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Hosu MC, Vasaikar SD, Okuthe GE, Apalata T. Detection of extended spectrum beta-lactamase genes in Pseudomonas aeruginosa isolated from patients in rural Eastern Cape Province, South Africa. Sci Rep 2021; 11:7110. [PMID: 33782509 PMCID: PMC8007629 DOI: 10.1038/s41598-021-86570-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Accepted: 02/24/2021] [Indexed: 01/01/2023] Open
Abstract
The proliferation of extended spectrum beta-lactamase (ESBL) producing Pseudomonas aeruginosa represent a major public health threat. In this study, we evaluated the antimicrobial resistance patterns of P. aeruginosa strains and characterized the ESBLs and Metallo- β-lactamases (MBL) produced. Strains of P. aeruginosa cultured from patients who attended Nelson Mandela Academic Hospital and other clinics in the four district municipalities of the Eastern Cape between August 2017 and May 2019 were identified; antimicrobial susceptibility testing was carried out against thirteen clinically relevant antibiotics using the BioMérieux VITEK 2 and confirmed by Beckman autoSCAN-4 System. Real-time PCR was done using Roche Light Cycler 2.0 to detect the presence of ESBLs; blaSHV, blaTEM and blaCTX-M genes; and MBLs; blaIMP, blaVIM. Strains of P. aeruginosa demonstrated resistance to wide-ranging clinically relevant antibiotics including piperacillin (64.2%), followed by aztreonam (57.8%), cefepime (51.5%), ceftazidime (51.0%), piperacillin/tazobactam (50.5%), and imipenem (46.6%). A total of 75 (36.8%) multidrug-resistant (MDR) strains were observed of the total pool of isolates. The blaTEM, blaSHV and blaCTX-M was detected in 79.3%, 69.5% and 31.7% isolates (n = 82), respectively. The blaIMP was detected in 1.25% while no blaVIM was detected in any of the strains tested. The study showed a high rate of MDR P. aeruginosa in our setting. The vast majority of these resistant strains carried blaTEM and blaSHV genes. Continuous monitoring of antimicrobial resistance and strict compliance towards infection prevention and control practices are the best defence against spread of MDR P. aeruginosa.
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Affiliation(s)
- Mojisola C Hosu
- Division of Medical Microbiology, Department of Laboratory Medicine and Pathology, Faculty of Health Sciences, Walter Sisulu University and National Health Laboratory Services, Mthatha, Eastern Cape, South Africa
| | - Sandeep D Vasaikar
- Division of Medical Microbiology, Department of Laboratory Medicine and Pathology, Faculty of Health Sciences, Walter Sisulu University and National Health Laboratory Services, Mthatha, Eastern Cape, South Africa
| | - Grace E Okuthe
- Department of Biological and Environmental Sciences, Walter Sisulu University, Mthatha, Eastern Cape, South Africa
| | - Teke Apalata
- Division of Medical Microbiology, Department of Laboratory Medicine and Pathology, Faculty of Health Sciences, Walter Sisulu University and National Health Laboratory Services, Mthatha, Eastern Cape, South Africa.
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Detection of diverse carbapenem and multidrug resistance genes and high-risk strain types among carbapenem non-susceptible clinical isolates of target gram-negative bacteria in Kenya. PLoS One 2021; 16:e0246937. [PMID: 33617559 PMCID: PMC7899328 DOI: 10.1371/journal.pone.0246937] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 01/29/2021] [Indexed: 11/19/2022] Open
Abstract
Carbapenem-resistant gram-negative bacteria are an increasingly significant clinical threat globally. This risk may be underestimated in Kenya as only four carbapenemase genes in three bacterial species have been described. The study aimed to understand the antibiotic resistance profiles, genes, sequence types, and distribution of carbapenem-resistant gram-negative bacteria from patients in six hospitals across five Kenyan counties by bacterial culture, antibiotic susceptibility testing, and whole-genome sequence analysis. Forty-eight, non-duplicate, carbapenem non-susceptible, clinical isolates were identified across the five counties (predominantly in Nairobi and Kisii): twenty-seven Acinetobacter baumannii, fourteen Pseudomonas aeruginosa, three Escherichia coli, two Enterobacter cloacae, and two Klebsiella pneumoniae. All isolates were non-susceptible to β-lactam drugs with variable susceptibility to tigecycline (66%), minocycline (52.9%), tetracycline (29.4%), and levofloxacin (22.9%). Thirteen P. aeruginosa isolates were resistant to all antibiotics tested. Eleven carbapenemase genes were identified: blaNDM-1, blaOXA-23, -58, -66, -69, and -91 in A. baumannii (STs 1, 2, 164 and a novel ST1475), blaNDM-1 in E. cloacae (STs 25,182), blaNDM-1, blaVIM-1and -6, blaOXA-50 in P. aeruginosa (STs 316, 357, 654, and1203), blaOXA-181, blaNDM-1 in K. pneumoniae (STs 147 and 219), and blaNDM-5 in E. coli (ST164). Five A. baumannii isolates had two carbapenemases, blaNDM-1, and either blaOXA-23 (4) or blaOXA-58 (1). AmpC genes were detected in A. baumannii (blaADC-25), E. cloacae (blaDHA-1 and blaACT-6, 16), and K. pneumoniae (blaCMY). Significant multiple-drug resistant genes were the pan-aminoglycoside resistance16srRNA methyltransferase armA, rmtB, rmtC, and rmtF genes. This study is the first to report blaOXA-420, -58, -181, VIM-6, and blaNDM-5 in Kenyan isolates. High-risk STs of A. baumannii (ST1475, ST2), E. cloacae ST182, K. pneumoniae ST147, P. aeruginosa (ST357, 654), and E. coli ST167, ST648 were identified which present considerable therapeutic danger. The study recommends urgent carbapenem use regulation and containment of high-risk carbapenem-resistant bacteria.
