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Şanlı K, Öncel B. Analysis of rectal carbapenem-resistant Enterobactericeae colonization results first report in Istanbul/Turkiye: Klebsiella pneumoniae co-producing bla KPC + bla NDM + bla OXA-48 in a single strain. BMC Infect Dis 2025; 25:773. [PMID: 40442618 PMCID: PMC12123834 DOI: 10.1186/s12879-025-11111-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 05/13/2025] [Indexed: 06/02/2025] Open
Abstract
BACKGROUND Carbapenemase-Producing Enterobacteriaceae (CPE) are known to be on the rise globally and are a major concern. Rapid screening of at-risk patients and implementation of infection control measures can prevent colonization from becoming a source of infection. OBJECTIVE We investigated the incidence of carbapenem-resistant Enterobacteriaceae (CRE) colonization, CRE-producing Enterobacteriaceae species, carbapenemase gene types and prevalence in patients subjected to CRE screening tests in rectal swab samples using the CHROMAgar culture method and real-time Polymerase Chain Reaction (PCR) method in a tertiary hospital in Istanbul, Turkiye. In addition, we investigated the effectiveness of diagnosis with PCR and CHROMAgar methods by examining whether meropenem-resistant infection foci developed in patients with CRE colonization from hospitalization to discharge. MATERIALS AND METHODS This study was conducted retrospectively in the Microbiology Laboratory of 3953 patients at Başakşehir Çam and Sakura City Hospital in Istanbul between January 2021 and December 2023. All data, including CRE colonization screening test results using CHROMAgar and PCR methods, age, gender, requesting clinic, and meropenem-resistant Enterobacteriaceae culture results in infection foci that developed during hospitalization, were obtained from the hospital automated system. RESULTS In all 3953 patients included in the study, CRE colonization was screened by CHROMAgar culture method on rectal swab samples and by real-time PCR method in 500 patients. The mean age of the patients was 42.9 ± 30.1 and 58.1% were male. There was no difference in age and gender distribution between the Upon admission to the hospital and during hospitalization groups (p > 0.05). Rectal CRE colonization was detected in 9.7% of all patients with the CROMAgar method and in 9.2% with the PCR method and in 16.2%. The most statistically significant increase was seen in intensive care units with the CHROMAgar method (p < 0.05). Among Enterobacteriaceae species, Klebsiella pneumoniae (69.6%) was most frequently grown, followed by Escherichia coli (13.7%). There was no statistically significant difference between the groups in terms of CRE growth status and microorganism distribution in rectal swab samples of patients during hospitalization and hospital admission (p > 0.05). Among the CRE genes detected by PCR, single genes were the most common. While OXA-48 positivity was detected in 113 (16.40%) of the patients, blaNDM was detected in 31 (4.50%), blaKPC was detected in 5 (0.73%) and bla VIM/IMP gene was detected in 5 (0.73%) of the others. Double gene positivity was observed in a single strain in 6 patients and blaKPC, blaNDM and blaOXA-48 genes were positive together in a single strain in 3 patients. Infection developed in one or more foci resistant to carbapenem in 159 of the patients colonized with CRE during their hospitalization. The rate of infection development was lower in patients colonized by PCR compared to chromogenic agar. CONCLUSION The CRE colonization rate is high and should be closely monitored with infection control precautions. Although the detection rate of CRE colonization was higher with PCR, the rate of progression to infection in any focus during hospitalization was found to be lower detected with the CHROMAgar method. This situation showed that rapid detection of CRE colonization with PCR, early diagnosis and isolation are important. Klebsiella pneumoniae colonization was the most common causative agent. Co-production of 3 CRE genes (blaKPC + blaNDM + blaOXA-48) in 3 patients in our hospital highlighted the importance of concerns about multi-resistant Enterobacteriaceae.
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Affiliation(s)
- Kamuran Şanlı
- University of Health Science, Başakşehir Çam and Sakura City Hospital, Medical Microbiyology, Başakşehir, Istanbul, 34480, Turkey.
| | - Beyza Öncel
- University of Health Science, Başakşehir Çam and Sakura City Hospital, Medical Microbiyology, Başakşehir, Istanbul, 34480, Turkey
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Reinicke M, Diezel C, Teimoori S, Haase B, Monecke S, Ehricht R, Braun SD. Rapid Simultaneous Detection of the Clinically Relevant Carbapenemase Resistance Genes blaKPC, blaOXA48, blaVIM and blaNDM with the Newly Developed Ready-to-Use qPCR CarbaScan LyoBead. Int J Mol Sci 2025; 26:1218. [PMID: 39940986 PMCID: PMC11818240 DOI: 10.3390/ijms26031218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/27/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
Antibiotic resistance, in particular the dissemination of carbapenemase-producing organisms, poses a significant threat to global healthcare. This study introduces the qPCR CarbaScan LyoBead assay, a robust, accurate, and efficient tool for detecting key carbapenemase genes, including blaKPC, blaNDM, blaOXA-48, and blaVIM. The assay utilizes lyophilized beads, a technological advancement that enhances stability, simplifies handling, and eliminates the need for refrigeration. This feature renders it particularly well-suited for point-of-care diagnostics and resource-limited settings. The assay's capacity to detect carbapenemase genes directly from bacterial colonies without the need for extensive sample preparation has been demonstrated to streamline workflows and enable rapid diagnostic results. The assay demonstrated 100% specificity and sensitivity across a diverse range of bacterial strains, including multiple allelic variants of target genes, facilitating precise identification of resistance mechanisms. Bacterial strains of the species Acinetobacter baumannii, Citrobacter freundii, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Pseudomonas aeruginosa were utilized as reference material for assay development (n = 9) and validation (n = 28). It is notable that the assay's long shelf life and minimal operational complexity further enhance its utility for large-scale implementation in healthcare, food safety, and environmental monitoring. The findings emphasize the necessity of continuous surveillance and the implementation of rapid diagnostic methods for the effective detection of resistance genes. Furthermore, the assay's potential applications in other fields, such as toxin-antitoxin system research and monitoring of resistant bacteria in the community, highlight its versatility. In conclusion, the qPCR CarbaScan LyoBead assay is a valuable tool that can contribute to the urgent need to combat antibiotic resistance and improve global public health outcomes.
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Affiliation(s)
- Martin Reinicke
- Leibniz Institute of Photonic Technology, Leibniz Centre for Photonics in Infection Research (LPI), 07745 Jena, Germany; (M.R.); (C.D.); (S.M.); (S.D.B.)
- InfectoGnostics Research Campus, 07743 Jena, Germany
| | - Celia Diezel
- Leibniz Institute of Photonic Technology, Leibniz Centre for Photonics in Infection Research (LPI), 07745 Jena, Germany; (M.R.); (C.D.); (S.M.); (S.D.B.)
- InfectoGnostics Research Campus, 07743 Jena, Germany
| | - Salma Teimoori
- biotechrabbit GmbH, 12489 Berlin, Germany; (S.T.); (B.H.)
| | - Bernd Haase
- biotechrabbit GmbH, 12489 Berlin, Germany; (S.T.); (B.H.)
| | - Stefan Monecke
- Leibniz Institute of Photonic Technology, Leibniz Centre for Photonics in Infection Research (LPI), 07745 Jena, Germany; (M.R.); (C.D.); (S.M.); (S.D.B.)
- InfectoGnostics Research Campus, 07743 Jena, Germany
| | - Ralf Ehricht
- Leibniz Institute of Photonic Technology, Leibniz Centre for Photonics in Infection Research (LPI), 07745 Jena, Germany; (M.R.); (C.D.); (S.M.); (S.D.B.)
- InfectoGnostics Research Campus, 07743 Jena, Germany
- Institute of Physical Chemistry, Friedrich-Schiller University, 07743 Jena, Germany
| | - Sascha D. Braun
- Leibniz Institute of Photonic Technology, Leibniz Centre for Photonics in Infection Research (LPI), 07745 Jena, Germany; (M.R.); (C.D.); (S.M.); (S.D.B.)
- InfectoGnostics Research Campus, 07743 Jena, Germany
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Avcu G, Erci E, Bilen NM, Ersayoglu I, Ozek G, Celtik U, Terek D, Cilli F, Bal ZS. Clinical outcomes and the impact of treatment modalities in children with carbapenem-resistant Enterobacteriaceae bloodstream infections: a retrospective cohort study from a tertiary university hospital. J Antimicrob Chemother 2025; 80:147-153. [PMID: 39475360 PMCID: PMC11695901 DOI: 10.1093/jac/dkae387] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 10/14/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND The increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infections among children represents a significant global concern, leading to elevated mortality rates. The aim of this study was to evaluate the risk factors, outcomes, 30-day mortality rates and contributing factors in children with CRE bloodstream infections (CRE-BSIs). METHODS Data regarding demographic characteristics, treatment approaches and outcomes of hospitalized children aged 0-18 years diagnosed with CRE-BSIs between January 2018 and December 2022 were extracted from medical records. Mortality within 30 days of diagnosis and the predictive factors were analysed. RESULTS A total of 114 children, with a median age of 11 months (range: 6-69.5), were included. All cases of CRE-BSIs were either healthcare associated or hospital acquired and presented with at least one underlying comorbidity. A previous history of CRE colonization or infection rate was 48.2% (55/114). Klebsiella pneumoniae 87.7% (100/114) was the most frequently isolated microorganism, with a 30-day mortality rate of 14% (16/114). Multivariate analysis identified paediatric intensive care unit admission, invasive mechanical ventilation, inotropic support and thrombocytopenia due to CRE-BSIs as the most discriminative predictors for 30-day mortality (P < 0.001). Central venous catheter (CVC) removal was associated with a reduced mortality rate (P = 0.012). High-dose prolonged infusion of MEM-based or polymyxin-based antibiotic combinations did not impact survival. Lower MEM MIC values were associated with improved survival. CONCLUSIONS The mortality rate of CRE-BSI is notably high in childhood. The use of antibiotic combination strategies did not demonstrate a significant impact on 30-day survival; however, the removal of CVCs was found to lower mortality rates.
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Affiliation(s)
- Gulhadiye Avcu
- Faculty of Medicine, Department of Pediatrics, Division of Pediatric Infectious Diseases, Ege University, Izmir, Turkey
| | - Ece Erci
- Faculty of Medicine, Department of Pediatrics, Division of Pediatric Infectious Diseases, Ege University, Izmir, Turkey
| | - Nimet Melis Bilen
- Faculty of Medicine, Department of Pediatrics, Division of Pediatric Infectious Diseases, Ege University, Izmir, Turkey
| | - Irem Ersayoglu
- Faculty of Medicine, Department of Pediatrics, Division of Pediatric Intensive Care, Ege University, Izmir, Turkey
| | - Gulcihan Ozek
- Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology and Oncology, Ege University, Izmir, Turkey
| | - Ulgen Celtik
- Faculty of Medicine, Department of Pediatric Surgery, Ege University, Izmir, Turkey
| | - Demet Terek
- Faculty of Medicine, Department of Neonatology, Ege University, Izmir, Turkey
| | - Feriha Cilli
- Faculty of Medicine, Department of Medical Microbiology, Ege University, Izmir, Turkey
| | - Zumrut Sahbudak Bal
- Faculty of Medicine, Department of Pediatrics, Division of Pediatric Infectious Diseases, Ege University, Izmir, Turkey
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Eshwarappa M, Gangula RS, Rajashekar R, Prabhu PP, Hamsa V, Yousuff M, Mathihally G, Konana G, Anish LS. Clinical, Microbiological Profile, and Treatment Outcomes of Carbapenem-Resistant Urinary Tract Infections in a Tertiary Care Hospital. Indian J Nephrol 2025; 35:53-58. [PMID: 39872259 PMCID: PMC11763310 DOI: 10.25259/ijn_530_23] [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: 01/11/2024] [Accepted: 03/04/2024] [Indexed: 01/30/2025] Open
Abstract
Background Carbapenem-resistant urinary tract infections (CR-UTIs) are a major global health threat. Many factors contribute to the increasing incidence of CR-UTI. Owing to the limited availability of treatment options, CR-UTIs are highly challenging to treat. Materials and Methods This was a single-center, hospital-based, observational, retrospective cohort study. We investigated the treatment results, microbiological profiles, and clinical manifestations of CR-UTI at our institution between January 2017 and December 2021. All patients exhibiting clinical signs and symptoms of urinary tract infection (UTI) and a urine culture that showed growth of a single organism greater than 105 colony-forming units/ml were included. All patients were considered for a 1-year follow-up. Results From January 2017 to December 2022, 3016 (31%) CR-UTI episodes were noted. Approximately, 75% of CR-UTI episodes were caused by the most prevalent urinary pathogens, Escherichia coli and Klebsiella pneumoniae. Within 28 days, 308 patients (12.59%) died. Enterobacteriaceae treated for a minimum of 7-10 days showed a greater response to Aminoglycosides, Fosfomycin, Ceftizoxime, Colistin with Carbapenem, Tigecycline with Carbapenem, and Ceftazidime/avibactam. Within a year, 994 CR-UTI episodes were identified in patients who were available for follow-up; and 38% of these episodes were the result of relapse. Three-quarters of the remaining incidents were recurrent, accounting for a higher mortality rate (14.2%) within a year. Conclusion Despite effective antibiotic treatment, CR-UTIs are associated with early relapse and recurrence. Newer effective treatment and preventive strategies are required to address this pandemic.
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Affiliation(s)
- Mahesh Eshwarappa
- Department of Nephrology, M S Ramaiah Medical College, Bangalore, India
| | - Rahul Sai Gangula
- Department of Nephrology, M S Ramaiah Medical College, Bangalore, India
| | - R Rajashekar
- Department of Nephrology, M S Ramaiah Medical College, Bangalore, India
| | | | - V Hamsa
- Department of Nephrology, M S Ramaiah Medical College, Bangalore, India
| | - Mohammad Yousuff
- Department of Nephrology, M S Ramaiah Medical College, Bangalore, India
| | | | - Gurudev Konana
- Department of Nephrology, M S Ramaiah Medical College, Bangalore, India
| | - Lia Sara Anish
- Department of Nephrology, M S Ramaiah Medical College, Bangalore, India
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Wang Y, Yu L, Zhu J, Liang G, Liu J, Zheng Y, Zhao Y, Yu Z. Cost-effectiveness analysis of polymyxin B versus colistin for treating patients with carbapenem-resistant gram-negative bacterial infections. Sci Rep 2024; 14:23635. [PMID: 39384871 PMCID: PMC11464736 DOI: 10.1038/s41598-024-74290-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 09/25/2024] [Indexed: 10/11/2024] Open
Abstract
The prevalence of carbapenem-resistant gram-negative bacterial (CRGNB) infection is continuously increasing, and polymyxin B and colistin are considered last-resort drugs. This study compared the cost-effectiveness of polymyxin B with that of colistin for the treatment of intensive care unit patients with CRGNB infection from the Chinese healthcare perspective. A decision-analytic Markov model was constructed to assess the cost-effectiveness of polymyxin B compared with colistin over a period of 5 years using evidence from phase trials and other publicly available studies. The model was developed in Treeage Pro 2022 and comprises a decision tree depicting initial hospitalization and a Markov model with four states projecting long-term health and economic impacts following discharge. Uncertainty was tested with one-way sensitivity analyses and probabilistic sensitivity analyses. The quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratio (ICER) were estimated at willingness-to-pay (WTP) thresholds of $12,674 to $38,024 per QALY. According to the base analyses, the cost incurred by patients receiving colistin treatment was $12,244.77, leading to a gain of 1.35 QALYs. In contrast, patients treated with polymyxin B had a lower cost of $7,306.71 but yielded 1.07 QALYs. The ICRE of colistin was $18032.25/QALY. At a $12,674/QALY threshold, the results were sensitive to several variables, including the probability of cure with polymyxin B, the cost of drugs, the utility of discharge to home, the utility of discharge to long-term care, and the cost of nephrotoxicity with renal replacement therapy. After all model inputs varied across a wide range of reasonable values, only the probability of being cured with polymyxin B resulted in an ICER above the $38,024/QALY threshold. According to the probabilistic sensitivity analyses, colistin was the optimal strategy in 38.2% and 62.8% of the simulations, at $12,674/QALY and $38,024/QALY, respectively. Our study findings suggest that, when considering the Chinese healthcare perspective, colistin is likely to be more cost-effective than polymyxin B for patients with CRGNB infection, especially when the WTP threshold is set at one-time the per capita GDP. However, as the WTP threshold increases from one to three times the per capita GDP, the cost-effectiveness acceptability of colistin improves, increasing from 38.2 to 62.8%.
