality rates. It currently takes 2–5 days to identify BSI pathogens and measure their susceptibility to antimicrobials – a timeline that directly contributes to preventable deaths. To address this, we demonstrate a rapid metabolic preference assay (MPA) that uses the pattern of metabolic fluxes observed in ex-vivo microbial cultures to identify common pathogens and determine their antimicrobial susceptibility profiles. In a head-to-head race with a leading platform (VITEK 2, BioMérieux) used in diagnostic laboratories, MPA decreases testing timelines from 40 hours to under 20. If put into practice, this assay could reduce septic shock mortality and reduce the use of broad spectrum antibiotics. It is currently slow to identify bloodstream infection pathogens. Here the authors report a rapid metabolic preference assay that uses the pattern of metabolic fluxes observed in ex-vivo microbial cultures to identify common pathogens and determine their antimicrobial susceptibility profiles.
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Hart RJ, Morici LA. Vaccination to Prevent Pseudomonas aeruginosa Bloodstream Infections. Front Microbiol 2022; 13:870104. [PMID: 35418967 PMCID: PMC8996235 DOI: 10.3389/fmicb.2022.870104] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 03/08/2022] [Indexed: 12/29/2022] Open
Abstract
The bacterium Pseudomonas aeruginosa (Pa) is ubiquitous in the environment and causes opportunistic infections in humans. Pa is increasingly becoming one of the most difficult to treat microorganisms due to its intrinsic and acquired resistance to multiple antibiotics. The World Health Organization estimates that at least 700,000 people die each year from drug resistant microbial infections and have listed Pa as one of three bacterial species for which there is the most critical need for the development of novel therapeutics. Pa is a common cause of bloodstream infections (BSI) and bacterial sepsis. With nearly 49 million sepsis cases and 11 million deaths worldwide, an effective vaccine against Pa could prevent the morbidity and mortality resulting from Pa BSI and lessen our dependence on antibiotics. We reviewed the current landscape of Pa vaccines in pre-clinical and clinical stages over the last two decades. It is readily apparent that Pa vaccine development efforts have been largely directed at the prevention of pulmonary infections, likely due to Pa's devastating impact on individuals with cystic fibrosis. However, the increase in nosocomial infections, BSI-related sepsis, and the emergence of widespread antibiotic resistance have converged as a major threat to global public health. In this perspective, we draw attention to potential Pa vaccine candidates and encourage a renewed effort for prophylactic vaccine development to prevent drug-resistant Pa BSI.
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Affiliation(s)
- Robert J Hart
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, United States
| | - Lisa A Morici
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, United States
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Teitelbaum D, Elligsen M, Katz K, Lam PW, Lo J, MacFadden D, Vermeiren C, Daneman N. Introducing the Escalation Antibiogram: A Simple Tool to Inform Changes in Empiric Antimicrobials in the Non-Responding Patient. Clin Infect Dis 2022; 75:1763-1771. [PMID: 35380628 DOI: 10.1093/cid/ciac256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Hospital antibiograms guide initial empiric antibiotic treatment selections, but do not directly inform escalation of treatment among non-responding patients. METHODS Using Gram-negative bacteremia (GNB) as an exemplar condition, we sought to introduce the concept of an Escalation Antibiogram. Among GNBs between 2017-2020 from six hospitals in the Greater Toronto Area, we generated escalation antibiograms for each of 12 commonly used agents. Among organisms resistant to that antibiotic, we calculated the likelihood of susceptibility to each of the other 11 agents. In subgroup analyses, we examined escalation antibiograms across study years, individual hospitals, community versus hospital onset, and pathogen type. RESULTS Among 6577 GNB episodes, the likelihood of coverage was: ampicillin 31.8%, cefazolin 62.7%, ceftriaxone 67.1%, piperacillin-tazobactam 72.5%, ceftazidime 74.1%, trimethoprim-sulfamethoxazole 74.4%, ciprofloxacin 77.1%, tobramycin 88.3%, gentamicin 88.8%, ertapenem 91.0%, amikacin 97.5%, and meropenem 98.2%. The escalation antibiograms revealed marked shifts in likelihood of coverage by the remaining 11 agents. For example, among ceftriaxone-resistant isolates piperacillin-tazobactam susceptibility (21.2%) was significantly lower than trimethoprim-sulfamethoxazole (54.2%, p<0.0001), ciprofloxacin (63.0%, p<0.0001), ertapenem (73.4%, p<0.0001), tobramycin (80.1%, p<0.0001), gentamicin (82.8%, p<0.0001), meropenem (94.3%, p<0.0001), and amikacin (97.1%, p<0.0001). Trimethoprim-sulfamethoxazole was the second ranked agent in the meropenem escalation antibiogram (49.6%), and first in the amikacin escalation antibiogram (86.0%). Escalation antibiograms were consistent across 4 study years and 6 hospitals. CONCLUSION Escalation antibiograms can be generated to inform empiric treatment changes in non-responding patients. These tools can yield important insights such as avoiding the common maneuver of escalating from ceftriaxone to piperacillin-tazobactam in suspected GNB.
