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Kong H, Liu Y, Yang L, Chen Q, Li Y, Hu Z, Feng X, Chai Y, Dong Z. Seven-year change of prevalence, clinical risk factors, and mortality of patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection in a Chinese teaching hospital: a case-case-control study. Front Microbiol 2025; 16:1531984. [PMID: 40177489 PMCID: PMC11962001 DOI: 10.3389/fmicb.2025.1531984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 03/07/2025] [Indexed: 04/05/2025] Open
Abstract
Carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) is a major public health threat worldwide. CRKP-BSI is associated with poor outcomes, elevated morbidity and mortality, and high healthcare costs. Therefore, the identification of risk factors for CRKP-BSI and mortality are critical for preventing and controlling CRKP in hospitals. This retrospective case-case-control study was conducted at General Hospital of Tianjin Medical University, a tertiary teaching hospital, from 2017 to 2023. It included 105 patients with CRKP-BSI (case group 1) and matched 105 patients with carbapenem-susceptible K. pneumoniae bloodstream infection (CSKP-BSI) (case group 2). The control group was selected at a ratio of 1:1:1 (case group 1: case group 2: control) from patients with a positive blood culture (except for K. pneumoniae infection) to analyze risk factors associated with the two case groups and compare the 30-day survival curves using multivariable logistic regression and Kaplan-Meier analyses. Multivariate analysis revealed that liver disease was a risk factor for K. pneumoniae-BSI, and exposure to carbapenem [odds ratio (OR) = 3.24], tigecycline (OR = 3.43), and glucocorticoids (OR = 4.64) were independent risk factors for CRKP-BSI. The 30-day mortality of the CRKP-BSI group was 30.5%, and patient groups, respiratory diseases (HR = 3.52), use of 3rd-generation cephalosporins (HR = 1.92), mechanical ventilation (HR = 2.14), and central venous catheter insertion (HR = 2.85) were independent risk factors, whereas a shorter length of hospitalization was a protective factor for 30-day mortality. The in-hospital mortality in the CRKP-BSI group was 55.2%, and arterial catheter use (OR = 3.76) was an independent risk factor for in-hospital mortality. Several factors were identified to contribute to the development of CRKP-BSI. CRKP isolates were resistant to most antibiotics. Reducing CRKP-BSI-related mortality requires comprehensive consideration of underlying diseases, judicious antibiotic use, and invasive procedures. The high morbidity, mortality, along with the limited therapeutic options for CRKP-BSI, underscore the need for improved detection, identification of risk factors to develop effective preventive measures, and development of novel agents with reliable clinical efficacy against CRKP.
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Affiliation(s)
- Haifang Kong
- Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Yong Liu
- Tianjin First Central Hospital of Nankai University, Tianjin, China
| | - Ling Yang
- Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Qianqian Chen
- Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Yanchun Li
- Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhidong Hu
- Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Xuequan Feng
- Tianjin First Central Hospital of Nankai University, Tianjin, China
| | - Yamin Chai
- Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Zuoliang Dong
- Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, China
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Naveed M, Jabeen K, Aziz T, Mughual MS, Ul-Hassan J, Sheraz M, Rehman HM, Alharbi M, Albekairi TH, Alasmari AF. Whole proteome analysis of MDR Klebsiella pneumoniae to identify mRNA and multiple epitope based vaccine targets against emerging nosocomial and lungs associated infections. J Biomol Struct Dyn 2025; 43:1915-1928. [PMID: 38141172 DOI: 10.1080/07391102.2023.2293266] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 11/29/2023] [Indexed: 12/25/2023]
Abstract
Klebsiella pneumonia is a Gram negative facultative anaerobic bacterium involved in various community-acquired pneumonia, nosocomial and lungs associated infections. Frequent usage of several antibiotics and acquired resistance mechanisms has made this bacterium multi-drug resistance (MDR), complicating the treatment of patients. To avoid the spread of this bacterium, there is an urgent need to develop a vaccine based on immuno-informatics approaches that is more efficient than conventional method of vaccine prediction or development. Initially, the complete proteomic sequence of K. pneumonia was picked over for specific and prospective vaccine targets. From the annotation of the whole proteome, eight immunogenic proteins were selected, and these shortlisted proteins were interpreted for CTL, B-cells, and HTL epitopes prediction, to construct mRNA and multi-epitope vaccines. The Antigenicity, allergenicity and toxicity analysis validate the vaccine's design, and its molecular docking was done with immuno-receptor the TLR-3. The docking interaction showed a stronger binding affinity with a minimum energy of -1153.2 kcal/mol and established 23 hydrogen bonds, 3 salt bridges, 1 disulfide bond, and 340 non-binding contacts. Further validation was done using In-silico cloning which shows the highest CAI score of 0.98 with higher GC contents of 72.25% which represents a vaccine construct with a high value of expression in E. coli. Immune Simulation shows that the antibodies (IgM, IgG1, and IgG2) production exceeded 650,000 in 2 to 3 days but the response was completely neutralized in the 5th day. In conclusion, the study provides the effective, safe and stable vaccine construct against Klebsiella pneumonia, which further needs in vitro and in vivo validations.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Muhammad Naveed
- Department of Biotechnology, Faculty of Life Sciences, University of Central Punjab, Lahore, Pakistan
| | - Khizra Jabeen
- Department of Biotechnology, Faculty of Life Sciences, University of Central Punjab, Lahore, Pakistan
| | - Tariq Aziz
- Department of Agriculture, University of Ioannina, Arta, Greece
| | - Muhammad Saad Mughual
- Department of Biotechnology, Faculty of Life Sciences, University of Central Punjab, Lahore, Pakistan
| | - Jawad Ul-Hassan
- Department of Biotechnology, Faculty of Life Sciences, University of Central Punjab, Lahore, Pakistan
| | - Mohsin Sheraz
- Department of Biotechnology, Faculty of Life Sciences, University of Central Punjab, Lahore, Pakistan
| | | | - Metab Alharbi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Thamer H Albekairi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Abdullah F Alasmari
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Cireșă A, Tălăpan D, Vasile CC, Popescu C, Popescu GA. Evolution of Antimicrobial Resistance in Klebsiella pneumoniae over 3 Years (2019-2021) in a Tertiary Hospital in Bucharest, Romania. Antibiotics (Basel) 2024; 13:431. [PMID: 38786159 PMCID: PMC11117972 DOI: 10.3390/antibiotics13050431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 04/26/2024] [Accepted: 05/09/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND The antimicrobial resistance (AMR) of Klebsiella pneumoniae recorded a steep upward trend over the last two decades, among which carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the most concerning strains considering the development and spread of AMR. The aim of this study was to analyze the evolution of AMR for Klebsiella pneumoniae and to describe the risk factors of AMR for Klebsiella pneumoniae, including the COVID-19 pandemic. METHODS We conducted a retrospective study on Klebsiella pneumoniae non-duplicative isolates collected from patients admitted to a tertiary hospital in Bucharest, Romania, from January 2019 to December 2021. We evaluated AMR changes by comparing resistance between 2019 and the mean of 2020-2021. RESULTS The rates of AMR increased for third-generation cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and colistin and decreased for trimethoprim/sulfamethoxazole (TMP/SMX), 45.7% in 2019 vs. 28.3% in 2021. A longer length of hospital stay (ꭓ2 = 49.68, p < 0.01); recent antibiotic consumption, RR = 1.38, 95% CI [1.21, 1.57]; and recent contact with hospital settings, RR = 1.54, 95% CI [1.32, 1.8] were risk factors for multidrug-resistant (MDR) Klebsiella pneumoniae. CONCLUSIONS The AMR of Klebsiella pneumoniae increased during 2020-2021 for most of the potential active antibiotics; only TMP/SMX resistance decreased, and it may represent a treatment option for CRKP or MDR Klebsiella pneumoniae infections. Decreasing the excessive use of antibiotics and the implementation of prevention and control measures in healthcare settings are mandatory for avoiding further increases in the AMR rate of Klebsiella pneumoniae.
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Affiliation(s)
- Alexandra Cireșă
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.-C.V.); (C.P.)
| | - Daniela Tălăpan
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.-C.V.); (C.P.)
- “Prof. Dr. Matei Balș” National Institute of Infectious Diseases, 021105 Bucharest, Romania
| | - Carmen-Cristina Vasile
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.-C.V.); (C.P.)
- “Prof. Dr. Matei Balș” National Institute of Infectious Diseases, 021105 Bucharest, Romania
| | - Cristina Popescu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.-C.V.); (C.P.)
- “Prof. Dr. Matei Balș” National Institute of Infectious Diseases, 021105 Bucharest, Romania
| | - Gabriel-Adrian Popescu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.-C.V.); (C.P.)
- “Prof. Dr. Matei Balș” National Institute of Infectious Diseases, 021105 Bucharest, Romania
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Müller M, Wiencierz A, Gehringer C, Muigg V, Bassetti S, Siegemund M, Hinic V, Tschudin-Sutter S, Egli A. Factors associated with non-carbapenemase mediated carbapenem resistance of Gram-negative bacteria: a retrospective case-control study. Int Microbiol 2024; 27:597-606. [PMID: 37556067 PMCID: PMC10991015 DOI: 10.1007/s10123-023-00405-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 07/10/2023] [Accepted: 07/15/2023] [Indexed: 08/10/2023]
Abstract
Infections with carbapenemase-producing Gram-negative bacteria are related to increased morbidity and mortality, yet little is known regarding infections caused by non-beta-lactamase mediated carbapenem-resistant bacteria. Our objective was to identify risk factors for, and the clinical impact of infections caused by carbapenem-resistant carbapenemase-negative Enterobacterales and Pseudomonas aeruginosa. This retrospective matched case-control study was performed at the University Hospital of Basel, Switzerland, in 2016. We focused on other resistance mechanisms by excluding laboratory-confirmed carbapenemase-positive cases. Carbapenem resistance was set as the primary endpoint, and important risk factors were investigated by conditional logistic regression. The clinical impact of carbapenem resistance was estimated using regression models containing the resistance indicator as explanatory factor and adjusting for potential confounders. Seventy-five cases of infections with carbapenem-resistant, carbapenemase-negative bacteria were identified and matched with 75 controls with carbapenem-susceptible infections. The matched data set was well-balanced regarding age, gender, and comorbidity. Duration of prior carbapenem treatment (OR 1.15, [1.01, 1.31]) correlated with resistance to carbapenems. Our study showed that patients with carbapenem-resistant bacteria stayed 1.59 times (CI [0.81, 3.14]) longer in an ICU. The analyzed dataset did not provide evidence for strong clinical implications of resistance to carbapenems or increased mortality. The duration of prior carbapenem treatment seems to be a strong risk factor for the development of carbapenem resistance. The higher risk for a longer ICU stay could be a consequence of a carbapenem resistance. In contrast to carbapenemase-producers, the clinical impact of carbapenamase-negative, carbapenem-resistant strains may be limited. Trial registration: The study design was prospectively approved by the local Ethics Commission on 10.08.2017 (EKNZ BASEC 2017-00222).
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Affiliation(s)
- Marius Müller
- Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland
- Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland
| | - Andrea Wiencierz
- Clinical Trial Unit, University Hospital Basel, Basel, Switzerland
| | - Christian Gehringer
- Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland
- Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland
- Internal Medicine, University Hospital Basel, Basel, Switzerland
| | - Veronika Muigg
- Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland
| | - Stefano Bassetti
- Internal Medicine, University Hospital Basel, Basel, Switzerland
| | - Martin Siegemund
- Intensive Care Medicine, Department of Acute Medicine, University Hospital Basel, Basel, Switzerland
- Department of Clinical Research, University of Basel, Basel, Switzerland
| | - Vladimira Hinic
- Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland
| | - Sarah Tschudin-Sutter
- Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Adrian Egli
- Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland.
- Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland.
- Institute of Medical Microbiology, University of Zurich, Gloriastrasse 28/30, 8006, Zurich, Switzerland.
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de Souza ILA, Cappellano P, Ferreira DB, Bergamasco MD, das Chagas Neto TC, Kerbauy FR, Baiocchi OCG, Pignatari ACC. Carbapenem-resistant Klebsiella pneumoniae bloodstream infections in haematological malignances and hematopoietic stem cell transplantation: Clinical impact of combination therapy in a 10-year Brazilian cohort. PLoS One 2024; 19:e0297161. [PMID: 38277372 PMCID: PMC10817138 DOI: 10.1371/journal.pone.0297161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 12/29/2023] [Indexed: 01/28/2024] Open
Abstract
Bacterial bloodstream infections (BSI) are a common threat among patients with haematological malignancies (HM) and hematopoietic stem cell transplant recipients (HSCT). The purpose of this research was to describe clinical and microbiological aspects of BSI caused by carbapenem-resistant Klebsiella pneumoniae (CRKp) and assess risk factors associated with 30-day mortality in a 10-year cohort of haematological patients. A total of 65 CRKp-BSI episodes occurring in HM patients and HSCT recipients and CRKp-BSI between January 2010 and December 2019 were retrospectively studied. Acute leukemias were the most frequently observed underlying disease (87.7%) and 18 patients (27.7%) received HSCT. Mucosal barrier injury in the gastrointestinal tract was the primary cause of bacteremia (86.1%). Also, 14 individuals (21.6%) had an Invasive Fungal Disease (IFD) throughout the episode. Regarding treatment, in 31 patients (47.7%) empirical therapy was deemed appropriate, whereas 33 (50.8%) patients received a combination therapy. Microbiological data revealed that the majority of isolates (53-58%) had the Polymyxin B co-resistance phenotype, while amikacin resistance was less common (16 samples, or 24.7%). The mortality rates at 14 and 30 days were 32.3% and 36.9%, respectively. In a multivariate Cox regression analysis, prompt appropriate antibiotic administration within three days was associated with a better outcome (Adjusted Hazard Ratio [aHR]: 0.33; 95% Confidence Interval [CI]: 0.14-0.76; p = 0.01), whereas hypotension at presentation (aHR: 3.88; 95% CI: 1.40-10.74; p = 0.01) and concurrent IFD (aHR: 2.97; 95% CI: 1.20-7.37; p = 0.02) were independently associated with death within 30 days. Additionally, a favorable correlation between combination therapy and overall survival was found (aHR: 0.18; 95%CI: 0.06-0.56; p = 0.002). In conclusion, 30-day mortality CRKp-BSI was elevated and most of the isolates were polymyxin B resistant. Early appropriate antimicrobial treatment and the use of combination therapy were linked to a better outcome.