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Affiliation(s)
- Ye Wang
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Lingyan Yu
- The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jianping Zhu
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Gang Liang
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jieqiong Liu
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, China
| | - Ying Zheng
- The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, China
| | - Yuhua Zhao
- Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China.
| | - Zhenwei Yu
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
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Paudel R, Shrestha E, Chapagain B, Tiwari BR. Carbapenemase producing Gram negative bacteria: Review of resistance and detection methods. Diagn Microbiol Infect Dis 2024; 110:116370. [PMID: 38924837 DOI: 10.1016/j.diagmicrobio.2024.116370] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 05/18/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024]
Abstract
Gram negative bacilli that are carbapenem resistant have emerged and are spreading worldwide. Infections caused by carbapenem resistant isolates posses a significant threat due to their high morbidity and mortality rates. Carbapenemases production by multi-drug resistant pathogens severely restricts treatment choices for illnesses caused by bacteria that are resistant to both carbapenems and majority of β-lactam antibiotics. Various phenotypic and genotypic methods for identification can distinguish between different classes of carbapenemase and identify pathogens that are resistant to carbapenems. The establishment of a quick, accurate and reliable test for identifying the clinical strains that produce the carbapenemase enzyme is essential for optimum diagnosis of microbial pathogens and management of the global rise in the prevalence of carbapenemase producing bacterial strains. The aim of this review was to summarize the mechanisms of carbapenem resistance and to provide an overview of different carbapenemase detection methods for carbapenem resistant Gram negative bacilli.
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Affiliation(s)
- Rajan Paudel
- School of Health and Allied Sciences, Pokhara University, Pokhara, Nepal.
| | - Elina Shrestha
- School of Health and Allied Sciences, Pokhara University, Pokhara, Nepal
| | - Bipin Chapagain
- School of Health and Allied Sciences, Pokhara University, Pokhara, Nepal
| | - Bishnu Raj Tiwari
- School of Health and Allied Sciences, Pokhara University, Pokhara, Nepal
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Denissen J, Havenga B, Reyneke B, Khan S, Khan W. Comparing antibiotic resistance and virulence profiles of Enterococcus faecium, Klebsiella pneumoniae, and Pseudomonas aeruginosa from environmental and clinical settings. Heliyon 2024; 10:e30215. [PMID: 38720709 PMCID: PMC11076977 DOI: 10.1016/j.heliyon.2024.e30215] [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: 08/17/2023] [Revised: 04/19/2024] [Accepted: 04/22/2024] [Indexed: 05/12/2024] Open
Abstract
Antibiotic resistance and virulence profiles of Enterococcus faecium, Klebsiella pneumoniae, and Pseudomonas aeruginosa, isolated from water sources collected in informal settlements, were compared to clinical counterparts. Cluster analysis using repetitive extragenic palindromic sequence-based polymerase chain reaction (REP-PCR) indicated that, for each respective species, low genetic relatedness was observed between most of the clinical and environmental isolates, with only one clinical P. aeruginosa (PAO1) and one clinical K. pneumoniae (P2) exhibiting high genetic similarity to the environmental strains. Based on the antibiograms, the clinical E. faecium Ef CD1 was extensively drug resistant (XDR); all K. pneumoniae isolates (n = 12) (except K. pneumoniae ATCC 13883) were multidrug resistant (MDR), while the P. aeruginosa (n = 16) isolates exhibited higher susceptibility profiles. The tetM gene (tetracycline resistance) was identified in 47.4 % (n = 6 environmental; n = 3 clinical) of the E. faecium isolates, while the blaKPC gene (carbapenem resistance) was detected in 52.6 % (n = 7 environmental; n = 3 clinical) and 15.4 % (n = 2 environmental) of the E. faecium and K. pneumoniae isolates, respectively. The E. faecium isolates were predominantly poor biofilm formers, the K. pneumoniae isolates were moderate biofilm formers, while the P. aeruginosa isolates were strong biofilm formers. All E. faecium and K. pneumoniae isolates were gamma (γ)-haemolytic, non-gelatinase producing (E. faecium only), and non-hypermucoviscous (K. pneumoniae only), while the P. aeruginosa isolates exhibited beta (β)-haemolysis and produced gelatinase. The fimH (type 1 fimbriae adhesion) and ugE (uridine diphosphate galacturonate 4-epimerase synthesis) virulence genes were detected in the K. pneumoniae isolates, while the P. aeruginosa isolates possessed the phzM (phenazine production) and algD (alginate biosynthesis) genes. Similarities in antibiotic resistance and virulence profiles of environmental and clinical E. faecium, K. pneumoniae, and P. aeruginosa, thus highlights the potential health risks posed by using environmental water sources for daily water needs in low-and-middle-income countries.
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Affiliation(s)
- Julia Denissen
- Department of Microbiology, Faculty of Science, Stellenbosch University, Private Bag X1, Stellenbosch, 7602, South Africa
| | - Benjamin Havenga
- Department of Microbiology, Faculty of Science, Stellenbosch University, Private Bag X1, Stellenbosch, 7602, South Africa
| | - Brandon Reyneke
- Faculty of Health Sciences, University of Johannesburg, PO Box 17011, Doornfontein, 2028, South Africa
| | - Sehaam Khan
- Faculty of Health Sciences, University of Johannesburg, PO Box 17011, Doornfontein, 2028, South Africa
| | - Wesaal Khan
- Department of Microbiology, Faculty of Science, Stellenbosch University, Private Bag X1, Stellenbosch, 7602, South Africa
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Guo B, Li P, Qin B, Wang S, Zhang W, Shi Y, Yang J, Niu J, Chen S, Chen X, Cui L, Fu Q, Guo L, Hou Z, Li H, Li X, Liu R, Liu X, Mao Z, Niu X, Qin C, Song X, Sun R, Sun T, Wang D, Wang Y, Xu L, Xu X, Yang Y, Zhang B, Zhou D, Li Z, Chen Y, Jin Y, Du J, Shao H. An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study. BMC Infect Dis 2024; 24:116. [PMID: 38254025 PMCID: PMC10804584 DOI: 10.1186/s12879-024-09005-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open
Abstract
OBJECTIVE This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.
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Affiliation(s)
- Bo Guo
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Peili Li
- Department of Public Utilities Development, Henan Provincial People's Hospital, Zhengzhou, China
| | - Bingyu Qin
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Shanmei Wang
- Department of Microbiology Laboratory, Henan Provincial People's Hospital, Zhengzhou, China
| | - Wenxiao Zhang
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Yuan Shi
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Jianxu Yang
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Jingjing Niu
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Shifeng Chen
- Department of Critical Care Medicine, The Second People's Hospital of Pingdingshan City, Pingdingshan, China
| | - Xiao Chen
- Department of Critical Care Medicine, Nanyang Nanshi Hospital, Nanyang, China
| | - Lin Cui
- Department of Critical Care Medicine, Yellow River Central Hospital, Zhengzhou, China
| | - Qizhi Fu
- Department of Critical Care Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
| | - Lin Guo
- Department of Critical Care Medicine, The Seventh People's Hospital of Zhengzhou, Zhengzhou, China
| | - Zhe Hou
- Department of Critical Care Medicine, Zhengzhou Orthopedic Hospital, Zhengzhou, China
| | - Hua Li
- Department of Critical Care Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, China
| | - Xiaohui Li
- Department of Critical Care Medicine, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China
| | - Ruifang Liu
- Department of Critical Care Medicine, The Third People's Hospital of Henan Province, Zhengzhou, China
| | - Xiaojun Liu
- Department of Critical Care Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhengrong Mao
- Department of Critical Care Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Xingguo Niu
- Department of Critical Care Medicine, Zhengzhou People's Hospital, Zhengzhou, 450000, China
| | - Chao Qin
- Department of Critical Care Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xianrong Song
- Department of Critical Care Medicine, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Rongqing Sun
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tongwen Sun
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Daoxie Wang
- Department of Critical Care Medicine, The Third People's Hospital of Zhengzhou, Zhengzhou, China
| | - Yong Wang
- Department of Critical Care Medicine, Huaihe Hospital of Henan University, Kaifeng, China
| | - Lanjuan Xu
- Department of Critical Care Medicine, Zhengzhou Central Hospital, Zhengzhou, China
| | - Xin Xu
- Department of Critical Care Medicine, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Yuejie Yang
- Department of Critical Care Medicine, The Sixth People's Hospital of Zhengzhou, Zhengzhou, China
| | - Baoquan Zhang
- Department of Critical Care Medicine, The Third Affiliated Hospital of Xinxiang Medical College, Xinxiang, China
| | - Dongmin Zhou
- Department of Critical Care Medicine, Henan Cancer Hospital, Zhengzhou, China
| | - Zhaozhen Li
- Department of Critical Care Medicine, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Yinyin Chen
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Yue Jin
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Juan Du
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Huanzhang Shao
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China.
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9
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Kyung SM, Lee JH, Lee ES, Hwang CY, Yoo HS. Whole genome structure and resistance genes in carbapenemase-producing multidrug resistant ST378 Klebsiella pneumoniae. BMC Microbiol 2023; 23:323. [PMID: 37924028 PMCID: PMC10623767 DOI: 10.1186/s12866-023-03074-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 10/17/2023] [Indexed: 11/06/2023] Open
Abstract
BACKGROUND Carbapenemase-producing Klebsiella pneumoniae (CPKP) is one of the most dangerous multidrug-resistant (MDR) pathogens in human health due to its widespread circulation in the nosocomial environment. CPKP carried by companion dogs, which are close to human beings, should be considered a common threat to public health. However, CPKP dissemination through companion animals is still under consideration of major diagnosis and surveillance systems. METHODS Two CPKP isolates which were genotyped to harbor bla NDM-5-encoding IncX3 plasmids, were subjected to the whole-genome study. Whole bacterial DNA was isolated, sequenced, and assembled with Oxford Nanopore long reads and corrected with short reads from the Illumina NovaSeq 6000 platform. The whole-genome structure and positions of antimicrobial resistance (AMR) genes were identified and visualized using CGView. Worldwide datasets were downloaded from the NCBI GenBank database for whole-genome comparative analysis. The whole-genome phylogenetic analysis was constructed using the identified whole-chromosome SNP sites from K. pneumoniae HS11286. RESULTS As a result of the whole-genome identification, 4 heterogenous plasmids and a single chromosome were identified, each carrying various AMR genes. Multiple novel structures were identified from the AMR genes, coupled with mobile gene elements (MGE). The comparative whole-genome epidemiology revealed that ST378 K. pneumoniae is a novel type of CPKP, carrying a higher prevalence of AMR genes. CONCLUSIONS The characterized whole-genome analysis of this study shows the emergence of a novel type of CPKP strain carrying various AMR genes with variated genomic structures. The presented data in this study show the necessity to develop additional surveillance programs and control measures for a novel type of CPKP strain.
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Affiliation(s)
- Su Min Kyung
- Department of Infectious Disease, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
| | - Jun Ho Lee
- Department of Infectious Disease, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
| | - Eun-Seo Lee
- Department of Infectious Disease, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
| | - Cheol-Yong Hwang
- Department of Veterinary Dermatology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
| | - Han Sang Yoo
- Department of Infectious Disease, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
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10
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Mekonnen Y, Solomon S, Gebreyohanns A, Teklu DS, Ayenew Z, Mihret A, Bonger ZT. Fecal Carriage of Carbapenem Resistant Enterobacterales and Associated Factors Among Admitted Patients in Saint Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia. Infect Drug Resist 2023; 16:6345-6355. [PMID: 37789843 PMCID: PMC10542572 DOI: 10.2147/idr.s418066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 09/15/2023] [Indexed: 10/05/2023] Open
Abstract
Purpose The Enterobacterales family colonizes the human gut as normal flora in all age groups, with bacterial infections being the most common cause. Resistance is currently observed in all normal flora. The aim of this study was to determine the frequency of fecal carriage of carbapenem-resistant Enterobacterales (CRE), carbapenemase-producing Enterobacterales (CPE), and associated factors in the faeces of admitted patients. Methods A cross-sectional study was conducted in Saint Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia. A total of 384 rectal swabs were collected from various wards in admitted patients who have consented to participate. The specimens were inoculated on a MacConkey agar plate, and then they were incubated at 37 °C for 18 to 24 hours. Using the BD PhoenixTM M50 compact system identification and antimicrobial susceptibility testing were performed. Using the modified carbapenem inactivation method, it was determined whether the carbapenem-resistant bacterial isolate produced carbapenemase or not. Results Overall prevalence of carbapenem-resistant Enterobacterales carriage and carbapenemase producing Enterobacterales in admitted patients was 17.2% (95%, Confidence Interval: 13.3-21.1%) and 7% (95%, Confidence Interval: 4.7-9.9%), respectively. The predominate carbapenem-resistant Enterobacterales in fecal carriage was K. pneumoniae, 15.4% (23/149), E. cloacae 15.4% (6/39), followed by E. coli 12.4% (37/307) of carbapenem-resistant Enterobacterales (CRE) isolate. Carbapenem-resistant Enterobacterales carriage isolates showed large level of resistance to ciprofloxacin, and sulfamethoxazole-trimethoprim. Prior intake of antibiotics (Odds Ratio 2.42, 95% CI: 11.186-4.95) was significantly associated with higher carbapenem-resistant Enterobacterales carriage. Conclusion We observed a high prevalence of carbapenem-resistant Enterobacterales carriage and carbapenemase-producing Enterobacterales among admitted patients. There were only amikacin and colistin that could be effective for carbapenem-resistant Enterobacterales isolates. Hence, the control of carbapenem-resistant Enterobacterales carriage should be given priority by carbapenem-resistant Enterobacterales screening for fecal of admitted patients, and adhering to good infection prevention practice in hospital settings.
