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AlBahrani S, Saad M, Alqahtani JS, Almoosa Z, Alabdulla M, Algezery M, AlShehri S, Al-Tawfiq JA. Multicomponent Approaches to Reduce Multidrug-Resistant Organisms in Critical Care: Determining the Ideal Strategy. J Epidemiol Glob Health 2024; 14:1371-1380. [PMID: 39347929 PMCID: PMC11652424 DOI: 10.1007/s44197-024-00297-3] [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: 09/18/2023] [Accepted: 09/02/2024] [Indexed: 10/01/2024] Open
Abstract
Although there is ample proof of the advantages of infection prevention and Control (IPC) in acute-care hospitals, there is still some questions about the efficacy of IPC interventions for multidrug-resistant organisms (MDROs), and there is a need for the development of evidence-based practices. No healthcare facility has found a single effective technique to reduce MDRO. However, a multicomponent intervention that included improved barrier protection, chlorhexidine bathing, microbiological monitoring, and staff involvement significantly decreased the likelihood of infection in the patient surroundings with multidrug-resistant organisms. A practical strategy suited to reducing the burden of MDROs and their transmission potential in the critical care unit must be established in light of the global development of AMR. In this review, we summarize key findings of a multicomponent approaches to reduce MDROs in critical care units.
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Affiliation(s)
- Salma AlBahrani
- Infectious Disease Unit, Specialty Internal Medicine, King Fahd Military Medical Complex, Dhahran, Saudi Arabia
- College of medicine-Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mustafa Saad
- Department of Infection Control, Alhasa, Saudi Arabia
- Infectious Disease Department, Almoosa specialist Hospital, Alhasa, Saudi Arabia
| | - Jaber S Alqahtani
- Department of Respiratory Care, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Zainab Almoosa
- Infectious Disease Department, Almoosa specialist Hospital, Alhasa, Saudi Arabia
| | - Mohammed Alabdulla
- Infectious Disease Department, Almoosa specialist Hospital, Alhasa, Saudi Arabia
| | - Mohammed Algezery
- Infection control Department, King Fahd Military Medical Complex, Dhahran, Saudi Arabia
| | - Sondos AlShehri
- Quality Department, King Fahd Military Medical Complex, Dhahran, Saudi Arabia
| | - Jaffar A Al-Tawfiq
- Infectious Disease Unit, Specialty Internal Medicine, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.
- Infectious Disease Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
- Infectious Disease Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Accreditation and Infection Control Division, Quality and Patient Safety Department, Johns Hopkins Aramco Healthcare, Dhahran, 31311, Saudi Arabia.
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Manesh A, George MM, Palanikumar P, Nagaraj V, Bhanuprasad K, Krishnan R, Nivetha G, Lal B, Triveni KR, Gautam P, George B, Kulkarni U, Mathews V, Subramani K, Rao S, Chacko B, Zachariah A, Sathyendra S, Hansdak SG, Abraham OC, Iyadurai R, Karthik R, Peter JV, Mo Y, Veeraraghavan B, Varghese GM, Paterson DL. Combination Versus Monotherapy for Carbapenem-Resistant Acinetobacter Species Serious Infections: A Prospective IPTW Adjusted Cohort Study. Infect Dis Ther 2024; 13:2351-2362. [PMID: 39322920 PMCID: PMC11499560 DOI: 10.1007/s40121-024-01042-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 09/02/2024] [Indexed: 09/27/2024] Open
Abstract
INTRODUCTION International guidelines recommend definitive combination antibiotic therapy for the management of serious infections involving carbapenem-resistant Acinetobacter (CRAB) species. The commonly available combination options include high-dose sulbactam, polymyxins, tetracyclines, and cefiderocol. Scanty prospective data exist to support this approach. METHODS Patients with CRAB bacteraemia, ventilator-associated pneumonia (VAP), or both were categorized based on whether they received combination therapy or monotherapy. The 30-day mortality was compared between the two groups. Inverse probability treatment weighting (IPTW) was done using propensity score (PS) for a balanced comparison between groups. RESULTS Between January 2021 and May 2023, of the 161 patients with CRAB bacteraemia (n = 55, 34.2%), VAP (n = 46, 28.6%), or both (n = 60, 37.3%) who received appropriate intravenous antibiotic therapy, 70% (112/161) received monotherapy, and the rest received combination therapy. The overall 30-day mortality was 62% (99/161) and not different (p = 0.76) between the combination therapy (31/49, 63.3%) and monotherapy (68/112, 60.7%) groups. The propensity score matching using IPTW did not show a statistical difference (p = 0.47) in 30-day mortality for receiving combination therapy with an adjusted odds ratio (OR) P of 1.29 (0.64, 2.58). CONCLUSION Combination therapy for CRAB infections needs further study in a randomised controlled trial, as this observational study showed no difference in 30-day mortality between monotherapy and combination therapy.
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Affiliation(s)
- Abi Manesh
- Department of Infectious Diseases, Christian Medical College, Tamil Nadu, Vellore, 632004, India.
| | - Mithun Mohan George
- Department of Infectious Diseases, Christian Medical College, Tamil Nadu, Vellore, 632004, India
| | | | - V Nagaraj
- Department of Infectious Diseases, Christian Medical College, Tamil Nadu, Vellore, 632004, India
| | - Kundakarla Bhanuprasad
- Department of Infectious Diseases, Christian Medical College, Tamil Nadu, Vellore, 632004, India
| | - Ramya Krishnan
- Department of Infectious Diseases, Christian Medical College, Tamil Nadu, Vellore, 632004, India
| | - G Nivetha
- Department of Infectious Diseases, Christian Medical College, Tamil Nadu, Vellore, 632004, India
| | - Binesh Lal
- Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India
| | - K Rajitha Triveni
- Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India
| | - Priyanka Gautam
- Department of Infectious Diseases, Christian Medical College, Tamil Nadu, Vellore, 632004, India
| | - Biju George
- Department of Heamatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Uday Kulkarni
- Department of Heamatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Vikram Mathews
- Department of Heamatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - K Subramani
- Department of Critical Care, Christian Medical College, Vellore, Tamil Nadu, India
| | - Shoma Rao
- Department of Critical Care, Christian Medical College, Vellore, Tamil Nadu, India
| | - Binila Chacko
- Department of Critical Care, Christian Medical College, Vellore, Tamil Nadu, India
| | - Anand Zachariah
- Department of Medicine, Christian Medical College, Vellore, Tamil Nadu, India
| | - Sowmya Sathyendra
- Department of Medicine, Christian Medical College, Vellore, Tamil Nadu, India
| | | | | | - Ramya Iyadurai
- Department of Medicine, Christian Medical College, Vellore, Tamil Nadu, India
| | - Rajiv Karthik
- Department of Infectious Diseases, Christian Medical College, Tamil Nadu, Vellore, 632004, India
| | - John Victor Peter
- Department of Critical Care, Christian Medical College, Vellore, Tamil Nadu, India
| | - Yin Mo
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Division of Infectious Diseases, University Medicine Cluster, National University Hospital, Singapore, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - Balaji Veeraraghavan
- Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India
| | - George M Varghese
- Department of Infectious Diseases, Christian Medical College, Tamil Nadu, Vellore, 632004, India
| | - David Leslie Paterson
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Tian X, Lin J, Zhou M, Ge Y, Li T, Zhang L, Liu Z. Optimizing Treatment Strategies for Carbapenem-Resistant Acinetobacter Baumannii-Associated Pneumonia: A Multicenter Study in Chinese Hospitals. Infect Drug Resist 2024; 17:4403-4415. [PMID: 39421018 PMCID: PMC11484767 DOI: 10.2147/idr.s473088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 10/02/2024] [Indexed: 10/19/2024] Open
Abstract
Purpose To evaluate the clinical outcomes and safety of tigecycline (TGC) plus cefoperazone/sulbactam (CPS) or TGC monotherapy in patients with hospital-acquired pneumonia (HAP) caused by Carbapenem-Resistant Acinetobacter baumannii (CRAB). Methods This was a retrospective analysis of multicenter data from 62 Chinese hospitals with CRAB HAP. Risk factors for receiving TGC with CPS therapy and predictors of mortality were assessed using multivariate logistic and Cox regression analyses, respectively. Propensity score matching (PSM) evaluated the efficacy and safety of antimicrobial regimens. Results A total of the 180 patients were included, with 95 receiving TGC monotherapy and 85 receiving combination therapy. Multivariate logistic regression analysis revealed that older age (P = 0.011), and intensive care unit (ICU) admission (P = 0.007) were significant risk factors for combination therapy. Multivariate Cox regression demonstrated that combination therapy was associated with a significantly higher risk of 90-day mortality (P = 0.031). Patients in the standard-dose TGC (SDT) plus CPS subgroup had significantly higher rates of SOFA scores ≥ 7 (P = 0.009) and MV used (P = 0.028), as well as higher 30-/90-day mortality compared to high-dose TGC (HDT) plus CPS group. TGC plus CPS significantly reduced CRP levels (P = 0.009), while the variations in ALT, TBIL, Cr, Hb, and PLT levels did not differ between different antimicrobial regimens after PSM. Conclusion HDT and CPS combination therapy was more effective in patients with advanced age and more severe condition. Safety profiles of different antimicrobial regimens were similar with liver, kidneys, and coagulation functions.
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Affiliation(s)
- Xiaotong Tian
- Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China
- Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Jing Lin
- Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China
- Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Menglan Zhou
- Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China
- Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People’s Republic of China
| | - Ying Ge
- Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China
| | - Taisheng Li
- Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China
| | - Li Zhang
- Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China
| | - Zhengyin Liu
- Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China
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Sodeifian F, Zangiabadian M, Arabpour E, Kian N, Yazarlou F, Goudarzi M, Centis R, Seghatoleslami ZS, Kameh MC, Danaei B, Goudarzi H, Nasiri MJ, Sotgiu G, Migliori GB. Tigecycline-Containing Regimens and Multi Drug-Resistant Acinetobacter baumannii: A Systematic Review and Meta-Analysis. Microb Drug Resist 2023. [PMID: 37192494 DOI: 10.1089/mdr.2022.0248] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2023] Open
Abstract
Introduction: The use of tigecycline (TG) for the treatment of Acinetobacter baumannii is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of TG for the treatment of multi drug-resistant (MDR) Acinetobacter. Methods: We searched PubMed/MEDLINE, Scopus, Cochrane Central, and Web of Science to identify studies reporting the clinical and microbiological efficacy and safety of regimens containing TG in patients with drug susceptibility testing (DST)-confirmed MDR A. baumannii, published until December 30, 2022. Observational studies were included if they reported clinical and microbiological efficacy of TG-based regimens. The Newcastle-Ottawa Scale (NOS) and Joana Briggs Institute (JBI) critical appraisal tool were used to assess the quality of included studies. Results: There were 30 observational studies, of which 19 studies were cohort and 11 studies were single group studies. Pooled clinical response and failure rates in the TG-containing regimens group were 58.1 (95% confidence interval [CI] 49.2-66.6) and 40.2 (95% CI 31.1-50.0), respectively. The pooled microbiological response rate was 32.1 (95% CI 19.8-47.5), and the pooled all-cause mortality rate was 41.1 (95% CI 34.1-48.4). Pooled clinical response and failure rates in the colistin-based regimens group were 52.7 (42.7-62.5) and 43.1 (33.1-53.8), respectively. The pooled microbiological response rate was 42.9 (16.2-74.5), and the pooled all-cause mortality rate was 34.3 (26.1-43.5). Conclusions: According to our results, the efficacy of the TG-based regimen is the same as other antibiotics. However, our study showed a high mortality rate and a lower rate of microbiological eradication for TG compared with colistin-based regimen. Therefore, our study does not recommend it for the treatment of MDR A. baumannii. However, this was a prevalence meta-analysis of observational studies, and for better conclusion experimental studies are required.