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Affiliation(s)
- Ingvar Ludwig Augusto de Souza
- Disciplina de Infectologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil
- Hcor–Hospital do Coracao, Sao Paulo, Brazil
| | - Paola Cappellano
- Disciplina de Infectologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil
- Fleury–Medicina e Saúde, Sao Paulo, Brazil
| | - Diogo Boldim Ferreira
- Disciplina de Infectologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil
- Hcor–Hospital do Coracao, Sao Paulo, Brazil
| | - Maria Daniela Bergamasco
- Disciplina de Infectologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil
- Hcor–Hospital do Coracao, Sao Paulo, Brazil
| | - Thomas Cardoso das Chagas Neto
- Laboratório Central, Hospital São Paulo, Disciplina de Medicina Laboratorial, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil
| | - Fabio Rodrigues Kerbauy
- Disciplina de Hematologia e Hemoterapia, Departamento de Oncologia Clínica e Experimental, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil
| | - Otavio Carvalho Guimarães Baiocchi
- Disciplina de Hematologia e Hemoterapia, Departamento de Oncologia Clínica e Experimental, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil
| | - Antonio Carlos Campos Pignatari
- Disciplina de Infectologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil
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Çölkesen F, Tarakçı A, Eroğlu E, Kacar F, Özdemir Armağan Ş, Can S, Erol B, Aksay O, Çölkesen F. Carbapenem-Resistant Klebsiella pneumoniae Infection and Its Risk Factors in Older Adult Patients. Clin Interv Aging 2023; 18:1037-1045. [PMID: 37435410 PMCID: PMC10332362 DOI: 10.2147/cia.s406214] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 05/08/2023] [Indexed: 07/13/2023] Open
Abstract
Introduction Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has recently gained worldwide interest due to limited treatment options and high morbidity and mortality rates. The aim of this study was to determine the risk factors of carbapenem-resistant K. pneumoniae (CRKP) infection in older adult patients. Material and Methods This retrospective, single-center study included 132 patients with healthcare-associated CRKP infection (case group) and 150 patients with healthcare-associated carbapenem-susceptible K. pneumoniae (CSKP) infection (control group), aged > 65 years. Results In the CRKP and CSKP groups, 79 (59.8%) and 80 (53.3%) patients were males, and the mean ages were 77.8 ± 7.8 and 76.6 ± 7.7 years, respectively. Diabetes mellitus (DM), malignancy, cardiovascular diseases (CVDs), surgical intervention, invasive mechanical ventilation, central venous catheter insertion, parenteral nutrition, hospitalization in the previous 6 months, antibiotic use in the previous 3 months, and exposure to cephalosporins, fluoroquinolones, and carbapenems were significantly more common in the CRKP than the CSKP group (all p < 0.05). The multivariate logistic regression analysis identified malignancy, CVDs, DM, invasive mechanical ventilation, hospitalization in the previous 6 months, ICU admission, and exposure to cephalosporins, quinolones, and carbapenems as independent risk factors for CRKP infection in older adult patients. Conclusion DM, malignancy, CVDs, ICU admission, invasive mechanical ventilation, and exposure to ceftriaxone, fluoroquinolones, and carbapenems were independent risk factors for CRKP infection in older adult patients. The identification of risk factors for CRKP infection can help to prevent and treat CRKP infection.
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Affiliation(s)
- Fatma Çölkesen
- Department of Infectious Diseases and Clinical Microbiology, Konya Numune Hospital, Konya, Turkey
| | - Arzu Tarakçı
- Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Konya City Hospital, Konya, Turkey
| | - Esma Eroğlu
- Department of Infectious Diseases and Clinical Microbiology, Meram State Hospital, Konya, Turkey
| | - Fatma Kacar
- Department of Infectious Diseases and Clinical Microbiology, Medova Hospital, Konya, Turkey
| | - Şule Özdemir Armağan
- Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Konya City Hospital, Konya, Turkey
| | - Selver Can
- Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Beyhekim Training and Research Hospital, Konya, Turkey
| | - Bağdat Erol
- Infection Control Committee, University of Health Sciences, Konya City Hospital, Konya, Turkey
| | - Oyagül Aksay
- Infection Control Committee, University of Health Sciences, Konya City Hospital, Konya, Turkey
| | - Fatih Çölkesen
- Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey
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Li M, Yang S, Yao H, Liu Y, Du M. Retrospective Analysis of Epidemiology, Risk Factors, and Outcomes of Health Care-Acquired Carbapenem-Resistant Klebsiella pneumoniae Bacteremia in a Chinese Tertiary Hospital, 2010-2019. Infect Dis Ther 2023; 12:473-485. [PMID: 36520329 PMCID: PMC9925657 DOI: 10.1007/s40121-022-00732-7] [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: 07/09/2022] [Accepted: 11/14/2022] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION In the present study, we aimed to describe the proportion of carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) in KP-BSI in one Chinese tertiary hospital over 10 years and determine the risk factors and outcomes of CRKP-BSI. METHODS We retrospectively analyzed clinical and microbiological data of patients with KP-BSI from January 2010 to December 2019 to identify risk factors, clinical features, and outcomes using multivariate logistic regression analysis. KP-BSI only included monomicrobial BSI and health care-acquired BSI. RESULTS Among the total 687 isolates of KP-BSI in this study, the rate of CRKP was 39.0% (268/687); this rate in the intensive care unit (ICU) was 65.6% and that in seven high-risk departments (including four ICUs, respiratory medicine, gastroenterology medicine, and hepatobiliary surgery) was 74.6%. The annual rate of CRKP in KP-BSI ranged from 0.0% in 2010 to 54.5% in 2019. The 28-day mortality was 36.2% in patients with CRKP-BSI and 11.7% in those with carbapenem-susceptible K. pneumoniae (CSKP) BSI. Multivariable logistic regression analysis showed that prior ICU stay (odds ratio [OR] 2.485, P < 0.001), hospital stay ≥ 30 days prior to BSI (OR 1.815, P = 0.007), prior mechanical ventilation (OR 2.020, P = 0.014), prior urinary catheter (OR 1.999, P = 0.003), prior carbapenem use (OR 3.840, P < 0.001), hepatobiliary disease (OR 2.943, P < 0.001), pancreatitis (OR 2.700, P = 0.026), and respiratory disease (OR 2.493, P = 0.009) were risk factors of CRKP-BSI. Patients with a first admission (OR 0.662, P = 0.046) had a lower percentage of CRKP-BSI. CONCLUSION The rapidly rising rate of CRKP-BSI in KP with high mortality requires increased attention. Exposure to carbapenems, ICU stay, invasive mechanical ventilation or urinary catheter, prolonged hospital stay, hepatobiliary disease, pancreatitis, and respiratory disease were found to be risk factors for CRKP-BSI. Strict control measures should be implemented to prevent the emergence and spread of CRKP, especially in high-risk departments.
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Affiliation(s)
- Meng Li
- Department of Hematology, The First Medical Center of Chinese PLA General Hospital, Beijing, China
- Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shanshan Yang
- Department of Disease Prevention and Control, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Rd, Haidian District, Beijing, 100853 China
| | - Hongwu Yao
- Department of Disease Prevention and Control, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Rd, Haidian District, Beijing, 100853 China
| | - Yunxi Liu
- Department of Disease Prevention and Control, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Rd, Haidian District, Beijing, 100853 China
| | - Mingmei Du
- Department of Disease Prevention and Control, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Rd, Haidian District, Beijing, 100853 China
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So-ngern A, Osaithai N, Meesing A, Chumpangern W. Mortality rate and factors associated with mortality of carbapenem-resistant Enterobacteriaceae infection. Drug Target Insights 2023; 17:120-125. [PMID: 38028024 PMCID: PMC10630699 DOI: 10.33393/dti.2023.2622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 10/11/2023] [Indexed: 12/01/2023] Open
Abstract
Background: Carbapenem-resistant Enterobacteriaceae (CRE) is a serious pathogen with high mortality. Recognition of factors associated with mortality and treating these modifiable factors are crucial to reducing mortality. Objective: To determine the 30-day mortality and factors associated with a 30-day mortality of CRE infection. Methods: A retrospective cohort study was conducted between January 1, 2015, and December 31, 2019. All patients diagnosed with CRE infection aged ≥18 years were included. Multivariate logistic regression was used for evaluating the factors associated with 30-day mortality and presented as adjusted odds ratio (aOR) with 95% confidence interval (CI). Result: One hundred and ninety-four patients were enrolled. The 30-day mortality occurred in 75 patients (38.7%). The common antibiotic regimen was monotherapy and combination of carbapenem, colistin, amikacin, tigecycline, and fosfomycin. CRE isolates were susceptible to tigecycline (93.8%), colistin (91.8%), fosfomycin (89.2%), and amikacin (89.2%). The independent factors associated with 30-day mortality were an increasing simplified acute physiology (SAP) II score (aOR 1.11, 95% CI 1.05-1.16, p < 0.001), sepsis at time of CRE infection diagnosis (aOR 7.93, 95% CI 2.21-28.51, p = 0.002), pneumonia (aOR 4.48, 95% CI 1.61-12.44, p = 0.004), monotherapy (aOR 4.69, 95% CI 1.71-12.85, p = 0.003), and improper empiric antibiotic (aOR 5.13, 95% CI 1.83-14.40, p = 0.002). Conclusion: The overall 30-day mortality of CRE infection was high. The factors associated with mortality were an increasing SAP II score, sepsis at time of CRE infection diagnosis, pneumonia, monotherapy, and improper empiric antibiotic. The study suggested that proper empiric antibiotic and combination antibiotics might reduce mortality from CRE infection.
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Affiliation(s)
- Apichart So-ngern
- Division of Sleep Medicine, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen - Thailand
| | - Naphol Osaithai
- Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen - Thailand
| | - Atibordee Meesing
- Division of Infectious Diseases and Tropical Medicines, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen - Thailand
- Research and Diagnostic Center for Emerging Infectious Diseases (RCEID), Khon Kaen University, Khon Kaen - Thailand
| | - Worawat Chumpangern
- Division of Pulmonary Medicine and Pulmonary Critical Care Medicine, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen - Thailand
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Inhibition of Klebsiella pneumoniae carbapenemases by mycocins produced by Wickerhamomyces anomalus. Arch Microbiol 2022; 204:702. [DOI: 10.1007/s00203-022-03311-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 10/05/2022] [Accepted: 10/28/2022] [Indexed: 11/13/2022]
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10
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Panda S, Dash A, Chhotray P, Nayak B, Mouli TC, Mishra SB. Risk factors and clinical outcomes of carbapenem-resistant Klebsiella pneumonia infection in intensive care unit: A retrospective observational study in a tertiary care hospital in Eastern India. Int J Crit Illn Inj Sci 2022; 12:217-221. [PMID: 36779211 PMCID: PMC9910118 DOI: 10.4103/ijciis.ijciis_34_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 07/30/2022] [Accepted: 08/03/2022] [Indexed: 12/24/2022] Open
Abstract
Background Carbapenem-resistant Enterobacteriaceae, especially Klebsiella pneumonia, have become a severe global problem with a significant threat to public health, but few studies have investigated the risk factors and epidemiology of carbapenem-resistant K. pneumonia (CRKP) infections in India. Methods We performed a retrospective observational study of 224 participants with K. pneumoniae who were admitted to the medical intensive care unit (ICU) of Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India, between January 1 and December 30, 2020. Antibiotic susceptibility testing was done by automated broth microdilution VITEK® 2 (BioMerieux, Inc., Hazelwood, USA). The Clinical and Laboratory Standards Institute document M100-S22 (January 2020) was used to interpret antimicrobial susceptibility testing. Data were obtained from paper medical records. Results Two hundred and twenty-four subjects with culture-positive for K. pneumonia were retrieved during the study period, out of which 108 had CRKP. The risk factors for univariate analysis were Acute Physiology and Chronic Health Evaluation II, ICU length of stay (LOS), invasive mechanical ventilator days, central venous catheter days, and arterial line days. The multivariate analysis showed invasive mechanical ventilation and ICU LOS were independent risk factors for CRKP infection. Mortality in the CRKP group was 48 (44%) compared to 27 (23%) in the carbapenem-sensitive K. pneumonia (CSKP) group, which was statistically significant (P < 0.01). Conclusion Infection due to CRKP in the ICU was associated with 1.9 times higher mortality as compared to CSKP. Invasive mechanical ventilation and ICU LOS were found to be independent risk factors for CRKP infection.
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Affiliation(s)
- Sagarika Panda
- 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
| | - Pritam Chhotray
- Department of Respiratory Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Biswajit Nayak
- Department of Critical Care Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | | | - Shakti Bedanta Mishra
- Department of Critical Care Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
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Stuever DM, Ferketich AK, Lee J, Stevenson KB, Wittum TE. Case-case-control study of risk factors for carbapenem-resistant Enterobacterales infections among hospitalized patients. ANTIMICROBIAL STEWARDSHIP & HEALTHCARE EPIDEMIOLOGY : ASHE 2022; 2:e118. [PMID: 36483348 PMCID: PMC9726559 DOI: 10.1017/ash.2022.244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/15/2022] [Accepted: 05/20/2022] [Indexed: 06/17/2023]
Abstract
OBJECTIVE To identify important risk factors for carbapenem-resistant Enterobacterales (CRE) infections among hospitalized patients. DESIGN We utilized a case-case-control design that compared patients with CRE infections to patients with carbapenem-susceptible Enterobacterales (CSE) infections and randomly selected controls during the period from January 2011 through December 2016. SETTING The study population was selected from patients at a large metropolitan tertiary-care and instructional medical center. PATIENTS Cases of CRE were defined as initial admission of adults diagnosed with a bacterial infection of an Enterobacterales species resistant clinically or through sensitivity testing to carbapenems 48 hours or more after admission. Cases of CSE were selected from the same patient population as the CRE cases within a 30-day window for admission, with diagnostic pathogens identified as susceptible to carbapenems. Controls were defined as adult patients admitted to any service within a 30-day window from a CRE case for >48 hours who did not meet either of the above case definitions during that admission. RESULTS Antibiotic exposure within 90 days prior to admission and length of hospital stay were both associated with increased odds of CRE and CSE infections compared to controls. Patients with CRE infections had >18 times greater odds of prior antibiotic exposure compared to patients with CSE infections. CONCLUSIONS Antibiotic exposure and increased length of hospital stay may result in increased patient risk of developing an infection resistant to carbapenems and other β-lactams.