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Healthcare-associated outbreaks of bacterial infections in Africa, 2009-2018: A review. Int J Infect Dis 2020; 103:469-477. [PMID: 33333248 DOI: 10.1016/j.ijid.2020.12.030] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/07/2020] [Accepted: 12/10/2020] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Healthcare-associated infections (HAIs) are a major global public health problem, increasing the transmission of drug-resistant infections. In Africa, the prevalence of HAIs among all hospital inpatients is estimated to be between 3% and 15%, but outbreaks are infrequently reported. Failure to detect and/or report outbreaks can increase the risk of ongoing infections and recurrent outbreaks. METHODS A search of the PubMed, Web of Science, Cochrane Library, and other outbreak databases was performed to identify published literature on bacterial HAI outbreaks in Africa (January 2009 to December 2018). Details of the outbreak characteristics, hospital environment, and the control measures implemented were extracted. RESULTS Twenty-two studies published over the 10-year period were identified. These reported 31 distinct outbreaks and a total of 31 causative pathogens, including Klebsiella pneumoniae (six outbreaks, 19%), Staphylococcus aureus (six outbreaks, 19%), and Enterococcus (five outbreaks, 16%). Most outbreaks were reported from university (n = 8, 26%) and tertiary hospitals (n = 11, 55%), from South Africa (n = 9, 41%) and Tunisia (n = 4, 18%). Interventions to control the outbreaks were described in 27 (90%) outbreaks, and all instituted or recommended enhancing hand hygiene and education. CONCLUSIONS Few facilities in Africa reported HAI outbreaks over the 10-year period, suggesting substantial under-detection and under-reporting. The quality and timeliness of reporting require improvement to ensure changes in public health practice.
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Ogbolu DO, Piddock LJ, Webber MA. Opening Pandora's box: High-level resistance to antibiotics of last resort in Gram-negative bacteria from Nigeria. J Glob Antimicrob Resist 2020; 21:211-217. [DOI: 10.1016/j.jgar.2019.10.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 10/14/2019] [Accepted: 10/15/2019] [Indexed: 10/25/2022] Open
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Iovene MR, Pota V, Galdiero M, Corvino G, Lella FMD, Stelitano D, Passavanti MB, Pace MC, Alfieri A, Franco SD, Aurilio C, Sansone P, Niyas VKM, Fiore M. First Italian outbreak of VIM-producing Serratia marcescensin an adult polyvalent intensive care unit, August-October 2018: A case report and literature review. World J Clin Cases 2019. [DOI: 10.12998/wjcc.v7.i21.3518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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Iovene MR, Pota V, Galdiero M, Corvino G, Di Lella FM, Stelitano D, Passavanti MB, Pace MC, Alfieri A, Di Franco S, Aurilio C, Sansone P, Niyas VKM, Fiore M. First Italian outbreak of VIM-producing Serratia marcescens in an adult polyvalent intensive care unit, August-October 2018: A case report and literature review. World J Clin Cases 2019; 7:3535-3548. [PMID: 31750335 PMCID: PMC6854422 DOI: 10.12998/wjcc.v7.i21.3535] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 05/15/2019] [Accepted: 07/27/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Carbapenem-resistant Enterobacteriaceae has become a significant public health concern as hospital outbreaks are now being frequently reported and these organisms are becoming difficult to treat with the available antibiotics. CASE SUMMARY An outbreak of VIM-producing Serratia marcescens occurred over a period of 11 wk (August, 1 to October, 18) in patients admitted to the adult polyvalent intensive care unit of the University of Campania "Luigi Vanvitelli" located in Naples. Four episodes occurred in three patients (two patients infected, and one patient colonized). All the strains revealed the production of VIM. CONCLUSION After three decades of carbapenem antibiotics use, the emergence of carbapenem-resistance in Enterobacteriaceae has become a significant concern and a stricter control to preserve its clinical application is mandatory. This is, to our knowledge, the first outbreak of VIM-producing Serratia marcescens in Europe. Surveillance policies must be implemented to avoid future outbreaks.