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Affiliation(s)
- Daniel Teitelbaum
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Marion Elligsen
- Department of Pharmacy, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Kevin Katz
- Department of Microbiology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.,Department of Laboratory Medicine, University of Toronto, Ontario, Canada.,Shared Hospital Laboratories, Toronto, Ontario, Canada
| | - Philip W Lam
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Infectious Diseases, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Jennifer Lo
- Department of Pharmacy, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Derek MacFadden
- Division of Infectious Diseases, The Ottawa Hospital, University of Ottawa, Ontario, Canada
| | - Christie Vermeiren
- Department of Laboratory Medicine, University of Toronto, Ontario, Canada.,Shared Hospital Laboratories, Toronto, Ontario, Canada
| | - Nick Daneman
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Infectious Diseases, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.,Sunnybrook Research Institute, Toronto Ontario Canada
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Chaftari AM, Hachem R, Malek AE, Mulanovich V, Szvalb A, Jiang Y, Yuan Y, Ali S, Deeba R, Chaftari P, Raad I. A Prospective Randomized Study Comparing Ceftolozane/Tazobactam to Standard of Care in the Management of Neutropenia and Fever in Patients with Hematological Malignancies. Open Forum Infect Dis 2022; 9:ofac079. [PMID: 35663286 PMCID: PMC9154317 DOI: 10.1093/ofid/ofac079] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 02/10/2022] [Indexed: 11/12/2022] Open
Abstract
Abstract
Background
With increased use of antibiotics in high risk patients, the investigation of new antibiotics to cover potentially resistant pathogens is warranted. In this prospective randomized trial (NCT03485950), we compared ceftolozane/tazobactam (C/T), a new cephalosporin/β-lactamase inhibitor, to the standard-of-care (SOC) for the empiric treatment of neutropenia and fever in patients with hematological malignancies.
Methods
We enrolled 100 patients to receive intravenous (IV) C/T or SOC antibiotics (cefepime, piperacillin/tazobactam, or meropenem) in combination with gram-positive antibacterial agents. We evaluated responses at the end of IV therapy (EOIV), test of cure (TOC; days 21-28), and late follow-up (LFU; days 35-42).
Results
We analyzed 47 C/T patients and 50 SOC patients. C/T patients had a higher rate of favorable clinical response at EOIV (87% vs 72%). A one-sided non-inferiority analysis indicated that C/T was at least not inferior to the SOC for favorable clinical response at EOIV (p=0.002), TOC (p=0.004) and LFU (p=0.002). Superiority tests showed that C/T led to significantly lower rates of clinical failure at TOC (6% vs 30%; p=0.003) and LFU (9% vs 30%; p=0.008). C/T and SOC patients with documented infections had similar rates of favorable microbiological response. Serious adverse events leading to drug discontinuation (2% vs 0%; p=0.48), and overall mortality (6% vs 4%; p=0.67) were similar in both groups.
Conclusions
The empiric use of C/T in high-risk patients with hematological malignancies and febrile neutropenia is safe and associated with better clinical outcomes than SOC antimicrobial agents.