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Affiliation(s)
- Fatemeh Sodeifian
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Moein Zangiabadian
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Erfan Arabpour
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Naghmeh Kian
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fartous Yazarlou
- Department of Pharmacy, Comenius University Bratislava, Bratislava, Slovakia
| | - Mehdi Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rosella Centis
- Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy
| | | | - Mahdis Chahar Kameh
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bardia Danaei
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Javad Nasiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Giovanni Sotgiu
- Clinical Epidemiology and Medical Statistics Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
| | - Giovanni Battista Migliori
- Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy
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Ardebili A, Izanloo A, Rastegar M. Polymyxin combination therapy for multidrug-resistant, extensively-drug resistant, and difficult-to-treat drug-resistant gram-negative infections: is it superior to polymyxin monotherapy? Expert Rev Anti Infect Ther 2023; 21:387-429. [PMID: 36820511 DOI: 10.1080/14787210.2023.2184346] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
INTRODUCTION The increasing prevalence of infections with multidrug-resistant (MDR), extensively-drug resistant (XDR) or difficult-to-treat drug resistant (DTR) Gram-negative bacilli (GNB), including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter species, and Escherichia coli poses a severe challenge. AREAS COVERED The rapid growing of multi-resistant GNB as well as the considerable deceleration in development of new anti-infective agents have made polymyxins (e.g. polymyxin B and colistin) a mainstay in clinical practices as either monotherapy or combination therapy. However, whether the polymyxin-based combinations lead to better outcomes remains unknown. This review mainly focuses on the effect of polymyxin combination therapy versus monotherapy on treating GNB-related infections. We also provide several factors in designing studies and their impact on optimizing polymyxin combinations. EXPERT OPINION An abundance of recent in vitro and preclinical in vivo data suggest clinical benefit for polymyxin-drug combination therapies, especially colistin plus meropenem and colistin plus rifampicin, with synergistic killing against MDR, XDR, and DTR P. aeruginosa, K. pneumoniae and A. baumannii. The beneficial effects of polymyxin-drug combinations (e.g. colistin or polymyxin B + carbapenem against carbapenem-resistant K. pneumoniae and carbapenem-resistant A. baumannii, polymyxin B + carbapenem + rifampin against carbapenem-resistant K. pneumoniae, and colistin + ceftolozan/tazobactam + rifampin against PDR-P. aeruginosa) have often been shown in clinical setting by retrospective studies. However, high-certainty evidence from large randomized controlled trials is necessary. These clinical trials should incorporate careful attention to patient's sample size, characteristics of patient's groups, PK/PD relationships and dosing, rapid detection of resistance, MIC determinations, and therapeutic drug monitoring.
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Affiliation(s)
- Abdollah Ardebili
- Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran.,Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Ahdieh Izanloo
- Department of Biology, Faculty of Sciences, Golestan University, Gorgan, Iran
| | - Mostafa Rastegar
- Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
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Abushanab D, Nasr ZG, Al-Badriyeh D. Efficacy and Safety of Colistin versus Tigecycline for Multi-Drug-Resistant and Extensively Drug-Resistant Gram-Negative Pathogens-A Meta-Analysis. Antibiotics (Basel) 2022; 11:1630. [PMID: 36421274 PMCID: PMC9686723 DOI: 10.3390/antibiotics11111630] [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: 08/15/2022] [Revised: 09/13/2022] [Accepted: 09/16/2022] [Indexed: 11/17/2022] Open
Abstract
Background: We intended to compare the efficacy and safety outcomes of colistin versus tigecycline as monotherapy or combination therapy against multi-drug resistant (MDR) and extensively drug-resistant (XDR) pathogens. Methods: A search was conducted in PubMed, Cochrane CENTRAL, EMBASE, and in the grey literature (i.e., ClinicalTrials.gov and Google Scholar) up to May 2021. Outcomes were clinical response, mortality, infection recurrence, and renal and hepatic toxicity. We pooled odd ratios (OR) using heterogeneity-guided random or fixed models at a statistical significance of p < 0.05. Results: Fourteen observational studies involving 1163 MDR/XDR pathogens, receiving tigecycline versus colistin monotherapy or combination, were included. Base-case analyses revealed insignificant differences in the clinical response, reinfection, and hepatic impairment. The 30-day mortality was significantly relatively reduced with tigecycline monotherapy (OR = 0.35, 95% CI 0.16−0.75, p = 0.007). The colistin monotherapy significantly relatively reduced in-hospital mortality (OR = 2.27, 95%CI 1.24−4.16, p = 0.008). Renal impairment rates were lower with tigecycline monotherapy or in combination, and were lower with monotherapy versus colistin-tigecycline combination. Low-risk of bias and moderate/high evidence quality were associated with all studies. Conclusions: Within the limitations of this study, it can be concluded that there were no statistically significant differences in main efficacy outcomes between colistin and tigecycline monotherapies or combinations against MDR/XDR infections, except for lower rates of 30-day mortality with tigecycline and in-hospital mortality with colistin. Tigecycline was associated with favourable renal toxicity outcomes.
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Affiliation(s)
- Dina Abushanab
- Department of Pharmacy, Hamad Medical Corporation, Doha 3050, Qatar
| | - Ziad G. Nasr
- College of Pharmacy, QU Health, Qatar University, Doha 2713, Qatar
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Ahmadpour F, Shaseb E, Izadpanah M, Rakhshan A, Hematian F. Optimal dosing interval of intravenous Colistin monotherapy versus combination therapy: A systematic review and meta-analysis. Eur J Transl Myol 2022; 32:10833. [PMID: 36533669 PMCID: PMC9830404 DOI: 10.4081/ejtm.2022.10833] [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: 09/03/2022] [Accepted: 09/09/2022] [Indexed: 01/13/2023] Open
Abstract
We aimed to maximize the clinical response and effectiveness of colistin antibiotics in patients with multi-drug (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, there is an increasing interest in colistin combination therapy with other antibiotics and extended interval dosing regimens. This systematic review and meta-analysis aim is to evaluate if the combination therapy is superior to monotherapy with colistin regarding increased survival and also which dose interval is the most effective to utilize. English language, peer-reviewed journal publications from the first date available to 25 January 2022 were identified by searching the PubMed and Web of Science databases. Forest plots for overall and subgroups and funnel plots were graphed. 42 studies were included in the study. Among them, 38 studies were on combination therapy, and four on dose interval. The overall pooled odds ratio is 0.77 (CI: 0.62; 0.95) (p value < 0.017). The I^2 value was 43% (p value < 0.01). The Begg correlation test of funnel plot asymmetry showed no significant publication bias (0.064). The overall pooled odds ratio for Carbapenem is 0.74 (CI: 0.48; 1.13). A prospective randomized controlled trials (RCT) on 40 adults intensive care unit (ICU) patients with ventilator-associated pneumonia (VAP), comparing the mortality and ICU length of stay of 8- or 24- hour intervals regimens, showed that the ICU length of stay and ICU mortality were; 31.31, 35.3 days, and 32.06, 22.2% in groups 24-h interval and 8- hour interval (p value: 0.39, 0.87), respectively. It seems that combination therapy is associated with drug synergism and increased survival. The extended interval colistin administration may result in higher peak concentration and bacterial eradication. In both cases, we face a dearth of literature.
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Affiliation(s)
- Forouzan Ahmadpour
- Department of Pharmacotherapy, School of Pharmacy, Lorestan University of Medical Sciences, Khoramabad, Iran
| | - Elnaz Shaseb
- Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mandana Izadpanah
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Amin Rakhshan
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzaneh Hematian
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,Assistant professor of clinical pharmacy, Department of Clinical Pharmacy, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ORCID ID: 0000-0001-7062-4669
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8
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Loest D, Uhland FC, Young KM, Li XZ, Mulvey MR, Reid-Smith R, Sherk LM, Carson CA. Carbapenem-resistant Escherichia coli from shrimp and salmon available for purchase by consumers in Canada: a risk profile using the Codex framework. Epidemiol Infect 2022; 150:e148. [PMID: 35968840 PMCID: PMC9386791 DOI: 10.1017/s0950268822001030] [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: 10/28/2021] [Revised: 04/28/2022] [Accepted: 05/21/2022] [Indexed: 11/05/2022] Open
Abstract
Resistance to carbapenems in human pathogens is a growing clinical and public health concern. The carbapenems are in an antimicrobial class considered last-resort, they are used to treat human infections caused by multidrug-resistant Enterobacterales, and they are classified by the World Health Organization as 'High Priority Critically Important Antimicrobials'. The presence of carbapenem-resistant Enterobacterales (CREs) of animal-origin is of concern because targeted studies of Canadian retail seafood revealed the presence of carbapenem resistance in a small number of Enterobacterales isolates. To further investigate this issue, a risk profile was developed examining shrimp and salmon, the two most important seafood commodities consumed by Canadians and Escherichia coli, a member of the Enterobacterales order. Carbapenem-resistant E. coli (CREc) isolates have been identified in shrimp and other seafood products. Although carbapenem use in aquaculture has not been reported, several classes of antimicrobials are utilised globally and co-selection of antimicrobial-resistant microorganisms in an aquaculture setting is also of concern. CREs have been identified in retail seafood purchased in Canada and are currently thought to be uncommon. However, data concerning CRE or CREc occurrence and distribution in seafood are limited, and argue for implementation of ongoing or periodic surveillance.
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Affiliation(s)
- Daleen Loest
- Centre for Food-borne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - F. Carl Uhland
- Centre for Food-borne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Kaitlin M. Young
- Centre for Food-borne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Xian-Zhi Li
- Veterinary Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada
| | - Michael R. Mulvey
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
| | - Richard Reid-Smith
- Centre for Food-borne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Lauren M. Sherk
- Centre for Food-borne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Carolee A. Carson
- Centre for Food-borne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada, Guelph, Ontario, Canada
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Lynch JP, Clark NM, Zhanel GG. Infections Due to Acinetobacter baumannii-calcoaceticus Complex: Escalation of Antimicrobial Resistance and Evolving Treatment Options. Semin Respir Crit Care Med 2022; 43:97-124. [PMID: 35172361 DOI: 10.1055/s-0041-1741019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Bacteria within the genus Acinetobacter (principally A. baumannii-calcoaceticus complex [ABC]) are gram-negative coccobacilli that most often cause infections in nosocomial settings. Community-acquired infections are rare, but may occur in patients with comorbidities, advanced age, diabetes mellitus, chronic lung or renal disease, malignancy, or impaired immunity. Most common sites of infections include blood stream, skin/soft-tissue/surgical wounds, ventilator-associated pneumonia, orthopaedic or neurosurgical procedures, and urinary tract. Acinetobacter species are intrinsically resistant to multiple antimicrobials, and have a remarkable ability to acquire new resistance determinants via plasmids, transposons, integrons, and resistance islands. Since the 1990s, antimicrobial resistance (AMR) has escalated dramatically among ABC. Global spread of multidrug-resistant (MDR)-ABC strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; excessive antibiotic use amplifies this spread. Many isolates are resistant to all antimicrobials except colistimethate sodium and tetracyclines (minocycline or tigecycline); some infections are untreatable with existing antimicrobial agents. AMR poses a serious threat to effectively treat or prevent ABC infections. Strategies to curtail environmental colonization with MDR-ABC require aggressive infection-control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy with existing antibiotics as well as development of novel antibiotic classes.