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Affiliation(s)
- David M. Stuever
- Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, Ohio
| | - Amy K. Ferketich
- Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, Ohio
| | - Jiyoung Lee
- Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio
- Infectious Diseases Institute, The Ohio State University, Columbus, Ohio
| | - Kurt B. Stevenson
- Division of Infectious Diseases, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
- Infectious Diseases Institute, The Ohio State University, Columbus, Ohio
| | - Thomas E. Wittum
- Department of Veterinary Preventive Medicine, The Ohio State University, Columbus, Ohio
- Infectious Diseases Institute, The Ohio State University, Columbus, Ohio
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Lashari Y, Rochmanti M, Purba AKR, Notobroto HB, Sarassari R, Kuntaman K. The Economic Impact of Carbapenem Resistant-Non Lactose Fermenter and Enterobacteriaceae Infections on Hospital Costs in Dr. Soetomo General Academic Hospital Surabaya, Indonesia. Antibiotics (Basel) 2022; 11:694. [PMID: 35625338 PMCID: PMC9137956 DOI: 10.3390/antibiotics11050694] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 05/04/2022] [Accepted: 05/17/2022] [Indexed: 02/05/2023] Open
Abstract
Background: Carbapenem resistant-non lactose fermenter (CR-NLF) and Carbapenem resistant-Enterobacteriaceae (CR-E) bacterial infections are likely to be a global threat to people’s health. However, studies on the economic impacts according to the hospital setting are very scarce. The study aimed to explore the impact of CR-NLF (Acinetobacter baumannii = CRAB) & Pseudomonas aeruginosa = CRPA) and CR-E (Escherichia coli = CREC) & Klebsiella pneumoniae = CRKP) infections on hospital costs from a payer perspective among patients admitted to Dr.Soetomo Hospital, Surabaya, Indonesia. Methods: In the retrospective case-control study, medical records of all included patients hospitalized during 2018−2021 were reviewed for CRAB, CRPA, CREC, CRKP, and carbapenem sensitive (CSAB, CSPA, CSEC, CSKP) were collected. We retrieved the data of age, gender, clinical specimen, dates of admission, and discharge status. The outcomes of interest were hospital length of stay and hospitalization cost. Results: The cost for CR-NLFs infections was higher than carbapenem sensitive, $3026.24 versus $1299.28 (p < 0.05). There was no significant difference between CR-E against carbapenem sensitive. It showed that the highest impact of the cost was CRAB, followed by CRPA, CRKP, and CREC. The bed, antibiotics, pharmacy, and diagnostic costs of CR-NLFIs were significantly higher than CR-E. Conclusion: This study showed that the hospital cost and expenditure of CR-NLFs per patient were higher than CS. The hospital cost per patient for CR-NLF was higher than CR-E.
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Affiliation(s)
- Yasmeen Lashari
- Doctoral Program, Faculty of Medicine, Universitas Airlangga, Surabaya 60286, Indonesia;
| | - Maftuchah Rochmanti
- Division of Pharmacology, Department of Anatomy, Histology and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya 60286, Indonesia; (M.R.); (A.K.R.P.)
| | - Abdul Khairul Rizki Purba
- Division of Pharmacology, Department of Anatomy, Histology and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya 60286, Indonesia; (M.R.); (A.K.R.P.)
| | - Hari Basuki Notobroto
- Department of Biostatistics and Population, Faculty of Public Health, Universitas Airlangga, Surabaya 60286, Indonesia;
| | - Rosantia Sarassari
- Clinical Microbiology Specialist Program, Faculty of Medicine, Universitas Airlangga, Surabaya 60286, Indonesia;
| | - Kuntaman Kuntaman
- Department of Medical Microbiology, Faculty of Medicine, Universitas Airlangga, Surabaya 60286, Indonesia
- Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia
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Han Y, Zhang J, Zhang HZ, Zhang XY, Wang YM. Multidrug-resistant organisms in intensive care units and logistic analysis of risk factors. World J Clin Cases 2022; 10:1795-1805. [PMID: 35317164 PMCID: PMC8891762 DOI: 10.12998/wjcc.v10.i6.1795] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 09/15/2021] [Accepted: 01/14/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Intensive care unit (ICU) patients are critically ill and have low immunity. They will undergo various trauma medical procedures during diagnosis and treatment. The use of high-dose hormones and broad-spectrum antibiotics will increase the incidence of nosocomial infection in ICU patients. Therefore, it is necessary to explore the causes of nosocomial infection in ICU and provide basis for the prevention and control of nosocomial infection in ICU.
AIM To explore major pathogens of nosocomial infection in ICUs, methods of detection and drug resistance trends.
METHODS Risk factors of multidrug-resistant infection were analyzed to provide a basis for clinical rational use of antimicrobial drugs in the ICU. These findings were used to standardize rational use of antimicrobial agents. BD PhoenixTM100 automatic bacterial identification analyzer was used to for cell identification in specimens collected from the ICU between January 2016 and December 2019. Drug sensitivity tests were carried out and drug resistance trends were analyzed using the optical disc diffusion method. Odds ratios and corresponding 95%CI of independent variables were calculated using a logistic regression model. Backward elimination (trend = 0.1) was used as an inclusion criterion for multivariate analysis. All data were analyzed using SPSS version 22.0, and P < 0.05 was considered statistically significant.
RESULTS We collected 2070 samples from ICU patients between January 2016 and December 2019. Sample types comprised sputum (1139 strains, 55.02%), blood (521 strains, 25.17%), and drainage fluid (117 strains, 5.65%). A total of 1051 strains of major pathogens, including Acinetobacter baumannii, Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae) and Staphylococcus aureus, were detected, with a detection rate of 35.97% (378/1051). Most of these strains were resistant to antibiotics. Detection rate of E. coli was 21.79% (229/1051), and it was generally sensitive to many antimicrobial drugs. Detection rate of P. aeruginosa was 24.74% (260/1051), and showed low sensitivity to most antibiotics. Detection rate of K. pneumoniae was 9.42% (99/1051), which was generally resistant to multiple antimicrobial drugs and resistant forms. K. pneumoniae was resistant to imipenem for approximate 4 years, and showed a 19.9% (19/99) and 20.20% (20/99) rate of meropenem resistance. Logistic analysis showed that mechanical ventilation and ureteral intubation were risk factors for multidrug-resistant bacterial infections.
CONCLUSION This study showed a high incidence of ICU infections. Mechanical ventilation and urine tube intubation were risk factors for infection with multidrug-resistant bacteria.
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Affiliation(s)
- Ying Han
- Infection Control Office, Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
| | - Jin Zhang
- Infection Control Office, Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
| | - Hong-Ze Zhang
- Infection Control Office, Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
| | - Xin-Ying Zhang
- Infection Control Office, Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
| | - Ya-Mei Wang
- Infection Control Office, Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
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Dankittipong N, Fischer EAJ, Swanenburg M, Wagenaar JA, Stegeman AJ, de Vos CJ. Quantitative Risk Assessment for the Introduction of Carbapenem-Resistant Enterobacteriaceae (CPE) into Dutch Livestock Farms. Antibiotics (Basel) 2022; 11:281. [PMID: 35203883 PMCID: PMC8868399 DOI: 10.3390/antibiotics11020281] [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: 01/13/2022] [Revised: 02/09/2022] [Accepted: 02/15/2022] [Indexed: 12/10/2022] Open
Abstract
Early detection of emerging carbapenem-resistant Enterobacteriaceae (CPE) in food-producing animals is essential to control the spread of CPE. We assessed the risk of CPE introduction from imported livestock, livestock feed, companion animals, hospital patients, and returning travelers into livestock farms in The Netherlands, including (1) broiler, (2) broiler breeder, (3) fattening pig, (4) breeding pig, (5) farrow-to-finish pig, and (6) veal calf farms. The expected annual number of introductions was calculated from the number of farms exposed to each CPE source and the probability that at least one animal in an exposed farm is colonized. The total number of farms with CPE colonization was estimated to be the highest for fattening pig farms, whereas the probability of introduction for an individual farm was the highest for broiler farms. Livestock feed and imported livestock are the most likely sources of CPE introduction into Dutch livestock farms. Sensitivity analysis indicated that the number of fattening pig farms determined the number of high introductions in fattening pigs from feed, and that uncertainty on CPE prevalence impacted the absolute risk estimate for all farm types. The results of this study can be used to inform risk-based surveillance for CPE in livestock farms.
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Affiliation(s)
- Natcha Dankittipong
- Department Population Health Sciences, Farm Animal Health, Utrecht University, Martinus G. de Bruingebouw, Yalelaan 7, 3584 CL Utrecht, The Netherlands; (E.A.J.F.); (A.J.S.)
| | - Egil A. J. Fischer
- Department Population Health Sciences, Farm Animal Health, Utrecht University, Martinus G. de Bruingebouw, Yalelaan 7, 3584 CL Utrecht, The Netherlands; (E.A.J.F.); (A.J.S.)
| | - Manon Swanenburg
- Wageningen Bioveterinary Research, Wageningen University & Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands; (M.S.); (C.J.d.V.)
| | - Jaap A. Wagenaar
- Department Biomolecular Health Science, Infectious Diseases & Immunology, Utrecht University, Androclusgebouw, Yalelaan 1, 3584 CL Utrecht, The Netherlands;
| | - Arjan J. Stegeman
- Department Population Health Sciences, Farm Animal Health, Utrecht University, Martinus G. de Bruingebouw, Yalelaan 7, 3584 CL Utrecht, The Netherlands; (E.A.J.F.); (A.J.S.)
| | - Clazien J. de Vos
- Wageningen Bioveterinary Research, Wageningen University & Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands; (M.S.); (C.J.d.V.)
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Zhou R, Fang X, Zhang J, Zheng X, Shangguan S, Chen S, Shen Y, Liu Z, Li J, Zhang R, Shen J, Walsh TR, Wang Y. Impact of carbapenem resistance on mortality in patients infected with Enterobacteriaceae: a systematic review and meta-analysis. BMJ Open 2021; 11:e054971. [PMID: 34907071 PMCID: PMC8672018 DOI: 10.1136/bmjopen-2021-054971] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVES To provide a comprehensive assessment of the impact of carbapenem resistance on mortality among patients infected with Enterobacteriaceae and to explore the source of heterogeneity across studies. DESIGN This systematic review was conducted following the guidelines of Cochrane Guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. DATA SOURCES We conducted a systematic literature search of the PubMed, Embase, Web of Science and Cochrane Library databases to identify relevant studies published between 1 January 1994 and 30 August 2020. ELIGIBILITY CRITERIA We included primary observational studies published in English that reported the mortality outcomes for hospitalised patients with confirmed infections due to carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-susceptible Enterobacteriaceae (CSE). Studies with no comparison group or with a comparison group of patients infected with unconfirmed CSE were excluded. DATA EXTRACTION AND SYNTHESIS Data extraction and assessment of risk bias were conducted independently by two reviewers. The pooled relative risk and risk difference were calculated as effect measures with 95% CIs using a random effects model. The heterogeneity across studies was assessed by Q-statistic and I2 measures. RESULTS Of 10 304 studies initially identified, 50 studies were included in the meta-analyses. The results of the meta-analyses showed that carbapenem resistance has a significant positive effect on the probability of death for patients infected with Enterobacteriaceae for any type of mortality outcome. The results of the stratified analysis and meta-regression suggested that the effect of carbapenem resistance on the risk of death varied by infection type, sample size and year of publication. CONCLUSIONS Our results suggested that patients with CRE infection still face a greater risk of death than patients with CSE infection do, and an urgent need to develop new antibiotics and appropriate treatments to reduce the risk of death. PROSPERO REGISTRATION NUMBER CRD42020176808.
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Affiliation(s)
- Ruyin Zhou
- Department of Economics and Trade, College of Economics and Management, China Agricultural University, Beijing, China
| | - Xiangming Fang
- Department of Economics and Trade, College of Economics and Management, China Agricultural University, Beijing, China
- Department of Health Policy and Behavioral Sciences, School of Public Health, Georgia State University, Atlanta, GA, USA
| | - Jinjin Zhang
- Department of Economics and Trade, College of Economics and Management, China Agricultural University, Beijing, China
| | - Xiaodong Zheng
- Department of Economics, School of Economics, Zhejiang Gongshang University, Hangzhou, China
| | - Shuangyue Shangguan
- Department of Economics and Trade, College of Economics and Management, China Agricultural University, Beijing, China
| | - Shibo Chen
- Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Yingbo Shen
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
| | - Zhihai Liu
- Agricultural Bio-pharmaceutical Laboratory, College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, China
| | - Juan Li
- State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, Beijing, China
| | - Rong Zhang
- Clinical Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, China
| | - Jianzhong Shen
- Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | | | - Yang Wang
- Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China
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Açma A, Williams A, Repetto E, Cabral S, Sunyoto T, Woolley SC, Mahama G. Prevalence of MDR bacteria in an acute trauma hospital in Port-au-Prince, Haiti: a retrospective analysis from 2012 to 2018. JAC Antimicrob Resist 2021; 3:dlab140. [PMID: 34514410 PMCID: PMC8419367 DOI: 10.1093/jacamr/dlab140] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 08/13/2021] [Indexed: 11/22/2022] Open
Abstract
Background Antibiotic resistance (ABR) is recognized as an increasing threat to global health. Haiti declared ABR an emerging public health threat in 2018, however, the current surveillance system is limited. We described the microbiological data from a Médecins Sans Frontières trauma hospital, to increase knowledge on ABR in Haiti for similar facilities. Methods A retrospective cross-sectional analysis of routine microbiological data of samples taken from patients admitted to the inpatient ward or followed up in the outpatient clinic of the trauma hospital from March 2012 to December 2018. Resistance trends were analysed per isolate and compared over the 7 year period. Results Among 1742 isolates, the most common samples were pus (53.4%), wound swabs (30.5%) and blood (6.9%). The most frequently detected bacteria from these sample types were Staphylococcus aureus (21.9%), Pseudomonas aeruginosa (20.9%) and Klebsiella pneumoniae (16.7%). MDR bacteria (32.0%), ESBL-producing bacteria (39.1%), MRSA (24.1%) and carbapenem-resistant Enterobacteriaceae (CRE) species (2.6%) were all detected. Between 2012 and 2018 the number of ESBL isolates significantly increased from 3.2% to 42.9% (P = 0.0001), and resistance to clindamycin in MSSA isolates rose from 3.7% to 29.6% (P = 0.003). Two critical WHO priority pathogens (ESBL-producing CRE and carbapenem-resistant P. aeruginosa) were also detected. Conclusions Over a 7 year period, a high prevalence of MDR bacteria was observed, while ESBL-producing bacteria showed a significantly increasing trend. ABR surveillance is important to inform clinical decisions, treatment guidelines and infection prevention and control practices.