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Affiliation(s)
- Anne-Marie Chaftari
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ray Hachem
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Alexandre E Malek
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Victor Mulanovich
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ariel Szvalb
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ying Jiang
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ying Yuan
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Shahnoor Ali
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Rita Deeba
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Patrick Chaftari
- Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Issam Raad
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Kunz Coyne AJ, El Ghali A, Holger D, Rebold N, Rybak MJ. Therapeutic Strategies for Emerging Multidrug-Resistant Pseudomonas aeruginosa. Infect Dis Ther 2022; 11:661-682. [PMID: 35150435 PMCID: PMC8960490 DOI: 10.1007/s40121-022-00591-2] [Citation(s) in RCA: 106] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 01/10/2022] [Indexed: 12/18/2022] Open
Abstract
Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates are frequent causes of serious nosocomial infections that may compromise the selection of antimicrobial therapy. The goal of this review is to summarize recent epidemiologic, microbiologic, and clinical data pertinent to the therapeutic management of patients with infections caused by MDR/XDR-P. aeruginosa. Historically, conventional antipseudomonal β-lactam antibiotics have been used for the empiric treatment of MDR/XDR-P. aeruginosa. Owing to the remarkable capacity of P. aeruginosa to confer resistance via multiple mechanisms, these traditional therapies are often rendered ineffective. To increase the likelihood of administering empiric antipseudomonal therapy with in vitro activity, a second agent from a different antibiotic class is often administered concomitantly with a traditional antipseudomonal β-lactam. However, combination therapy may pose an increased risk of antibiotic toxicity and secondary infection, notably, Clostridioides difficile. Multiple novel agents that demonstrate in vitro activity against MDR-P. aeruginosa (e.g., β-lactam/β-lactamase inhibitor combinations and cefiderocol) have been recently granted US Food and Drug Administration (FDA) approval and are promising additions to the antipseudomonal armamentarium. Even so, comparative clinical data pertaining to these novel agents is sparse, and concerns surrounding the scarcity of antibiotics active against refractory MDR/XDR-P. aeruginosa necessitates continued assessment of alternative therapies. This is particularly important in patients with cystic fibrosis (CF) who may be chronically colonized and suffer from recurrent infections and disease exacerbations due in part to limited efficacious antipseudomonal agents. Bacteriophages represent a promising candidate for combatting recurrent and refractory infections with their ability to target specific host bacteria and circumvent traditional mechanisms of antibiotic resistance seen in MDR/XDR-P. aeruginosa. Future goals for the management of these infections include increased comparator clinical data of novel agents to determine in what scenario certain agents may be preferred over others. Until then, appropriate treatment of these infections requires a thorough evaluation of patient- and infection-specific factors to guide empiric and definitive therapeutic decisions.
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Affiliation(s)
- Ashlan J Kunz Coyne
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI, 48201, USA
| | - Amer El Ghali
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI, 48201, USA
| | - Dana Holger
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI, 48201, USA
| | - Nicholas Rebold
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI, 48201, USA
| | - Michael J Rybak
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI, 48201, USA.
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46
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Lynch JP, Zhanel GG. Pseudomonas aeruginosa Pneumonia: Evolution of Antimicrobial Resistance and Implications for Therapy. Semin Respir Crit Care Med 2022; 43:191-218. [PMID: 35062038 DOI: 10.1055/s-0041-1740109] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Pseudomonas aeruginosa (PA), a non-lactose-fermenting gram-negative bacillus, is a common cause of nosocomial infections in critically ill or debilitated patients, particularly ventilator-associated pneumonia (VAP), and infections of urinary tract, intra-abdominal, wounds, skin/soft tissue, and bloodstream. PA rarely affects healthy individuals, but may cause serious infections in patients with chronic structural lung disease, comorbidities, advanced age, impaired immune defenses, or with medical devices (e.g., urinary or intravascular catheters, foreign bodies). Treatment of pseudomonal infections is difficult, as PA is intrinsically resistant to multiple antimicrobials, and may acquire new resistance determinants even while on antimicrobial therapy. Mortality associated with pseudomonal VAP or bacteremias is high (> 35%) and optimal therapy is controversial. Over the past three decades, antimicrobial resistance (AMR) among PA has escalated globally, via dissemination of several international multidrug resistant "epidemic" clones. We discuss the importance of PA as a cause of pneumonia including health care-associated pneumonia, hospital-acquired pneumonia, VAP, the emergence of AMR to this pathogen, and approaches to therapy (both empirical and definitive).