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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
| | - Nina M Clark
- Division of Infectious Diseases, Department of Medicine, Loyola University Medical Center, Maywood, Illinois
| | - George G Zhanel
- Department of Medical Microbiology/Infectious Diseases, University of Manitoba, Max Rady College of Medicine, Winnipeg, Manitoba, Canada
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OUP accepted manuscript. J Antimicrob Chemother 2022; 77:2094-2104. [DOI: 10.1093/jac/dkac145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 04/13/2022] [Indexed: 11/14/2022] Open
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Paul M, Carrara E, Retamar P, Tängdén T, Bitterman R, Bonomo RA, de Waele J, Daikos GL, Akova M, Harbarth S, Pulcini C, Garnacho-Montero J, Seme K, Tumbarello M, Lindemann PC, Gandra S, Yu Y, Bassetti M, Mouton JW, Tacconelli E, Baño JR. European Society of clinical microbiology and infectious diseases (ESCMID) guidelines for the treatment of infections caused by Multidrug-resistant Gram-negative bacilli (endorsed by ESICM -European Society of intensive care Medicine). Clin Microbiol Infect 2021; 28:521-547. [PMID: 34923128 DOI: 10.1016/j.cmi.2021.11.025] [Citation(s) in RCA: 476] [Impact Index Per Article: 119.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 11/28/2021] [Accepted: 11/29/2021] [Indexed: 12/16/2022]
Abstract
SCOPE These ESCMID guidelines address the targeted antibiotic treatment of 3rd generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination vs. monotherapy. METHODS An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumanni (CRAB). Treatments were classified as head-to-head comparisons between individual antibiotics and monotherapy vs. combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy vs. combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak). RECOMMENDATIONS The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, beta-lactam beta-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low and low certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed.
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Affiliation(s)
- Mical Paul
- Infectious Diseases Institute, Rambam Health Care Campus, Haifa, Israel; Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
| | - Elena Carrara
- Division of Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, Verona, Italy
| | - Pilar Retamar
- Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain; Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/ Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
| | - Thomas Tängdén
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Roni Bitterman
- Infectious Diseases Institute, Rambam Health Care Campus, Haifa, Israel; Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
| | - Robert A Bonomo
- Department of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Medical Service, Research Service, and GRECC, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA;; VAMC Center for Antimicrobial Resistance and Epidemiology, Cleveland, OH, USA
| | - Jan de Waele
- Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium
| | - George L Daikos
- First Department of Medicine, National and Kapodistrian University of Athens
| | - Murat Akova
- Hacettepe University School of Medicine, Department Of Infectious Diseases, Ankara, Turkey
| | - Stephan Harbarth
- Infection Control Programme, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Celine Pulcini
- Université de Lorraine, APEMAC, Nancy, France; Université de Lorraine, CHRU-Nancy, Infectious Diseases Department, Nancy, France
| | | | - Katja Seme
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia
| | - Mario Tumbarello
- Department of Medical Biotechnologies, University of Siena, Italy
| | | | - Sumanth Gandra
- Division of Infectious Diseases, Washington University School of Medicine in St. Louis, Missouri, USA
| | - Yunsong Yu
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Matteo Bassetti
- Department of Health Sciences, University of Genoa, 16132 Genoa, Italy; Clinica Malattie Infettive, San Martino Policlinico Hospital, Genoa, Italy
| | - Johan W Mouton
- Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands
| | - Evelina Tacconelli
- Division of Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, Verona, Italy; Division of Infectious Diseases, Department of Internal Medicine I, German Center for Infection Research, University of Tübingen, Tübingen, Germany; German Centre for Infection Research (DZIF), Clinical Research Unit for Healthcare Associated Infections, Tübingen, Germany.
| | - Jesus Rodriguez Baño
- Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain; Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/ Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
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Samal S, Samir SB, Patra SK, Rath A, Dash A, Nayak B, Mohanty D. Polymyxin Monotherapy vs. Combination Therapy for the Treatment of Multidrug-resistant Infections: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2021; 25:199-206. [PMID: 33707900 PMCID: PMC7922466 DOI: 10.5005/jp-journals-10071-23720] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Objectives The objective of this review was to compare the effectiveness of Colistin monotherapy and combination therapy for the treatment of multidrug-resistant gram-negative bacterial infections. Data sources PubMed, Cochrane Library. Study eligibility interventions and exclusions In this systematic review, we included all retrospective and prospective studies and randomized controlled trials (RCTs) that compared intravenous polymyxin monotherapy and combination therapy with any other antibiotic for treating multidrug-resistant infections. Studies using inhaled polymyxins with 5 or less than 5 patients were excluded. The primary outcome was 30-day all-cause mortality and if not reported at day 30 we extracted and documented the closest time point. Both crude outcome rates and adjusted effect estimates were extracted for mortality. Study appraisal data extraction and synthesis Search string used was "(Colistin OR polymyxin) AND (Enterobacteriaceae OR Klebsiella OR Acinetobacter OR Escherichia coli OR Pseudomonas) AND (random OR prospective OR retrospective OR cohort OR observational OR blind)." Thirty-nine studies were included in our analysis; out of which 6 RCTs were included and 9 studies used carbapenem as the adjunctive antibiotic. Each study was screened and reviewed for eligibility independently by two authors and data extrapolated on an Excel sheet. Results The meta-analysis of polymyxin monotherapy vs. combination therapy in multidrug-resistant infections yielded an odds ratio (OR) of 0.81 (95% confidence interval [CI]: 0.65-1.01) with minimal heterogeneity (I 2 = 40%), whereas pooled analysis of this comparison in studies that included carbapenem as combination therapy yielded an OR of 0.64 (CI: 0.40-1.03; I 2 = 62%). Likewise, the pooled analysis of the RCTs yielded an OR of 0.82 (95% CI: 0.58-1.16, I 2 = 22%). All these showed no statistical significance. However, it was seen that polymyxin combination therapy was more effective in multidrug-resistant infections compared to polymyxin monotherapy. The effectiveness was more glaring when carbapenems were used as the combination drug instead of any other antibiotic and more so in many in vitro studies that used polymyxin combination therapy. Conclusion Although statistically insignificant, it would be prudent to use polymyxin combination therapy to treat multidrug-resistant gram-negative bacilli (GNB) infection over monotherapy with preference to use carbapenem as the adjunct alongside polymyxins. How to cite this article Samal S, Mishra SB, Patra SK, Rath A, Dash A, Nayak B, et al. Polymyxin Monotherapy vs. Combination Therapy for the Treatment of Multidrug-resistant Infections: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2021;25(2):199-206.
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Affiliation(s)
- Samir Samal
- Department of Critical Care Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Shakti B Samir
- Department of Critical Care Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Shantanu K Patra
- Department of Critical Care Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Arun Rath
- Department of Critical Care Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Abhilash Dash
- Department of Critical Care Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Biswajit Nayak
- Department of Critical Care Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Diganta Mohanty
- Department of Critical Care Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
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Osme SF, Almeida APS, Lemes MF, Barbosa WO, Arantes A, Mendes-Rodrigues C, Gontijo Filho PP, Ribas RM. Costs of healthcare-associated infections to the Brazilian public Unified Health System in a tertiary-care teaching hospital: a matched case-control study. J Hosp Infect 2020; 106:303-310. [PMID: 32693085 DOI: 10.1016/j.jhin.2020.07.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Accepted: 07/13/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Little is known about the economic burden of healthcare-associated infections (HAIs) in Brazil. AIM To analyse the costs of hospitalization by reimbursement from the Brazilian government, via the Brazilian Unified Health System (SUS) affiliation, and direct costs in the adult Intensive Care Unit (ICU). METHODS The matched-pairs case-control study (83 patients with HAIs and 83 without HAIs) was performed at a referral tertiary-care teaching hospital in Brazil in January 2018. In order to calculate the HAI costs from the perspective of the payer, the total cost for each hospitalization was obtained through the Hospital's Billing Sector. Direct costs were calculated annually for 949 critical patients during 2018. FINDINGS The reimbursement cost per hospitalization of patients with HAIs was 75% (US$2721) higher than patients without HAIs (US$1553). When a patient has an HAI, in addition to a longer length of stay (15 days), there was an extra increase (US$996) in the reimbursement cost per hospitalization. An HAI in the ICU was associated with a total direct cost eight times higher compared with patients who did not develop infections in this unit, US$11,776 × US$1329, respectively. The direct cost of hospitalization in the ICU without HAI was 56.5% less than the reimbursement (US$1329 × US$3052, respectively), whereas for the patient with an HAI, the direct cost was 111.5% above the reimbursement (US$11,776 × US$5569, respectively). CONCLUSION HAIs contribute to a longer stay and an eight-fold increase in direct costs. It is necessary to reinforce programmes that prevent HAIs in Brazilian hospitals.
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Affiliation(s)
- S F Osme
- Federal University of Uberlandia, Clinical Hospital, Uberlandia, Brazil
| | - A P S Almeida
- Federal University of Uberlandia, Clinical Hospital, Uberlandia, Brazil
| | - M F Lemes
- Federal University of Uberlandia, Clinical Hospital, Uberlandia, Brazil
| | - W O Barbosa
- Federal University of Uberlandia, Clinical Hospital, Uberlandia, Brazil
| | - A Arantes
- Federal University of Uberlandia, Clinical Hospital, Uberlandia, Brazil
| | - C Mendes-Rodrigues
- Institute of Biomedical Sciences, Federal University of Uberlandia, Uberlandia, Brazil
| | - P P Gontijo Filho
- Institute of Biomedical Sciences, Federal University of Uberlandia, Uberlandia, Brazil
| | - R M Ribas
- Institute of Biomedical Sciences, Federal University of Uberlandia, Uberlandia, Brazil.
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Gajic I, Ranin L, Kekic D, Opavski N, Smitran A, Mijac V, Jovanovic S, Hadnadjev M, Travar M, Mijovic G. Tigecycline susceptibility of multidrug-resistant Acinetobacter baumannii from intensive care units in the western Balkans. Acta Microbiol Immunol Hung 2020; 67:176-181. [PMID: 32160781 DOI: 10.1556/030.2020.01079] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 12/17/2019] [Indexed: 11/19/2022]
Abstract
Tigecycline can be effective to treat infections of carbapenem-resistant Acinetobacter baumannii (CRAB) however, no interpretive criteria have been approved so far. The objectives of this study were to evaluate the proportion of CRAB isolates and to compare gradient test with a broth microdilution (BMD) method for tigecycline susceptibility testing of A. baumannii.This study included 349 multidrug-resistant (MDR) Acinetobacter spp. collected from Serbia, Montenegro, Bosnia and Herzegovina in 2016 and 2017. Antibiotic susceptibility testing was performed by disk diffusion, VITEK2, gradient, ComASP Colistin. Tigecycline susceptibilities were interpreted according to breakpoints of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA).Majority of the tested isolates were CRAB (92.8%). Tigecycline MIC50/MIC90 values were 4/8 μg/mL by BMD and 0.5/4 μg/mL by gradient test. Essential agreement for BMD and gradient test amounted to 65.1%. With EUCAST breakpoints, categorical agreement (CA) was achieved in 38% isolates. Major discordance (MD-false susceptibility/resistance) and minor discordance (mD-false categorization involving intermediate results) were observed in 10% and 57% A. baumannii, respectively. With FDA breakpoints, CA, MD and mD were observed in 44%, 16% and 47% isolates, respectively. Colistin resistance was 2.1%.The study highlights a high proportion of CRAB and several discordances between BMD and gradient test which may lead to inappropriate therapy.