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Affiliation(s)
- Ayşe Açma
- Médecins Sans Frontières-Operational Centre Brussels (MSFOCB), Haiti Mission, Port-au-Prince, Haiti
| | - Anita Williams
- MSFOCB Luxembourg Operational Research (LuxOR) Unit, Luxembourg.,MSFOCB, Middle East Medical Unit (MEMU), Beirut, Lebanon
| | - Ernestina Repetto
- Medecins Sans Frontieres -Operational Centre Geneva (MSFOCG), Medical Department, Geneva, Switzerland
| | - Sèrgio Cabral
- MSFOCB Nap Kembe Acute Trauma Hospital, Tabarre, Haiti
| | - Temmy Sunyoto
- MSFOCB Luxembourg Operational Research (LuxOR) Unit, Luxembourg
| | - Sophie Cherestal Woolley
- Médecins Sans Frontières-Operational Centre Brussels (MSFOCB), Haiti Mission, Port-au-Prince, Haiti
| | - Gabane Mahama
- MSFOCB Operations Department Cell 3, Brussels, Belgium
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Dai G, Xu Y, Kong H, Xie W, Wang H. Risk factors for carbapenem-resistant Klebsiella pneumoniae infection and associated clinical outcomes. Am J Transl Res 2021; 13:7276-7281. [PMID: 34306493 PMCID: PMC8290679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 02/24/2021] [Indexed: 06/13/2023]
Abstract
OBJECTIVE To evaluate the risk factors and clinical outcomes of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) (CRKP) infection. MATERIALS AND METHODS A case-control study was performed from January 2017 to September 2017. The risk factors and clinical outcomes of CRKP cases (n = 91) were compared with those of the controls infected with carbapenem-susceptible K. pneumoniae (CSKP) (n = 91). Antibiotic susceptibility was determined using Etest while the type of bacteria was identified by Vitek 2. RESULTS CRKP infection was associated with prior use of carbapenems, β-lactam antibiotics, tigecycline, and hormones; complications with cerebrovascular lesions; chronic obstructive pulmonary disease; as well as prolonged hospitalization. Multivariable analysis showed that the use of carbapenem independently correlates with carbapenem resistance in the multivariable analysis. Carbapenem resistance, mechanical ventilation, tracheotomy, deep vein cannulation, indwelling urinary tract catheter, ICU treatment, and high Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) scores were related to in-hospital mortality. CONCLUSION CRKP is a widely spread pathogen associated with high in-hospital mortality. Minimizing the use of antimicrobials, specifically the carbapenems, may be effective to reduce CRKP infection.
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Affiliation(s)
- Guanqun Dai
- Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu, China
| | - Yanling Xu
- Department of General Practice, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu, China
| | - Hui Kong
- Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu, China
| | - Weiping Xie
- Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu, China
| | - Hong Wang
- Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu, China
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Incidence of a subsequent carbapenem-resistant Enterobacteriaceae infection after previous colonisation or infection: a prospective cohort study. Int J Antimicrob Agents 2021; 57:106340. [PMID: 33857538 DOI: 10.1016/j.ijantimicag.2021.106340] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 03/31/2021] [Accepted: 04/03/2021] [Indexed: 01/28/2023]
Abstract
OBJECTIVES In patients with a history of carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE), the need for CP-CRE targeted treatment in subsequent sepsis episodes is unclear. This study aimed to characterise the incidence of subsequent CP-CRE infective episodes in individuals with prior CP-CRE colonisation and/or infection, and identify predictors for these subsequent CP-CRE infections. METHODS All adult inpatients with CP-CRE detected from any site between June 2012 and May 2014 at a tertiary-care hospital were prospectively followed for two years to assess for any subsequent CP-CRE infections. Potential factors to which patients were exposed during the follow-up period were collected from medical records and analysed. RESULTS A total of 171 patients were enrolled. Of 151 patients who entered the follow-up period, 16 (10.6%) developed a subsequent CP-CRE infection. The median time to a subsequent infective episode was 24.5 days (12-105 days). The type of carbapenemase was highly conserved within index and subsequent paired episodes (16 of 17 pairs). Patients with first CP-CRE isolated from intra-abdominal or respiratory sources were ≥7 times more likely to develop a subsequent infection, while most rectal carriers remain colonised. For carriers (n = 133), Klebsiella spp. (OR 4.7) and OXA carbapenemase (OR 9.4) were significant predictors of subsequent infection. In patients with initial infection (n = 18), end-stage renal failure requiring dialysis (OR 22.0) was the only predisposing factor. CONCLUSION The incidence of subsequent infections in patients with prior colonisation was low. Consideration for CP-CRE targeted therapy is recommended in patients on dialysis and previous CP-CRE infections involving the bloodstream and/or respiratory tract.
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Lau MY, Teng FE, Chua KH, Ponnampalavanar S, Chong CW, Abdul Jabar K, Teh CSJ. Molecular Characterization of Carbapenem Resistant Klebsiella pneumoniae in Malaysia Hospital. Pathogens 2021; 10:pathogens10030279. [PMID: 33801250 PMCID: PMC8001961 DOI: 10.3390/pathogens10030279] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/19/2021] [Accepted: 02/25/2021] [Indexed: 11/16/2022] Open
Abstract
The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great concern, as carbapenems are the last-line therapy for multidrug-resistant Gram-negative bacteria infections. This study aims to report the epidemiology of CRKP in a teaching hospital in Malaysia based on the molecular genotypic and clinical characteristics of the isolates. Sixty-three CRKP strains were isolated from a tertiary teaching hospital from January 2016 until August 2017. Carbapenemase genes were detected in 55 isolates, with blaOXA-48 (63.5%) as the predominant carbapenemase gene, followed by blaNDM (36.5%). At least one porin loss was detected in nine isolates. Overall, 63 isolates were divided into 30 clusters at similarity of 80% with PFGE analysis. Statistical analysis showed that in-hospital mortality was significantly associated with the usage of central venous catheter, infection or colonization by CRKP, particularly NDM-producers. In comparison, survival analysis using Cox proportional hazards regression identified a higher hazard ratio for patients with a stoma and patients treated with imipenem but a lower hazard ratio for patients with NDM-producing CRKP. OXA-48 carbapenemase gene was the predominant carbapenemase gene in this study. As CRKP infection could lead to a high rate of in-hospital mortality, early detection of the isolates was important to reduce their dissemination.
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Affiliation(s)
- Min Yi Lau
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (M.Y.L.); (F.E.T.)
| | - Fui Enn Teng
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (M.Y.L.); (F.E.T.)
| | - Kek Heng Chua
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia;
| | - Sasheela Ponnampalavanar
- Department of Infectious Diseases, University Malaya Medical Centre, Kuala Lumpur 50603, Malaysia;
| | - Chun Wie Chong
- School of Pharmacy, Monash University Malaysia, Subang Jaya 47500, Malaysia;
- Centre for Translational Research, Institute of Research, Development and Innovation, Kuala Lumpur 57000, Malaysia
| | - Kartini Abdul Jabar
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (M.Y.L.); (F.E.T.)
- Correspondence: (K.A.J.); (C.S.J.T.); Tel.: +603-79676674 (C.S.J.T.)
| | - Cindy Shuan Ju Teh
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; (M.Y.L.); (F.E.T.)
- Correspondence: (K.A.J.); (C.S.J.T.); Tel.: +603-79676674 (C.S.J.T.)
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da Silva KE, Thi Nguyen TN, Boinett CJ, Baker S, Simionatto S. Molecular and epidemiological surveillance of polymyxin-resistant Klebsiella pneumoniae strains isolated from Brazil with multiple mgrB gene mutations. Int J Med Microbiol 2020; 310:151448. [PMID: 33092694 DOI: 10.1016/j.ijmm.2020.151448] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 08/21/2020] [Accepted: 08/24/2020] [Indexed: 11/17/2022] Open
Abstract
The prevalence of polymyxin-resistant Enterobacteriaceae is increasing worldwide. Their emergence is worrisome and limits therapeutic options for severely ill patients. We aimed to investigate the molecular and epidemiological characteristics of polymyxin-resistant Klebsiella pneumoniae circulating in Brazilian hospitals. Polymyxin-resistant K. pneumoniae isolates from two Brazilian healthcare facilities were characterized phenotypically and subjected to whole genome sequencing (WGS). Using the WGS data we determined their sequence type, resistance gene content (resistome), their composition of virulence genes and plasmids. ST11 was the most common (80 %) sequence type among the isolates followed by ST345, ST15 and ST258. A resistome analysis revealed the common presence of blaKPC-2 and less frequently blaSHV-11, blaTEM-1, blaCTX-M-15, and blaOXA-9. Genes conferring resistance to aminoglycosides, fluoroquinolones, phenicols, sulphonamides, tetracyclines, trimethoprim and macrolide-lincosamide-streptogramin were also detected. We observed a clonal spread of polymyxin-resistant K. pneumoniae isolates, with polymyxin-resistance associated with various alterations in the mgrB gene including inactivation by an insertion sequence and nonsense point mutations. We additionally identified a novel 78-bp repeat sequence, encoding a MgrB protein with 26 amino acids duplicated in six isolates. This is the first observation of this type of alteration being associated with polymyxin resistance. Our findings demonstrate that mgrB alterations were the most common source of polymyxin-resistance in Brazilian clinical settings. Interestingly, distinct genetic events were identified among clonally related isolates, including a new amino acid alteration. The clinical implications and investigation of the resistance mechanisms is of great importance to patient safety and control of these infections, particularly in long-term care facilities.
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Affiliation(s)
- Kesia Esther da Silva
- Laboratório de Pesquisa em Ciências da Saúde, Universidade Federal da Grande Dourados - UFGD, Dourados, MS, Brazil
| | - To Nguyen Thi Nguyen
- Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Viet Nam
| | - Christine J Boinett
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK
| | - Stephen Baker
- Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK; Department of Medicine, Cambridge University, Cambridge, UK
| | - Simone Simionatto
- Laboratório de Pesquisa em Ciências da Saúde, Universidade Federal da Grande Dourados - UFGD, Dourados, MS, Brazil.
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Zhu J, Li Q, Li X, Kang J, Song Y, Song J, Yin D, Duan J. Successful control of the first carbapenem-resistant Klebsiella pneumoniae outbreak in a Chinese hospital 2017-2019. Antimicrob Resist Infect Control 2020; 9:91. [PMID: 32571431 PMCID: PMC7310137 DOI: 10.1186/s13756-020-00757-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 06/11/2020] [Indexed: 12/13/2022] Open
Abstract
Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is considered as a serious global threat. CRKPs occurred only sporadically in the Second Hospital of Shanxi Medical University. Our study aimed to investigate and control the first outbreak of CRKP in our hospital occurred between October 2017 and August 2019. Methods The antimicrobial stewardship (AMS) workers have been implemented control measures properly. Clinical and epidemiological data were retrospectively collected from medical records. Carbapenemase genes were detected by modified carbapenem inactivation method (mCIM) test and the EDTA-modified carbapenem inactivation method (eCIM) test. Resistance genes were identified by polymerase chain reaction (PCR) and sequencing. Genetic relatedness was studied by multilocus sequence typing (MLST). Results During the outbreak, 31 patients were infected with CRKP isolates. 20 (64.5%) patients were infected with KPC-2 and/or NDM-1 producing K. pneumoniae. Mostly MLST-sequence types belonged to ST11 (21/31). The outbreak was two major K. pneumoniae clusters present in epidemiologically linked patients. Conclusions Setting up AMS workers is potentially a highly efficient strategy for the successful control of the outbreak. A multimodal and multidisciplinary infection control strategy proved to be crucial. The emergence of CRKP in our hospital emphasizes the importance of continuous monitoring of these isolates, which helps to limit the spread of CRKPs and improve the level of management.
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Affiliation(s)
- Jiaying Zhu
- Department of Pharmacy, school of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China.,Department of Pharmacy, Baotou Hospital of Traditional Mongolian and Chinese Medicine, Baotou, Inner Mongolia, People's Republic of China
| | - Qi Li
- Department of Pharmacy, school of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China
| | - Xiaoxia Li
- Department of Pharmacy, Second Hospital of Shanxi Medical University, No 382, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People's Republic of China
| | - Jianbang Kang
- Department of Pharmacy, Second Hospital of Shanxi Medical University, No 382, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People's Republic of China
| | - Yan Song
- Department of Pharmacy, Second Hospital of Shanxi Medical University, No 382, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People's Republic of China
| | - Junli Song
- Department of Pharmacy, Second Hospital of Shanxi Medical University, No 382, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People's Republic of China
| | - Donghong Yin
- Department of Pharmacy, Second Hospital of Shanxi Medical University, No 382, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People's Republic of China
| | - Jinju Duan
- Department of Pharmacy, Second Hospital of Shanxi Medical University, No 382, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People's Republic of China.