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Affiliation(s)
- Joseph P Lynch
- Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California
| | - George G Zhanel
- Department of Medical Microbiology/Infectious Diseases, University of Manitoba, Max Rady College of Medicine, Winnipeg, Manitoba, Canada
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47
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Predictors of multidrug resistant Pseudomonas aeruginosa involvement in bloodstream infections. Curr Opin Infect Dis 2021; 34:686-692. [PMID: 34310454 DOI: 10.1097/qco.0000000000000768] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW In the last decades, there has been a worldwide worrisome spread of multidrug resistant (MDR) Pseudomonas aeruginosa. Treatment of these infections is challenging, in part due to the lack of therapeutic options, and the importance of prescribing an adequate empirical treatment. Bacteraemia is one of the most severe infections, with mortality rates ranging between 20 and 40%. RECENT FINDINGS It is key to understand which patients are at a higher risk of MDR P. aeruginosa bloodstream infection (BSI) to better direct empirical therapies and improve overall survival. Immunocompromised patients are among the most vulnerable for the worst outcomes. Environmental exposure, integrity of the microbiota, and host immunity are the key determinants for the initial colonization and expansion on mucosal surfaces and potential invasion afterwards by MDR P. aeruginosa. SUMMARY Available data suggest that high colonization pressure (settings with high prevalence like intensive care units), disruption of healthy microbiota (prior use of antibiotics, in particular fluoroquinolones), immunosuppression (neutropenia) and breaking natural barriers (venous or urine catheters), are the main risk factors for MDR P. aeruginosa BSI.
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48
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Sid Ahmed MA, Hamid JM, Husain AA, Hadi HA, Skariah S, Sultan AA, Ibrahim EB, Al Khal AL, Soderquist B, Jass J, Omrani AS. Clinical outcomes, molecular epidemiology and resistance mechanisms of multidrug-resistant Pseudomonas aeruginosa isolated from bloodstream infections from Qatar. Ann Med 2021; 53:2345-2353. [PMID: 34882052 PMCID: PMC8667892 DOI: 10.1080/07853890.2021.2012588] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Bloodstream infections (BSIs) caused by multidrug-resistant (MDR)-Pseudomonas aeruginosa are associated with poor clinical outcomes, at least partly due to delayed appropriate antimicrobial therapy. The characteristics of MDR-P. aeruginosa bloodstream isolates have not been evaluated in Qatar. Our study aimed to examine in vitro susceptibility, clinical and molecular characteristics, and mechanisms of resistance of MDR-P. aeruginosa bloodstream isolates from Qatar. MATERIALS AND METHODS We included all MDR-P. aeruginosa isolated from blood cultures taken between October 2014 and September 2017. Blood cultures were processed using BD BACTEC™ FX automated system. BD Phoenix™ was used for identification, Liofilchem® MIC Test Strips for MIC determination. Whole-genome sequencing was performed using the Illumina-HiSeq-2000. RESULTS Out of 362 P. aeruginosa bloodstream isolates, 16 (4.4%) were MDR. The median patient age was 55 years (range 43-81) and all patients presented with septic shock. Most patients received meropenem (12/16) and/or colistin (10/16). Clinical response was achieved in eight patients, and five patients died within 30-days. MDR-P. aeruginosa isolates belonged to 13 different sequence types. All isolates were non-susceptible to cefepime and ciprofloxacin. The most active agents were colistin (16/16) and aztreonam (10/16). Seven isolates produced blaVIM, and four possessed genes encoding extended-spectrum β-lactamases. Aminoglycoside modifying enzymes were present in 15/16, transferable qnr-mediated quinolone resistance gene was detected in 3/16, and the novel ciprofloxacin modifying enzyme CrpP-encoding gene in one isolate. CONCLUSION MDR-P. aeruginosa BSIs are relatively uncommon in Qatar but are highly resistant, harbour multiple resistance genes, and are commonly associated with unfavourable clinical outcomes. Colistin was the only agent with consistent activity against the study isolates.Key messagesMDR-P. aeruginosa constituted <5% of P. aeruginosa blood isolates over three years.Typical risk factors for MDR infections were highly prevalent in the study population and overall clinical outcomes are consistent with those previously reported.Colistin was the only agent with consistent antibacterial activity against the study isolates.