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Affiliation(s)
- Ina Gajic
- 1Institute of Microbiology and Immunology, Medical Faculty, University of Belgrade, Belgrade, 11000, Serbia
| | - Lazar Ranin
- 1Institute of Microbiology and Immunology, Medical Faculty, University of Belgrade, Belgrade, 11000, Serbia
| | - Dusan Kekic
- 1Institute of Microbiology and Immunology, Medical Faculty, University of Belgrade, Belgrade, 11000, Serbia
| | - Natasa Opavski
- 1Institute of Microbiology and Immunology, Medical Faculty, University of Belgrade, Belgrade, 11000, Serbia
| | - Aleksandra Smitran
- 2Department of Microbiology and Immunology, Faculty of Medicine, University of Banja Luka, Banja Luka, Republic of Srpska, 78000, Bosnia and Herzegovina
| | - Vera Mijac
- 1Institute of Microbiology and Immunology, Medical Faculty, University of Belgrade, Belgrade, 11000, Serbia
| | - Snezana Jovanovic
- 3Department of Microbiology, Clinical Centre of Serbia, Belgrade, 11000, Serbia
| | - Mirjana Hadnadjev
- 4Center for Microbiology, Virology and Immunology, Institute for Pulmonary Diseases of Vojvodina, Novi Sad, 21000, Serbia
| | - Maja Travar
- 2Department of Microbiology and Immunology, Faculty of Medicine, University of Banja Luka, Banja Luka, Republic of Srpska, 78000, Bosnia and Herzegovina
- 5Department of Microbiology, Clinical Centre of Banja Luka, Banja Luka, Republic of Srpska, 78000, Bosnia and Herzegovina
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Zhou K, Tang X, Wang L, Guo Z, Xiao S, Wang Q, Zhuo C. An Emerging Clone (ST457) of Acinetobacter baumannii Clonal Complex 92 With Enhanced Virulence and Increasing Endemicity in South China. Clin Infect Dis 2019; 67:S179-S188. [PMID: 30423046 DOI: 10.1093/cid/ciy691] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Background The global dissemination of carbapenem-resistant Acinetobacter baumannii clonal complex (CC) 92 has become an urgent public health concern. Methods A. baumannii isolates were collected in 5 tertiary hospitals in south China during 2012-2015, and their clinical data were obtained. The clinical characterization was studied by statistical analysis. Whole-genome sequencing and a Galleria mellonella infection model were used to investigate the genetic characterization and pathogenicity of isolates, respectively. Results Sequence type (ST)457, following ST195, become the second-most prevalent clone in our collection. Patients infected by ST457 had significantly higher 7-day mortality rates (44.4% vs 14.3%; P = .01) and proportions of 7-day deaths (70.6% vs 26.7%; P = .01) than those infected by the other STs of CC92, except for ST195 and ST208. Consistently, the day of death after culture was significantly sooner in patients infected with ST457 than those with the non-ST195/208 members of CC92 (8.71 ± 15.27 vs 25.20 ± 6.51; P = .02). This is accordant with results that ST457 had enhanced virulence with a high mortality rate through use of the G. mellonella larvae infection model. Genomic analysis suggests that ST457 evolved distinctly from the other CC92 members mainly via recombinations. This clone exclusively shared a few virulence factors with the hypervirulence strain LAC-4, including a capsule biosynthesis locus (KL49) that is supposed to be important for the hypervirulence in LAC-4. Conclusions The rising trends in prevalence and enhanced virulence of ST457 highlight the urgent need for tailored surveillance to control the further dissemination of this clone.
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Affiliation(s)
- Kai Zhou
- Shenzhen Institute of Respiratory Diseases, the First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou
| | - Xiang Tang
- State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University
| | - Luxia Wang
- Guangzhou General Hospital of Guangzhou Military, China
| | - Zhenghui Guo
- Guangzhou General Hospital of Guangzhou Military, China
| | - Shunian Xiao
- State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University
| | - Qin Wang
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou
| | - Chao Zhuo
- State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University
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Paul M, Zusman O, Leibovici L. Meta-analysis of Polymyxin Use in Patients. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1145:143-153. [PMID: 31364077 DOI: 10.1007/978-3-030-16373-0_11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
In this chapter, we systematically reviewed studies that assessed polymyxin's effectiveness and summarized results through meta-analysis. The outcomes addressed were all-cause mortality, assuming that for patients with severe multidrug-resistant infections survival is the most important outcome, and resistance development, important for future patients. Most clinical data on polymyxins in the literature are from retrospective, observational studies at high risk of bias. The majority of clinical studies were unpowered to examine mortality controlling for other risk factors. The studies had no control of dosage regimens and treatment modifications. We identified several areas of missing data, in particular randomized controlled trials (RCTs) examining treatment options for carbapenem-resistant Gram-negative bacteria, different dosage regimens, polymyxins versus alternative antibiotics (e.g. aminoglycosides, tigecycline), and monotherapy versus specific combination therapies. Ideally, mortality and development of resistance should be examined in RCTs, with further longitudinal studies required for the latter.
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Affiliation(s)
- Mical Paul
- Division of Infectious Diseases, Rambam Health Care Center and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
| | - Oren Zusman
- Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva and Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel Aviv, Israel
| | - Leonard Leibovici
- Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva and Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel Aviv, Israel
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Carbapenem-resistant Acinetobacter baumannii: in pursuit of an effective treatment. Clin Microbiol Infect 2019; 25:951-957. [DOI: 10.1016/j.cmi.2019.03.014] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 03/11/2019] [Accepted: 03/18/2019] [Indexed: 12/27/2022]
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Marchaim D, Kaye D, Kaye KS. Use of Colistin in Critically Ill Patients. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1145:155-179. [PMID: 31364078 DOI: 10.1007/978-3-030-16373-0_12] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Due to lack of better therapeutic options, colistin use for extensively drug-resistant Gram-negative organisms was revived in the past two decades, including in patients in intensive-care units (ICU). There are multiple knowledge gaps pertaining to the clinical use and utility of colistin in critically-ill patients, but due to lack of options, it is used in these high risk patients. In this chapter, we critically review the various topics pertaining to colistin use in critically-ill patients, while highlighting the (lack of) controlled evidence supporting common current practices pertaining to colistin use by clinicians.
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Affiliation(s)
- Dror Marchaim
- Unit of Infection Control, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel. .,Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
| | - Donald Kaye
- Drexel University College of Medicine, Philadelphia, PA, USA
| | - Keith S Kaye
- Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI, USA
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Abstract
PURPOSE OF REVIEW Bacteria within the genus Acinetobacter [principally Acinetobacter baumannii-calcoaceticus complex (ABC)] are Gram-negative coccobacilli that may cause serious nosocomial infections (particularly ventilator-associated pneumonia and infections of the bloodstream, urinary tract, and wounds) as well as community-acquired infections (often skin/soft tissue infections in the context of trauma). Within the past two decades, Acinetobacter spp. have been responsible for an increasing number of infections in intensive care units (ICUs) globally. Treatment of Acinetobacter infections is difficult, as Acinetobacter spp. are intrinsically resistant to multiple antimicrobial agents, and have a remarkable ability to acquire new resistance determinants via multiple mechanisms. RECENT FINDINGS Since the 1990s, global resistance to antimicrobials has escalated dramatically among ABC. Global spread of multidrug-resistant (MDR) A. baumannii strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; this spread is amplified by excessive use of antibiotics. Many isolates are resistant to all antimicrobials except colistin (polymyxin E), and some infections are untreatable with existing antimicrobial agents. SUMMARY Antimicrobial resistance poses a serious threat to control infections due to ABC. Strategies to curtail environmental colonization with MDR-ABD will require aggressive infection control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the consequences and spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy of existing antibiotics as well as development of novel antibiotic classes.
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Vardakas KZ, Mavroudis AD, Georgiou M, Falagas ME. Intravenous colistin combination antimicrobial treatment vs. monotherapy: a systematic review and meta-analysis. Int J Antimicrob Agents 2018; 51:535-547. [PMID: 29288723 DOI: 10.1016/j.ijantimicag.2017.12.020] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Revised: 11/20/2017] [Accepted: 12/16/2017] [Indexed: 01/25/2023]
Abstract
BACKGROUND To evaluate whether intravenous colistin in combination with other antibiotics (IVCC) is associated with lower mortality compared with intravenous colistin monotherapy (IVCM), and to identify factors influencing study outcomes. METHODS PubMed and Scopus were searched up to November 2016. Studies were included if they evaluated adult patients with multi-drug-resistant (MDR) or extensively-drug-resistant Gram-negative infections, and reported comparative mortality data (adjusted and unadjusted) for patients receiving IVCC vs. IVCM. Random effects meta-analyses were performed. FINDINGS Thirty-two studies (29 observational, three randomized) were included. The overall quality of data was low to very low, and studies were characterized by the lack of adjusted data. The majority of studies were not designed to evaluate the outcome of the meta-analysis, and focused mainly on infections due to Acinetobacter baumannii and Klebsiella pneumoniae. Colistin was administered at variable doses, with or without a loading dose, and in combination with several antibiotics. Overall, IVCC was not associated with lower mortality than IVCM [32 studies, 2328 patients, risk ratio (RR) 0.91, 95% confidence interval (CI) 0.81-1.02, I2 8%]. A significant difference was observed in favour of IVCC when high-dose (>6 million international units) colistin was used (RR 0.80, 95% CI 0.69-0.93), in studies conducted in Asia (RR 0.82, 95% CI 0.71-0.95), in patients with bacteraemia (RR 0.75, 95% CI 0.57-0.98) and in patients with acinetobacter infections (RR 0.88, 95% CI 0.78-1.00). INTERPRETATION Overall, low-quality data suggest that IVCC did not lower mortality in patients with MDR Gram-negative infections. However, there is some evidence for a benefit observed with high intravenous doses of colistin.
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Affiliation(s)
- Konstantinos Z Vardakas
- Alfa Institute of Biomedical Sciences, Athens, Greece; Department of Medicine, Henry Dunant Hospital Centre, Athens, Greece
| | | | | | - Matthew E Falagas
- Alfa Institute of Biomedical Sciences, Athens, Greece; Department of Medicine, Henry Dunant Hospital Centre, Athens, Greece; Department of Medicine, Tufts University School of Medicine, Boston, MA, USA.
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21
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Bai XR, Liu JM, Jiang DC, Yan SY. Efficacy and safety of tigecycline monotherapy versus combination therapy for the treatment of hospital-acquired pneumonia (HAP): a meta-analysis of cohort studies. J Chemother 2018; 30:172-178. [PMID: 29405898 DOI: 10.1080/1120009x.2018.1425279] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The broad spectrum antibiotic tigecycline shows promising efficacy against many multiple drug resistant (MDR) pathogens. However, its clinical efficacy in the treatment of hospital-acquired pneumonia (HAP) is unclear. Several studies have reported on the treatment failures of tigecycline monotherapy, suggesting that it may not be sufficient to control severe infections. Combination therapy has become an option to treat MDR bacterial infections. We conducted a literature search using PubMed, Cochrane Library, Embase, Elsevier and the Web of Knowledge databases up to 29 February 2017 to identify relevant published studies. Studies were considered eligible if they were a cohort study that assessed mortality and the safety of tigecycline monotherapy versus combination therapy with other antimicrobial agents for HAP. The primary outcome was treatment mortality rate, while the secondary outcomes were adverse events. Meta-analysis was done using fixed-effects models. Five trials were included. The monotherapy tigecycline had a higher mortality compared to the combination therapy group. There was a significant difference for the treatment of HAP. However, two prospective cohort studies showed that there was no significant difference in mortality rate between the tigecycline monotherapy and the tigecycline combination therapy. Three retrospective cohort studies showed that tigecycline monotherapy had a high mortality rate. Tigecycline combination therapy efficiently treats HAP. There is a great need for well-designed studies to evaluate the effectiveness and safety of combination therapies as they compare to tigecycline monotherapy.