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Li Y, Li J, Hu T, Hu J, Song N, Zhang Y, Chen Y. Five-year change of prevalence and risk factors for infection and mortality of carbapenem-resistant Klebsiella pneumoniae bloodstream infection in a tertiary hospital in North China. Antimicrob Resist Infect Control 2020; 9:79. [PMID: 32487221 PMCID: PMC7268443 DOI: 10.1186/s13756-020-00728-3] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 05/05/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND There are few studies focused on carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI). The aim of this study is to identify the prevalence and risk factors for infection and mortality of CRKP BSI. METHODS Susceptibility of Klebsiella pneumoniae (KP) isolated from blood samples and the proportion of CRKP were recorded annually. One hundred sixty-four patients with CRKP and 328 with carbapenem-susceptible Klebsiella pneumoniae (CSKP) BSI were categorized as the case group and control group to identify risk factors for CRKP infection and mortality by univariable analysis and multivariable logistic-regression analysis. RESULTS The proportion and mortality of CRKP BSI increased significantly, with the percentage of KP in BSI increasing from 7 to 12% from 2014 to 2019 with a concomitant resistance to meropenem increasing from 16.7 to 41.8%. Compared with CSKP group, patients in CRKP group had longer hospitalization time before bacteremia (median 14 vs 4, P < 0.001) and longer total hospitalization time (median 31 vs 19, P < 0.001). The proportion of admission to ICU was higher (70.7% vs 17.7%, P < 0.001), and APACHE II score was higher (median 12 vs 8, P < 0.001). The mortality in CRKP group was 43.9% (72/164), while 14.9% (49/328) in CSKP group (p < 0.001). KP detection in other sites(P = 0.036, OR 1.964), blood purification(P = 0.018, OR 3.326), bronchoscopy(P = 0.011, OR 5.423), surgery (P = 0.001, OR 3.084), carbapenem use(P = 0.001, OR 3.395), tigecycline use(P = 0.006, OR 4.595) were independent risk factors for CRKP BSI. Previous hospitalization (P = 0.048, OR 2.755), long hospitalization (P = 0.003, OR 1.035), bone marrow puncture (P = 0.037, OR3.856), use of β-lactamase inhibitor (P = 0.005, OR 3.890) were independent risk factors for mortality in CRKP BSI. CONCLUSION The prevalence and mortality of CRKP BSI are still increasing. Timely treatment of KP infection in other site, strengthening the hospital infection control of blood purification, bronchoscopy and surgery, control the use of carbapenem and tigecycline, may help to prevent CRKP BSI. More preventative hospital resources are needed for severely ill patients with prolonged hospitalizations and intensive care.
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Affiliation(s)
- Yuanyuan Li
- Department of Infectious Diseases, The Second Hospital of Hebei Medical University, No. 215 Heping Western Road, Xinhua District, Shijiazhuang, 050000, China
| | - Jihong Li
- Department of Laboratory Medicine, The Second Hospital of Hebei Medical University, No. 215 Heping Western Road, Shijiazhuang, 050000, China
| | - Tong Hu
- Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, No.12 Jiankang Road, Shijiazhuang, 050000, China
| | - Jia Hu
- Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, No.12 Jiankang Road, Shijiazhuang, 050000, China
| | - Ning Song
- Department of Infectious Diseases, The Second Hospital of Hebei Medical University, No. 215 Heping Western Road, Xinhua District, Shijiazhuang, 050000, China.
| | - Yu Zhang
- Department of Infectious Diseases, The Second Hospital of Hebei Medical University, No. 215 Heping Western Road, Xinhua District, Shijiazhuang, 050000, China
| | - Yuan Chen
- Department of Pediatrics, The Second Hospital of Hebei Medical University, No. 215 Heping Western Road, Shijiazhuang, 050000, China
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Bloodstream infections caused by Entero-bacteriaceae in China. THE LANCET. INFECTIOUS DISEASES 2020; 19:810-811. [PMID: 31345454 DOI: 10.1016/s1473-3099(19)30352-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 06/20/2019] [Indexed: 11/21/2022]
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Hashemizadeh Z, Hosseinzadeh Z, Azimzadeh N, Motamedifar M. Dissemination Pattern of Multidrug Resistant Carbapenemase Producing Klebsiella pneumoniae Isolates Using Pulsed-Field Gel Electrophoresis in Southwestern Iran. Infect Drug Resist 2020; 13:921-929. [PMID: 32280248 PMCID: PMC7125322 DOI: 10.2147/idr.s227955] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Accepted: 01/23/2020] [Indexed: 11/23/2022] Open
Abstract
Background Klebsiella pneumoniae is an important cause of healthcare-associated infection. Carbapenemases have increasingly been reported in Enterobacteriaceae, especially in K. pneumoniae. Propose The objective of this study was to determine antibiotic resistance patterns, and the molecular epidemiology of multidrug resistant K. pneumoniae isolates, obtained from hospitalized patients in Shiraz, Iran. Methods In this study, 60 K. pneumoniaeisolates were collected from Nemazee and Faghihi referral hospitals. Antibiotic susceptibility testing and MIC were performed by disk diffusion test and Epsilometer (E)-test strips, respectively. Carbapenemase genes were identified by polymerase chain reaction and sequencing. Then, clonal relationships were analyzed, using PFGE. Results Thirty-three out of 60 K. pneumoniae isolates were resistant to carbapenems. Among the isolates, 86.6% were multidrug resistant (MDR). Polymyxin B (18.3%) and tigecycline (23.3%) were shown to be the most active agents against K. pneumoniae isolates. In our study, the high prevalence of blaNDM (45%) and blaOXA-48 (10%) was detected. Conclusion The results of this study revealed the widespread carbapenemase gene between different wards in hospitals as a risk factor for treatment options. PFGE analysis showed 11 clusters and 3 singletons based on an 80% similarity level. Also, PFGE analysis showed that there were similar genetic patterns among K. pneumoniae isolates and these patterns were responsible for the distribution of infection in hospitals.
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Affiliation(s)
- Zahra Hashemizadeh
- Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Hosseinzadeh
- Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Azimzadeh
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Mohammad Motamedifar
- Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, Iran.,Shiraz HIV/Aids Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
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Fang L, Lu X, Xu H, Ma X, Chen Y, Liu Y, Hong G, Liang X. Epidemiology and risk factors for carbapenem-resistant Enterobacteriaceae colonisation and infections: case-controlled study from an academic medical center in a southern area of China. Pathog Dis 2020; 77:5529390. [PMID: 31281931 DOI: 10.1093/femspd/ftz034] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 07/05/2019] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE While the emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) and related infections pose serious threats to global public health, the epidemiology and associated risk factors remain poorly understood and vary by geography. METHODS In a case-controlled retrospective study, we examined the prevalence, patient background and risk factors for CRE colonisation and infections, and all patient-derived CRE from January 2015 to January 2017. Isolated carbapenem-susceptible Enterobacteriaceae (CSE) from 2875 enrolled patients were randomly selected during the study. RESULTS CRE colonisation and infections detection rates were 47/2875 (1.6%). Respiratory tract specimens were most frequently seen in 20/47 (42.6%) cases. Klebsiella pneumoniae was the main isolate in 35/47 (74.5%) CRE. As for carbapenemase, KPC-2-producing bacteria was most frequently detected in 38/47 (80.9%) Enterobacteriaceae. No underlying conditions (P = 0.004), pulmonary diseases (P = 0.018) and no antibiotics used prior to culture within 30 days (P < 0.001) were statistically significant between the CRE and CSE groups. CONCLUSION Klebsiellapneumoniae was the main isolate of CRE. The blaKPC-2 was the predominant CRE gene. Underlying conditions especially pulmonary diseases and antibiotics used prior to culture within 30 days represented key risk factors for acquisition of CRE.
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Affiliation(s)
- Lili Fang
- Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, China.,School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xiaohui Lu
- Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, China.,School of Public Health, Xiamen University, Xiamen 361102, China
| | - Heping Xu
- Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, China.,School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xiaobo Ma
- Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, China.,School of Public Health, Xiamen University, Xiamen 361102, China
| | - Yilan Chen
- Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, China
| | - Yue Liu
- Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, China
| | - Guolin Hong
- Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, China.,School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xianming Liang
- Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen 361004, China.,Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China
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Manuel-Vázquez A, Palacios-Ortega F, García-Septiem J, Thuissard IJ, Sanz-Rosa D, Arias-Díaz J, Maríajover-Navalón J, Ramia JM. Antimicrobial Stewardship Programs Are Required in a Department of Surgery: "How" Is the Question A Quasi-Experimental Study: Results after Three Years. Surg Infect (Larchmt) 2020; 21:35-42. [PMID: 31347989 DOI: 10.1089/sur.2018.311] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Objective: Our aim was to describe our antimicrobial stewardship program and the methodology based on the results in a surgical department. Methods: Our study was a quasi-experimental study conducted from January 1, 2009, through September 30, 2017. The site was the General and Digestive Surgery Department in a public primary referral center, the University Hospital of Getafe (Madrid, Spain). We implemented the antimicrobial stewardship program following a prospective audit and feedback model, with a surgeon incorporated into the manaagement group. We studied the deaths and 30-day re-admission rates, length of stay, prevalence of gram-negative bacilli, meropenem resistance, and days of treatment with meropenem. Results: After three years of the program, we recorded a significant decrease in Pseudomonas aeruginosa prevalence, a significant increase in Klebsiella pneumoniae prevalence, a decrease in meropenem resistance, and a reduction in meropenem days of treatment. Conclusions: Antimicrobial stewardship programs have a desirable effect on patients. In our experience, the program team should be led by a staff from the particular department. When human resources are limited, the sustainability, efficiency, and effectiveness of interventions are feasible only with adequate computer support. Finally, but no less important, the necessary feedback between the prescribers and the team must be based on an ad hoc method such as that provided by statistical control charts, a median chart in our study.
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Affiliation(s)
- Alba Manuel-Vázquez
- General and Digestive Surgery Department, University Hospital of Guadalajara, Guadalajara, Spain
| | | | - Javier García-Septiem
- General and Digestive Surgery Department, University Hospital of Getafe, Getafe, Madrid, Spain
| | - Israel John Thuissard
- School of Doctoral Studies and Research.Universidad Europea de Madrid, Madrid, Spain
| | - David Sanz-Rosa
- School of Doctoral Studies and Research.Universidad Europea de Madrid, Madrid, Spain
| | - Javier Arias-Díaz
- San Carlos Clinical Hospital, General and Digestive Surgery Department, Faculty of Medicine, Universidad Complutense, Madrid, Spain
| | - José Maríajover-Navalón
- General and Digestive Surgery Department, University Hospital of Getafe, Getafe, Madrid, Spain
| | - José Manuel Ramia
- General and Digestive Surgery Department, University Hospital of Guadalajara, Guadalajara, Spain
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Zhu WM, Yuan Z, Zhou HY. Risk factors for carbapenem-resistant Klebsiella pneumoniae infection relative to two types of control patients: a systematic review and meta-analysis. Antimicrob Resist Infect Control 2020; 9:23. [PMID: 32005246 PMCID: PMC6995231 DOI: 10.1186/s13756-020-0686-0] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 01/23/2020] [Indexed: 01/11/2023] Open
Abstract
Background Studies on risk factors for carbapenem-resistant Klebsiella pneumoniae (CRKP) infection have provided inconsistent results, partly due to the choice of the control group. We conducted a systematic review and meta-analysis to assess the risk factors for CRKP infection by comparing CRKP-infected patients with two types of controls: patients infected with carbapenem-susceptible Klebsiella pneumoniae (comparison 1) or patients not infected with CRKP (comparison 2). Methods Data on potentially relevant risk factors for CRKP infection were extracted from studies indexed in PubMed, EMBASE, Web of Science or EBSCO databases from January 1996 to April 2019, and meta-analyzed based on the outcomes for each type of comparison. Results The meta-analysis included 18 studies for comparison 1 and 14 studies for comparison 2. The following eight risk factors were common to both comparisons: admission to intensive care unit (ICU; odds ratio, ORcomparison 1 = 3.20, ORcomparison 2 = 4.44), central venous catheter use (2.62, 3.85), mechanical ventilation (2.70, 4.78), tracheostomy (2.11, 8.48), urinary catheter use (1.99, 0.27), prior use of antibiotic (6.07, 1.61), exposure to carbapenems (4.16, 3.84) and exposure to aminoglycosides (1.85, 1.80). Another 10 risk factors were unique to comparison 1: longer length of hospital stay (OR = 15.28); prior hospitalization (within the previous 6 months) (OR = 1.91); renal dysfunction (OR = 2.17); neurological disorders (OR = 1.52); nasogastric tube use (OR = 2.62); dialysis (OR = 3.56); and exposure to quinolones (OR = 2.11), fluoroquinolones (OR = 2.03), glycopeptides (OR = 3.70) and vancomycin (OR = 2.82). Conclusions Eighteen factors may increase the risk of carbapenem resistance in K. pneumoniae infection; eight factors may be associated with both K. pneumoniae infections in general and CRKP in particular. The eight shared factors are likely to be ‘true’ risk factors for CRKP infection. Evaluation of risk factors in different situations may be helpful for empirical treatment and prevention of CRKP infections.
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Affiliation(s)
- Wei-Min Zhu
- Division of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Yuan Jia Gang, Yuzhong District, Chongqing, 400016, China
| | - Zhe Yuan
- Division of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Yuan Jia Gang, Yuzhong District, Chongqing, 400016, China.,Department of Hospital Infection Control, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Yuan Jia Gang, Yuzhong District, Chongqing, 400016, China
| | - Hong-Yu Zhou
- Department of Hospital Infection Control, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Yuan Jia Gang, Yuzhong District, Chongqing, 400016, China.
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Kotb S, Lyman M, Ismail G, Abd El Fattah M, Girgis SA, Etman A, Hafez S, El-Kholy J, Zaki MES, Rashed HAG, Khalil GM, Sayyouh O, Talaat M. Epidemiology of Carbapenem-resistant Enterobacteriaceae in Egyptian intensive care units using National Healthcare-associated Infections Surveillance Data, 2011-2017. Antimicrob Resist Infect Control 2020; 9:2. [PMID: 31911830 PMCID: PMC6942386 DOI: 10.1186/s13756-019-0639-7] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Accepted: 10/31/2019] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVE To describe the epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) healthcare-associated infections (HAI) in Egyptian hospitals reporting to the national HAI surveillance system. METHODS Design: Descriptive analysis of CRE HAIs and retrospective observational cohort study using national HAI surveillance data. Setting: Egyptian hospitals participating in the HAI surveillance system. The patient population included patients admitted to the intensive care unit (ICU) in participating hospitals. Enterobacteriaceae HAI cases were Klebsiella, Escherichia coli, and Enterobacter isolates from blood, urine, wound or respiratory specimen collected on or after day 3 of ICU admission. CRE HAI cases were those resistant to at least one carbapenem. For CRE HAI cases reported during 2011-2017, a hospital-level and patient-level analysis were conducted using only the first CRE isolate by pathogen and specimen type for each patient. For facility, microbiology, and clinical characteristics, frequencies and means were calculated among CRE HAI cases and compared with carbapenem-susceptible Enterobacteriaceae HAI cases through univariate and multivariate logistic regression using STATA 13. RESULTS There were 1598 Enterobacteriaceae HAI cases, of which 871 (54.1%) were carbapenem resistant. The multivariate regression analysis demonstrated that carbapenem resistance was associated with specimen type, pathogen, location prior to admission, and length of ICU stay. Between 2011 and 2017, there was an increase in the proportion of Enterobacteriaceae HAI cases due to CRE (p-value = 0.003) and the incidence of CRE HAIs (p-value = 0.09). CONCLUSIONS This analysis demonstrated a high and increasing burden of CRE in Egyptian hospitals, highlighting the importance of enhancing infection prevention and control (IPC) programs and antimicrobial stewardship activities and guiding the implementation of targeted IPC measures to contain CRE in Egyptian ICU's .