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Affiliation(s)
- Yonas Mekonnen
- Department of Medical Microbiology, Immunology and Parasitology, Saint Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
- Clinical Bacteriology and Mycology National Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Semaria Solomon
- Department of Medical Microbiology, Immunology and Parasitology, Saint Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Alganesh Gebreyohanns
- Department of Medical Microbiology, Immunology and Parasitology, Saint Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Dejenie Shiferaw Teklu
- Clinical Bacteriology and Mycology National Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Zeleke Ayenew
- Clinical Bacteriology and Mycology National Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Amete Mihret
- Clinical Bacteriology and Mycology National Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia
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11
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Fouad A, Gill CM, Simner PJ, Nicolau DP, Asempa TE. Cefepime in vivo activity against carbapenem-resistant Enterobacterales that test as cefepime susceptible or susceptible-dose dependent in vitro: implications for clinical microbiology laboratory and clinicians. J Antimicrob Chemother 2023; 78:2242-2253. [PMID: 37522258 DOI: 10.1093/jac/dkad229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 07/11/2023] [Indexed: 08/01/2023] Open
Abstract
BACKGROUND Carbapenem-resistant Enterobacterales (CRE) are a public health concern. Among these isolates, there are reports of isolates that test as cefepime susceptible or susceptible-dose dependent (SDD) in vitro despite presence of a carbapenemase. This study aimed to evaluate the pharmacokinetic/pharmacodynamic profile of cefepime against carbapenemase-producing (CP-CRE) and non-producing (non-CP-CRE) isolates with a range of cefepime MICs. METHODS Reference broth microdilution and modified carbapenem inactivation method (mCIM) were performed on genotypically characterized clinical CRE isolates. Ultimately, CP-CRE (n = 21; blaKPC) and non-CP-CRE (n = 19) isolates with a distribution of cefepime MICs (≤0.5 to >256 mg/L) were utilized in the murine thigh infection model. Mice were treated with cefepime human-simulated regimens (HSRs) representative of a standard dose (1 g q12h 0.5 h infusion) or the SDD dose (2 g q8h 0.5 h infusion). Efficacy was assessed as the change in bacterial growth at 24 h compared with 0 h control, where ≥1 log bacterial reduction is considered translational value for clinical efficacy. RESULTS Among both cohorts of CRE isolates, i.e. CP-CRE and non-CP-CRE, that tested as SDD to cefepime in vitro, 1 log bacterial reduction was not attainable with cefepime. Further blunting of cefepime efficacy was observed among CP-CRE isolates compared with non-CP-CRE across both susceptible and SDD categories. CONCLUSIONS Data indicate to avoid cefepime for the treatment of serious infections caused by CRE isolates that test as cefepime susceptible or SDD. Data also provide evidence that isolates with the same antibiotic MIC may have different pharmacokinetic/pharmacodynamic profiles due to their antimicrobial resistance mechanism.
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Affiliation(s)
- Aliaa Fouad
- Center for Anti-Infective Research and Development (CAIRD), Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA
| | - Christian M Gill
- Center for Anti-Infective Research and Development (CAIRD), Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA
| | - Patricia J Simner
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David P Nicolau
- Center for Anti-Infective Research and Development (CAIRD), Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA
- Division of Infectious Diseases, Hartford Hospital, Hartford, CT, USA
| | - Tomefa E Asempa
- Center for Anti-Infective Research and Development (CAIRD), Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA
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12
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Fadlallah M, Salman A, Salem-Sokhn E. Updates on the Status of Carbapenem-Resistant Enterobacterales in Lebanon. Int J Microbiol 2023; 2023:8831804. [PMID: 37283804 PMCID: PMC10241595 DOI: 10.1155/2023/8831804] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 04/10/2023] [Accepted: 05/15/2023] [Indexed: 06/08/2023] Open
Abstract
Carbapenem-resistant Enterobacterales (CRE) pathogens have been increasingly isolated and reported in Lebanon. Several studies have been published over the last two decades about the CRE situation in the country. However, compared to the worldwide data, those studies are scarce and mostly restricted to single center studies. In this review, we aim to present a comprehensive and reliable report illustrating the current situation regarding CRE in Lebanon. Variable studies have shown an increasing pattern of carbapenem resistance in Enterobacterales since the first reports of CRE isolates in 2007 and 2008. Escherichia coli and Klebsiella pneumoniae were the most detected ones. The OXA-48 class D carbapenemases were the most prevalent carbapenemases among CRE isolates. Moreover, the emergence of other carbapenemases like the NDM class B carbapenemase has been noticed. Strict infection control measures in hospitals, including the identification of CRE carriers, are needed in Lebanese hospitals since carriage is a potential risk for the spread of CRE in healthcare settings. The dissemination of CRE in the community is noticed and attributed to multiple causes, such as the refugee crisis, water contamination, and antimicrobial misuse. In conclusion, strict infection control measures in healthcare settings, in addition to accurate antimicrobial stewardship program implementation, are urgently needed.
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Affiliation(s)
- Mahdi Fadlallah
- Laboratory Medicine, Lebanese University, Faculty of Medical Sciences, Beirut, Lebanon
| | - Ahmad Salman
- Infectious Diseases, Lebanese University, Faculty of Medical Sciences, Beirut, Lebanon
| | - Elie Salem-Sokhn
- Department of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, P.O. Box 11-5020, Beirut, Lebanon
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13
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Yin L, Lu L, He L, Lu G, Cao Y, Wang L, Zhai X, Wang C. Molecular characteristics of carbapenem-resistant gram-negative bacilli in pediatric patients in China. BMC Microbiol 2023; 23:136. [PMID: 37202716 PMCID: PMC10192778 DOI: 10.1186/s12866-023-02875-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 04/29/2023] [Indexed: 05/20/2023] Open
Abstract
BACKGROUND Carbapenem-resistant gram-negative bacilli (CR-GNB) have been increasingly reported in China. However, dynamic monitoring data on molecular epidemiology of CR-GNB are limited in pediatric patients. RESULTS 300 CR-GNB isolates (200 Carbapenem-resistant K. pneumoniae (CRKP), 50 carbapenem-resistant A.baumannii (CRAB) and 50 carbapenem-resistant P. aeruginosa (CRPA)) were investigated. The predominant carbapenemase gene was blaNDM-1 (73%) and blaKPC-2 (65%) in neonates and non-neonates. Meanwhile, the predominant STs were ST11 (54%) in neonates and ST17 (27.0%) and ST278 (20.0%) in non-neonates. Notably, a shift in the dominant sequence type of CRKP infections from ST17 /ST278-NDM-1 to ST11-KPC-2 was observed during the years 2017-2021 and KPC-KP showed relatively higher resistance to aminoglycosides and quinolones than NDM-KP.BlaOXA-23 was isolated from all the CRAB isolates while only one isolate expressing blaBIC and 2 isolates expressing blaVIM-2 were found in CRPA isolates. ST195 (22.0%) and ST244 (24.0%) were the most common in CRAB and CRPA isolates and all the STs of CRAB belonged to CC92 while CRPA presents ST types with diversity distribution. CONCLUSION CRKP showed different molecular phenotypes in neonates and non-neonates and was changing dynamically and high-risk clone of ST11 KPC-KP should be paid more attention. Most CRKP and CRAB strains shared the same CCs, suggesting that intrahospital transmission may occur, and large-scale screening and more effective measures are urgently needed.
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Affiliation(s)
- Lijun Yin
- Department of Nosocomial Infection Control, Children's Hospital of Fudan University, Shanghai, China
| | - Lu Lu
- Department of Nosocomial Infection Control, Children's Hospital of Fudan University, Shanghai, China
| | - Leiyan He
- The Clinical Microbiology Laboratory, Children's Hospital of Fudan University, Shanghai, China
| | - Guoping Lu
- Department of Pediatric Intensive Care Unit, Children's Hospital of Fudan University, Shanghai, China
| | - Yun Cao
- Department of neonatal intensive care unit, Children's Hospital of Fudan University, Shanghai, China
| | - Laishuan Wang
- Department of Neonatal room, Children's Hospital of Fudan University, Shanghai, China
| | - Xiaowen Zhai
- Department of Hematology, Children's Hospital of Fudan University, Shanghai, China.
| | - Chuanqing Wang
- Department of Nosocomial Infection Control and the Clinical Microbiology Laboratory, Children's Hospital of Fudan University, Shanghai, China.
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14
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Gelfusa M, Murari A, Ludovici GM, Franchi C, Gelfusa C, Malizia A, Gaudio P, Farinelli G, Panella G, Gargiulo C, Casinelli K. On the Potential of Relational Databases for the Detection of Clusters of Infection and Antibiotic Resistance Patterns. Antibiotics (Basel) 2023; 12:antibiotics12040784. [PMID: 37107146 PMCID: PMC10135313 DOI: 10.3390/antibiotics12040784] [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: 02/27/2023] [Revised: 04/05/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
In recent years, several bacterial strains have acquired significant antibiotic resistance and can, therefore, become difficult to contain. To counteract such trends, relational databases can be a powerful tool for supporting the decision-making process. The case of Klebsiella pneumoniae diffusion in a central region of Italy was analyzed as a case study. A specific relational database is shown to provide very detailed and timely information about the spatial-temporal diffusion of the contagion, together with a clear assessment of the multidrug resistance of the strains. The analysis is particularized for both internal and external patients. Tools such as the one proposed can, therefore, be considered important elements in the identification of infection hotspots, a key ingredient of any strategy to reduce the diffusion of an infectious disease at the community level and in hospitals. These types of tools are also very valuable in the decision-making process related to antibiotic prescription and to the management of stockpiles. The application of this processing technology to viral diseases such as COVID-19 is under investigation.
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Affiliation(s)
- Michela Gelfusa
- Department of Industrial Engineering, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Andrea Murari
- Consorzio RFX (CNR, ENEA, INFN), University of Padua, 35127 Padua, Italy
- Istituto per la Scienza e la Tecnologia dei Plasmi, CNR, 35100 Padua, Italy
| | - Gian Marco Ludovici
- Department of Industrial Engineering, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Cristiano Franchi
- Department of Industrial Engineering, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Claudio Gelfusa
- Department of Industrial Engineering, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Andrea Malizia
- Department of Biomedicine and Prevention, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Pasqualino Gaudio
- Department of Industrial Engineering, University of Rome "Tor Vergata", 00133 Rome, Italy
| | | | - Giacinto Panella
- ASL and Fabrizio Spaziani, Frosinone Hospital, 03100 Frosinone, Italy
| | - Carla Gargiulo
- ASL and Fabrizio Spaziani, Frosinone Hospital, 03100 Frosinone, Italy
| | - Katia Casinelli
- ASL and Fabrizio Spaziani, Frosinone Hospital, 03100 Frosinone, Italy
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15
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Yang X, Liu X, Li W, Shi L, Zeng Y, Xia H, Huang Q, Li J, Li X, Hu B, Yang L. Epidemiological Characteristics and Antimicrobial Resistance Changes of Carbapenem-Resistant Klebsiella pneumoniae and Acinetobacter baumannii under the COVID-19 Outbreak: An Interrupted Time Series Analysis in a Large Teaching Hospital. Antibiotics (Basel) 2023; 12:antibiotics12030431. [PMID: 36978298 PMCID: PMC10044178 DOI: 10.3390/antibiotics12030431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 01/14/2023] [Accepted: 01/25/2023] [Indexed: 02/24/2023] Open
Abstract
Background: To investigate the epidemiological characteristics and resistance changes of carbapenem-resistant organisms (CROs) under the COVID-19 outbreak to provide evidence for precise prevention and control measures against hospital-acquired infections during the pandemic. Methods: The distribution characteristics of CROs (i.e., carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii) were analyzed by collecting the results of the antibiotic susceptibility tests of diagnostic isolates from all patients. Using interrupted time series analysis, we applied Poisson and linear segmented regression models to evaluate the effects of COVID-19 on the numbers and drug resistance of CROs. We also conducted a stratified analysis using the Cochran–Mantel–Haenszel test. Results: The resistance rate of carbapenem-resistant Acinetobacter baumannii (CRAB) was 38.73% higher after the COVID-19 outbreak compared with before (p < 0.05). In addition, the long-term effect indicated that the prevalence of CRAB had a decreasing trend (p < 0.05). However, the overall resistance rate of Klebsiella pneumoniae did not significantly change after the COVID-19 outbreak. Stratified analysis revealed that the carbapenem-resistant Klebsiella pneumoniae (CRKP) rate increased in females (OR = 1.98, p < 0.05), those over 65 years old (OR = 1.49, p < 0.05), those with sputum samples (OR = 1.40, p < 0.05), and those in the neurology group (OR = 2.14, p < 0.05). Conclusion: The COVID-19 pandemic has affected the change in nosocomial infections and resistance rates in CROs, highlighting the need for hospitals to closely monitor CROs, especially in high-risk populations and clinical departments. It is possible that lower adherence to infection control in crowded wards and staffing shortages may have contributed to this trend during the COVID-19 pandemic, which warrants further research.
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Affiliation(s)
- Xinyi Yang
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Xu Liu
- Department of Infectious Disease, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
| | - Weibin Li
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Lin Shi
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Yingchao Zeng
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Haohai Xia
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Qixian Huang
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Jia Li
- Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Xiaojie Li
- Department of Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Bo Hu
- Department of Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
- Correspondence: (B.H.); (L.Y.)
| | - Lianping Yang
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
- Correspondence: (B.H.); (L.Y.)
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16
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Nishida S, Ihashi Y, Yoshino Y, Ono Y. Evaluation of an immunological assay for the identification of multiple carbapenemase-producing Gram-negative bacteria. Pathology 2022; 54:917-921. [PMID: 35934532 DOI: 10.1016/j.pathol.2022.05.007] [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: 11/10/2021] [Revised: 04/24/2022] [Accepted: 05/08/2022] [Indexed: 12/31/2022]
Abstract
Carbapenemase-producing Gram-negative organisms (CPOs) frequently gain multidrug-resistant phenotypes and thereby limit the therapeutic options available. Colonisation and infection with CPOs are critical risks for mortality in clinical settings, especially in critical care medicine. Carbapenemase genes on plasmids have transferred to many Gram-negative species, and these species have spread, leading to global concern regarding antimicrobial resistance. A molecular rapid diagnostic test (mRDT) for CPOs is urgently required in critical care medicine. Here, we evaluated a rapid lateral flow immunoassay (LFIA) for CPOs isolated from patients at university hospitals, including intensive care units, and compared the results with those obtained using the multiplex polymerase chain reaction (PCR) method. NG-test CARBA 5 detected multiple carbapenemases, KPC, OXA-48, NDM, VIM, and IMP variants expressed in clinical isolates. Quick Chaser IMP detected IMP variants. The LFIAs exhibited 100% sensitivity and specificity relative to clinical isolates on agar plates. By contrast, the multiplex PCR method exhibited a limited ability to detect IMP-7-producing isolates not belonging to the IMP1 group, which resulted in 97% sensitivity and 100% specificity for IMP-producing isolates. Our results demonstrate that the LFIA is a useful mRDT to identify CPOs and has an advantage over the PCR method for both detection time and sensitivity to the IMP groups. LFIA could complement the nucleic acid amplification test used to identify CPOs. In conclusion, we evaluated sensitive and specific LFIAs capable of detecting carbapenemase production in Gram-negative bacteria. We anticipate that LFIAs will become a point-of-care test enabling rapid detection of carbapenemases in hospital settings, particularly in intensive care units.