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Affiliation(s)
- Xiang-Rong Bai
- a Department of Pharmacy , Xuan Wu Hospital Capital Medical University , Beijing , China.,b National Clinical Research Center for Geriatric Disorder , Beijing , China
| | - Jia-Ming Liu
- a Department of Pharmacy , Xuan Wu Hospital Capital Medical University , Beijing , China.,b National Clinical Research Center for Geriatric Disorder , Beijing , China
| | - De-Chun Jiang
- a Department of Pharmacy , Xuan Wu Hospital Capital Medical University , Beijing , China.,b National Clinical Research Center for Geriatric Disorder , Beijing , China
| | - Su-Ying Yan
- a Department of Pharmacy , Xuan Wu Hospital Capital Medical University , Beijing , China.,b National Clinical Research Center for Geriatric Disorder , Beijing , China
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22
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Karaiskos I, Antoniadou A, Giamarellou H. Combination therapy for extensively-drug resistant gram-negative bacteria. Expert Rev Anti Infect Ther 2017; 15:1123-1140. [DOI: 10.1080/14787210.2017.1410434] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Ilias Karaiskos
- 6th Department of Internal Medicine, Hygeia General hospital, Athens, Greece
| | - Anastasia Antoniadou
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens School of Medicine, University General Hospital ATTIKON, Athens, Greece
| | - Helen Giamarellou
- 6th Department of Internal Medicine, Hygeia General hospital, Athens, Greece
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23
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Ku YH, Chen CC, Lee MF, Chuang YC, Tang HJ, Yu WL. Comparison of synergism between colistin, fosfomycin and tigecycline against extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates or with carbapenem resistance. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2017; 50:931-939. [PMID: 28716360 DOI: 10.1016/j.jmii.2016.12.008] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Revised: 11/16/2016] [Accepted: 12/07/2016] [Indexed: 12/24/2022]
Abstract
PURPOSE To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains. METHODS In vitro synergism and bactericidal activity of combination of colistin, fosfomycin and tigecycline were evaluated by time-kill studies in standard inoculum of bacterial densities of a suspension containing 5 × 105 CFU/mL by using 1/2× MIC for each alone, and both 1/2× and 1/4× MIC for any two drugs. The settings of low MIC dosing were allowed to rapidly survey the most active drug combination. RESULTS The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2× MIC and 1/4× MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2× MIC and 1/4× MIC, respectively. CONCLUSIONS The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance.
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Affiliation(s)
- Yee-Huang Ku
- Division of Infectious Disease, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan City, Taiwan
| | - Chi-Chung Chen
- Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan
| | - Mei-Feng Lee
- Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan
| | - Yin-Ching Chuang
- Division of Infectious Disease, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan City, Taiwan; Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan
| | - Hung-Jen Tang
- Division of Infectious Disease, Department of Internal Medicine, Chi Mei Hospital, Tainan City, Taiwan; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan City, Taiwan
| | - Wen-Liang Yu
- Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan City, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan.
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24
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Richter SS, Marchaim D. Screening for carbapenem-resistant Enterobacteriaceae: Who, When, and How? Virulence 2017; 8:417-426. [PMID: 27813699 PMCID: PMC5477693 DOI: 10.1080/21505594.2016.1255381] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 10/23/2016] [Accepted: 10/25/2016] [Indexed: 10/20/2022] Open
Abstract
The global spread of carbapenem-resistant Enterobacteriaceae (CRE) has been fostered by the lack of preemptive screening of patients in healthcare facilities that could prevent patient-to-patient transmission. Outbreaks of CRE infections have led some institutions to implement rigorous screening programs, although controlled comparative data are frequently lacking. Resource limitations and uncertainty regarding the optimal approach has kept many facilities from enacting more active routine surveillance policies that could reduce the prevalence of CRE. The ideal population to target for screening, the frequency of testing, and the preferred test method are components of surveillance programs that remain open to debate. This review discusses the rationale for different screening policies in use and the performance characteristics of laboratory methods available to detect CRE carriage.
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Affiliation(s)
- Sandra S. Richter
- Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Dror Marchaim
- Division of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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25
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Wenzler E, Goff DA, Humphries R, Goldstein EJC. Anticipating the Unpredictable: A Review of Antimicrobial Stewardship and Acinetobacter Infections. Infect Dis Ther 2017; 6:149-172. [PMID: 28260148 PMCID: PMC5446362 DOI: 10.1007/s40121-017-0149-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Indexed: 11/29/2022] Open
Abstract
Acinetobacter remains one of the most challenging pathogens in the field of infectious diseases owing primarily to the uniqueness and multiplicity of its resistance mechanisms. This resistance often leads to devastatingly long delays in time to appropriate therapy and increased mortality for patients afflicted with Acinetobacter infections. Selecting appropriate empiric and definitive antibacterial therapy for Acinetobacter is further complicated by the lack of reliability in commercial antimicrobial susceptibility testing devices and limited breakpoint interpretations for available agents. Existing treatment options for infections due to Acinetobacter are limited by a lack of robust efficacy and safety data along with concerns regarding appropriate dosing, pharmacokinetic/pharmacodynamic targets, and toxicity. Antimicrobial stewardship programs are essential to combat this unpredictable pathogen through use of infection prevention, rapid diagnostics, antibiogram-optimized treatment regimens, and avoidance of overuse of antimicrobials. The drug development pipeline includes several agents with encouraging in vitro activity against Acinetobacter, but their place in therapy and contribution to the armamentarium against this pathogen remain to be defined. The objective of this review is to highlight the unique challenge of treating infections due to Acinetobacter and summarize recent literature regarding optimal antimicrobial treatment for this pathogen. The drug development pipeline is also explored for future potentially effective treatment options.
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Affiliation(s)
- Eric Wenzler
- College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
| | - Debra A Goff
- Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Romney Humphries
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA
| | - Ellie J C Goldstein
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.,R M Alden Research Laboratory, Santa Monica, CA, USA
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26
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Marchaim D, Levit D, Zigron R, Gordon M, Lazarovitch T, Carrico JA, Chalifa-Caspi V, Moran-Gilad J. Clinical and molecular epidemiology of Acinetobacter baumannii bloodstream infections in an endemic setting. Future Microbiol 2017; 12:271-283. [PMID: 28287300 DOI: 10.2217/fmb-2016-0158] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
AIM The transmission dynamics of Acinetobacter baumannii in endemic settings, and the relation between microbial properties and patients' clinical outcomes, are yet obscure and hampered by insufficient metadata. METHODS & RESULTS Of 20 consecutive patients with A. baumannii bloodstream infection that were thoroughly analyzed at a single center, at least one transmission opportunity was evident for 85% of patients. This implies that patient-to-patient transmission is the major mode of A. baumannii acquisitions in health facilities. Moreover, all patients who died immediately (<24 h of admission) were infected with a single clone (ST457; relative risk = 1.6; p = 0.05). CONCLUSION This preliminary analysis should prompt further investigation by mapping genomic virulence determinants among A. baumannii ST457 lineage compared with other strains.
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Affiliation(s)
- Dror Marchaim
- Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, Israel.,Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Dana Levit
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Roy Zigron
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Michal Gordon
- NIBN, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Tsillia Lazarovitch
- Clinical Microbiology Laboratory, Assaf Harofeh Medical Center, Zerifin, Israel
| | - Joao A Carrico
- Instituto de Microbiologia & Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | | | - Jacob Moran-Gilad
- Public Health Services, Ministry of Health, Jerusalem, Israel.,Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.,ESCMID Study Group for Genomic & Molecular Diagnostics (ESGMD), Basel, Switzerland
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27
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Wang W, Jiang T, Zhang W, Li C, Chen J, Xiang D, Cao K, Qi LW, Li P, Zhu W, Chen W, Chen Y. Predictors of mortality in bloodstream infections caused by multidrug-resistant gram-negative bacteria: 4 years of collection. Am J Infect Control 2017; 45:59-64. [PMID: 27765296 DOI: 10.1016/j.ajic.2016.08.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 08/22/2016] [Accepted: 08/22/2016] [Indexed: 11/29/2022]
Abstract
The study was undertaken to describe the profile of patients and the characteristics of all multidrug-resistant gram-negative bacteria (MDR-GNB) and to assess mortality. We examined 138 patients with bloodstream infections (BSIs) caused by MDR-GNB. Clinical characteristics, antibiotic therapy, and in-hospital mortality were analyzed. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. The in-hospital mortality rate was 25.4%. Univariate analysis revealed that comorbidities and inadequate initial antimicrobial treatment could increase risk of death. In Cox regression analysis, mortality was independently associated with the age (P = .034), hospitalization in an intensive care unit (ICU) (P = .04), invasive procedures (P < .001), and Acute Physiology and Chronic Health Evaluation II scores (P < .001), whereas combination therapy or monotherapy was not associated with mortality (P = .829). Postantibiogram therapy was associated with hospitalization in an ICU (P = .006), Charlson comorbidity index score (P = .003), and inadequate initial antimicrobial treatment (P < .001). MDR-GNB strains and antimicrobial regimens were not the major risk factors of mortality. Inadequate initial antimicrobial treatment, invasive procedures, high Acute Physiology And Chronic Health Evaluation II scores, hospitalization in an ICU, and comorbidities were the important factors responsible for mortality. Although there was no difference between combination therapy and monotherapy in mortality, combined treatment may be more effective than monotherapy for patients in an ICU, with a Charlson comorbidity index score < 4, or inadequate initial antimicrobial treatment.
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28
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Carbapenem-Resistant Pseudomonas aeruginosa Bacteremia: Risk Factors for Mortality and Microbiologic Treatment Failure. Antimicrob Agents Chemother 2016; 61:AAC.01243-16. [PMID: 27821456 DOI: 10.1128/aac.01243-16] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Accepted: 11/03/2016] [Indexed: 12/11/2022] Open
Abstract
We reviewed 37 patients treated for bacteremia due to carbapenem-resistant (CR) Pseudomonas aeruginosa Although 65% of isolates were multiple-drug resistant, therapeutic options were available, as all were susceptible to ≥1 antibiotic. A total of 92% of patients received active antimicrobial therapy, but only 57% received early active therapy (within 48 h). Fourteen-day mortality was 19%. Microbiologic failure occurred in 29%. The Pitt bacteremia score (P = 0.046) and delayed active therapy (P = 0.027) were predictive of death and microbiologic failure, respectively.
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29
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Adler A, Friedman ND, Marchaim D. Multidrug-Resistant Gram-Negative Bacilli: Infection Control Implications. Infect Dis Clin North Am 2016; 30:967-997. [PMID: 27660090 DOI: 10.1016/j.idc.2016.08.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Antimicrobial resistance is a common iatrogenic complication of both modern life and medical care. Certain multidrug resistant and extensively drug resistant Gram-negative organisms pose the biggest challenges to health care today, predominantly owing to a lack of therapeutic options. Containing the spread of these organisms is challenging, and in reality, the application of multiple control measures during an evolving outbreak makes it difficult to measure the relative impact of each measure. This article reviews the usefulness of various infection control measures in containing the spread of multidrug-resistant Gram-negative bacilli.
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Affiliation(s)
- Amos Adler
- Clinical Microbiology Laboratory, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Department of Medicine, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | | | - Dror Marchaim
- Department of Medicine, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin 70300, Israel.