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Affiliation(s)
- Mazen A Sid Ahmed
- Department of Pathology and Laboratory Medicine, Division of Microbiology, Hamad Medical Corporation, Doha, Qatar.,The Life Science Centre, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Jemal M Hamid
- Department of Pathology and Laboratory Medicine, Division of Microbiology, Hamad Medical Corporation, Doha, Qatar
| | - Ahmed A Husain
- Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar.,Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Hamad Abdel Hadi
- Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar.,Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Sini Skariah
- Department of Microbiology and Immunology, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Ali A Sultan
- Department of Microbiology and Immunology, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Emad Bashir Ibrahim
- Department of Pathology and Laboratory Medicine, Division of Microbiology, Hamad Medical Corporation, Doha, Qatar.,Biomedical Research Centre, Qatar University, Doha, Qatar
| | - Abdul Latif Al Khal
- Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar.,Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Bo Soderquist
- School of Medical Sciences, Faculty of Medicine and Health, Orebro University, Orebro, Sweden
| | - Jana Jass
- The Life Science Centre, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Ali S Omrani
- Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar.,Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
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49
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Goto-Fujibayashi A, Niwa T, Yonetamari J, Ito-Takeichi S, Suzuki K, Ohta H, Niwa A, Tsuchiya M, Ito Y, Hatakeyama D, Hayashi H, Sugiyama T, Baba H, Suzuki A, Murakami N. Clinical impact of monitoring frequency per day as a prospective audit and feedback strategy for patients receiving antimicrobial agents by injection. Int J Clin Pract 2021; 75:e14785. [PMID: 34480837 DOI: 10.1111/ijcp.14785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 03/06/2021] [Accepted: 09/02/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Implementation of antimicrobial stewardship programmes improve antimicrobial therapies and thus result in better patient outcomes and safety. The impact of prospective audit and feedback (PAF) is likely dependent on how frequently it is conducted, and how quickly after antibiotic prescription it is initiated. To our knowledge, however, no report has yet investigated the impact of an increase in monitoring frequency per day on PAF strategy. Here, we evaluated the clinical impact of an increase in monitoring frequency per day as a PAF strategy in patients receiving antimicrobial injections. METHODS We conducted a single-centre, retrospective observational pre-post study to evaluate the impact of increasing the frequency of monitoring from once daily (once daily review group) to twice daily (twice daily review group). Time to intervention and clinical outcomes were compared before and after implementation of twice daily review. RESULTS Time to intervention for inappropriate antimicrobial therapy was significantly shorter in the twice daily review group than the once daily review group (5.1 ± 6.1 hours vs 29.9 ± 21.5 hours, HR: 4.53, 95% CI: 2.90-7.07, P < .001). The twice daily review group had a significantly lower rate of clinical failure (16.2% vs 38.3%, P = .004) and hepatotoxicity (4.1% vs 15.0%, P = .035) than the once daily review group. CONCLUSIONS An increase in monitoring frequency from once daily to twice daily significantly shortened the time to intervention for inappropriate antimicrobial therapy, with a concomitant reduction in clinical failure and hepatotoxicity.
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Affiliation(s)
- Ayasa Goto-Fujibayashi
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Takashi Niwa
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Jun Yonetamari
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Syuri Ito-Takeichi
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Keiko Suzuki
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Hirotoshi Ohta
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Ayumi Niwa
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Mayumi Tsuchiya
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Yukiko Ito
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Daijiro Hatakeyama
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Hideki Hayashi
- Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan
| | - Tadashi Sugiyama
- Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan
| | - Hisashi Baba
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Akio Suzuki
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan
| | - Nobuo Murakami
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
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50
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Kollef MH, Shorr AF, Bassetti M, Timsit JF, Micek ST, Michelson AP, Garnacho-Montero J. Timing of antibiotic therapy in the ICU. Crit Care 2021; 25:360. [PMID: 34654462 PMCID: PMC8518273 DOI: 10.1186/s13054-021-03787-z] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 10/06/2021] [Indexed: 12/15/2022] Open
Abstract
Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics.
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Affiliation(s)
- Marin H Kollef
- Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, 660 South Euclid Avenue, MSC 8052-43-14, St. Louis, MO, 63110, USA.
| | - Andrew F Shorr
- Pulmonary and Critical Care Medicine, Medstar Washington Hospital, Washington, DC, USA
| | - Matteo Bassetti
- Infectious Diseases Unit, Department of Health Sciences, San Martino Policlinico Hospital - IRCCS, University of Genoa, Genoa, Italy
| | - Jean-Francois Timsit
- AP-HP, Bichat Claude Bernard Hospital, Medical and Infectious Diseases ICU (MI2), IAME, INSERM, Université de Paris, Paris, France
| | - Scott T Micek
- Department of Pharmacy Practice, University of Health Sciences and Pharmacy, St. Louis, MO, USA
| | - Andrew P Michelson
- Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, 660 South Euclid Avenue, MSC 8052-43-14, St. Louis, MO, 63110, USA
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