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Affiliation(s)
- Satoshi Nishida
- Department of Microbiology and Immunology, Teikyo University School of Medicine, Itabashi, Tokyo, Japan.
| | - Yusuke Ihashi
- Department of Microbiology and Immunology, Teikyo University School of Medicine, Itabashi, Tokyo, Japan
| | - Yusuke Yoshino
- Department of Microbiology and Immunology, Teikyo University School of Medicine, Itabashi, Tokyo, Japan
| | - Yasuo Ono
- Department of Microbiology and Immunology, Teikyo University School of Medicine, Itabashi, Tokyo, Japan; Faculty of Health and Medical Science, Teikyo Heisei University, Toshima, Tokyo, Japan
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17
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Outbreak of KPC-producing Klebsiella pneumoniae at a Portuguese university hospital: Epidemiological characterization and containment measures. Porto Biomed J 2022; 7:e186. [PMID: 37152080 PMCID: PMC10158887 DOI: 10.1097/j.pbj.0000000000000186] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 04/21/2022] [Indexed: 12/03/2022] Open
Abstract
Background KPC-producing K pneumoniae (KPC-Kp) is a public health problem with important clinical and epidemiological implications. We describe an outbreak of KPC-Kp at vascular surgery and neurosurgery wards in a central hospital in Porto, Portugal. Methods A case of KPC-Kp was considered to be a patient positive for KPC-Kp with strong epidemiological plausibility of having acquired this microorganism in the affected wards and/or with genetic relationship ≥92% between KPC-Kp isolates. Active surveillance cultures (ASCs) and real-time polymerase chain reaction were used for the detection of carbapenemase genes through rectal swab in a selected population. Molecular analysis was performed using pulsed-field gel electrophoresis at the National Reference Laboratory. Patient risk factors were collected from the electronic medical record system. Information regarding outbreak containment strategy was collected from the Infection Control Unit records. Results Of the 16 cases, 11 (69%) were identified through active screening, representing 1.4% of the total 766 ASCs collected. The most frequent risk factors identified were previous admission (63%), antibiotic exposure in the past 6 months (50%), and immunodepression (44%). The length of stay until KPC-Kp detection was high (0-121 days, mean 35.6), as was the total length of stay (5-173 days, mean 56.6). Three patients (19%) were infected by KPC-Kp, 2 of whom died. One previously colonized patient died later because of KPC-Kp infection. Conclusions Multifactorial strategy based on contact precautions (with patient and healthcare professional cohorts) and ASC, as well as Antibiotic Stewardship Program reinforcement, allowed to contain this KPC-Kp outbreak.
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Ruvinsky S, Voto C, Roel M, Deschutter V, Ferraro D, Aquino N, Reijtman V, Galvan ME, Motto E, García M, Sarkis C, Bologna R. Carbapenem-resistant Enterobacteriaceae bloodstream infections: A case-control study from a pediatric referral hospital in Argentina. Front Public Health 2022; 10:983174. [PMID: 36091556 PMCID: PMC9452880 DOI: 10.3389/fpubh.2022.983174] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 08/05/2022] [Indexed: 01/25/2023] Open
Abstract
Background Antibiotic-resistant gram-negative bloodstream infections (BSI) remain a leading cause morbidity and mortality in pediatric patients with a high impact on the public health system. Data in resource-limited countries, including those in Latin America and the Caribbean region, are scarce. The aim of the study was to identify risk factors for acquiring carbapenem-resistant Enterobacteriaceae (CRE) bacteremia in children and to assess the use of resources. Methods A retrospective case-control study was conducted to analyze demographic, epidemiological, clinical, microbiological, and outcome data as well as the use of resources between 2014 and 2019. Univariate and logistic regression analysis was performed in order to identify risk factors associated with CRE-BSI. The R software version 4.1.2 was used. Results A total of 46 cases with CRE-BSI and 92 controls with gram-negative non-CRE-BSI were included. No statistical difference was observed regarding: median age (36 months; IQR, 11.2-117 vs. 48 months, IQR 13-119), male sex (50 vs. 60%), and underlying disease (98 vs. 91%) in cases vs. controls, respectively. The most frequent mechanism of CRE bacteremia were: KPC in 74%, OXA in 15%, and NDM in 6.5%. A total of 54.3% of cases vs. 32.6 % (p = 0.016) of controls were admitted to the pediatric intensive care unit (PICU), and 48 vs. 21% (p = 0.001) required mechanical ventilation. Bacteremia secondary to intra-abdominal infection was observed in 56.5% of cases vs. 35% of controls (p = 0.032). Previous colonization with CRE was detected in 76% of cases vs. 8% of controls. Combination antimicrobial treatment was most frequent in cases vs. control (100 vs. 56.5%). No difference was observed in median length of hospital stay (22 days; IQR, 19-31 in cases vs. 17.5 days; IQR, 10-31 in controls; p = 0.8). Overall case fatality ratio was 13 vs. 5.5%, respectively. The most statistically significant risk factors included previous PICU stay (OR, 4; 95%CI, 2-8), invasive procedures/surgery (OR, 3; 95%CI, 1-7), central venous catheter placement (OR, 6.5; 95%CI, 2-19), urinary catheter placement (OR, 9; 95%CI 4-20), mechanical ventilation (OR, 4; 95%CI, 2-10), liver transplantation (OR, 8; 95%CI, 2-26), meropenem treatment (OR, 8.4; 3.5-22.6) in univariate analysis. The logistic regression model used for multivariate analysis yielded significant differences for previous meropenem treatment (OR, 13; 95%CI, 3-77; p = 0.001), liver transplantation (OR, 13; 95%CI, 2.5-100; p = 0.006), and urinary catheter placement (OR, 9; 95%CI, 1.4-94; p = 0.03). Conclusion CRE-BSI affects hospitalized children with underlying disease, mainly after liver transplantation, with previous urinary catheter use and receiving broad-spectrum antibiotics, leading to high PICU requirement and mortality. These risk factors will have to be taken into account in our region in order to establish adequate health policies and programs to improve antimicrobial stewardship.
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Affiliation(s)
- Silvina Ruvinsky
- Coordinación de Investigación Clínica y Sanitaria, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina,*Correspondence: Silvina Ruvinsky
| | - Carla Voto
- Coordinación de Investigación Clínica y Sanitaria, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Macarena Roel
- Coordinación de Investigación Clínica y Sanitaria, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Verónica Deschutter
- Servicio de Infectologia y Epidemiologia, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Daiana Ferraro
- Servicio de Infectologia y Epidemiologia, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Norma Aquino
- Coordinación de Investigación Clínica y Sanitaria, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Vanesa Reijtman
- Servicio de Microbiología, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - María Eugenia Galvan
- Servicio de Terapia Intensiva, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Eduardo Motto
- Servicio de Terapia Intensiva, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Mauro García
- Servicio de Terapia Intensiva, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Claudia Sarkis
- Servicio de Infectologia y Epidemiologia, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Rosa Bologna
- Servicio de Infectologia y Epidemiologia, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
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Chudyk EI, Beer M, Limb MAL, Jones CA, Spencer J, van der Kamp MW, Mulholland AJ. QM/MM Simulations Reveal the Determinants of Carbapenemase Activity in Class A β-Lactamases. ACS Infect Dis 2022; 8:1521-1532. [PMID: 35877936 PMCID: PMC9379904 DOI: 10.1021/acsinfecdis.2c00152] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Indexed: 11/28/2022]
Abstract
β-lactam antibiotic resistance in Gram-negative bacteria, primarily caused by β-lactamase enzymes that hydrolyze the β-lactam ring, has become a serious clinical problem. Carbapenems were formerly considered "last resort" antibiotics because they escaped breakdown by most β-lactamases, due to slow deacylation of the acyl-enzyme intermediate. However, an increasing number of Gram-negative bacteria now produce β-lactamases with carbapenemase activity: these efficiently hydrolyze the carbapenem β-lactam ring, severely limiting the treatment of some bacterial infections. Here, we use quantum mechanics/molecular mechanics (QM/MM) simulations of the deacylation reactions of acyl-enzyme complexes of eight β-lactamases of class A (the most widely distributed β-lactamase group) with the carbapenem meropenem to investigate differences between those inhibited by carbapenems (TEM-1, SHV-1, BlaC, and CTX-M-16) and those that hydrolyze them (SFC-1, KPC-2, NMC-A, and SME-1). QM/MM molecular dynamics simulations confirm the two enzyme groups to differ in the preferred acyl-enzyme orientation: carbapenem-inhibited enzymes favor hydrogen bonding of the carbapenem hydroxyethyl group to deacylating water (DW). QM/MM simulations of deacylation give activation free energies in good agreement with experimental hydrolysis rates, correctly distinguishing carbapenemases. For the carbapenem-inhibited enzymes, free energies for deacylation are significantly higher than for the carbapenemases, even when the hydroxyethyl group was restrained to prevent interaction with the DW. Analysis of these simulations, and additional simulations of mutant enzymes, shows how factors including the hydroxyethyl orientation, the active site volume, and architecture (conformations of Asn170 and Asn132; organization of the oxyanion hole; and the Cys69-Cys238 disulfide bond) collectively determine catalytic efficiency toward carbapenems.
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Affiliation(s)
- Ewa I. Chudyk
- Centre
for Computational Chemistry, School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, United Kingdom
| | - Michael Beer
- Centre
for Computational Chemistry, School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, United Kingdom
- School
of Cellular and Molecular Medicine, University
of Bristol Medical Sciences Building, University Walk, Bristol BS8 1TD, United Kingdom
| | - Michael A. L. Limb
- Centre
for Computational Chemistry, School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, United Kingdom
| | - Charlotte A. Jones
- Centre
for Computational Chemistry, School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, United Kingdom
| | - James Spencer
- School
of Cellular and Molecular Medicine, University
of Bristol Medical Sciences Building, University Walk, Bristol BS8 1TD, United Kingdom
| | - Marc W. van der Kamp
- Centre
for Computational Chemistry, School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, United Kingdom
- School
of Biochemistry, University of Bristol Medical
Sciences Building, University Walk, Bristol BS8 1TD, United
Kingdom
| | - Adrian J. Mulholland
- Centre
for Computational Chemistry, School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, United Kingdom
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Denissen J, Reyneke B, Waso-Reyneke M, Havenga B, Barnard T, Khan S, Khan W. Prevalence of ESKAPE pathogens in the environment: Antibiotic resistance status, community-acquired infection and risk to human health. Int J Hyg Environ Health 2022; 244:114006. [PMID: 35841823 DOI: 10.1016/j.ijheh.2022.114006] [Citation(s) in RCA: 145] [Impact Index Per Article: 48.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/30/2022] [Accepted: 06/30/2022] [Indexed: 01/10/2023]
Abstract
The ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens are characterised by increased levels of resistance towards multiple classes of first line and last-resort antibiotics. Although these pathogens are frequently isolated from clinical environments and are implicated in a variety of life-threatening, hospital-associated infections; antibiotic resistant ESKAPE strains have been isolated from environmental reservoirs such as surface water, wastewater, food, and soil. Literature on the persistence and subsequent health risks posed by the ESKAPE isolates in extra-hospital settings is however, limited and the current review aims to elucidate the primary reservoirs of these pathogens in the environment, their antibiotic resistance profiles, and the link to community-acquired infections. Additionally, information on the current state of research regarding health-risk assessments linked to exposure of the ESKAPE pathogens in the natural environment, is outlined.
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Affiliation(s)
- Julia Denissen
- Department of Microbiology, Faculty of Science, Stellenbosch University, Private Bag X1, Stellenbosch, 7602, South Africa
| | - Brandon Reyneke
- Department of Microbiology, Faculty of Science, Stellenbosch University, Private Bag X1, Stellenbosch, 7602, South Africa
| | - Monique Waso-Reyneke
- Faculty of Health Sciences, University of Johannesburg, PO Box 17011, Doornfontein, 2028, South Africa
| | - Benjamin Havenga
- Department of Microbiology, Faculty of Science, Stellenbosch University, Private Bag X1, Stellenbosch, 7602, South Africa
| | - Tobias Barnard
- Water and Health Research Centre, University of Johannesburg, PO Box 17011, Doornfontein, 7305, South Africa
| | - Sehaam Khan
- Faculty of Health Sciences, University of Johannesburg, PO Box 17011, Doornfontein, 2028, South Africa
| | - Wesaal Khan
- Department of Microbiology, Faculty of Science, Stellenbosch University, Private Bag X1, Stellenbosch, 7602, South Africa.
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21
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Tuncer G, Aktas Z, Basaran S, Cagatay A, Eraksoy H. Biofilm formation of panresistant Klebsiella pneumoniae. Future Microbiol 2022; 17:723-735. [PMID: 35443798 DOI: 10.2217/fmb-2021-0108] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Introduction: The authors aimed to investigate the biofilm-forming features of panresistant Klebsiella pneumoniae (PRKp). Material & methods: The biofilm formations were shown under light microscope and laser scanning confocal microscopy. The optical densities of the wells were measured and classified according to biofilm-forming capacities. Results: The ratio of biofilm-forming K. pneumoniae was established to be 100%. All isolates were found to form high-level biofilms in classification compared with positive and negative controls. No significant difference was detected in the biofilm-forming capacities of K. pneumoniae strains isolated from different sample types. Conclusion: No previous study associated with PRKp isolates was identified in the literature search. There is a need for different approaches characterizing the biofilm-forming features of PRKp.
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Affiliation(s)
- Gulsah Tuncer
- Department of Infectious Diseases & Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, 34104, Turkey
| | - Zerrin Aktas
- Department of Microbiology & Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, 34104, Turkey
| | - Seniha Basaran
- Department of Infectious Diseases & Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, 34104, Turkey
| | - Atahan Cagatay
- Department of Infectious Diseases & Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, 34104, Turkey
| | - Haluk Eraksoy
- Department of Infectious Diseases & Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, 34104, Turkey
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22
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Chang D, Sharma L, Dela Cruz CS, Zhang D. Clinical Epidemiology, Risk Factors, and Control Strategies of Klebsiella pneumoniae Infection. Front Microbiol 2021; 12:750662. [PMID: 34992583 PMCID: PMC8724557 DOI: 10.3389/fmicb.2021.750662] [Citation(s) in RCA: 137] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 11/26/2021] [Indexed: 12/15/2022] Open
Abstract
Klebsiella species cause infections at multiple sites, including lung, urinary tract, bloodstream, wound or surgical site, and brain. These infections are more likely to occur in people with preexisting health conditions. Klebsiella pneumoniae (K. pneumoniae) has emerged as a major pathogen of international concern due to the increasing incidences of hypervirulent and carbapenem-resistant strains. It is imperative to understand risk factors, prevention strategies, and therapeutic avenues to treat multidrug-resistant Klebsiella infections. Here, we highlight the epidemiology, risk factors, and control strategies against K. pneumoniae infections to highlight the grave risk posed by this pathogen and currently available options to treat Klebsiella-associated diseases.
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Affiliation(s)
- De Chang
- Department of Pulmonary and Critical Care Medicine, The Third Medical Center of Chinese PLA General Hospital, Beijing, China
- College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing, China
| | - Lokesh Sharma
- Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, United States
| | - Charles S. Dela Cruz
- Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, United States
| | - Dong Zhang
- Department of Oncology, The Second Medical Center of Chinese PLA General Hospital, Beijing, China
- College of Tuberculosis Medicine, Chinese PLA General Hospital, Beijing, China
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Sabour S, Huang JY, Bhatnagar A, Gilbert SE, Karlsson M, Lonsway D, Lutgring JD, Rasheed JK, Halpin AL, Stanton RA, Gumbis S, Elkins CA, Brown AC. Detection and Characterization of Targeted Carbapenem-Resistant Health Care-Associated Threats: Findings from the Antibiotic Resistance Laboratory Network, 2017 to 2019. Antimicrob Agents Chemother 2021; 65:e0110521. [PMID: 34570648 PMCID: PMC8597727 DOI: 10.1128/aac.01105-21] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 09/20/2021] [Indexed: 11/20/2022] Open
Abstract
Carbapenemase gene-positive (CP) Gram-negative bacilli are of significant clinical and public health concern. Their rapid detection and containment are critical to preventing their spread and additional infections they can cause. To this end, CDC developed the Antibiotic Resistance Laboratory Network (AR Lab Network), in which public health laboratories across all 50 states, several cities, and Puerto Rico characterize clinical isolates of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB) and conduct colonization screens to detect the presence of mobile carbapenemase genes. In its first 3 years, the AR Lab Network tested 76,887 isolates and 31,001 rectal swab colonization screens. Targeted carbapenemase genes (blaKPC, blaNDM, blaOXA-48-like, blaVIM, or blaIMP) were detected by PCR in 35% of CRE, 2% of CRPA, and <1% of CRAB isolates and 8% of colonization screens tested, respectively. blaKPC and blaVIM were the most common genes in CP-CRE and CP-CRPA isolates, respectively, but regional differences in the frequency of carbapenemase genes detected were apparent. In CRE and CRPA isolates tested for carbapenemase production and the presence of the targeted genes, 97% had concordant results; 3% of CRE and 2% of CRPA isolates were carbapenemase production positive but PCR negative for those genes. Isolates harboring blaNDM showed the highest frequency of resistance across the carbapenems tested, and those harboring blaIMP and blaOXA-48-like genes showed the lowest frequency of carbapenem resistance. The AR Lab Network provides a national snapshot of rare and emerging carbapenemase genes, delivering data to inform public health actions to limit the spread of these antibiotic resistance threats.