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Affiliation(s)
- Maria Rosaria Iovene
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Vincenzo Pota
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Massimiliano Galdiero
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Giusy Corvino
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Federica Maria Di Lella
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Debora Stelitano
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Maria Beatrice Passavanti
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Maria Caterina Pace
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Aniello Alfieri
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Sveva Di Franco
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Caterina Aurilio
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Pasquale Sansone
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | | | - Marco Fiore
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
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Soliman AM, Zarad HO, Nariya H, Shimamoto T, Shimamoto T. Genetic analysis of carbapenemase-producing Gram-negative bacteria isolated from a university teaching hospital in Egypt. INFECTION GENETICS AND EVOLUTION 2019; 77:104065. [PMID: 31634643 DOI: 10.1016/j.meegid.2019.104065] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 09/27/2019] [Accepted: 10/07/2019] [Indexed: 12/11/2022]
Abstract
A total of 65 non-replicate Gram-negative bacterial strains were recovered from clinical specimens between April and September 2014 at a University Hospital in Egypt. This collection was screened by PCR for carbapenemase-encoding genes, 16S rRNA methylases, and colistin resistance genes (mcr-1-mcr-8). Twenty-two strains (22/65, 33.8%) were positive for carbapenemase-encoding genes [13 NDM-1-producers (four Escherichia coli, two Klebsiella pneumoniae, and seven Providencia stuartii), two E. coli co-carrying NDM-5 and OXA-181, and seven Pseudomonas aeruginosa (three VIM-2, four VIM-24) strains]. The 16S rRNA methylase RmtC was detected in 12 NDM-1-producers for the first time in Egypt; no mcr genes were detected. A self-transmissible A/C plasmid was found to carry blaNDM-1 in all NDM-1-producing strains. NDM-5 and OXA-181 were located on an untypeable and IncX3 plasmid, respectively. Additionally, Enterobacterial repetitive intergenic consensus (ERIC)-PCR revealed five clonally related P. stuartii isolates collected over a 1.5-month period. Thirteen carbapenemase-producing strains were isolated from burn patients who are at a high risk of developing infections and require special medical care. To our knowledge, this is the first report of NDM-1-producing-P. stuartii strains in an African burn unit, NDM-1- and RmtC-positive non-lactose fermenting E. coli globally, VIM-24-producing P. aeruginosa in Africa, and 16S RMTase rmtC-NDM-1-producers in Egypt. This work highlights the detection of different carbapenemase-producing bacterial strains within an Egyptian teaching hospital compromising the effectiveness of carbapenems and urgently asking the Egyptian medical authorities for implementation of antimicrobial surveillance plans and infection control policies to early detect and to effectively halt the rapid spread of these superbugs.