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30
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Zusman O, Altunin S, Koppel F, Dishon Benattar Y, Gedik H, Paul M. Polymyxin monotherapy or in combination against carbapenem-resistant bacteria: systematic review and meta-analysis. J Antimicrob Chemother 2016; 72:29-39. [PMID: 27624572 DOI: 10.1093/jac/dkw377] [Citation(s) in RCA: 122] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 08/01/2016] [Accepted: 08/10/2016] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVES The objective of this study was to summarize available data on polymyxin-based combination therapy or monotherapy for carbapenem-resistant Gram-negative bacteria. METHODS This is a systematic review. We included observational studies and randomized controlled trials (RCTs) comparing polymyxin monotherapy versus polymyxin-based combination therapy in adult patients with infections caused by carbapenem-resistant or carbapenemase-producing Gram-negative bacteria. Only named antibiotic regimens were included. The primary outcome was 30 day mortality. Unadjusted OR (uOR) and adjusted OR where available with 95% CI were pooled in random-effects meta-analyses. RESULTS Twenty-two studies including 28 comparisons were included. Polymyxin monotherapy was associated with a uOR of 1.58 (95% CI = 1.03-2.42) for mortality compared with polymyxin/carbapenem combination therapy (seven observational studies, 537 patients), without heterogeneity. Subgrouping studies to serious and critical risk of bias resulted in uORs of 0.94 (95% CI = 0.42-2.09) and 1.94 (95% CI = 1.17-3.23), respectively. Mortality was significantly higher with polymyxin monotherapy compared with combination therapy with tigecycline, aminoglycosides or fosfomycin (potentially double-coverage regimens): uOR of 1.57 (95% CI = 1.06-2.32) overall (10 observational studies and 1 RCT, 585 patients, no heterogeneity) and uOR of 2.09 (95% CI = 1.21-3.6) for Klebsiella pneumoniae bacteraemia (7 observational studies, 285 patients, no heterogeneity); very low quality evidence. Two RCTs and one observational study assessing rifampicin/colistin combination therapy for Acinetobacter baumannii infections showed no difference in mortality compared with colistin monotherapy; moderate quality evidence. CONCLUSIONS The significant association observed in observational studies between polymyxin monotherapy and mortality cannot be taken as proof of combination therapy effects due to the low quality of the evidence. The only three RCTs to date show no effect of rifampicin/colistin or fosfomycin/colistin on mortality for Acinetobacter infections.
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Affiliation(s)
- Oren Zusman
- Department of Medicine E, Rabin Medical Center, Petah-Tiqva, Israel
| | - Sergey Altunin
- Infectious Diseases Unit, Rambam Medical Center, Haifa, Israel.,The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
| | - Fidi Koppel
- Infectious Diseases Unit, Rambam Medical Center, Haifa, Israel
| | - Yael Dishon Benattar
- Infectious Diseases Unit, Rambam Medical Center, Haifa, Israel.,The Cheryl Spencer Department of Nursing, University of Haifa, Haifa, Israel
| | - Habip Gedik
- Department of Infectious Diseases and Clinical Microbiology, MoH Bakirkoy Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Mical Paul
- Infectious Diseases Unit, Rambam Medical Center, Haifa, Israel.,The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
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31
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Osei Sekyere J, Govinden U, Bester LA, Essack SY. Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods. J Appl Microbiol 2016; 121:601-17. [PMID: 27153928 DOI: 10.1111/jam.13169] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Revised: 04/13/2016] [Accepted: 05/02/2016] [Indexed: 01/31/2023]
Abstract
A literature review was undertaken to ascertain the molecular basis for tigecycline and colistin resistance mechanisms and the experimental basis for the detection and delineation of this resistance particularly in carbapenemase-producing Gram-negative bacteria. Pubmed, Google Scholar and Science Direct were searched with the keywords colistin, tigecycline, resistance mechanisms and detection methods. Trans-complementation and comparative MIC studies, mass spectrometry, chromatography, spectrofluorometry, PCR, qRT-PCR and whole genome sequencing (WGS) were commonly used to determine tigecycline and colistin resistance mechanisms, specifically modifications in the structural and regulatory efflux (acrAB, OqxAB, kpgABC adeABC-FGH-IJK, mexAB-XY-oprJM and soxS, rarA robA, ramRAB marRABC, adeLRS, mexRZ and nfxb) and lipid A (pmrHFIJFKLM, lpxA, lpxC lpxD and mgrB, pmrAB, phoPQ,) genes respectively. Mutations in the ribosomal 16S rRNA operon rrnBC, also yielded resistance to tigecycline through target site modifications. The mcr-1 gene conferring resistance to colistin was identified via WGS, trans-complementation and a murine thigh infection model studies. Common detection methods are mainly antibiotic sensitivity testing with broth microdilution while molecular identification tools are mostly PCR and WGS. Spectrofluorometry, MALDI-TOF MS, micro-array and real-time multiplex PCR hold much promise for the future as new detection tools.
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Affiliation(s)
- J Osei Sekyere
- Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - U Govinden
- Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - L A Bester
- Biomedical Resource Unit, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - S Y Essack
- Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
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32
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Clinical and Epidemiological Significance of Carbapenem Resistance in Acinetobacter baumannii Infections. Antimicrob Agents Chemother 2016; 60:3127-31. [PMID: 26883694 DOI: 10.1128/aac.02656-15] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 02/07/2016] [Indexed: 02/07/2023] Open
Abstract
Carbapenems are considered the treatment of choice for Acinetobacter baumannii infections. Many facilities implement preventive measures toward only carbapenem-resistant A. baumannii (CRAB). However, the independent role of the carbapenem resistance determinant on patient outcomes remains controversial. In a 6-year analysis of adults with A. baumannii bloodstream infection (BSI), the outcomes of 149 CRAB isolates were compared to those of 91 patients with carbapenem-susceptible A. baumannii In bivariable analyses, CRAB BSIs were significantly associated with worse outcomes and with a delay in the initiation of appropriate antimicrobial therapy (DAAT). However, in multivariable analyses, carbapenem resistance status was no longer associated with poor outcomes, while DAAT remained an independent predictor. The epidemiological significance of A. baumannii should not be determined by its resistance to carbapenems.
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34
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Kim WY, Moon JY, Huh JW, Choi SH, Lim CM, Koh Y, Chong YP, Hong SB. Comparable Efficacy of Tigecycline versus Colistin Therapy for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Pneumonia in Critically Ill Patients. PLoS One 2016; 11:e0150642. [PMID: 26934182 PMCID: PMC4775052 DOI: 10.1371/journal.pone.0150642] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 02/17/2016] [Indexed: 11/21/2022] Open
Abstract
Tigecycline has in vitro activity against multidrug-resistant and extensively drug-resistant Acinetobacter baumannii (MDR/XDRAB), and may constitute an alternative therapy for treating pneumonia caused by MDR/XDRAB. The aim of this study was to compare the efficacy of tigecycline-based therapy with colistin-based therapy in patients with MDR/XDRAB pneumonia. Between January 2009 and December 2010, patients in the intensive care unit who were diagnosed with MDR/XDRAB pneumonia and treated with either tigecycline or colistin mono-/combination therapy were reviewed. A total of 70 patients were included in our analysis. Among them, 30 patients received tigecycline-based therapy, and 40 patients received colistin-based therapy. Baseline characteristics were similar in the two groups. Clinical success rate was 47% in the tigecycline group and 48% in the colistin group (P = 0.95). There were no differences between the groups with regard to other clinical outcomes, with the exception that nephrotoxicity was observed only in the colistin group (0% vs. 20%; P = 0.009). Clinical and microbiological success rates were numerically higher, and mortality rates were numerically lower in combination therapy group than in the monotherapy group. Multivariate analysis indicated that monotherapy was independently associated with increased clinical failure (aOR, 3.96; 95% CI, 1.03–15.26; P = 0.046). Our results suggest that tigecycline-based therapy was tolerable and the clinical outcome was comparable to that of colistin-based therapy for patients with MDR/XDRAB pneumonia. In addition, combination therapy may be more useful than monotherapy in treatment of MDR/XDRAB pneumonia.
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Affiliation(s)
- Won-Young Kim
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae-Young Moon
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Won Huh
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chae-Man Lim
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Younsuck Koh
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Pil Chong
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- * E-mail: (YPC); (SBH)
| | - Sang-Bum Hong
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- * E-mail: (YPC); (SBH)
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Marie MAM, Krishnappa LG, Alzahrani AJ, Mubaraki MA, Alyousef AA. A prospective evaluation of synergistic effect of sulbactam and tazobactam combination with meropenem or colistin against multidrug resistant Acinetobacter baumannii. Bosn J Basic Med Sci 2015; 15:24-9. [PMID: 26614848 DOI: 10.17305/bjbms.2015.526] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Revised: 07/07/2015] [Accepted: 07/13/2015] [Indexed: 11/16/2022] Open
Abstract
The present study evaluates the synergistic effect of sulbactam/tazobactam in combination with meropenem or colistin against multidrug resistant (MDR) Acinetobacter baumannii isolated from hospitalized patients from a tertiary care hospital in Saudi Arabia. During the study period, 54 multidrug and carbapenem-resistant isolates of A. baumannii isolates were collected from blood and respiratory samples of patients with ventilator-associated pneumonia or bacteremia. Microbroth checkerboard assay (CBA) and E-test were performed to look for synergistic interface of sulbactam and tazobactam with meropenem or colistin. All 54 MDR isolates of A. baumannii were resistant to carbapenem. Minimum inhibitory concentration [50/90] value against sulbactam, tazobactam, meropenem, colistin was found to be 64/128, 64/128, 64/256, and 0.5/1.0 respectively. Synergy was detected in more isolates with CBA compared to E-test. All four combinations showed significant synergistic bactericidal activity. However, the combination with colistin showed greater synergistic effect than combination with meropenem. Antagonism was not detected with any of the combinations and any method, but indifference was seen in tazobactam and colistin combination alone. A significant bactericidal effect was seen with sulbactam combination with meropenem or colistin in both methods. A combination therapy can be a choice of treatment. As colistin is known to exhibit nephrotoxicity, the combination of sulbactam and meropenem might be considered as an alternative antibiotic treatment for such multi- and extremely resistant bacteria. Yet, sample size is small in our study, so further well-designed in vitro and clinical studies on large scale should confirm our findings.
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Leibman V, Martin ET, Tal-Jasper R, Grin L, Hayakawa K, Shefler C, Azouri T, Kaplansky T, Maskit M, Lazarovitch T, Zaidenstein R, Kaye KS, Marchaim D. Simple bedside score to optimize the time and the decision to initiate appropriate therapy for carbapenem-resistant Enterobacteriaceae. Ann Clin Microbiol Antimicrob 2015; 14:31. [PMID: 26041137 PMCID: PMC4460756 DOI: 10.1186/s12941-015-0088-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Accepted: 05/25/2015] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Epidemiological characteristics of patients with bloodstream infections (BSI) due to extended-spectrum β-lactamase producing (ESBL) and carbapenem-resistant (CRE) strains are often similar. Mortality rates for CRE BSI are 70%, and mean time to initiation of appropriate therapy is ~5 days. A bedside score was developed to differentiate CRE-BSIs from ESBL-BSIs, in order to help decrease the time to initiation of appropriate therapy for CRE and mortality rates. FINDINGS Score was developed based of data (2007-2010) abstracted from charts of adult patients from Assaf Harofeh Medical Center (AHMC, Zeriffin, Israel), and validated on a cohort of patients from Detroit Medical Center (DMC, MI, USA). A multivariate model for presence of CRE was generated. A clinical prediction score and ROC curve was derived. 451 patients with ESBL BSIs (285 from AHMC and 166 from DMC) and 74 patients with CRE BSIs (58 from AHMC and 16 from DMC) were included. The prediction score included chemotherapy in the past 3 months (19 points), presence of foreign invasive devices (10 points), no peripheral vascular disease (10 points), reduced consciousness or cognition at time of acute illness (9 points), time in hospital prior to BSI ≥ 3 days (7 points), and age younger than 65 years (6 points). A score of ≥32 to define "high CRE risk" had sensitivity of 59%, specificity of 76%, PPV of 34% and NPV of 90%. CONCLUSIONS The score's 90% NPV implies it could reduce un-necessary (and toxic) empiric use of anti-CRE therapeutics, but this should be studied prospectively and on broader populations in order to test its potential role in reducing mortality.