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Affiliation(s)
- Sarah Sabour
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Jennifer Y. Huang
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Amelia Bhatnagar
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Sarah E. Gilbert
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Maria Karlsson
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - David Lonsway
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Joseph D. Lutgring
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - J. Kamile Rasheed
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Alison Laufer Halpin
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Richard A. Stanton
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Stephanie Gumbis
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Christopher A. Elkins
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Allison C. Brown
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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Multidrug-Resistant and Carbapenemase-Producing Enterobacteriaceae in Addis Ababa, Ethiopia. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9999638. [PMID: 34195291 PMCID: PMC8214486 DOI: 10.1155/2021/9999638] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/31/2021] [Accepted: 06/01/2021] [Indexed: 11/18/2022]
Abstract
Background The emergence and spread of multi-drug resistant (MDR) bacteria have become a public health problem in recent years. For the last many years, carbapenem antibiotics have been used successfully to treat infections caused by MDR Enterobacteriaceae. However, recently, Enterobacteriaceae producing carbapenemases have emerged, which confer broad resistance to most β-lactam antibiotics including carbapenems. Therefore, this study is aimed at determining the magnitude of MDR and carbapenemase-producing Enterobacteriaceae (CPE) isolated from various clinical specimens in Addis Ababa, Ethiopia. Methods A cross-sectional study was conducted from January to April 2018. A total of 312 Enterobacteriaceae isolates were identified from various clinical specimens. The Phoenix automated system (BD Phoenix100) was used for bacterial identification and antimicrobial susceptibility testing. Potential carbapenemase producers were confirmed by the modified carbapenem inactivation test, and KPC, MBL, and OXA-48 were phenotypically characterized by the disk diffusion method. The data obtained were entered and analyzed using SPSS version 20 software. Descriptive statistics, chi square, bivariate and multivariable logistic regression analyses were performed. P value ≤ 0.05 with corresponding 95% confidence interval was considered for statistical significance. Results A total of 312 Enterobacteriaceae were recovered. Of these isolates, 68.6% were MDR and 2.6% were CPE with different classes including OXA-48 1.6% (5/312), MBL 0.6% (2/312), and KPC and OXA-48 0.3% (1/312). The predominant bacterial isolates were E. coli 72.4% (226/312) followed by K. pneumoniae 13.8% (43/312). The antibiotic resistance rates of CPE isolates were significantly higher than other MDRE including ampicillin (100% versus 77.6%), cefoxitin (75% versus 20.6%), and piperacillin/tazobactam (50% versus 13.1%). Conclusion In this study, a relatively higher prevalence of MDR was observed, and the highest resistance was recorded against ampicillin, amoxicillin with clavulanic acid, and sulfamethoxazole-trimethoprim. Detection of CPE is important for implementing appropriate antimicrobial therapy and in controlling the spread of the infection. Furthermore, continuous screening and investigations, including genotypic characterization of CPE, are required for the prevention and control of the spread of antimicrobial-resistant pathogens.
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25
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Vasilakopoulou A, Karakosta P, Vourli S, Kalogeropoulou E, Pournaras S. Detection of KPC, NDM and VIM-Producing Organisms Directly from Rectal Swabs by a Multiplex Lateral Flow Immunoassay. Microorganisms 2021; 9:microorganisms9050942. [PMID: 33925719 PMCID: PMC8146855 DOI: 10.3390/microorganisms9050942] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 11/16/2022] Open
Abstract
We report a preliminary evaluation of the NG-Test CARBA 5 immunochromatographic assay for detecting carbapenemases directly from rectal swabs on the same day of sampling. Thirty fecal swabs were examined for carbapenemase-producing organisms (CPOs) by conventional culture, PCR, and NG-Test CARBA 5. Each sample was tested by the immunochromatographic assay five times, including direct testing and incubation in trypticase soy broth for 1, 2, 3, and 4 h. Twenty patients yielded CPOs by culture. Immunochromatographic and PCR results were concordant and detected the same 25 carbapenemases (11 KPC, 8 VIM, and 6 NDM). In five cases, we detected co-carriage of KPC and VIM. Compared with PCR, the sensitivity of NG-Test CARBA 5 for the detection of KPC, VIM, and NDM was 80% without incubation, 88% with one hour, 92% with two, and 100% with three hours incubation, while specificity was 100% for all time points. All samples containing adequate fecal content were detected by NG-Test CARBA 5 concordantly with PCR, without incubation. NG-Test CARBA 5 is a reliable test that rapidly detects the presence of carbapenemases at the same day of sampling, directly from rectal swabs. It thus provides early information to guide antimicrobial treatment and infection control interventions.
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Alebel M, Mekonnen F, Mulu W. Extended-Spectrum β-Lactamase and Carbapenemase Producing Gram-Negative Bacilli Infections Among Patients in Intensive Care Units of Felegehiwot Referral Hospital: A Prospective Cross-Sectional Study. Infect Drug Resist 2021; 14:391-405. [PMID: 33564247 PMCID: PMC7867495 DOI: 10.2147/idr.s292246] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 01/08/2021] [Indexed: 11/23/2022] Open
Abstract
Background Owing to the specific risk profile of its residents, intensive care units (ICUs) are the best place for selection pressure and the epicenter for resistance development and dissemination. Infections with β-lactamase releasing Gram-negative bacilli (GNB) at ICUs are an emerging global threat. This study dogged the magnitude of extended-spectrum β-lactamase (ESBL) and carbapenemase releasing Gram-negative bacilli infections and associated factors among patients in the ICUs of Felegehiwot Referral Hospital, Ethiopia. Methods A cross-sectional study was done through February to June 2020. Wound swabs, urine, blood and sputum samples were collected from patients in the ICUs symptomatic for infections while excluding those under coma and shock. Bacterial species were verified using standard microbiological methods. Carbapenemase and ESBL production were identified using modified carbapenem inactivation and combined disk diffusion methods, respectively. Multivariable analysis was calculated for factors associated with ESBL production. P-value < 0.05 was taken as cut-off for statistical significance. Results Out of 270 patients in the ICU, 67 (24.8%) and 14 (5.2%) had infections with ESBL and carbapenemase releasing GNB, respectively. The most frequent ESBL producing isolates were P. aeruginosa (100%), E. cloacae (100%), K. pneumoniae (82.8%) and E. coli (64%). The predominant carbapenemase producer isolates were K. pneumoniae (27.6%) and E. cloacae (33.3%). Overall, 77 (81.1%) of species were multi-drug resistant. All GNB species were 100% resistant to tetracycline and ampicillin. They are also resistant to cefuroxime, ceftazidime, sulfamethoxazole-trimethoprim and cefotaxime. Prior hospitalization (AOR = 5.5, CI = 2.63-11.46), support with medical care devices (AOR = 23.7, CI = 4.6-12) and arterial intravenous catheterization (AOR = 2.7, CI = 1.3-5.3) had significant association with β-lactamase producing GNB infection. Conclusion Infection with ESBL and carbapenemase producing Gram-negative bacilli linked with an alarming degree of multi-drug resistant isolates is a major healthcare threat among patients in ICUs. Hence, strict adherence to infection prevention practices and wise use of antibiotics are recommended to slow the spread of antimicrobial resistance.
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Affiliation(s)
- Mekonnen Alebel
- Department of Clinical Laboratory Science, Chagni Hospital, Chagni, Ethiopia
| | - Feleke Mekonnen
- Department of Medical Laboratory Science, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Wondemagegn Mulu
- Department of Medical Laboratory Science, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
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[Chinese guidelines for the clinical application of antibacterial drugs for agranulocytosis with fever (2020)]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2020; 41:969-978. [PMID: 33445842 PMCID: PMC7840550 DOI: 10.3760/cma.j.issn.0253-2727.2020.12.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Indexed: 12/13/2022]
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28
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Lee NY, Lo CL, Chen PL, Syue LS, Li CW, Li MC, Ko WC. Clinical impact of cefepime breakpoint in patients with carbapenem-resistant Klebsiella pneumoniae bacteraemia. Int J Antimicrob Agents 2020; 57:106250. [PMID: 33264671 DOI: 10.1016/j.ijantimicag.2020.106250] [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: 04/14/2020] [Revised: 11/16/2020] [Accepted: 11/22/2020] [Indexed: 01/09/2023]
Abstract
The application of cefepime breakpoint for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteraemia has not been explored. Adult cases of monomicrobial bloodstream infection (BSI) caused by cefepime-susceptible [minimum inhibitory concentration (MIC) ≤8 mg/L] K. pneumoniae isolates with carbapenem resistance between 2010 and 2015 were reviewed. Patients treated with cefepime were compared with those treated by other active agents using a propensity score-matched analysis to assess therapeutic effectiveness. The primary endpoint was 30-day crude mortality. A total of 114 patients experienced cefepime-susceptible CRKP bacteraemia and 40 (35.1%) died during hospitalisation. A total of 33 patients (28.9%) received cefepime therapy. Fifteen patients (13.2%) had BSI due to carbapenemase-producing isolates, and 86.7% (13/15) of carbapenemase-producing isolates were classified as cefepime susceptible dose-dependent (SDD). In the multivariate logistic regression analysis, 30-day mortality was independently associated with the presence of a critical illness [adjusted odds ratio (aOR) = 12.89, 95% confidence interval (CI) 3.88-42.83; P < 0.001], pneumonia (aOR = 5.97, 95% CI 1.65-21.76; P = 0.007) and rapidly fatal underlying disease (aOR = 6.43, 95% CI 1.30-31.09; P = 0.02). In contrast, cefepime-based therapy (aOR = 0.03, 95% CI 0.003-0.38; P = 0.006) and combination therapy (aOR = 0.09, 95% CI 0.02-0.36; P = 0.001) were protective against a fatal outcome. Based on current breakpoints for Enterobacterales, cefepime therapy was not associated with an unfavourable outcome for CRKP BSI with MIC-based dosing strategies. However, the susceptibility result of SDD to cefepime should alert clinicians for possible therapeutic failure.
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Affiliation(s)
- Nan-Yao Lee
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ching-Lung Lo
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Po-Lin Chen
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ling-Shan Syue
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Wen Li
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Chi Li
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Chien Ko
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Carbapenemase-producing Enterobacterales: changing epidemiology in a highly endemic Italian area. J Hosp Infect 2020; 108:221-223. [PMID: 33127457 DOI: 10.1016/j.jhin.2020.10.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 10/24/2020] [Accepted: 10/24/2020] [Indexed: 12/29/2022]
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Mateos M, Hernández-García M, Del Campo R, Martínez-García L, Gijón D, Morosini MI, Ruiz-Garbajosa P, Cantón R. Emergence and Persistence over Time of Carbapenemase-Producing Enterobacter Isolates in a Spanish University Hospital in Madrid, Spain (2005-2018). Microb Drug Resist 2020; 27:895-903. [PMID: 33090918 DOI: 10.1089/mdr.2020.0265] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Carbapenemase production is constantly increasing among different Enterobacterales species. We analyzed the microbiological characteristics and population structure of all carbapenemase-producing Enterobacter spp. (CP-Ent) isolates recovered at the Ramón y Cajal Hospital between 2005 and 2018. Overall, 178 CP-Ent isolates (60.7% colonization, 39.3% clinical) were recovered from 165 hospitalized patients (165/176, 93.7%; medical [102/165], surgical [34/165], and intensive care unit [29/165] areas), emergency unit (4/176, 2.3%), and ambulatory patients (7/176, 4.0%). In addition, three CP-Ent were found in environmental sources. Clinical samples were mainly urine (37.1%). The most frequent matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)-identified species were Enterobacter cloacae (n = 85) and Enterobacter asburiae (n = 49). hsp60 gene sequencing showed a higher species diversity than MALDI-TOF: 70 Enterobacter hormaechei-clusters III, VI, VIII; 69 Enterobacter roggenkampii-IV; 15 Enterobacter kobei-II; 9 E. asburiae-I; 3 Enterobacter ludwigii-V; and 1 E. cloacae subsp. dissolvens-XII. Nine Klebsiella aerogenes were also identified. Overall, a high clonal diversity (Simpson Diversity Index >0.90) was found among CP-Ent-clusters. Environmental isolates were clonally related to clinical ones. Amikacin and tigecycline showed the highest susceptibility (>93%). VIM-1 (n = 133/181, 73.5%) and OXA-48 (n = 34/181, 18.8%) carbapenemases were predominant, followed by KPC-2 (n = 9/181, 5.0%), KPC-3 (n = 2/181, 1.1%), VIM-2 (n = 1/181, 0.6%), and two coproducers (VIM-1+KPC-2 and VIM-1+KPC-3). Extended-spectrum beta-lactamase (ESBL) coproduction (14.4%) emerged in 2012, mainly associated with blaSHV-12 (p < 0.001), E. roggenkampii (p < 0.001), and colonization (p = 0.03). VIM-1- and OXA-48-CP-Ent fecal carriers increased in our hospital, particularly between 2011 and 2018 (p < 0.001). Moreover, KPC and OXA-48 producers emerged in 2010 and 2012, respectively. They superimposed over VIM producers, which were persistently recovered since first detection in 2005. These results depict increased complexity over time of CP-Ent.
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Affiliation(s)
- Miriam Mateos
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Marta Hernández-García
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Rosa Del Campo
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Laura Martínez-García
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Desirée Gijón
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - María Isabel Morosini
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Patricia Ruiz-Garbajosa
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Rafael Cantón
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
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31
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Gelmez GA, Can B, Hasdemir U, Soyletir G. Evaluation of two commercial methods for rapid detection of the carbapenemase-producing Klebsiella pneumoniae. J Microbiol Methods 2020; 178:106084. [PMID: 33049329 DOI: 10.1016/j.mimet.2020.106084] [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: 05/05/2020] [Revised: 09/24/2020] [Accepted: 10/06/2020] [Indexed: 11/21/2022]
Abstract
In this study, we evaluated the performance of the two commercial methods (Rapidec Carba NP and NG-Test Carba-5) for the rapid detection of carbapenemase-producing Klebsiella pneumoniae. A total of 224 Klebsiella pneumoniae strains previously characterized for carbapenemase genes by polymerase chain reaction were included in the study. The strain collection included 30 non-carbapenemase producers, 85 OXA-48-like, 59 NDM, 14 IMP, 7 KPC, 7 VIM, 19 OXA-48-like plus NDM, and 3 KPC plus NDM producers. Rapidec Carba NP and NG-Test Carba 5 was performed according to the manufacturer's instructions. NG-Test Carba 5 correctly detected all carbapenemase-producing K. pneumoniae, however, Rapidec Carba NP failed to detect 41% of OXA-48-like producers even with extended incubation time. The overall sensitivity and specificity were 81,9% and 100% for Rapidec Carba NP, 100% and 100% for NG-Test Carba 5, respectively. Both tests seem to be fast and reliable for the detection of carbapenemase-producing K. pneumoniae especially for microbiology laboratories where molecular tests cannot be performed. However, Rapidec Carba NP with weak hydrolysis activity for OXA-48 like might be used in regions where OXA-48 is not prevalent. The additional advantage of NG-Test Carba 5 is that it specifically detects carbapenemases giving way to threat-related infections with an effective drug such as ceftazidime-avibactam or meropenem- vaborbactam.