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Affiliation(s)
- Ahmed M Soliman
- Laboratory of Food Microbiology and Hygiene, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan; Department of Microbiology and Immunology, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh 33516, Egypt
| | - Hoda O Zarad
- Laboratory of Food Microbiology and Hygiene, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
| | - Hirofumi Nariya
- Laboratory of Food Microbiology and Hygiene, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
| | - Toshi Shimamoto
- Laboratory of Food Microbiology and Hygiene, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
| | - Tadashi Shimamoto
- Laboratory of Food Microbiology and Hygiene, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
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Ekwanzala MD, Dewar JB, Kamika I, Momba MNB. Systematic review in South Africa reveals antibiotic resistance genes shared between clinical and environmental settings. Infect Drug Resist 2018; 11:1907-1920. [PMID: 30425540 PMCID: PMC6203169 DOI: 10.2147/idr.s170715] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
A systematic review was conducted to determine the distribution and prevalence of antibiotic-resistant bacteria (ARB), antimicrobial-resistant genes (ARGs), and antimicrobial-resistant gene determinants (ARGDs) in clinical, environmental, and farm settings and to identify key knowledge gaps in a bid to contain their spread. Fifty-three articles were included. The prevalence of a wide range of antimicrobial-resistant bacteria and their genes was reviewed. Based on the studies reviewed in this systematic review, mutation was found to be the main genetic element investigated. All settings shared 39 ARGs and ARGDs. Despite the fact that ARGs found in clinical settings are present in the environment, in reviewed articles only 12 were found to be shared between environmental and clinical settings; the inclusion of farm settings with these two settings increased this figure to 32. Data extracted from this review revealed farm settings to be one of the main contributors of antibiotic resistance in healthcare settings. ARB, ARGs, and ARGDs were found to be ubiquitous in all settings examined.
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Affiliation(s)
| | - John Barr Dewar
- Department of Life and Consumer Sciences, University of South Africa, Johannesburg, South Africa
| | - Ilunga Kamika
- Department of Environmental, Water and Earth Sciences, Tshwane University of Technology, Pretoria, South Africa,
| | - Maggy Ndombo Benteke Momba
- Department of Environmental, Water and Earth Sciences, Tshwane University of Technology, Pretoria, South Africa,
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Annear D, Black J, Govender S. MULTILOCUS SEQUENCE TYPING OF CARBAPENEM RESISTANT PSEUDOMONAS AERUGINOSA ISOLATES FROM PATIENTS PRESENTING AT PORT ELIZABETH HOSPITALS, SOUTH AFRICA. Afr J Infect Dis 2017; 11:68-74. [PMID: 28670642 PMCID: PMC5476815 DOI: 10.21010/ajid.v11i2.9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background: Pseudomonas aeruginosa is an important nosocomial pathogen that exhibits multiple drug resistance with increasing frequency, especially to carbapenems making patient treatment difficult. Carbapenem-resistance may be caused by porin gene mutations, active drug efflux, and carbapenemase production. This study evaluated the incidence of genes responsible for carbapenemase production in carbapenem-resistant Pseudomonas aeruginosa and assessed the genetic relatedness of the isolates by multi locus sequence typing (MLST). Materials and Methods: Identification and antimicrobial susceptibility testing of P. aeruginosa isolates (n=234) by the VITEK 2 system detected 81 carbapenem resistant P. aeruginosa isolates. PCR and DNA sequencing were used to screen isolates for three metallo-β-lactamase encoding genes. MLST included amplification of seven housekeeping genes and sequence type alignment using the online P. aeruginosa MLST database. Results: Only the blaVIM-2 gene was detected in 15 of the 81 carbapenem resistant isolates. MLST indicated six different novel sequence types among the blaVIM-2 positive P. aeruginosa isolates with the majority of the isolates (9/15) containing identical allelic profiles of the sequence type allocated ST1 (provisionally assigned sequence type, awaiting addition of new sequence types to PubMLST database). Five of these ST1 isolates were from patients and an environmental sample in the same hospital ward suggesting an environmental reservoir. Carbapenem resistance in the blaVIM-2 negative isolates may be due to other mechanisms. Conclusion: The incidence of genes responsible for carbapenemase production in carbapenem-resistant Pseudomonas aeruginosa and genetic relatedness of these isolates in public healthcare facilities within the Port Elizabeth area is of concern and requires further investigation.