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Affiliation(s)
- Violet Leibman
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Emily T Martin
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Ruthy Tal-Jasper
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Leonti Grin
- Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, 70300, Israel
| | - Kayoko Hayakawa
- Division of Infectious Diseases, Detroit Medical Center, Wayne State University, Detroit, MI, USA
| | - Coral Shefler
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Tal Azouri
- Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, 70300, Israel
| | - Tamir Kaplansky
- Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, 70300, Israel
| | - Moran Maskit
- Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, 70300, Israel
| | - Tsilia Lazarovitch
- Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, 70300, Israel
| | - Ronit Zaidenstein
- Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, 70300, Israel
| | - Keith S Kaye
- Division of Infectious Diseases, Detroit Medical Center, Wayne State University, Detroit, MI, USA
| | - Dror Marchaim
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. .,Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, 70300, Israel.
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Cheng A, Chuang YC, Sun HY, Sheng WH, Yang CJ, Liao CH, Hsueh PR, Yang JL, Shen NJ, Wang JT, Hung CC, Chen YC, Chang SC. Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study. Crit Care Med 2015; 43:1194-204. [PMID: 25793437 DOI: 10.1097/ccm.0000000000000933] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVES Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. DESIGN Prospective, observational, multicenter study. SETTING, PATIENTS, AND INTERVENTIONS Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. MEASUREMENTS AND MAIN RESULTS Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline minimum inhibitory concentration greater than 2 mg/L compared with the use of colistin-carbapenem (hazard ratio, 6.93; 95% CI, 1.61-29.78; p=0.009). CONCLUSIONS Increased 14-day mortality was associated with colistin-tigecycline therapy given tigecycline minimum inhibitory concentration greater than 2 mg/L compared with colistin-carbapenem therapy for extensively drug-resistant A. baumannii bacteremia.
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Affiliation(s)
- Aristine Cheng
- 1Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. 2Department of Internal Medicine, National Taiwan University Hospital Hsin-chu Branch, Hsin-chu, Taiwan. 3Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. 4Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan. 5Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-lin, Taiwan. 6Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Rodríguez-Baño J, Cisneros JM, Cobos-Trigueros N, Fresco G, Navarro-San Francisco C, Gudiol C, Horcajada JP, López-Cerero L, Martínez JA, Molina J, Montero M, Paño-Pardo JR, Pascual A, Peña C, Pintado V, Retamar P, Tomás M, Borges-Sa M, Garnacho-Montero J, Bou G. Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology. Enferm Infecc Microbiol Clin 2015; 33:337.e1-337.e21. [DOI: 10.1016/j.eimc.2014.11.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Accepted: 11/21/2014] [Indexed: 12/21/2022]
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Pogue J, Kaye K, Cohen D, Marchaim D. Appropriate antimicrobial therapy in the era of multidrug-resistant human pathogens. Clin Microbiol Infect 2015; 21:302-12. [DOI: 10.1016/j.cmi.2014.12.025] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Revised: 12/22/2014] [Accepted: 12/27/2014] [Indexed: 01/02/2023]
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Gao F, Ye Q, Wan Q, Liu S, Zhou J. Distribution and resistance of pathogens in liver transplant recipients with Acinetobacter baumannii infection. Ther Clin Risk Manag 2015. [PMID: 25848296 DOI: 10.2147/tcrm.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Drug-resistant Acinetobacter baumannii has become a major problem in liver transplant recipients. The aim of this study was to investigate the clinical presentation, distribution, and drug susceptibility characteristics in liver recipients with A. baumannii infection. METHODS We retrospectively investigated 17 liver recipients who developed A. baumannii infection between January 1, 2007 and December 31, 2014. The distribution of A. baumannii and drug susceptibility characteristics were reviewed. RESULTS Infectious complications due to A. baumannii appeared in 17 liver recipients, with a total of 24 episodes. Approximately 63% (15/24) of A. baumannii infections occurred within 2 weeks after transplantation. The most common source of infection was multiple culture-positive sites (35.3%, n=6), followed by the intra-abdominal/biliary tract (23.5%, n=4) and lung (23.5%, n=4). Eight patients (47.1%) had a body temperature of 38°C or higher at the onset of A. baumannii infection. Nine, seven, and 12 recipients had a serum creatinine level of >1.5 mg/dL, a white blood cell count of >15,000/mm(3), and a platelet count of <50,000/mm(3), respectively. There were five (29.4%) cases of septic shock and eight (47.1%) deaths. The rate of antibiotic resistance of A. baumannii to ten of 12 antibiotics investigated was more than 60%. Among the 24 infections caused by A. baumannii, 75% were carbapenem-resistant. The rods were relatively sensitive to tigecycline and cefoperazone-sulbactam. CONCLUSION The clinical manifestations of A. baumannii infection included a high body temperature, a decreased platelet count, an elevated white blood cell count, and onset in the early period after transplantation as well as high mortality. The antibiotic resistance rate of A. baumannii was extremely high. Prevention measures and combination antibiotic therapy are needed to improve the outcomes of liver recipients with A. baumannii infections.
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Affiliation(s)
- Fei Gao
- Infectious Disease Department of Henan Province People's Hospital, Zhengzhou, People's Republic of China
| | - Qifa Ye
- Department of Transplant Surgery, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China ; Department of Transplant Surgery, Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of China
| | - Qiquan Wan
- Department of Transplant Surgery, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Shan Liu
- Adelphi University College of Nursing and Public Health, New York, NY, USA
| | - Jiandang Zhou
- Department of Clinical Laboratory of Microbiology, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China
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Gao F, Ye Q, Wan Q, Liu S, Zhou J. Distribution and resistance of pathogens in liver transplant recipients with Acinetobacter baumannii infection. Ther Clin Risk Manag 2015; 11:501-5. [PMID: 25848296 PMCID: PMC4381901 DOI: 10.2147/tcrm.s82251] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background Drug-resistant Acinetobacter baumannii has become a major problem in liver transplant recipients. The aim of this study was to investigate the clinical presentation, distribution, and drug susceptibility characteristics in liver recipients with A. baumannii infection. Methods We retrospectively investigated 17 liver recipients who developed A. baumannii infection between January 1, 2007 and December 31, 2014. The distribution of A. baumannii and drug susceptibility characteristics were reviewed. Results Infectious complications due to A. baumannii appeared in 17 liver recipients, with a total of 24 episodes. Approximately 63% (15/24) of A. baumannii infections occurred within 2 weeks after transplantation. The most common source of infection was multiple culture-positive sites (35.3%, n=6), followed by the intra-abdominal/biliary tract (23.5%, n=4) and lung (23.5%, n=4). Eight patients (47.1%) had a body temperature of 38°C or higher at the onset of A. baumannii infection. Nine, seven, and 12 recipients had a serum creatinine level of >1.5 mg/dL, a white blood cell count of >15,000/mm3, and a platelet count of <50,000/mm3, respectively. There were five (29.4%) cases of septic shock and eight (47.1%) deaths. The rate of antibiotic resistance of A. baumannii to ten of 12 antibiotics investigated was more than 60%. Among the 24 infections caused by A. baumannii, 75% were carbapenem-resistant. The rods were relatively sensitive to tigecycline and cefoperazone-sulbactam. Conclusion The clinical manifestations of A. baumannii infection included a high body temperature, a decreased platelet count, an elevated white blood cell count, and onset in the early period after transplantation as well as high mortality. The antibiotic resistance rate of A. baumannii was extremely high. Prevention measures and combination antibiotic therapy are needed to improve the outcomes of liver recipients with A. baumannii infections.
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Affiliation(s)
- Fei Gao
- Infectious Disease Department of Henan Province People's Hospital, Zhengzhou, People's Republic of China
| | - Qifa Ye
- Department of Transplant Surgery, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China ; Department of Transplant Surgery, Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of China
| | - Qiquan Wan
- Department of Transplant Surgery, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Shan Liu
- Adelphi University College of Nursing and Public Health, New York, NY, USA
| | - Jiandang Zhou
- Department of Clinical Laboratory of Microbiology, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China
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Pogue JM, Cohen DA, Marchaim D. Editorial commentary: Polymyxin-resistant Acinetobacter baumannii: urgent action needed. Clin Infect Dis 2015; 60:1304-7. [PMID: 25632011 PMCID: PMC4392843 DOI: 10.1093/cid/civ044] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2014] [Accepted: 01/02/2015] [Indexed: 11/14/2022] Open
Affiliation(s)
- Jason M Pogue
- Department of Pharmacy Services, Sinai-Grace Hospital, Detroit Medical Center, Wayne State University School of Medicine, Michigan
| | - David A Cohen
- Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin
| | - Dror Marchaim
- Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin Sackler School of Medicine, Tel-Aviv University, Israel
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Brennan BM, Coyle JR, Marchaim D, Pogue JM, Boehme M, Finks J, Malani AN, VerLee KE, Buckley BO, Mollon N, Sundin DR, Washer LL, Kaye KS. Statewide surveillance of carbapenem-resistant enterobacteriaceae in Michigan. Infect Control Hosp Epidemiol 2014; 35:342-9. [PMID: 24602937 DOI: 10.1086/675611] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Carbapenem-resistant Enterobacteriaceae (CRE) are clinically challenging, threaten patient safety, and represent an emerging public health issue. CRE reporting is not mandated in Michigan. METHODS The Michigan Department of Community Health-led CRE Surveillance and Prevention Initiative enrolled 21 facilities (17 acute care and 4 long-term acute care facilities) across the state. Baseline data collection began September 1, 2012, and ended February 28, 2013 (duration, 6 months). Enrolled facilities voluntarily reported cases of Klebsiella pneumoniae and Escherichia coli according to the surveillance algorithm. Patient demographic characteristics, laboratory testing, microbiology, clinical, and antimicrobial information were captured via standardized data collection forms. Facilities reported admissions and patient-days each month. RESULTS One-hundred two cases over 957,220 patient-days were reported, resulting in a crude incidence rate of 1.07 cases per 10,000 patient-days. Eighty-nine case patients had test results positive for K. pneumoniae, whereas 13 had results positive for E. coli. CRE case patients had a mean age of 63 years, and 51% were male. Urine cultures (61%) were the most frequently reported specimen source. Thirty-five percent of cases were hospital onset; sixty-five percent were community onset (CO), although 75% of CO case patients reported healthcare exposure within the previous 90 days. Cardiovascular disease, renal failure, and diabetes mellitus were the most frequently reported comorbid conditions. Common ris k factors included surgery within the previous 90 days, recent infection or colonization with a multidrug-resistant organism, and recent exposures to antimicrobials, especially third- or fourth-generation cephalosporins. CONCLUSIONS CRE are found throughout Michigan healthcare facilities. Implementing a regional, coordinated surveillance and prevention initiative may prevent CRE from becoming hyperendemic in Michigan.