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Affiliation(s)
| | - Barıs Can
- Marmara University Pendik Training and Research Hospital, Medical Microbiology Laboratory, Istanbul, Turkey
| | - Ufuk Hasdemir
- Marmara University School of Medicine, Department of Medical Microbiology, Istanbul, Turkey
| | - Guner Soyletir
- Marmara University School of Medicine, Department of Medical Microbiology, Istanbul, Turkey
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Gelmez GA, Can B, Hasdemir U, Soyletir G. Evaluation of phenotypic tests for detection of carbapenemases: New modifications with new interpretation. J Infect Chemother 2020; 27:226-231. [PMID: 33008736 DOI: 10.1016/j.jiac.2020.09.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 08/15/2020] [Accepted: 09/17/2020] [Indexed: 01/08/2023]
Abstract
INTRODUCTION The emergence and spread of carbapenemase-producing Enterobacterales (CPE) is a worldwide public health threat. Rapid and accurate detection of CPE is essential to prevent their dissemination within health care settings. The aim of this study was to evaluate the performance of CIM, mCIM and mCIM with ammonium bicarbonate (mCIM-A) methods by using different interpretation criteria for detection of carbapenemases. METHODS One hundred and fifty-three Klebsiella pneumoniae isolates previously characterized by molecular tests, including 133 carbapenemase producers and 20 non-carbapenemase producers, were collected in this study. CIM and mCIM tests were performed as described previously. mCIM-A by adding 50 mM ammonium bicarbonate to the bacterial suspension prepared in tryptic soy broth. The inhibition zone diameter of around meropenem disc was measured and interpreted as positive according to i) Pierce and colleagues (<19 mm), ii) EUCAST meropenem susceptibility breakpoint (<22). RESULTS CIM, although seems to be good for carbapenemases other than OXA-48-like and NDM, is not satisfactory (42.3% and 83.4%, respectively) for those enzymes with any of the interpretation criteria. OXA-48-like and NDM were detected with a better performance (88.7% and 92.8, respectively) with mCIM when results were interpreted according to <22 mm zone diameter for OXA-48-like and NDM. The best results were obtained with mCIM-A using <22 mm criteria without any difference in the results of other enzymes and negative strains. CONCLUSIONS mCIM-A method interpreted with <22 mm meropenem zone diameter seems to be preferable compared to CIM and mCIM. mCIM-A is simple and useful tool for identification of CPEs in clinical microbiology laboratories.
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Affiliation(s)
| | - Baris Can
- Marmara University Pendik Training and Research Hospital, Medical Microbiology Laboratory, Istanbul, Turkey
| | - Ufuk Hasdemir
- Marmara University School of Medicine, Department of Medical Microbiology, Istanbul, Turkey
| | - Guner Soyletir
- Marmara University School of Medicine, Department of Medical Microbiology, Istanbul, Turkey
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Zalas-Więcek P, Gospodarek-Komkowska E, Smalczewska A. Rapid Detection of Genes Encoding Extended-Spectrum Beta-Lactamase and Carbapenemase in Clinical Escherichia coli Isolates with eazyplex SuperBug CRE System. Microb Drug Resist 2020; 26:1245-1249. [DOI: 10.1089/mdr.2019.0311] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Affiliation(s)
- Patrycja Zalas-Więcek
- Department of Microbiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Dr Antoni Jurasz University Hospital No 1, Bydgoszcz, Poland
| | - Eugenia Gospodarek-Komkowska
- Department of Microbiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Dr Antoni Jurasz University Hospital No 1, Bydgoszcz, Poland
| | - Agata Smalczewska
- Student Research Club at Department of Microbiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
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Ota K, Kaku N, Yanagihara K. Efficacy of meropenem and amikacin combination therapy against carbapenemase-producing Klebsiella pneumoniae mouse model of pneumonia. J Infect Chemother 2020; 26:1237-1243. [PMID: 32868198 DOI: 10.1016/j.jiac.2020.07.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 05/27/2020] [Accepted: 07/08/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) is a global health problem due to its high mortality and limited treatment options. Combination antimicrobial therapy is reported to be effective against CRE in vitro; however, its efficacy in vivo has not been thoroughly evaluated. Thus, this study assessed the efficacy of combination therapy of meropenem (MEPM) and amikacin (AMK) in a carbapenem-resistant Klebsiella pneumoniae (CR-Kp) mouse model of pneumonia. MATERIALS AND METHODS Agar-based bacterial suspension of CR-Kp clinical isolates was inoculated into the trachea of BALB/c mice. Treatment was initiated 6 h post infection, with 100 mg/kg MEPM every 6 h, 100 mg/kg AMK every 12 h, or in combination; survival was evaluated for 7 days. The number of viable bacteria in the lungs, lung histopathology, and neutrophil counts in broncho-alveolar lavage fluid (BALF) were evaluated 42 h after infection. RESULTS All mice in the untreated control group died in 48 h, while all the mice in treatment groups survived past 7 days following infection. The bacterial count in the lungs (log10 CFU/mL, mean ± SEM) in the combination group (2.00 ± 0.00) decreased significantly compared to that in control (10.19 ± 0.11, p < 0.0001), MEPM (6.38 ± 0.17, p < 0.0001), and AMK (6.17 ± 0.16, p < 0.0001) groups. BALF neutrophil count reduced only in the combination therapy group. Combination therapy prevented the progression of lung inflammation, including alveolar neutrophil infiltration and hemorrhage. CONCLUSIONS This study demonstrates in vivo efficacy of MEPM and AMK combination therapy against CR-Kp pneumonia.
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Affiliation(s)
- Kenji Ota
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan
| | - Norihito Kaku
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan
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Jakovac S, Goić-Barišić I, Pirija M, Kovačić A, Hrenović J, Petrović T, Tutiš B, Tonkić M. Molecular Characterization and Survival of Carbapenem-Resistant Acinetobacter baumannii Isolated from Hospitalized Patients in Mostar, Bosnia and Herzegovina. Microb Drug Resist 2020; 27:383-390. [PMID: 32721271 DOI: 10.1089/mdr.2020.0163] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Increasingly difficult treatment of multidrug-resistant (MDR) bacteria has become a global problem of the 21st century. Within a group of multiresistant bacteria, the Acinetobacter baumannii convincingly occupies the position at the top of the group designated as ESKAPE pathogens. In this study, 61 isolates of A. baumannii were recovered from different samples originating from various departments of the University Clinical Hospital Mostar during 2018. All of the isolates were identified using conventional phenotypic methods and the VITEK® 2 Compact System, and were confirmed by MALDI-TOF mass spectrometry. The minimum inhibitory concentrations (MICs) were determined by the microbroth dilution method using MICRONAUT-S MDR MRGN-Screening and VITEK 2 Compact System. All strains were resistant to carbapenems and classified in eight different resistotypes according to their antibiotic resistance and macrorestriction pulsed-field gel electrophoresis profiles, with all belonging to IC II. One isolate displayed resistance to colistin (MIC ≥16 mg/L). The presence of blaOXA genes encoding OXA-type carbapenemases was investigated by multiplex PCR and the Eazyplex® SuperBugAcineto system and showed 100% compatibility with the detection of acquired oxacillinases. Molecular characterization of the isolates tested in this study revealed the OXA-23- and OXA-40-like groups of acquired oxacillinases. Sequencing of two PCR products of the OXA-40-like group confirmed the presence of OXA-72. Survival assays with two selected isolates of A. baumannii encoding different mechanisms of carbapenem resistance revealed that one isolate was able to survive on a fragment of white laboratory coat during 90 days of monitoring. To the best of our knowledge, this is the first article to present the results of a comprehensive phenotypic, genotypic, and molecular analysis of A. baumannii isolates from the leading clinical hospital center in the southwestern part of Bosnia and Herzegovina, including data for the survival of this pathogen on the white laboratory coats used as compulsory medical clothing.
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Affiliation(s)
- Sanja Jakovac
- Institute for Microbiological Diagnostics, University Clinical Hospital Mostar and School of Medicine University of Mostar, Mostar, Bosnia and Herzegovina
| | - Ivana Goić-Barišić
- University Hospital of Split and University of Split School of Medicine, Split, Croatia
| | - Mario Pirija
- Department of Clinical Microbiology, University Hospital of Split, Split, Croatia
| | - Ana Kovačić
- Institute of Public Health of Split and Dalmatia Country, Split, Croatia
| | - Jasna Hrenović
- Department of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia
| | - Tanja Petrović
- Institute for Microbiological Diagnostics, University Clinical Hospital Mostar and School of Medicine University of Mostar, Mostar, Bosnia and Herzegovina
| | - Borka Tutiš
- University Clinical Hospital Mostar, Mostar, Bosnia and Herzegovina
| | - Marija Tonkić
- University Hospital of Split and University of Split School of Medicine, Split, Croatia
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Kumudunie WGM, Wijesooriya LI, Namalie KD, Sunil-Chandra NP, Wijayasinghe YS. Epidemiology of multidrug-resistant Enterobacteriaceae in Sri Lanka: First evidence of bla KPC harboring Klebsiella pneumoniae. J Infect Public Health 2020; 13:1330-1335. [PMID: 32439355 DOI: 10.1016/j.jiph.2020.04.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 04/16/2020] [Accepted: 04/19/2020] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-PE) and carbapenem-resistant Enterobacteriaceae (CRE) are disseminated worldwide posing a serious public health concern. Although, the presence of ESBL-PE and CRE in Sri Lanka has been reported, the prevalence is unknown. This study aimed to provide up-to-date epidemiological data on multidrug-resistant Enterobacteriaceae and to characterize the molecular determinants of carbapenemase-producing Enterobacteriaceae (CPE) in Sri Lanka. METHODS A prospective cross-sectional study was conducted at a tertiary care hospital in Sri Lanka between December 2017 and February 2018. ESBL-PE and CRE were identified by disc diffusion method. Carbapenemase production was determined by carbapenem inactivation method and the presence of selected carbapenemase genes were detected by PCR. RESULTS Five hundred and ninety three Enterobacteriaceae were isolated from variety of clinical samples. Overall prevalence of ESBL-PE and CRE were 26.0% (n = 154) and 9.6% (n = 57), respectively. The highest rate of ESBL-PE (30.8%) was found in urine samples, while the highest occurrence of CRE (20.8%) was seen in respiratory specimens. The most common CRE species identified was K. pneumoniae (n = 46, 80.7%), followed by C. freundii (n = 4, 7.0%), E. coli (n = 3, 5.3%), P. rettgeri (n = 2, 3.5%), E. cloacae (n = 1, 1.7%), and K. aerogenes (n = 1, 1.7%). Carbapenemase production was observed in 54 (94.7%) of CRE isolates. Fifty eight carbapenemase encoding genes were identified in 54 CPE. The most prevalent carbapenemase gene was blaOXA-48-like (n = 48, 88.9%), followed by blaNDM (n = 8, 14.8%), and blaKPC (n = 2, 3.7%). CONCLUSION This study reports an alarming rate of CRE and the emergence of blaKPC harboring K. pneumoniae in Sri Lanka. The need for preventive measures is highlighted to limit the spread of these difficult-to-treat bacteria in the country.
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Wong YL, Kang WCM, Reyes M, Teo JWP, Kah JCY. Rapid Detection of Carbapenemase-Producing Enterobacteriacae Based on Surface-Enhanced Raman Spectroscopy with Gold Nanostars. ACS Infect Dis 2020; 6:947-953. [PMID: 32191032 DOI: 10.1021/acsinfecdis.9b00318] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The emergence and rapid spread of antibiotic resistance poses a serious threat to healthcare systems across the globe. The existence of carbapenemase-producing Enterobacteriaceae (CPE) such as Klebsiella pneumoniae renders the use of carbapenems, the last-resort class of β-lactam antibiotics, ineffective against bacterial infections, often leading to CPE-associated mortalities. Current methods of detection such as the Carba NP test and modified Hodge's test require hours to days to detect, which delays the response to isolate patients for rapid intervention. Here, we developed a surface-enhanced Raman scattering (SERS)-based detection scheme which utilizes gold nanostars conjugated to a β-lactam antibiotic ceftriaxone (CRO) as a beacon for rapid detection of bacterial β-lactamase secreted by Delhi metalloproteinase (NDM)-producing Escherichia coli as our CPE model with carbapenemase activity. The cleavage of β-lactam ring in CRO by NDM (Class B β-lactamase) caused a detectable reduction in SERS intensities at 722, 1358, and 1495 cm-1 within 25 min. Ratiometric analysis of the SERS peaks at 722, 1358, and 1495 cm-1 normalized against the Raman peak of polystyrene cuvette at 620 cm-1 showed the peak at 1358 cm-1 having the most significant change in intensity upon CPE detection. This reduced detection time has not been reported to date for CPE detection, and our novel approach using SERS could be extended to detect the activity of other classes of β-lactamases to broaden its clinical utility.
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Affiliation(s)
- Yen Lynn Wong
- Department of Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3, Blk E4, #04-08, Singapore 117583
| | - Wei Cherng Malvin Kang
- NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, University Hall, Tan Chin Tuan Wing, Level 04, #04-02, 21 Lower Kent Ridge, Singapore 119077
| | - Miguel Reyes
- Department of Materials Science and Engineering, National University of Singapore, 9 Engineering Drive 1, Blk EA, #03-09, Singapore 117575
| | - Jeanette Woon Pei Teo
- Department of Laboratory Medicine, National University Health System, 1E Kent Ridge Road, Singapore 119228
| | - James Chen Yong Kah
- Department of Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3, Blk E4, #04-08, Singapore 117583
- NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, University Hall, Tan Chin Tuan Wing, Level 04, #04-02, 21 Lower Kent Ridge, Singapore 119077
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Vasilakopoulou A, Karakosta P, Vourli S, Tarpatzi A, Varda P, Kostoula M, Antoniadou A, Pournaras S. Gastrointestinal Carriage of Vancomycin-Resistant Enterococci and Carbapenem-Resistant Gram-Negative Bacteria in an Endemic Setting: Prevalence, Risk Factors, and Outcomes. Front Public Health 2020; 8:55. [PMID: 32257988 PMCID: PMC7093565 DOI: 10.3389/fpubh.2020.00055] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 02/14/2020] [Indexed: 11/13/2022] Open
Abstract
Background: Gastrointestinal carriage of vancomycin-resistant enterococci (VRE) and carbapenem-resistant Gram-negative bacteria (CRGN) constitutes a major public health concern as it may be followed by clinical infection development or lead to intra-hospital dissemination. Detection of carriers and implementation of infection control measures are essential in every hospital. In this study we determined the point prevalence of VRE and CRGN in the fecal flora of the inpatients of a tertiary university hospital in Greece. We determined risk factors for carriage and examined the impact of carriage on hospital outcomes. Materials/Methods: A point prevalence study of VRE/CRGN rectal carriage of inpatients was conducted on March 2018. Specimens were selectively cultured for VRE/CRGN, microorganisms were biochemically identified, submitted to antibiotic susceptibility testing, and tested for carbapenemase production. Data on potential risk factors and hospital outcomes were collected at the time of culture and until hospital discharge. Multivariable logistic and linear regression models were used, adjusting for confounders. Results: Four hundred ninety-one patients were enrolled in the study. Of them, 64 (13.0%) were positive for VRE carriage, 40 (8.2%) for CRGN, and 10 patients (2.1%) for both VRE and CRGN. VRE carriage was independently associated with age over 65 years (adjusted OR: 2.4 [95%CI: 1.3, 4.5]) and length of stay (LOS) before rectal sampling (OR: 1.1 [95%CI: 1.0, 1.1]). Carriage of CRGN was associated with 11 days increase of LOS after rectal sampling (β-coef: 11.4 [95%CI: 1.6, 21.2]), with a 3.5-fold increased risk of acquiring a resistant pathogen after rectal swabbing (RR: 3.5 [95%CI 1.2, 9.9]) and with a 6-fold increased risk of mortality (RR: 6.1 [95%CI: 2.1, 17.9]), after adjusting for sex, age, and comorbidity index. Conclusions: High prevalence rates were found for VRE and CRGN carriage among the inpatients of our hospital. Prolonged hospitalization and age were independent risk factors for VRE carriage, while CRGN carriage was associated with increased risk of acquiring a resistant pathogen, prolonged hospital stay, and increased mortality.