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Affiliation(s)
- D Annear
- Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, Port Elizabeth, South Africa
| | - J Black
- Department of Infectious Diseases, Livingstone Hospital, Port Elizabeth, South Africa.,Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - S Govender
- Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, Port Elizabeth, South Africa
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Osei Sekyere J. Current State of Resistance to Antibiotics of Last-Resort in South Africa: A Review from a Public Health Perspective. Front Public Health 2016; 4:209. [PMID: 27747206 PMCID: PMC5042966 DOI: 10.3389/fpubh.2016.00209] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 09/12/2016] [Indexed: 12/12/2022] Open
Abstract
A review of the literature was undertaken to delineate the current level and mechanisms of resistance to carbapenems, colistin, and tigecycline in South Africa. Thirty-two English publications and 32 National Institute of Communicable Diseases communiqués identified between early January 2000 and 20 May, 2016 showed substantial reports of NDM (n = 860), OXA-48 (n = 584), VIM (n = 131), and IMP (n = 45) carbapenemases within this period, mainly in Klebsiella pneumoniae (n = 1138), Acinetobacter baumannii (n = 332), Enterobacter cloacae (n = 201), and Serratia marcescens (n = 108). Colistin and tigecycline resistance was prevalent among K. pneumoniae, A. baumannii, S. marcescens, and E. cloacae. The first mcr-1 colistin resistance gene to be detected in South Africa was reported in Escherichia coli from livestock as well as from hospitalized and outpatients. There are increasing reports of NDM and OXA-48 carbapenemases among Enterobacteriaceae and A. baumannii in South Africa. Mcr-1 is now present in South African patients and livestock. Resistance to carbapenems, colistin, and tigecycline restricts infection management options for clinicians.
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Affiliation(s)
- John Osei Sekyere
- Department of Pharmaceutics, Division of Microbiology, Kwame Nkrumah University of Science and Technology , Kumasi , Ghana
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Oliver A, Mulet X, López-Causapé C, Juan C. The increasing threat of Pseudomonas aeruginosa high-risk clones. Drug Resist Updat 2015; 21-22:41-59. [PMID: 26304792 DOI: 10.1016/j.drup.2015.08.002] [Citation(s) in RCA: 438] [Impact Index Per Article: 43.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2015] [Accepted: 08/04/2015] [Indexed: 01/01/2023]
Abstract
The increasing prevalence of chronic and hospital-acquired infections produced by multidrug-resistant (MDR) or extensively drug-resistant (XDR) Pseudomonas aeruginosa strains is associated with significant morbidity and mortality. This growing threat results from the extraordinary capacity of this pathogen for developing resistance through chromosomal mutations and from the increasing prevalence of transferable resistance determinants, particularly those encoding carbapenemases or extended-spectrum β-lactamases (ESBLs). P. aeruginosa has a nonclonal epidemic population structure, composed of a limited number of widespread clones which are selected from a background of a large quantity of rare and unrelated genotypes that are recombining at high frequency. Indeed, recent concerning reports have provided evidence of the existence of MDR/XDR global clones, denominated high-risk clones, disseminated in hospitals worldwide; ST235, ST111, and ST175 are likely those more widespread. Noteworthy, the vast majority of infections by MDR, and specially XDR, strains are produced by these and few other clones worldwide. Moreover, the association of high-risk clones, particularly ST235, with transferable resistance is overwhelming; nearly 100 different horizontally-acquired resistance elements and up to 39 different acquired β-lactamases have been reported so far among ST235 isolates. Likewise, MDR internationally-disseminated epidemic strains, such as the Liverpool Epidemic Strain (LES, ST146), have been noted as well among cystic fibrosis patients. Here we review the population structure, epidemiology, antimicrobial resistance mechanisms and virulence of the P. aeruginosa high-risk clones. The phenotypic and genetic factors potentially driving the success of high-risk clones, the aspects related to their detection in the clinical microbiology laboratory and the implications for infection control and public health are also discussed.
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Affiliation(s)
- Antonio Oliver
- Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Ctra. Valldemossa 79, 07010 Palma de Mallorca, Spain.
| | - Xavier Mulet
- Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Ctra. Valldemossa 79, 07010 Palma de Mallorca, Spain
| | - Carla López-Causapé
- Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Ctra. Valldemossa 79, 07010 Palma de Mallorca, Spain
| | - Carlos Juan
- Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Ctra. Valldemossa 79, 07010 Palma de Mallorca, Spain
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Xiao J, Fang M, Shi Y, Chen H, Shen B, Chen J, Lao X, Xu H, Zheng H. Identification and Validation Novel of VIM-2 Metallo-β-lactamase Tripeptide Inhibitors. Mol Inform 2015; 34:559-67. [DOI: 10.1002/minf.201400178] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Accepted: 03/16/2015] [Indexed: 11/07/2022]
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Nordmann P, Poirel L. The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clin Microbiol Infect 2015; 20:821-30. [PMID: 24930781 DOI: 10.1111/1469-0691.12719] [Citation(s) in RCA: 497] [Impact Index Per Article: 49.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
The spread of carbapenemase producers in Enterobacteriaceae has now been identified worldwide. Three main carbapenemases have been reported; they belong to three classes of β-lactamases, which are KPC, NDM, and OXA-48. The main reservoirs of KPC are Klebsiella pneumoniae in the USA, Israel, Greece, and Italy, those of NDM are K. pneumoniae and Escherichia coli in the Indian subcontinent, and those of OXA-48 are K. pneumoniae and Escherichia coli in North Africa and Turkey. KPC producers have been mostly identified among nosocomial isolates, whereas NDM and OXA-48 producers are both nosocomial and community-acquired pathogens. Control of their spread is still possible in hospital settings, and relies on the use of rapid diagnostic techniques and the strict implemention of hygiene measures.