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Affiliation(s)
- Brenda M Brennan
- Division of Communicable Diseases, Bureau of Disease Control, Prevention and Epidemiology, Michigan Department of Community Health, Lansing, Michigan
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Rizek C, Ferraz JR, van der Heijden IM, Giudice M, Mostachio AK, Paez J, Carrilho C, Levin AS, Costa SF. In vitro activity of potential old and new drugs against multidrug-resistant gram-negatives. J Infect Chemother 2014; 21:114-7. [PMID: 25456893 DOI: 10.1016/j.jiac.2014.10.009] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2014] [Revised: 10/01/2014] [Accepted: 10/15/2014] [Indexed: 10/24/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the in vitro susceptibility of MDR gram-negatives bacteria to old drugs such as polymyxin B, minocycline and fosfomycin and new drugs such as tigecycline. METHODS One hundred and fifty-three isolates from 4 Brazilian hospitals were evaluated. Forty-seven Acinetobacter baumannii resistant to carbapenens harboring adeB, blaOxA23, blaOxA51, blaOxA143 and blaIMP genes, 48 Stenotrophomonas maltophilia including isolates resistant to levofloxacin and/or trimethoprim-sulfamethoxazole harboring sul-1, sul-2 and qnrMR and 8 Serratia marcescens and 50 Klebsiella pneumoniae resistant to carbapenens harboring blaKPC-2 were tested to determine their minimum inhibitory concentrations (MICs) by microdilution to the following drugs: minocycline, ampicillin-sulbactam, tigecycline, and polymyxin B and by agar dilution to fosfomycin according with breakpoint criteria of CLSI and EUCAST (fosfomycin). In addition, EUCAST fosfomycin breakpoint for Pseudomonas spp. was applied for Acinetobacter spp and S. maltophilia, the FDA criteria for tigecycline was used for Acinetobacter spp and S. maltophilia and the Pseudomonas spp polymyxin B CLSI criterion was used for S. maltophilia. RESULTS Tigecycline showed the best in vitro activity against the MDR gram-negative evaluated, followed by polymyxin B and fosfomycin. Polymyxin B resistance among K. pneumoniae was detected in 6 isolates, using the breakpoint of MIC > 8 ug/mL. Two of these isolates were resistant to tigecycline. Minocycline was tested only against S. maltophilia and A. baumannii and showed excellent activity against both. CONCLUSIONS Fosfomycin seems to not be an option to treat infections due to the A. baumannii and S. maltophilia isolates according with EUCAST breakpoint, on the other hand, showed excellent activity against S. marcescens and K. pneumoniae.
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Affiliation(s)
- Camila Rizek
- LIM-54, Departamento de Doenças Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 500, 1 andar, sala 112, CEP05403-000 Sao Paulo, SP, Brazil
| | - Juliana Rosa Ferraz
- LIM-54, Departamento de Doenças Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 500, 1 andar, sala 112, CEP05403-000 Sao Paulo, SP, Brazil
| | - Inneke Marie van der Heijden
- LIM-54, Departamento de Doenças Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 500, 1 andar, sala 112, CEP05403-000 Sao Paulo, SP, Brazil
| | - Mauro Giudice
- LIM-54, Departamento de Doenças Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 500, 1 andar, sala 112, CEP05403-000 Sao Paulo, SP, Brazil
| | - Anna Karina Mostachio
- LIM-54, Departamento de Doenças Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 500, 1 andar, sala 112, CEP05403-000 Sao Paulo, SP, Brazil
| | - Jorge Paez
- LIM-54, Departamento de Doenças Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 500, 1 andar, sala 112, CEP05403-000 Sao Paulo, SP, Brazil
| | | | - Anna Sara Levin
- LIM-54, Departamento de Doenças Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 500, 1 andar, sala 112, CEP05403-000 Sao Paulo, SP, Brazil
| | - Silvia F Costa
- LIM-54, Departamento de Doenças Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 500, 1 andar, sala 112, CEP05403-000 Sao Paulo, SP, Brazil.
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Outcomes of carbapenem-resistant Enterobacteriaceae isolation: matched analysis. Am J Infect Control 2014; 42:612-20. [PMID: 24837111 DOI: 10.1016/j.ajic.2014.02.013] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Revised: 02/13/2014] [Accepted: 02/13/2014] [Indexed: 11/21/2022]
Abstract
BACKGROUND Carbapenem-resistant Enterobacteriaceae (CRE) isolation is associated with poor outcomes. The matched cohort study design enables investigation of specific role of resistance in contributing to patients' outcomes. Patients with CRE were matched to 3 groups: (1) patients with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL), (2) patients with carbapenem-susceptible non-ESBL Enterobacteriaceae, and (3) uninfected controls. METHODS Patients with CRE isolated at Detroit Medical Center (September 1, 2008, to August 31, 2009) were matched (1:1 ratio) to the 3 groups based on (1) bacteria type, (2) hospital/facility, (3) unit/clinic, (4) calendar year, and (5) time at risk (ie, from admission to culture). Multivariable logistic regression models for outcomes were constructed. RESULTS Ninety-one patients with CRE were enrolled. CRE isolation was not an independent predictor for in-hospital mortality in any of the models (ie, vs uncolonized controls, vs ESBL, vs non-ESBL Enterobacteriaceae, and vs all 3 non-CRE groups combined), despite high significance of association in bivariate analyses. CRE isolation was independently associated with deterioration in functional status [odds ratio, 9; P = .002] and being discharged to a long-term care facility after being admitted to the hospital from home [odds ratio, 13.7; P < .001]. CONCLUSION Underlying condition and comorbidities are the principal factors responsible for in-hospital mortality in CRE infections; however, in-hospital mortality is not independently correlated to the offending pathogen. In addition, we found that the pathogen contributes significantly to patients' degree of morbidity.
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Bassetti M, Poulakou G, Giamarellou H. Is there a future for tigecycline? Intensive Care Med 2014; 40:1039-45. [DOI: 10.1007/s00134-014-3343-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Accepted: 05/13/2014] [Indexed: 01/07/2023]
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Paul M, Carmeli Y, Durante-Mangoni E, Mouton JW, Tacconelli E, Theuretzbacher U, Mussini C, Leibovici L. Combination therapy for carbapenem-resistant Gram-negative bacteria. J Antimicrob Chemother 2014; 69:2305-9. [DOI: 10.1093/jac/dku168] [Citation(s) in RCA: 150] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Santoro-Lopes G, Gouvêa EFD. Multidrug-resistant bacterial infections after liver transplantation: An ever-growing challenge. World J Gastroenterol 2014; 20:6201-6210. [PMID: 24876740 PMCID: PMC4033457 DOI: 10.3748/wjg.v20.i20.6201] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 01/20/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients. Over the last two decades, various multidrug-resistant (MDR) pathogens have emerged as relevant causes of infection in this population. Although this fact reflects the spread of MDR pathogens in health care facilities worldwide, several factors relating to the care of transplant donor candidates and recipients render these patients particularly prone to the acquisition of MDR bacteria and increase the likelihood of MDR infectious outbreaks in transplant units. The awareness of this high vulnerability of transplant recipients to infection leads to the more frequent use of broad-spectrum empiric antibiotic therapy, which further contributes to the selection of drug resistance. This vicious cycle is difficult to avoid and leads to a scenario of increased complexity and narrowed therapeutic options. Infection by MDR pathogens is more frequently associated with a failure to start appropriate empiric antimicrobial therapy. The lack of appropriate treatment may contribute to the high mortality occurring in transplant recipients with MDR infections. Furthermore, high therapeutic failure rates have been observed in patients infected with extensively-resistant pathogens, such as carbapenem-resistant Enterobacteriaceae, for which optimal treatment remains undefined. In such a context, the careful implementation of preventive strategies is of utmost importance to minimize the negative impact that MDR infections may have on the outcome of liver transplant recipients. This article reviews the current literature regarding the incidence and outcome of MDR infections in liver transplant recipients, and summarizes current preventive and therapeutic recommendations.
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Major variation in MICs of tigecycline in Gram-negative bacilli as a function of testing method. J Clin Microbiol 2014; 52:1617-21. [PMID: 24599978 DOI: 10.1128/jcm.00001-14] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Tigecycline is one of the few remaining therapeutic options for extensively drug-resistant (XDR) Gram-negative bacilli (GNB). MICs of tigecycline to Acinetobacter baumannii have been reported to be elevated when determined by the Etest compared to determinations by the broth microdilution (BMD) method. The study aim was to compare the susceptibility of GNB to tigecycline by four different testing methods. GNB were collected from six health care systems (25 hospitals) in southeast Michigan from January 2010 to September 2011. Tigecycline MICs among A. baumannii, carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, and susceptible Enterobacteriaceae isolates were determined by Etest, BMD, Vitek-2, and MicroScan. Nonsusceptibility was categorized as a tigecycline MIC of ≥4 μg/ml for both A. baumannii and Enterobacteriaceae. The study included 4,427 isolates: 2,065 ESBL-producing Enterobacteriaceae, 1,105 A. baumannii, 888 susceptible Enterobacteriaceae, and 369 CRE isolates. Tigecycline nonsusceptibility among A. baumannii isolates was significantly more common as determined by Etest compared to that determined by BMD (odds ratio [OR], 10.3; P<0.001), MicroScan (OR, 12.4; P<0.001), or Vitek-2 (OR, 9.4; P<0.001). These differences were not evident with the other pathogens. Tigecycline MICs varied greatly according to the in vitro testing methods among A. baumannii isolates. Etest should probably not be used by laboratories for tigecycline MIC testing of A. baumannii isolates, since MICs are significantly elevated with Etest compared to those determined by the three other methods.
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Chuang YC, Cheng CY, Sheng WH, Sun HY, Wang JT, Chen YC, Chang SC. Effectiveness of tigecycline-based versus colistin- based therapy for treatment of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical setting: a matched cohort analysis. BMC Infect Dis 2014; 14:102. [PMID: 24564226 PMCID: PMC3936940 DOI: 10.1186/1471-2334-14-102] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 02/10/2014] [Indexed: 02/06/2023] Open
Abstract
Background Colistin and tigecycline have both been shown good in vitro activity among multi-drug resistant Acinetobacter baumannii (MDRAB). A comparative study of colistin versus tigecycline for MDRAB pneumonia is lacking. Methods The study enrolled adults with MDRAB pneumonia admitted to intensive care units at a referral medical center during 2009–2010. Since there were no standardized minimum inhibitory concentration (MIC) interpretation criteria of tigecycline against A. baumannii, MIC of tigecycline was not routinely tested at our hospital. During the study periods, MIC of colistin was not routinely tested also. We consider both colistin and tigecycline as definite treatments of MDRAB pneumonia. Patients who received tigecycline were selected as potential controls for those who had received colistin. We performed a propensity score analysis, by considering the criteria of age, gender, underlying diseases, and disease severity, in order to match and equalize potential prognostic factors and severity in the two groups. Results A total of 294 adults with MDRAB pneumonia were enrolled, including 119 who received colistin and 175 who received tigecycline. We matched 84 adults who received colistin with an equal number of controls who received tigecycline. The two well matched cohorts share similar characteristics: the propensity scores are colistin: 0.37 vs. tigecycline: 0.37, (P = .97); baseline creatinine (1.70 vs. 1.81, P = .50), and the APACHE II score (21.6 vs. 22.0, P = .99). The tigecycline group has an excess mortality of 16.7% (60.7% vs. 44%, 95% confidence interval 0.9% – 32.4%, P = .04). The excess mortality of tigecycline is significant only among those with MIC >2 μg/mL (10/12 vs. 37/84, P = .01), but not for those with MIC ≦ 2 μg/mL (4/10 vs. 37/84, P = .81). Conclusions Our data disfavors the use of tigecycline-based treatment in treating MDRAB pneumonia when tigecycline and colistin susceptibilities are unknown, since choosing tigecycline-based treatment might result in higher mortality. The excess mortality of tigecycline-based group may be related to higher MIC of tigecycline (> 2 μg/mL). Choosing tigecycline empirically for treating MDRAB pneumonia in the critical setting should be cautious.
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Affiliation(s)
| | | | - Wang-Huei Sheng
- Department of Internal Medicine, National Taiwan University Hospital, No, 7 Chung-Shan South Road, Taipei 100, Taiwan.
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