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Affiliation(s)
- Sara Kotb
- Division of Global Health Protection, US Centers for Disease Control and Prevention, Cairo, Egypt
| | - Meghan Lyman
- Centers for Disease Control and Prevention, Atlanta, GA USA
| | | | | | | | - Ahmed Etman
- Ministry of Health and Population, Cairo, Egypt
| | - Soad Hafez
- Alexandria University Hospitals, Alexandria, Egypt
| | | | | | | | | | - Omar Sayyouh
- Division of Global Health Protection, US Centers for Disease Control and Prevention, Cairo, Egypt
| | - Maha Talaat
- Division of Global Health Protection, US Centers for Disease Control and Prevention, Cairo, Egypt
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Cienfuegos-Gallet AV, Ocampo de Los Ríos AM, Sierra Viana P, Ramirez Brinez F, Restrepo Castro C, Roncancio Villamil G, del Corral Londoño H, Jiménez JN. Risk factors and survival of patients infected with carbapenem-resistant Klebsiella pneumoniae in a KPC endemic setting: a case-control and cohort study. BMC Infect Dis 2019; 19:830. [PMID: 31590648 PMCID: PMC6781339 DOI: 10.1186/s12879-019-4461-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 09/11/2019] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Many gaps in the burden of resistant pathogens exist in endemic areas of low- and middle-income economies, especially those endemic for carbapenem resistance. The aim of this study is to evaluate risk factors for carbapenem-resistance, to estimate the association between carbapenem-resistance and all-cause 30-day mortality and to examine whether mortality is mediated by inappropriate therapy. METHODS A case-control and a cohort study were conducted in one tertiary-care hospital in Medellín, Colombia from 2014 to 2015. Phenotypic and genotypic characterization of isolates was performed. In the case-control study, cases were defined as patients infected with carbapenem-resistant K. pneumoniae (CRKP) and controls as patients infected with carbapenem-susceptible K. pneumoniae (CSKP). A risk factor analysis was conducted using logistic regression models. In the cohort study, the exposed group was defined as patients infected with CRKP and the non-exposed group as patients infected with CSKP. A survival analysis using an accelerated failure time model with a lognormal distribution was performed to estimate the association between carbapenem resistance and all-cause 30-day-mortality and to examine whether mortality is mediated by inappropriate therapy. RESULTS A total of 338 patients were enrolled; 49 were infected with CRKP and 289 with CSKP. Among CRKP isolates CG258 (n = 29), ST25 (n = 5) and ST307 (n = 4) were detected. Of importance, every day of meropenem (OR 1.18, 95%CI 1.10-1.28) and cefepime (OR 1.22, 95%CI 1.03-1.49) use increase the risk of carbapenem resistance. Additional risk factors were previous use of ciprofloxacin (OR 2.37, 95%CI 1.00-5.35) and urinary catheter (OR 2.60, 95%CI 1.25-5.37). Furthermore, a significant lower survival time was estimated for patients infected with CRKP compared to CSKP (Relative Times 0.44, 95%CI 0.24-0.82). The strength of association was reduced when appropriate therapy was included in the model (RT = 0.81 95%CI 0.48-1.37). CONCLUSION Short antibiotic courses had the potential to reduce the selection and transmission of CRKP. A high burden in mortality occurred in patients infected with CRKP in a KPC endemic setting and CRKP leads to increased mortality via inappropriate antibiotic treatment. Furthermore, dissemination of recognized hypervirulent clones could add to the list of challenges for antibiotic resistance control.
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Affiliation(s)
- Astrid V. Cienfuegos-Gallet
- Línea de Epidemiología Molecular Bacteriana, Grupo de Microbiología Básica y Aplicada, Escuela de Microbiología, Universidad de Antioquia, 050010 Medellín, Colombia
| | - Ana M. Ocampo de Los Ríos
- Línea de Epidemiología Molecular Bacteriana, Grupo de Microbiología Básica y Aplicada, Escuela de Microbiología, Universidad de Antioquia, 050010 Medellín, Colombia
| | | | | | | | - Gustavo Roncancio Villamil
- Línea de Epidemiología Molecular Bacteriana, Grupo de Microbiología Básica y Aplicada, Escuela de Microbiología, Universidad de Antioquia, 050010 Medellín, Colombia
- Clínica CardioVID, 050034 Medellín, Colombia
| | - Helena del Corral Londoño
- Línea de Epidemiología Molecular Bacteriana, Grupo de Microbiología Básica y Aplicada, Escuela de Microbiología, Universidad de Antioquia, 050010 Medellín, Colombia
| | - J. Natalia Jiménez
- Línea de Epidemiología Molecular Bacteriana, Grupo de Microbiología Básica y Aplicada, Escuela de Microbiología, Universidad de Antioquia, 050010 Medellín, Colombia
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Association between carbapenem-resistant Enterobacteriaceae and death: A systematic review and meta-analysis. Am J Infect Control 2019; 47:1200-1212. [PMID: 31072673 DOI: 10.1016/j.ajic.2019.03.020] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 03/16/2019] [Accepted: 03/17/2019] [Indexed: 11/23/2022]
Abstract
BACKGROUND Carbapenem-resistant Enterobacteriaceae (CRE) has emerged in health care facilities around the world. Several studies demonstrated data regarding clinical outcomes for CRE infections including death. This systematic review and meta-analysis summarized literature discussing association between CRE and mortality. METHODS A systematic literature review was performed by searching EMBASE, International Pharmaceutical Abstract databases, PubMed, and Scopus and to identify studies that assessed the association between CRE and death published from April 2012 to October 2017. A meta-analysis was performed using a random effect model. Heterogeneity was assessed using the I2-statistic. RESULTS Twenty-one studies were included in this meta-analysis. The underlying populations were moderately heterogeneous (I2 = 60%; P = .01). Pooled risk estimates from 9 studies revealed a significant association between CRE and death (pooled-adjusted odds ratio: 2.85; 95% confidence interval: 1.88, 4.30). The unadjusted variable pooled from 18 studies demonstrated a significant association between CRE and death (pooled-unadjusted odds ratio: 3.73; 95% confidence interval: 2.02, 6.88). DISCUSSION The finding that CRE infection was positively associated with death agreed with the previous meta-analysis of studies published before April 2012. CONCLUSIONS This meta-analysis found that CRE was associated with increased risk of death. Our analysis implies a need for strict infection control measures.
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Li J, Li Y, Song N, Chen Y. Risk factors for carbapenem-resistant Klebsiella pneumoniae infection: A meta-analysis. J Glob Antimicrob Resist 2019; 21:306-313. [PMID: 31525540 DOI: 10.1016/j.jgar.2019.09.006] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 08/21/2019] [Accepted: 09/07/2019] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVES Rates of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) have increased. A meta-analysis was conducted to explore risk factors for CRKP infection in order to provide a theoretical basis for reducing the CRKP infection rate and actively preventing CRKP infection. METHODS Online databases, including PubMed, EMBASE, OVID, ClinicalKey, CNKI, CBM, Wanfang Database and CHKD, were searched from inception up to 31 October 2018 for articles regarding risk factors for CRKP infection. Relevant articles were retrieved, supplemented by retrospective and manual search literature. RevMan 5.3 software was used for statistical analysis. RESULTS A total of 30 articles comprising 5075 cases were included in the study, of which 24 were in English and 6 were in Chinese. The results showed that age, sex and diabetes mellitus were not associated with CRKP infection. The odds ratio (95% confidence interval) of risk factors for CRKP infection were as follows: immunosuppression, 1.47 (1.14-1.90); ICU admission, 3.25 (2.36-4.47); antibiotic exposure, 2.53 (1.56-4.11); carbapenem exposure, 3.99 (2.86-5.56); quinolone exposure, 1.75 (1.38-2.22); glycopeptide exposure, 3.08 (1.93-4.91); β‑lactam/β‑lactamase inhibitor (BL/BLI) exposure, 2.28 (1.37-3.80); surgery, 1.59 (1.08-2.34); mechanical ventilation, 2.91 (1.96-4.31); central venous catheterisation, 2.93 (2.00-4.28); indwelling catheter, 2.62 (1.65-4.17); and nasogastric intubation, 2.38 (1.22-4.62). CONCLUSION Immunosuppression, ICU admission, antibiotic exposure (including carbapenems, quinolones, glycopeptides and BL/BLIs), surgery, mechanical ventilation, central venous catheterisation, indwelling catheter and nasogastric intubation were identified as risk factors for CRKP infection and should to be considered in clinical practice.
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Affiliation(s)
- Jihong Li
- Department of Laboratory Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Yuanyuan Li
- Department of Infectious Diseases, The Second Hospital of Hebei Medical University, No. 215 Heping Western Road, Xinhua District, Shijiazhuang 050000, Hebei, China
| | - Ning Song
- Department of Infectious Diseases, The Second Hospital of Hebei Medical University, No. 215 Heping Western Road, Xinhua District, Shijiazhuang 050000, Hebei, China.
| | - Yuan Chen
- Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
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Morley VJ, Woods RJ, Read AF. Bystander Selection for Antimicrobial Resistance: Implications for Patient Health. Trends Microbiol 2019; 27:864-877. [PMID: 31288975 PMCID: PMC7079199 DOI: 10.1016/j.tim.2019.06.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 05/29/2019] [Accepted: 06/13/2019] [Indexed: 12/15/2022]
Abstract
Antimicrobial therapy promotes resistance emergence in target infections and in off-target microbiota. Off-target resistance emergence threatens patient health when off-target populations are a source of future infections, as they are for many important drug-resistant pathogens. However, the health risks of antimicrobial exposure in off-target populations remain largely unquantified, making rational antibiotic stewardship challenging. Here, we discuss the contribution of bystander antimicrobial exposure to the resistance crisis, the implications for antimicrobial stewardship, and some novel opportunities to limit resistance evolution while treating target pathogens.
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Affiliation(s)
- Valerie J Morley
- Center for Infectious Disease Dynamics, Departments of Biology and Entomology, The Pennsylvania State University, University Park, PA, USA.
| | - Robert J Woods
- Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Andrew F Read
- Center for Infectious Disease Dynamics, Departments of Biology and Entomology, The Pennsylvania State University, University Park, PA, USA; Huck Institutes for the Life Sciences, The Pennsylvania State University, University Park, PA, USA
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Taminato M, Fram D, Pereira RRF, Sesso R, Belasco AGS, Pignatari AC, Barbosa DA. Infection related to Klebsiella pneumoniae producing carbapenemase in renal transplant patients. Rev Bras Enferm 2019; 72:760-766. [PMID: 31269143 DOI: 10.1590/0034-7167-2019-0009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 03/23/2019] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE To evaluate the risk factors related to Klebsiella pneumoniae carbapenemase infection after renal transplantation. METHODS This was a retrospective epidemiological (case-control) study, conducted from October 2011 to march 2016. Transplanted patients with infection by this bacteria during hospitalization were selected as cases. The controls were paired by age, sex, type of donor and transplant time. The proportion of cases and controls was 1:2. RESULTS Thirty hundred and five patients were included in the study (45 cases and 90 controls). The risk factors found for infection by KPC were: time of hospitalization after the transplant (OR: 4.82; CI95% 2.46-9.44), delayed kidney function (OR: 5.60; CI95% 1.91-11.01) and previous infectious for another microorganism ( OR: 34.13 CI95% 3.52-132.00). CONCLUSION The risk of acquisition of this bacterium was directly related to invasive procedures and exposure to the hospital environment. The findings reinforce the importance of prevention measures and control of infection by this microorganism.
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Affiliation(s)
| | - Dayana Fram
- Universidade Federal de São Paulo. São Paulo, Brasil
| | | | - Ricardo Sesso
- Universidade Federal de São Paulo. São Paulo, Brasil
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Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study. THE LANCET. INFECTIOUS DISEASES 2019; 19:601-610. [PMID: 31047852 DOI: 10.1016/s1473-3099(18)30792-8] [Citation(s) in RCA: 133] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 11/15/2018] [Accepted: 12/07/2018] [Indexed: 11/20/2022]
Abstract
BACKGROUND Low-income and middle-income countries (LMICs) are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. METHODS The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE) and carbapenem-resistant Entero-bacteriaceae (CRE) bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. FINDINGS Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15-61). Crude mortality was 20% (35 of 174 patients) for patients with CSE bloodstream infection and 35% (43 of 123 patients) for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3-6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04-2·94), and decreased probability of discharge alive (0·61, 0·45-0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. INTERPRETATION Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs. FUNDING bioMérieux.
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Giannella M, Pascale R, Gutiérrez-Gutiérrez B, Cano A, Viale P. The use of predictive scores in the management of patients with carbapenem-resistant Klebsiella pneumoniae infection. Expert Rev Anti Infect Ther 2019; 17:265-273. [PMID: 30876375 DOI: 10.1080/14787210.2019.1595590] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections are associated with high morbidity and mortality rates. A therapeutic approach based on the patient risk stratification could improve outcome and avoid antibiotic misuse. Areas covered: English literature search, from 2008 to 2018, was done using PubMed database. Risk factors for developing CR-KP infection in several settings were reviewed. Since, rectal carriage was a main risk factor for developing infection, we revised in deep clinical score to predict infection among colonized patients. Furthermore, we investigated overall and treatment-related risk factors for poor outcome in patients with CR-KP infection, in particular the carbapenem producing Enterobacteriacieae (CPE)-INCREMENT score. Finally, an algorithm, based on such scores, for the therapeutic management of patients with CR-KP colonization was commented. Expert opinion: The therapeutic approach analyzed in this review could help physicians to avoid antibiotic overuse as well as to start promptly with the most appropriate antibiotic regimen. However, it has to be validated in further studies, mainly among special population such as immunocompromised patients. The availability of new drugs, fast microbiology, and analysis of gut microbiome could significantly improve the management of CR-KP colonized and/or infected patients.