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Affiliation(s)
- Alexandra Vasilakopoulou
- Clinical Microbiology Laboratory, Medical School, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Polyxeni Karakosta
- Clinical Microbiology Laboratory, Medical School, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Sophia Vourli
- Clinical Microbiology Laboratory, Medical School, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece.,Infection Control Committee, Attikon University General Hospital, Athens, Greece
| | - Aikaterini Tarpatzi
- Clinical Microbiology Laboratory, Medical School, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece.,Infection Control Committee, Attikon University General Hospital, Athens, Greece
| | - Paraskevi Varda
- Infection Control Committee, Attikon University General Hospital, Athens, Greece
| | - Maria Kostoula
- Infection Control Committee, Attikon University General Hospital, Athens, Greece
| | - Anastasia Antoniadou
- Infection Control Committee, Attikon University General Hospital, Athens, Greece.,4th Department of Internal Medicine, Medical School, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Spyros Pournaras
- Clinical Microbiology Laboratory, Medical School, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece.,Infection Control Committee, Attikon University General Hospital, Athens, Greece
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Miltgen G, Cholley P, Martak D, Thouverez M, Seraphin P, Leclaire A, Traversier N, Roquebert B, Jaffar-Bandjee MC, Lugagne N, Cimon CB, Ramiandrisoa M, Picot S, Lignereux A, Masson G, Allyn J, Allou N, Mavingui P, Belmonte O, Bertrand X, Hocquet D. Carbapenemase-producing Enterobacteriaceae circulating in the Reunion Island, a French territory in the Southwest Indian Ocean. Antimicrob Resist Infect Control 2020; 9:36. [PMID: 32075697 PMCID: PMC7031992 DOI: 10.1186/s13756-020-0703-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 02/14/2020] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND The spread of carbapenemase-producing Enterobacteriaceae (CPE) in the Southwest Indian Ocean area (SIOA) is poorly documented. Reunion Island is a French overseas territory located close to Madagascar and connected with Southern Africa, Indian sub-continent and Europe, with several weekly flights. Here we report the results of the CPE surveillance program in Reunion Island over a six-year period. METHODS All CPE were collected between January 2011 and December 2016. Demographics and clinical data of the carrier patients were collected. We determined their susceptibility to antimicrobials, identified the carbapenemases and ESBL by PCR and sequencing, and explored their genetic relationship using pulsed-field gel electrophoresis and multi-locus sequence typing. RESULTS A total of 61 CPEs isolated from 53 patients were retrieved in 6 public or private laboratories of the island. We found that 69.8% of CPE patients were linked to a foreign country of SIOA and that almost half of CPE cases (47.2%) reached the island through a medical evacuation. The annual number of CPE cases strongly increased over the studied period (one case in 2011 vs. 21 cases in 2016). A proportion of 17.5% of CPE isolates were non-susceptible to colistin. blaNDM was the most frequent carbapenemase (79.4%), followed by blaIMI (11.1%), and blaIMP-10 (4.8%). Autochtonous CPE cases (30.2%) harboured CPE isolates belonging to a polyclonal population. CONCLUSIONS Because the hospital of Reunion Island is the only reference healthcare setting of the SIOA, we can reasonably estimate that its CPE epidemiology reflects that of this area. Mauritius was the main provider of foreign CPE cases (35.5%). We also showed that autochthonous isolates of CPEs are mostly polyclonal, thus unrelated to cross-transmission. This demonstrates the local spread of carbapenemase-encoding genes (i.e. blaNDM) in a polyclonal bacterial population and raises fears that Reunion Island could contribute to the influx of NDM-carbapenemase producers into the French mainland territory.
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Affiliation(s)
- Guillaume Miltgen
- Laboratoire de Bactériologie, CHU Félix Guyon, Allée des Topazes, 97400, Saint-Denis, La Réunion, France. .,UMR Processus Infectieux en Milieu Insulaire Tropical, CNRS 9192, INSERM U1187, IRD 249, Université de La Réunion, Sainte-Clotilde, La Réunion, France.
| | - Pascal Cholley
- Laboratoire d'Hygiène Hospitalière, CHRU Jean Minjoz, Besançon, France.,UMR Chrono-Environnement, CNRS 6249, Université de Bourgogne Franche-Comté, Besançon, France
| | - Daniel Martak
- Laboratoire d'Hygiène Hospitalière, CHRU Jean Minjoz, Besançon, France.,UMR Chrono-Environnement, CNRS 6249, Université de Bourgogne Franche-Comté, Besançon, France
| | | | - Paul Seraphin
- Laboratoire de Bactériologie, CHU Félix Guyon, Allée des Topazes, 97400, Saint-Denis, La Réunion, France
| | - Alexandre Leclaire
- Laboratoire de Bactériologie, CHU Félix Guyon, Allée des Topazes, 97400, Saint-Denis, La Réunion, France
| | - Nicolas Traversier
- Laboratoire de Bactériologie, CHU Félix Guyon, Allée des Topazes, 97400, Saint-Denis, La Réunion, France
| | - Bénédicte Roquebert
- Laboratoire de Bactériologie, CHU Félix Guyon, Allée des Topazes, 97400, Saint-Denis, La Réunion, France.,UMR Processus Infectieux en Milieu Insulaire Tropical, CNRS 9192, INSERM U1187, IRD 249, Université de La Réunion, Sainte-Clotilde, La Réunion, France
| | - Marie-Christine Jaffar-Bandjee
- Laboratoire de Bactériologie, CHU Félix Guyon, Allée des Topazes, 97400, Saint-Denis, La Réunion, France.,UMR Processus Infectieux en Milieu Insulaire Tropical, CNRS 9192, INSERM U1187, IRD 249, Université de La Réunion, Sainte-Clotilde, La Réunion, France
| | - Nathalie Lugagne
- Service d'hygiène hospitalière, CHU Félix Guyon, Saint-Denis, La Réunion, France
| | | | | | - Sandrine Picot
- Laboratoire de Bactériologie, Groupe Hospitalier Sud Réunion, Saint-Pierre, La Réunion, France
| | - Anne Lignereux
- Laboratoire de biologie, Centre Hospitalier Gabriel Martin, Saint-Paul, La Réunion, France
| | - Geoffrey Masson
- Laboratoire de biologie, Groupe Hospitalier Est Réunion, Saint-Benoit, La Réunion, France
| | - Jérôme Allyn
- Service de Réanimation polyvalente. Département d'Informatique clinique, CHU Félix Guyon, Saint-Denis, La Réunion, France
| | - Nicolas Allou
- Service de Réanimation polyvalente. Département d'Informatique clinique, CHU Félix Guyon, Saint-Denis, La Réunion, France
| | - Patrick Mavingui
- UMR Processus Infectieux en Milieu Insulaire Tropical, CNRS 9192, INSERM U1187, IRD 249, Université de La Réunion, Sainte-Clotilde, La Réunion, France
| | - Olivier Belmonte
- Laboratoire de Bactériologie, CHU Félix Guyon, Allée des Topazes, 97400, Saint-Denis, La Réunion, France
| | - Xavier Bertrand
- Laboratoire d'Hygiène Hospitalière, CHRU Jean Minjoz, Besançon, France.,UMR Chrono-Environnement, CNRS 6249, Université de Bourgogne Franche-Comté, Besançon, France
| | - Didier Hocquet
- Laboratoire d'Hygiène Hospitalière, CHRU Jean Minjoz, Besançon, France.,UMR Chrono-Environnement, CNRS 6249, Université de Bourgogne Franche-Comté, Besançon, France
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Integrating multiple genomic technologies to investigate an outbreak of carbapenemase-producing Enterobacter hormaechei. Nat Commun 2020; 11:466. [PMID: 31980604 PMCID: PMC6981164 DOI: 10.1038/s41467-019-14139-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Accepted: 12/02/2019] [Indexed: 12/19/2022] Open
Abstract
Carbapenem-resistant Enterobacteriaceae (CRE) represent an urgent threat to human health. Here we report the application of several complementary whole-genome sequencing (WGS) technologies to characterise a hospital outbreak of blaIMP-4 carbapenemase-producing E. hormaechei. Using Illumina sequencing, we determined that all outbreak strains were sequence type 90 (ST90) and near-identical. Comparison to publicly available data linked all outbreak isolates to a 2013 isolate from the same ward, suggesting an environmental source in the hospital. Using Pacific Biosciences sequencing, we resolved the complete context of the blaIMP-4 gene on a large IncHI2 plasmid carried by all IMP-4-producing strains across different hospitals. Shotgun metagenomic sequencing of environmental samples also found evidence of ST90 E. hormaechei and the IncHI2 plasmid within the hospital plumbing. Finally, Oxford Nanopore sequencing rapidly resolved the true relationship of subsequent isolates to the initial outbreak. Overall, our strategic application of three WGS technologies provided an in-depth analysis of the outbreak. Antibiotic-resistant bacteria are an urgent threat to human health. Here, Roberts et al. characterise and monitor an ongoing hospital outbreak of carbapenemase-producing Enterobacter hormaechei by integrating several technologies for whole-genome sequencing and shotgun metagenomics.
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41
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Barman S, Mukherjee S, Ghosh S, Haldar J. Amino-Acid-Conjugated Polymer-Rifampicin Combination: Effective at Tackling Drug-Resistant Gram-Negative Clinical Isolates. ACS APPLIED BIO MATERIALS 2019; 2:5404-5414. [DOI: 10.1021/acsabm.9b00732] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Swagatam Barman
- Antimicrobial Research Laboratory, New Chemistry Unit and School of Advanced Materials, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560064, Karnataka, India
| | - Sudip Mukherjee
- Antimicrobial Research Laboratory, New Chemistry Unit and School of Advanced Materials, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560064, Karnataka, India
| | - Sreyan Ghosh
- Antimicrobial Research Laboratory, New Chemistry Unit and School of Advanced Materials, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560064, Karnataka, India
| | - Jayanta Haldar
- Antimicrobial Research Laboratory, New Chemistry Unit and School of Advanced Materials, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560064, Karnataka, India
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42
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Foschi C, Gaibani P, Lombardo D, Re MC, Ambretti S. Rectal screening for carbapenemase-producing Enterobacteriaceae: a proposed workflow. J Glob Antimicrob Resist 2019; 21:86-90. [PMID: 31639545 DOI: 10.1016/j.jgar.2019.10.012] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 10/10/2019] [Accepted: 10/14/2019] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVES Active screening is a crucial element for the prevention of carbapenemase-producing Enterobacteriaceae (CPE) transmission in healthcare settings. Here we propose a culture-based protocol for rectal swab CPE screening that combines CPE detection with identification of the carbapenemase type. METHODS The workflow integrates an automatic digital analysis of selective chromogenic media (WASPLab®; Copan), with subsequent rapid tests for the confirmation of carbapenemase production [i.e. detection of Klebsiella pneumoniae carbapenemase (KPC)-specific peak by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) or a multiplex immunochromatographic assay identifying the five commonest carbapenemase types]. To evaluate the performance of this protocol in depth, data for 21 162 rectal swabs submitted for CPE screening to the Microbiology Unit of S. Orsola-Malpighi Hospital (Bologna, Italy) were analysed. RESULTS Considering its ability to correctly segregate plates with/without Enterobacteriaceae, WASPLab Image Analysis Software showed globally a sensitivity and specificity of 100% and 79.4%, respectively. Of the plates with bacterial growth (n = 901), 693 (76.9%) were found to be positive for CPE by MALDI-TOF/MS (KPC-specific peak for K. pneumoniae) or by immunochromatographic assay. Only 2.8% (16/570) of KPC-positive K. pneumoniae strains were missed by the specific MALDI-TOF/MS algorithm, being detected by the immunochromatographic assay. The mean turnaround time needed from sample arrival to the final report ranged between 18 and 24 h, representing a significant time saving compared with manual reading. CONCLUSION This workflow proved to be fast and reliable, being particularly suitable for areas endemic for KPC-producing K. pneumoniae and for high-throughput laboratories.
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Affiliation(s)
- Claudio Foschi
- Microbiology Unit, DIMES, University of Bologna, via Massarenti 9, Bologna, Italy; Microbiology Unit, S. Orsola-Malpighi Hospital, Via Massarenti 9, Bologna, Italy.
| | - Paolo Gaibani
- Microbiology Unit, S. Orsola-Malpighi Hospital, Via Massarenti 9, Bologna, Italy
| | - Donatella Lombardo
- Microbiology Unit, S. Orsola-Malpighi Hospital, Via Massarenti 9, Bologna, Italy
| | - Maria Carla Re
- Microbiology Unit, DIMES, University of Bologna, via Massarenti 9, Bologna, Italy; Microbiology Unit, S. Orsola-Malpighi Hospital, Via Massarenti 9, Bologna, Italy
| | - Simone Ambretti
- Microbiology Unit, S. Orsola-Malpighi Hospital, Via Massarenti 9, Bologna, Italy
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Schneider A, Coope C, Michie S, Puleston R, Hopkins S, Oliver I. Implementing a toolkit for the prevention, management and control of carbapenemase-producing Enterobacteriaceae in English acute hospitals trusts: a qualitative evaluation. BMC Health Serv Res 2019; 19:689. [PMID: 31606053 PMCID: PMC6790044 DOI: 10.1186/s12913-019-4492-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 08/29/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Antimicrobial resistance is an increasing problem in hospitals world-wide. Following other countries, English hospitals experienced outbreaks of carbapenemase-producing Enterobacteriaceae (CPE), a bacterial infection commonly resistant to last resort antibiotics. One way to improve CPE prevention, management and control is the production of guidelines, such as the CPE toolkit published by Public Health England in December 2013. The aim of this research was to investigate the implementation of the CPE toolkit and to identify barriers and facilitators to inform future policies. METHODS Acute hospital trusts (N = 12) were purposively sampled based on their self-assessed CPE colonisation rates and time point of introducing local CPE action plans. Following maximum variation sampling, 44 interviews with hospital staff were conducted between April and August 2017 using a semi-structured topic guide based on the Capability, Opportunity, Motivation and Behaviour Model and the Theoretical Domains Framework, covering areas of influences on behaviour. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS The national CPE toolkit was widely disseminated within infection prevention and control teams (IPCT), but awareness was rare among other hospital staff. Local plans, developed by IPCTs referring to the CPE toolkit while considering local circumstances, were in place in all hospitals. Implementation barriers included: shortage of isolation facilities for CPE patients, time pressures, and competing demands. Facilitators were within hospital and across-hospital collaborations and knowledge sharing, availability of dedicated IPCTs, leadership support and prioritisation of CPE as an important concern. Participants using the CPE toolkit had mixed views, appreciating its readability and clarity about patient management, but voicing concerns about the lack of transparency on the level of evidence and the practicality of implementation. They recommended regular updates, additional clarifications, tailored information and implementation guidance. CONCLUSIONS There were problems with the awareness and implementation of the CPE toolkit and frontline staff saw room for improvement, identifying implementation barriers and facilitators. An updated CPE toolkit version should provide comprehensive and instructive guidance on evidence-based CPE prevention, management and control procedures and their implementation in a modular format with sections tailored to hospitals' CPE status and to different staff groups.