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Affiliation(s)
- Maddalena Giannella
- a Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi , University of Bologna , Bologna , Italy
| | - Renato Pascale
- a Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi , University of Bologna , Bologna , Italy
| | - Belén Gutiérrez-Gutiérrez
- b Infectious Diseases Unit, Hospital Universitario Virgen Macarena-Instituto de Biomedicina de Sevilla (IBiS) and Department of Medicine , Universidad de Sevilla , Sevilla , Spain
| | - Angela Cano
- c Infectious Diseases Unit , Hospital Univesritario Reina Sofia-Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC)-Unversidad de Cordoba , Cordoba , Spain
| | - Pierluigi Viale
- a Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi , University of Bologna , Bologna , Italy
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Han YH, Bae MJ, Hur YR, Hwang K. Prevalence and Risk Factors for Carbapenem-Resistant Enterobacteriaceae Colonization in Patients with Stroke. BRAIN & NEUROREHABILITATION 2019. [DOI: 10.12786/bn.2019.12.e16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Affiliation(s)
- Yong Hyun Han
- Department of Rehabilitation Medicine, Dong-Eui Medical Center, Busan, Korea
| | - Min Joon Bae
- Department of Rehabilitation Medicine, Dong-Eui Medical Center, Busan, Korea
| | - Yang Rok Hur
- Department of Rehabilitation Medicine, Dong-Eui Medical Center, Busan, Korea
| | - Kihun Hwang
- Department of Rehabilitation Medicine, Dong-Eui Medical Center, Busan, Korea
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Risk Factors for Carbapenem Resistant Klebsiella pneumoniae Hospital Infection in the Intensive Care Unit. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2018. [DOI: 10.2478/sjecr-2018-0002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract
Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) has become a major threat to patients in hospitals, increasing mortality, length of stay and costs.
The aim of this study was to discover risk factors for the development of hospital infections (HIs) caused by CR-Kp.
A prospective cohort study was conducted in the Medical-Surgical Intensive Care Unit of the Clinical Centre in Kragujevac, Kragujevac, Serbia, from January 1, 2011, to December 31, 2015. The “cases” were patients with HIs caused by CR-Kp, while the “controls” were patients infected with carbapenem-sensitive Klebsiella pneumoniae (CS-Kp). The significance of multiple putative risk factors for HIs caused by CR-Kp was tested using multivariate logistic regression.
Although univariate analyses pointed to many risk factors, with a significant influence on the occurrence of hospital CR-Kp infections, the multivariate logistic regression identified five independent risk factors: use of mechanical ventilation (OR=6.090; 95% CI=1.030-36.020; p=0.046); length of antibiotic therapy before HIs (days) (OR=1.080; 95% CI=1.003-1.387; p=0.045); previous use of carbapenems (OR=7.005; 95% CI=1.054-46.572; p=0.044); previous use of ciprofloxacin (OR=20.628; 95% CI=2.292-185.687; p=0.007) and previous use of metronidazole (OR=40.320; 95% CI=2.347-692.795; p=0.011)
HIs caused by CR-Kp are strongly associated with the use of mechanical ventilation and the duration of the previous use of certain antibiotics (carbapenems, ciprofloxacin and metronidazole).
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Li C, Li Y, Zhao Z, Liu Q, Li B. Treatment options and clinical outcomes for carbapenem-resistant Enterobacteriaceae bloodstream infection in a Chinese university hospital. J Infect Public Health 2018; 12:26-31. [PMID: 30145151 DOI: 10.1016/j.jiph.2018.08.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2017] [Revised: 06/28/2018] [Accepted: 08/02/2018] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Carbapenem resistant Enterobacteriaceae (CRE) has become a serious public health problem. Limited information is available about the treatment options that physicians used to fight CRE infections and related clinical outcomes in China. The aim of the present study was to explore the treatment options and clinical outcomes of patients with CRE bloodstream infection (BSI) in a Chinese teaching hospital. METHODS A retrospective study was conducted during 2011 to 2015 in one Chinese teaching hospital. Demographic, microbiological and clinical characteristics of enrolled subjects were collected from medical records. Data were analyzed by Kaplan-Meier graphs, log-rank test, and Cox regression. RESULTS A total of 98 inpatients with CRE BSI were enrolled in this study. For empirical therapy, 26 patients (26.5%) received at least one active drug within 48h after the onset of bacteremia. For definitive treatment, 59.2% (49/82) patients received at least one active drug and 40.2% (33/82) patients received therapy with no active drug. The overall 30-day mortality was 53.1% (52/98). Adverse outcome appeared to be more likely among patients with previous carbapenem exposure, neutropenia, severity of septic and time to initiation of BSIs. There was no significant difference in the mortality between the two groups of patients with combination therapy versus monotherapy (p=0.105). Severity of sepsis and neutropenia were identified as independent predictors of mortality. CONCLUSIONS Our study demonstrated a high mortality associated with CRE BSI and a high percentage of inappropriate empirical treatment for CRE BSI patients in a Chinese teaching hospital. Particular attention should be given to the patients with CRE BSI.
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Affiliation(s)
- Chen Li
- Department of Infectious Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
| | - Yi Li
- Department of Clinical Laboratory, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China.
| | - Zhichang Zhao
- Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
| | - Qing Liu
- Department of Infectious Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
| | - Bin Li
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350004, China.
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Koppe U, von Laer A, Kroll LE, Noll I, Feig M, Schneider M, Claus H, Eckmanns T, Abu Sin M. Carbapenem non-susceptibility of Klebsiella pneumoniae isolates in hospitals from 2011 to 2016, data from the German Antimicrobial Resistance Surveillance (ARS). Antimicrob Resist Infect Control 2018; 7:71. [PMID: 29992016 PMCID: PMC5987571 DOI: 10.1186/s13756-018-0362-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 05/22/2018] [Indexed: 01/08/2023] Open
Abstract
Background Carbapenem resistance in Klebsiella pneumoniae is of significant public health concern and recently spread across several countries. We investigated the extent of carbapenem non-susceptibility in K. pneumoniae isolates in Germany. Methods We analysed 2011-2016 data from the German Antimicrobial Resistance Surveillance (ARS) System, which contains routine data of antimicrobial susceptibility testing from voluntarily participating German laboratories. Klebsiella pneumoniae isolates tested resistant or intermediate against an antibiotic were classified as non-susceptible. Results We included 154,734 isolates from 655 hospitals in the analysis. Carbapenem non-susceptibility in K. pneumoniae isolates was low in Germany 0.63% (95% CI 0.51-0.76%). However, in continuously participating hospitals the number of K. pneumoniae isolates almost doubled and we found evidence for a slowly increasing trend for non-susceptibility (OR = 1.20 per year, 95% CI 1.09-1.33, p < 0.001). Carbapenem non-susceptibility was highest among isolates from patients aged 20-39 in men but not in women. Moreover, carbapenem non-susceptibility was more frequently reported for isolates from tertiary care, specialist care, and prevention and rehabilitation care hospitals as well as from intensive care units. Co-resistance of carbapenem non-susceptible isolates against antibiotics such as tigecycline, gentamicin, and co-trimoxazole was common. Co-resistance against colistin was 13.3% (95% CI 9.8-17.9%) in carbapenem non-susceptible isolates. Conclusion Carbapenem non-susceptibility in K. pneumoniae isolates in Germany is still low. However, it is slowly increasing and in the light of the strong increase of K. pneumoniae isolates over the last year this poses a significant challenge to public health. Continued surveillance to closely monitor trends as well as infection control and antibiotic stewardship activities are necessary to preserve treatment options.
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Affiliation(s)
- Uwe Koppe
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany
| | - Anja von Laer
- Postgraduate Training for Applied Epidemiology, Department of Infectious Disease Epidemiology, Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany
| | - Lars E. Kroll
- Department of Epidemiology and Health Monitoring, Robert Koch Institute, General-Pape-Strasse 62-66, 12101 Berlin, Germany
| | - Ines Noll
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany
| | - Marcel Feig
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany
| | - Marc Schneider
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany
| | - Hermann Claus
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany
| | - Tim Eckmanns
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany
| | - Muna Abu Sin
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany
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Su CF, Chuang C, Lin YT, Chan YJ, Lin JC, Lu PL, Huang CT, Wang JT, Chuang YC, Siu LK, Fung CP. Treatment outcome of non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae infections: a multicenter study in Taiwan. Eur J Clin Microbiol Infect Dis 2018; 37:651-659. [PMID: 29238934 DOI: 10.1007/s10096-017-3156-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 11/28/2017] [Indexed: 02/07/2023]
Abstract
Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with high mortality, and experiences with its treatment are usually based on carbapenemase-producing strains. Non-carbapenemase-producing CRKP is of clinical significance, but relevant studies are lacking. This nationwide study aimed to evaluate the outcome of antimicrobial therapy in patients with non-carbapenemase-producing CRKP infections. Patients with non-carbapenemase-producing CRKP infections were enrolled from 16 hospitals during January 2013 to December 2014 in Taiwan. Carbapenem resistance was defined as reduced susceptibility with a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. The resistance mechanisms of CRKP isolates were analyzed, and the clinical data of these patients were collected retrospectively. Independent risk factors of 14-day morality were determined by Cox regression analysis. A total of 99 patients with non-carbapenemase-producing CRKP infections were enrolled, and 14-day mortality was 27.3%. Among 67 patients treated with appropriate antimicrobial therapy, most (n = 61) patients received monotherapy. The 14-day mortality was lower in patients treated with appropriate monotherapy (21.3%) than in those with inappropriate therapy (37.5%). The multivariate regression model identified monotherapy (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.13-0.71; P = 0.005) as protective factor, and APACHE II scores (HR, 1.09; 95% CI, 1.01-1.18; P = 0.022) as risk factor associated with 14-day mortality. Tigecycline, colistin, and carbapenem were the most commonly used drugs in monotherapy. This study provides evidence supporting the efficacy of monotherapy in the treatment of non-carbapenemase-producing CRKP infections, and provides a future target for antibiotics stewardship for CRKP infection.
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Affiliation(s)
- Chin-Fang Su
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chien Chuang
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Tsung Lin
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, 112, Taiwan.
- Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Yu-Jiun Chan
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, 112, Taiwan
- Division of Microbiology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jung-Chung Lin
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Po-Liang Lu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-Tai Huang
- Division of Infectious Diseases, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan
| | - Jann-Tay Wang
- Division of Infectious Diseases, Department of Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yin-Ching Chuang
- Department of Internal Medicine and Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - L Kristopher Siu
- Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan
| | - Chang-Phone Fung
- Division of Infectious Diseases, Sijhih Cathy General Hospital, New Taipei City, Taiwan
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Asai N, Sakanashi D, Suematsu H, Kato H, Hagihara M, Nishiyama N, Koizumi Y, Yamagishi Y, Mikamo H. The epidemiology and risk factor of carbapenem-resistant enterobacteriaceae colonization and infections: Case control study in a single institute in Japan. J Infect Chemother 2018; 24:505-509. [PMID: 29548627 DOI: 10.1016/j.jiac.2018.02.005] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 01/24/2018] [Accepted: 02/08/2018] [Indexed: 01/08/2023]
Abstract
INTRODUCTION While the emergence and spread of carbapenem-resistant enterobacteriaceae (CRE) carriage and infections are serious threats to public health worldwide, its prevalence and epidemiology are still unknown. METHODS AND PATIENTS For the purpose of examining the prevalence, patients' background and risk factors for CRE carriage and infections, we conducted this case-control study. We retrospectively reviewed all patients isolating CRE at Aichi Medical University hospital from January 2010 until March 2017. The patients isolated with carbapenem-susceptible enterobacteriaceae (CSE) were randomly selected during the study period. RESULTS A total of 26 patients, isolating 28 CRE infections were enrolled in this study. The detection rate of CRE carriage and infection was 0.22% (28/12,600). Compared to the CSE group, the CRE group had poorer PS and higher CCI scores. The CRE group tended to stay longer in hospital (121 v.s. 63 days, p = 0.052) and admission fee was much more expensive than CSE group (220,710 v.s. 69,904 JPY, p < 0.001). PS 2-4 (ECOG) and CCI≧3 (p = 0.002), prior hospitalization within 90 days (p = 0.006) and prior antibiotics use within 90 days (p = 0.005) were risk factors for acquisition of CRE by univariate analysis. The combination of PS 2-4 and CCI≧3 was an independent risk factor for CRE carriage and infection by multivariate logistic regression analysis. CONCLUSION The combination of PS 2-4 (ECOG) and CCI score≧3 was an independent risk factor of CRE carriage and infections. The CRE group tended to stay longer in hospital, and the medical expense was much more expensive than those in the CSE group.
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Affiliation(s)
- Nobuhiro Asai
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi, Japan
| | - Daisuke Sakanashi
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi, Japan
| | - Hiroyuki Suematsu
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi, Japan
| | - Hideo Kato
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi, Japan
| | - Mao Hagihara
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi, Japan
| | - Naoya Nishiyama
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi, Japan
| | - Yusuke Koizumi
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi, Japan
| | - Yuka Yamagishi
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi, Japan
| | - Hiroshige Mikamo
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi, Japan.
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Liu P, Li X, Luo M, Xu X, Su K, Chen S, Qing Y, Li Y, Qiu J. Risk Factors for Carbapenem-Resistant Klebsiella pneumoniae Infection: A Meta-Analysis. Microb Drug Resist 2018; 24:190-198. [PMID: 28749714 PMCID: PMC5873294 DOI: 10.1089/mdr.2017.0061] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
AIMS Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has been rapidly emerging as a life-threatening nosocomial disease in many countries. However, studies on the corresponding risk factors of CRKP infection showed inconsistent results. To resolve these inconsistencies, we conducted a meta-analysis of previous studies on the potential risk factors of CRKP infection. The results of this study could be used to develop CRKP infection prevention strategies. METHODS Relevant works were systematically searched from five electronic databases up to September 2016. Z-test was used to determine the significance of the pooled odds ratios (ORs). ORs and 95% confidence intervals were utilized to compare the risk factors of CRKP infection. RESULTS Sixteen studies that involved 3,627 participants were included in the meta-analysis. We identified the following risk factors that were associated with CRKP infection: (1) longer length of hospital stay (LOS) (OR = 12.92), (2) admission to intensive care unit (ICU) (OR = 2.48), (3) prior hospitalization (OR = 1.85), (4) longer days of ICU stay (OR = 4.58), (5) transplant recipient (OR = 2.01), (6) steroid use (OR = 1.43), (7) central venous catheter use (OR = 2.30), (8) mechanical ventilation (OR = 2.54), (9) presence of tracheostomy (OR = 3.63), (10) parenteral nutrition (OR = 2.38), (11) previous antibiotic use (OR = 3.31), and (12) exposure to carbapenems (OR = 4.01), (13) aminoglycosides (OR = 2.05), (14) glycopeptides (OR = 2.40), (15) quinolones (OR = 2.28), and (16) anti-pseudomonal penicillins (OR = 2.67). CONCLUSIONS Sixteen risk factors including longer LOS, admission to ICU, previous antibiotic use, and exposure to carbapenems were associated with the development of CRKP infection. Identification of modifiable risk factors could play an important role in the prevention of CRKP infection.