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Affiliation(s)
- Annegret Schneider
- University College London, Gower St, Bloomsbury, London, WC1E 6BT, UK. .,National Institute for Health Research Health Protection Unit in Evaluation of Interventions, Bristol Medical School, University of Bristol, Bristol, BS8 2PS, UK.
| | - Caroline Coope
- National Institute for Health Research Health Protection Unit in Evaluation of Interventions, Bristol Medical School, University of Bristol, Bristol, BS8 2PS, UK.,Field Service South West, National Infection Service, Public Health England, 2 Rivergate, Bristol, BS1 6EH, UK
| | - Susan Michie
- University College London, Gower St, Bloomsbury, London, WC1E 6BT, UK.,National Institute for Health Research Health Protection Unit in Evaluation of Interventions, Bristol Medical School, University of Bristol, Bristol, BS8 2PS, UK
| | - Richard Puleston
- Field Service East Midlands, National Infection Service, Public Health England, Nottingham, NG24LA, UK
| | - Susan Hopkins
- Division of Healthcare-Associated Infection and Antimicrobial Resistance, National Infection Service, Public Health England, London, UK
| | - Isabel Oliver
- National Institute for Health Research Health Protection Unit in Evaluation of Interventions, Bristol Medical School, University of Bristol, Bristol, BS8 2PS, UK.,Field Service South West, National Infection Service, Public Health England, 2 Rivergate, Bristol, BS1 6EH, UK
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Hernández-García M, Pérez-Viso B, Navarro-San Francisco C, Baquero F, Morosini MI, Ruiz-Garbajosa P, Cantón R. Intestinal co-colonization with different carbapenemase-producing Enterobacterales isolates is not a rare event in an OXA-48 endemic area. EClinicalMedicine 2019; 15:72-79. [PMID: 31709416 PMCID: PMC6833436 DOI: 10.1016/j.eclinm.2019.09.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 09/12/2019] [Accepted: 09/12/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The current spread of carbapenemase-producing Enterobacterales (CPE) is a great concern. METHODS We recovered 198 CPE from 162 patients admitted in our Hospital (March 2014-March 2016) during the R-GNOSIS European Project. Microbiological features and plasmid characteristics of CPE recovered from patients co-colonized with multiple CPE were studied. FINDINGS Thirty patients (18.5%; CI 95%= 12.5%-24.5%) presented co-colonization with multiple CPE producing the same (CPE-SC) (15.4%) or a different carbapenemase (CPE-DC) (4.3%). OXA-48 (83.3%) was the most frequent carbapenemase, followed by VIM-1 (26.7%), NDM-1 (10%) and KPC-3 (3.3%). CPE-DC-patients had longer admissions [63 days (20-107)] than the other patients. Moreover, hospital stay until CPE detection was lower [9 days (5-14)] (p = 0.0052) in CPE-SC-patients than in those with a single colonization; 56% showed co-colonization in the first positive sample, although most of them had previous admissions and had received multiple antibiotic treatments. CPE were more frequently recovered in clinical samples from co-colonized [CPE-DC (28.6%), CPE-SC (24%)] patients than from patients with a single CPE (15.2%). Among CPE-SC-OXA-48 [80% (p = 0.11)], K. pneumoniae [88% (p = 0.006)] and E. coli [84% (p < 0.001)] were the most frequent species. In 60% of patients, K. pneumoniae and E. coli species were simultaneously recovered, frequently after a single OXA-48-K. pneumoniae colonization. High-risk clones (ST11, ST15, ST307) were detected in OXA-48-K. pneumoniae but a higher clonal diversity was found among E. coli. A frequent in-vivo cross-species plasmid transmission was shown, due to a dominant plasmid (IncL-pOXA-48), but also involving related or unrelated bla VIM-1-, bla NDM-1- and bla KPC-3-encoding plasmids. INTERPRETATION CPE co-colonization status should be monitored during epidemiological surveillance cultures, as these patients might be at a higher risk for infection. FUNDING European Commission Framework Programme 7 and Instituto de Salud Carlos III, Spain.
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Affiliation(s)
- Marta Hernández-García
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Blanca Pérez-Viso
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Carolina Navarro-San Francisco
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Fernando Baquero
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - María Isabel Morosini
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Patricia Ruiz-Garbajosa
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Rafael Cantón
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
- Corresponding author at: Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Carretera de Colmenar Km 9,1. 28034-Madrid. Spain.
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Identification of a Carbapenemase-Producing Hypervirulent Klebsiella pneumoniae Isolate in the United States. Antimicrob Agents Chemother 2019; 63:AAC.00519-19. [PMID: 31061159 DOI: 10.1128/aac.00519-19] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 04/28/2019] [Indexed: 01/19/2023] Open
Abstract
We report on a carbapenemase-producing hypervirulent Klebsiella pneumoniae (CP-hvKP) isolate collected from a U.S. patient at an outpatient clinic. The isolate was identified as K. pneumoniae serotype K1 sequence type 23 and included both a hypervirulence (with rmpA, rmpA2 iroBCDN, peg-344, and iucABCD-iutA genes) and a carbapenemase-encoding (bla KPC-2) plasmid. The emergence of CP-hvKP underscores the importance of clinical awareness of this pathotype and the need for continued monitoring of CP-hvKP in the United States.
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Shi Y, Huang Y, Zhang TT, Cao B, Wang H, Zhuo C, Ye F, Su X, Fan H, Xu JF, Zhang J, Lai GX, She DY, Zhang XY, He B, He LX, Liu YN, Qu JM. Chinese guidelines for the diagnosis and treatment of hospital-acquired pneumonia and ventilator-associated pneumonia in adults (2018 Edition). J Thorac Dis 2019; 11:2581-2616. [PMID: 31372297 PMCID: PMC6626807 DOI: 10.21037/jtd.2019.06.09] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 05/19/2019] [Indexed: 02/05/2023]
Affiliation(s)
- Yi Shi
- Department of Pulmonary and Critical Care Medicine, Nanjing Jinling Hospital, Nanjing University, School of Medicine, Nanjing 210002, China
| | - Yi Huang
- Department of Pulmonary and Critical Care Medicine, Shanghai Changhai hospital, Navy Medical University, Shanghai 200433, China
| | - Tian-Tuo Zhang
- Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Bin Cao
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing 100029, China
| | - Hui Wang
- Department of Clinical Laboratory Medicine, Peking University People’s Hospital, Beijing 100044, China
| | - Chao Zhuo
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China
| | - Feng Ye
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China
| | - Xin Su
- Department of Pulmonary and Critical Care Medicine, Nanjing Jinling Hospital, Nanjing University, School of Medicine, Nanjing 210002, China
| | - Hong Fan
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jin-Fu Xu
- Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China
| | - Jing Zhang
- Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Guo-Xiang Lai
- Department of Pulmonary and Critical Care Medicine, Dongfang Hospital, Xiamen University, Fuzhou 350025, China
| | - Dan-Yang She
- Department of Pulmonary and Critical Care Medicine, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Xiang-Yan Zhang
- Department of Pulmonary and Critical Care Medicine, Guizhou Provincial People’s Hospital, Guizhou 550002, China
| | - Bei He
- Department of Respiratory Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Li-Xian He
- Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - You-Ning Liu
- Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China
| | - Jie-Ming Qu
- Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Devereaux BM, Athan E, Brown RR, Greig SM, Jones DM, Bailey FK, Wallis DJ, Singh R. Australian infection control in endoscopy consensus statements on carbapenemase-producing Enterobacteriaceae. J Gastroenterol Hepatol 2019; 34:650-658. [PMID: 30345549 DOI: 10.1111/jgh.14511] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 10/14/2018] [Indexed: 01/27/2023]
Abstract
Outbreaks of carbapenemase-producing Enterobacteriaceae clinical infections related to endoscopic transmission are well documented. The high morbidity and mortality associated with these infections emphasizes the need to reassess endoscopic reprocessing protocols. The Gastroenterological Society of Australia established a multi-society committee to formulate evidence-based consensus statements on the prevention and management of endoscopic transmission of carbapenemase-producing Enterobacteriaceae. A literature search was undertaken utilizing the MEDLINE database. Further references were sourced from published paper bibliographies. Nine statements were formulated. Using the Delphi methodology, the statements were initially reviewed electronically by the committee members and subsequently at a face-to-face meeting in Melbourne, Australia. After further discussion, four additional sub-statements were added resulting in a total of 13 statements. Each statement was assessed for level of evidence, recommendation grade and the voting on recommendation was recorded. For a statement to be accepted, five out of six committee members had to "accept completely" or "accept with some reservation." All 13 statements achieved consensus agreement. Eleven statements achieved 100% "accepted completely." Two statements were 83% "accepted completely" and 17% "accepted with some reservation." Of particular significance, automated flexible endoscope reprocessors were mandated for high-level disinfection, and the use of forced-air drying cabinets was mandated for endoscope storage. These evidence-based statements encourage preventative strategies with the aim of ensuring the highest possible standards in flexible endoscope reprocessing thereby optimizing patient safety. They must be considered in addition to the broader published guidelines on infection control in endoscopy.
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Affiliation(s)
- Benedict M Devereaux
- University of Queensland, Herston, Queensland, Australia
- Gastroenterological Society of Australia (GESA), Melbourne, Victoria, Australia
| | - Eugene Athan
- Deakin University, Geelong, Victoria, Australia
- Australasian Society for Infectious Diseases (ASID), Surrey Hills, NSW, Australia
| | - Robyn R Brown
- Gastroenterological Nurses College of Australia (GENCA), Beaumaris, Victoria, Australia
| | - Sue M Greig
- Australasian College for Infection Prevention and Control (ACIPC), Brisbane, Tasmania, Australia
| | - Dianne M Jones
- Gastroenterological Nurses College of Australia (GENCA), Beaumaris, Victoria, Australia
| | - Fiona K Bailey
- Gastroenterological Society of Australia (GESA), Melbourne, Victoria, Australia
| | - David J Wallis
- Gastroenterological Society of Australia (GESA), Melbourne, Victoria, Australia
| | - Rajvinder Singh
- Gastroenterological Society of Australia (GESA), Melbourne, Victoria, Australia
- University of Adelaide, Adelaide, South Australia, Australia
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Gómara M, Ramón-García S. The FICI paradigm: Correcting flaws in antimicrobial in vitro synergy screens at their inception. Biochem Pharmacol 2019; 163:299-307. [PMID: 30836058 DOI: 10.1016/j.bcp.2019.03.001] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 03/01/2019] [Indexed: 10/27/2022]
Abstract
Antibiotics have become the corner stone of modern medicine. However, our society is currently facing one of the greatest challenges of its time: the emergence of antimicrobial resistance. It is estimated that if no new therapies are implemented by 2050, 10 million people will die worldwide every year as a result of infections caused by bacteria resistant to current antibiotics; new antimicrobials are thus urgently needed. However, drug development is a tedious and very costly endeavor of hundreds of millions that can take up to 15-20 years from the bench discovery to the bedside. Under this scenario, drug repurposing, which consists in identifying new uses for old, clinically approved drugs, has gathered momentum within the pharmaceutical industry. Because most of these drugs have safety and toxicity information packages available, clinical evaluation could be done in a much shorter period than standard timelines. Synergistic combinations of these clinically approved drugs could also be a promising approach to identify novel antimicrobial therapies that might provide rational choices of available drugs to shorten treatment, increase efficacy, reduce toxicity, prevent resistance and treat infections caused by drug-resistant strains. However, although simple in its conception, translating results from in vitro synergy screens into in vivo efficacy or the clinical practice has proven to be a paramount challenge. In this Commentary, we will discuss common flaws at the inception of synergy research programs, with a special focus on the use of the Fractional Inhibitory Concentration Index (FICI), and evaluate potential interventions that can be made at different developmental pre-clinical stages in order to improve the odds of translation from in vitro studies.
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Affiliation(s)
- Marta Gómara
- Mycobacterial Genetics Group, Department of Microbiology, Preventive Medicine and Public Health. Faculty of Medicine, University of Zaragoza, Spain
| | - Santiago Ramón-García
- Mycobacterial Genetics Group, Department of Microbiology, Preventive Medicine and Public Health. Faculty of Medicine, University of Zaragoza, Spain; Research & Development Agency of Aragon (ARAID) Foundation, Spain; CIBER Respiratory Diseases, Carlos III Health Institute, Madrid, Spain.
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Liming S, Guixia L, Wenxin S, Guirong T. HMGB1 signaling blocking protects against carbapenem-resistant klebsiella pneumoniae in a murine model of infection. Exp Lung Res 2018; 44:263-271. [PMID: 30595050 DOI: 10.1080/01902148.2018.1505976] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF THE STUDY Pulmonary infection with Klebsiella pneumoniae (KP) and carbapenem-resistant Klebsiella pneumoniae (CRKP) significantly contribute to morbidity and mortality in pneumonia. Recent studies have indicated that High-Mobility Group Box 1 Protein (HMGB1) plays an important role in the prevention and treatment of pneumonia. However the role of HMGB1 in CRKP-induced pneumonia has not been addressed. Materials andMethods: In vivo, we successfully established the KP and CRKP-induced pneumonia mouse model. We then tested the anti-HMGB1 IgG prevents CRKP-induced pneumonia. RESULTS The mice treated with the anti-HMGB1 IgG ameliorated CRKP-induced pulmonary infiltration of inflammatory cells, dissemination of bacteria and the cytokine storm by suppressing the HMGB1 signaling pathways. CONCLUSION These results indicate that HMGB1 may be an important contributor in these changes of CRKP-induced pneumonia. Thus, HMGB1 may provide a therapeutic target for reducing bacterial infection and lung inflammation in CRKP pneumonia.
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Affiliation(s)
- Shi Liming
- a Department of Clinical Laboratory , Heze municipal Hospital , Heze , China
| | - Li Guixia
- a Department of Clinical Laboratory , Heze municipal Hospital , Heze , China
| | - Shi Wenxin
- b Department of Scientific Research and Teaching , Heze municipal Hospital , Heze , China
| | - Tian Guirong
- b Department of Scientific Research and Teaching , Heze municipal Hospital , Heze , China
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50
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Treatment of central line-associated bloodstream infections. Crit Care 2018; 22:303. [PMID: 30445990 PMCID: PMC6240203 DOI: 10.1186/s13054-018-2249-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 10/29/2018] [Indexed: 02/02/2023] Open
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