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Affiliation(s)
- Pin Liu
- School of Public Health and Management, Chongqing Medical University , Chongqing, China
| | - Xuan Li
- School of Public Health and Management, Chongqing Medical University , Chongqing, China
| | - Mei Luo
- School of Public Health and Management, Chongqing Medical University , Chongqing, China
| | - Xuan Xu
- School of Public Health and Management, Chongqing Medical University , Chongqing, China
| | - Kewen Su
- School of Public Health and Management, Chongqing Medical University , Chongqing, China
| | - Shuai Chen
- School of Public Health and Management, Chongqing Medical University , Chongqing, China
| | - Ying Qing
- School of Public Health and Management, Chongqing Medical University , Chongqing, China
| | - Yingli Li
- School of Public Health and Management, Chongqing Medical University , Chongqing, China
| | - Jingfu Qiu
- School of Public Health and Management, Chongqing Medical University , Chongqing, China
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Provider Role in Transmission of Carbapenem-Resistant Enterobacteriaceae. Infect Control Hosp Epidemiol 2017; 38:1329-1334. [PMID: 29061201 DOI: 10.1017/ice.2017.216] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE We sought to evaluate the role healthcare providers play in carbapenem-resistant Enterobacteriaceae (CRE) acquisition among hospitalized patients. DESIGN A 1:4 case-control study with incidence density sampling. SETTING Academic healthcare center with regular CRE perirectal screening in high-risk units. PATIENTS We included case patients with ≥1 negative CRE test followed by positive culture with a length of stay (LOS) >9 days. For controls, we included patients with ≥2 negative CRE tests and assignment to the same unit set as case patients with a LOS >9 days. METHODS Controls were time-matched to each case patient. Case exposure was evaluated between days 2 and 9 before positive culture and control evaluation was based on maximizing overlap with the case window. Exposure sources were all CRE-colonized or -infected patients. Nonphysician providers were compared between study patients and sources during their evaluation windows. Dichotomous and continuous exposures were developed from the number of source-shared providers and were used in univariate and multivariate regression. RESULTS In total, 121 cases and 484 controls were included. Multivariate analysis showed odds of dichotomous exposure (≥1 source-shared provider) of 2.27 (95% confidence interval [CI], 1.25-4.15; P=.006) for case patients compared to controls. Multivariate continuous exposure showed odds of 1.02 (95% CI, 1.01-1.03; P=.009) for case patients compared to controls. CONCLUSIONS Patients who acquire CRE during hospitalization are more likely to receive care from a provider caring for a patient with CRE than those patients who do not acquire CRE. These data support the importance of hand hygiene and cohorting measures for CRE patients to reduce transmission risk. Infect Control Hosp Epidemiol 2017;38:1329-1334.
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Li L, Huang H. Risk factors of mortality in bloodstream infections caused by Klebsiella pneumonia: A single-center retrospective study in China. Medicine (Baltimore) 2017; 96:e7924. [PMID: 28858116 PMCID: PMC5585510 DOI: 10.1097/md.0000000000007924] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The prevalence of Klebsiella pneumonia bloodstream infections (KP-BSIs) is increasing worldwide. Few study reports focus on the KP-BSIs published in Mainland China over the previous years. This study aimed to describe the risk factors of mortality from KP-BSIs.A retrospective study was conducted in a teaching hospital in Shanghai, China, for a period of 4 years. Risk factors related to the patient mortality were analyzed using the binary logistic regression model.Of 104 patients with KP-BSIs, the overall 30-day mortality rate was 25%. The logistic regression analysis revealed that thrombocytopenia (TB) (odds ratio [OR]: 1.007, 95% confidence interval [CI]: 1.002-1.013), pancreaticobiliary tract (PBT) (OR: 4.059, 95% CI: 1.398-11.78), and intra-abdominal infection (OR: 6.816, 95% CI: 1.806-25.716) were powerful risk factors leading to the mortality associated with KP-BSIs. Although prior antibiotic exposure, inappropriate empirical antibiotics, and inappropriate definitive antibiotics were not associated with mortality, multidrug-resistant (MDR) of KP-BSIs in the present study was high in both survivors and nonsurvivors (67.9% and 88.5%, respectively).TB, PBT, and intra-abdominal infection caused significant mortality rates increase in KP-BSIs during the study period.
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Affiliation(s)
- Lanyu Li
- Department of Emergency Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations. Transplant Rev (Orlando) 2017; 32:36-57. [PMID: 28811074 DOI: 10.1016/j.trre.2017.07.001] [Citation(s) in RCA: 97] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Accepted: 07/02/2017] [Indexed: 12/17/2022]
Abstract
Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.
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A hospital-based matched case-control study to identify risk factors for clinical infection with OXA-48-producing Klebsiella pneumoniae in rectal carriers. Epidemiol Infect 2017; 145:2626-2630. [PMID: 28712369 DOI: 10.1017/s095026881700142x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Asymptomatic colonisation of the gastrointestinal tract by carbapenemase-producing Enterobacteriaceae is an important reservoir for transmission, which may precede infection. This retrospective observational case-control study was designed to identify risk factors for developing clinical infection with OXA-48-producing Klebsiella pneumoniae in rectal carriers during hospitalisation. Case patients (n = 76) had carbapenemase-producing K. pneumoniae (CPKP) infection and positive rectal culture for CPKP. Control patients (n = 174) were those with rectal colonisation with CPKP but without CPKP infection. Multivariate analysis identified the presence of a central venous catheter (OR 4·38; 95% CI 2·27-8·42; P = 0·008), the number of transfers between hospital units (OR 1·27; 95% CI (1·06-1·52); P < 0·001) and time at risk (OR 1·02 95% CI 1·01-1·03; P = 0·01) as independent risk factors for CPKP infection in rectal carriers. Awareness of these risk factors may help to identify patients at higher risk of developing CPKP infection.
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Tichy EM, Hardwick SW, Luisi BF, Salmond GPC. 1.8 Å resolution crystal structure of the carbapenem intrinsic resistance protein CarF. Acta Crystallogr D Struct Biol 2017; 73:549-556. [PMID: 28695855 PMCID: PMC7610886 DOI: 10.1107/s2059798317002236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2016] [Accepted: 02/09/2017] [Indexed: 11/10/2022] Open
Abstract
The natural production of the β-lactam antibiotic carbapenem in bacteria involves a group of enzymes that form a synthetic pathway as well as proteins that protect the cell from self-intoxification by the products. Here, the crystal structure of CarF, one of the two proteins that confer resistance to synthesis of the antibiotic in the host organism, is reported. The CarF fold places it within a widely occurring structural family, indicating an ancient structural origin from which the resistance function has been derived.
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Affiliation(s)
- Evelyn M. Tichy
- Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, England
| | - Steven W. Hardwick
- Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, England
| | - Ben F. Luisi
- Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, England
| | - George P. C. Salmond
- Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, England
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High burden of Carbapenem-resistant Enterobacteriaceae (CRE) fecal carriage at a teaching hospital: cost-effectiveness of screening in low-resource setting. Antimicrob Resist Infect Control 2017; 6:42. [PMID: 28473912 PMCID: PMC5414356 DOI: 10.1186/s13756-017-0200-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Accepted: 04/22/2017] [Indexed: 11/30/2022] Open
Abstract
Background Infections by multidrug-resistant gram-negative bacteria (MDR-GNB) have been continuously growing and pose challenge to health institution globally. Carbapenem-resistant Enterobacteriacea (CRE) was identified as one of the MDR-GNB which has limited treatment options and higher mortality compared to those of sensitive strains. We report an increased burden of CRE fecal carriage at a hospital in the North-eastern region of Malaysia. Methods A retrospective descriptive study from August 2013 to December 2015 was conducted in the Medical Microbiology & Parasitology laboratory of Hospital Universiti Sains Malaysia, which is a tertiary teaching hospital with more than 700 beds. This hospital treats patients with various medical and surgical conditions. Suspected CRE from any clinical specimens received by the laboratory was identified and confirmed using standard protocols. Polymerase chain reaction (PCR) assay was performed to determine the genotype. Results Altogether, 8306 Enterobacteriaceae was isolated from various clinical specimens during the study period and 477/8306 (5.74%) were CRE. Majority of the isolated CRE were Klebsiella [408/477, (85.5%)], of which Klebsiella pneumoniae was the predominant species, 388/408 (95%). CRE were mainly isolated from rectal swab (screening), 235/477 (49.3%); urine, 76/477 (15.9%); blood, 46/477 (9.6%) and about 7.1% from tracheal aspirate. One hundred and thirty-six isolates were subjected to genotype determination and., 112/136 (82.4%) showed positive detection of New Delhi metallo-β-lactamase 1 (NDM-1) gene (blaNDM1). Conclusion The study noted a high numbers of CRE isolated especially from rectal swabs. Active screening results in significant cost pressures and therefore should be revisited and revised, especially in low resource settings.
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Xu L, Sun X, Ma X. Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann Clin Microbiol Antimicrob 2017; 16:18. [PMID: 28356109 PMCID: PMC5371217 DOI: 10.1186/s12941-017-0191-3] [Citation(s) in RCA: 411] [Impact Index Per Article: 51.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 03/15/2017] [Indexed: 01/05/2023] Open
Abstract
PURPOSE Carbapenem resistant K. pneumoniae (CRKP) has aroused widespread attention owing to its very limited therapeutic options, and this strain has increased rapidly in recent years. Although it is accepted that drug resistance is associated with increased mortality in general, but some other studies found no such relationship. To estimate mortality of patients infected with CRKP in general and analyze factors for mortality of this infection, thus, we conducted this systematic review and meta-analysis. METHODS A systematic literature review of relevant studies published until December 2015 was conducted. We selected and assessed articles reporting mortality of patients infected with CRKP. RESULTS Pooled mortality was 42.14% among 2462 patients infected with CRKP versus 21.16% in those infected with carbapenem-susceptible K. pneumoniae (CSKP). The mortality of patients with bloodstream infection (BSI) or urinary tract infection was 54.30 and 13.52%, respectively, and 48.9 and 43.13% in patients admitted to the intensive care unit (ICU) or who underwent solid organ transplantation (SOT). Mortality was 47.66% in patients infected with K. pneumoniae carbapenemase-producing K. pneumoniae and 46.71% in those infected with VIM-producing K. pneumoniae. Geographically, mortality reported in studies from North America, South America, Europe, and Asia was 33.24, 46.71, 50.06, and 44.82%, respectively. CONCLUSIONS Our study suggests that patients infected with CRKP have higher mortality than those infected with CSKP, especially in association with BSI, ICU admission, or SOT. We also considered that patients' survival has a close relationship with their physical condition. Our results imply that attention should be paid to CRKP infection, and that strict infection control measures and new antibiotics are required to protect against CRKP infection.
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Affiliation(s)
- Liangfei Xu
- Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001 Anhui China
| | - Xiaoxi Sun
- Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001 Anhui China
| | - Xiaoling Ma
- Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001 Anhui China
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Kerbaj J, Toure Y, Soto Aladro A, Boudjema S, Giorgi R, Dufour JC, Brouqui P. Smartphone text message service to foster hand hygiene compliance in health care workers. Am J Infect Control 2017; 45:234-239. [PMID: 27955945 DOI: 10.1016/j.ajic.2016.10.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 10/17/2016] [Accepted: 10/17/2016] [Indexed: 11/15/2022]
Abstract
BACKGROUND Health care-associated infections are a major worldwide public health issue. Hand hygiene is a major component in the prevention of pathogen transmission in hospitals, and hand hygiene adherence by health care workers is low in many studies. We report an intervention using text messages as reminders and feedback to improve hand hygiene adherence. MATERIALS AND METHODS The study is a historical comparison proof-of-concept study. Eighteen health care workers were monitored during 12 months by a radiofrequency identification system. Afterward we sent 2 types of text messages, congratulation or encouragement, and we studied the evolution of hand hygiene adherence. RESULTS We recorded 15,723 hand hygiene opportunities, 8,973 before intervention and 6,750 during and after the intervention. Using a multilevel logistic regression analysis, we found a significant increase in hand hygiene adherence during the intervention (odds ratio, 1.68) compared with the historical period. DISCUSSION Despite limitations due to the type of study, a text message encouraging personnel to be more vigilant is effective in increasing hand hygiene adherence in health care workers. CONCLUSIONS Text message feedback should be incorporated into multimodal approaches for improving hand hygiene compliance.
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Affiliation(s)
- Jad Kerbaj
- CHU Nord, AP-HM, Pôle des Maladies Infectieuses et Tropicales, Maladies Infectieuses et Tropicales, France
| | - Youssoupha Toure
- Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France
| | - Alberto Soto Aladro
- Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France; URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Aix Marseille Université, Marseille, France
| | - Sophia Boudjema
- CHU Nord, AP-HM, Pôle des Maladies Infectieuses et Tropicales, Maladies Infectieuses et Tropicales, France; Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France; URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Aix Marseille Université, Marseille, France
| | - Roch Giorgi
- Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France; INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Aix Marseille Univ, Marseille, France; APHM, Hôpital de la Timone, Service Biostatistique et Technologies de l'Information et de la Communication, Marseille, France
| | - Jean Charles Dufour
- Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France; INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Aix Marseille Univ, Marseille, France; APHM, Hôpital de la Timone, Service Biostatistique et Technologies de l'Information et de la Communication, Marseille, France
| | - Philippe Brouqui
- CHU Nord, AP-HM, Pôle des Maladies Infectieuses et Tropicales, Maladies Infectieuses et Tropicales, France; Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France; URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Aix Marseille Université, Marseille, France.
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