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Affiliation(s)
- P Nordmann
- Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland; Hôpital Fribourgeois - Hôpital Cantonal de Fribourg, Fribourg, Switzerland; INSERM U914, South-Paris Medical School, K.-Bicêtre, France
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Identification of VIM-2-producing Pseudomonas aeruginosa from Tanzania is associated with sequence types 244 and 640 and the location of blaVIM-2 in a TniC integron. Antimicrob Agents Chemother 2014; 59:682-5. [PMID: 25331700 DOI: 10.1128/aac.01436-13] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Epidemiological data on carbapenemase-producing Gram-negative bacteria on the African continent are limited. Here, we report the identification of VIM-2-producing Pseudomonas aeruginosa isolates in Tanzania. Eight out of 90 clinical isolates of P. aeruginosa from a tertiary care hospital in Dar es Salaam were shown to harbor bla(VIM-2). The bla(VIM-2)-positive isolates belonged to two different sequence types (ST), ST244 and ST640, with bla(VIM-2) located in an unusual integron structure lacking the 3' conserved region of qacΔE1-sul1.
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15
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Lowman W, Marais M, Ahmed K, Marcus L. Routine active surveillance for carbapenemase-producing Enterobacteriaceae from rectal swabs: diagnostic implications of multiplex polymerase chain reaction. J Hosp Infect 2014; 88:66-71. [DOI: 10.1016/j.jhin.2014.06.009] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Accepted: 06/27/2014] [Indexed: 11/29/2022]
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Manenzhe RI, Zar HJ, Nicol MP, Kaba M. The spread of carbapenemase-producing bacteria in Africa: a systematic review. J Antimicrob Chemother 2014; 70:23-40. [PMID: 25261423 DOI: 10.1093/jac/dku356] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Carbapenems are the last line of defence against ever more prevalent MDR Gram-negative bacteria, but their efficacy is threatened worldwide by bacteria that produce carbapenemase enzymes. The epidemiology of bacteria producing carbapenemases has been described in considerable detail in Europe, North America and Asia; however, little is known about their spread and clinical relevance in Africa. METHODS We systematically searched in PubMed, EBSCOhost, Web of Science, Scopus, Elsevier Masson Consulte and African Journals Online, international conference proceedings, published theses and dissertations for studies reporting on carbapenemase-producing bacteria in Africa. We included articles published in English or French up to 28 February 2014. We calculated the prevalence of carbapenemase producers only including studies where the total number of isolates tested was at least 30. RESULTS Eighty-three studies were included and analysed. Most studies were conducted in North Africa (74%, 61/83), followed by Southern Africa (12%, 10/83), especially South Africa (90%, 9/10), West Africa (8%, 7/83) and East Africa (6%, 6/83). Carbapenemase-producing bacteria were isolated from humans, the hospital environment and community environmental water samples, but not from animals. The prevalence of carbapenemase-producing isolates in hospital settings ranged from 2.3% to 67.7% in North Africa and from 9% to 60% in sub-Saharan Africa. CONCLUSIONS Carbapenemase-producing bacteria have been described in many African countries; however, their prevalence is poorly defined and has not been systematically studied. Antibiotic stewardship and surveillance systems, including molecular detection and genotyping of resistant isolates, should be implemented to monitor and reduce the spread of carbapenemase-producing bacteria.
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Affiliation(s)
- Rendani I Manenzhe
- Division of Medical Microbiology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Heather J Zar
- Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa Red Cross War Memorial Children's Hospital, Cape Town, South Africa
| | - Mark P Nicol
- Division of Medical Microbiology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa Institute for Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa
| | - Mamadou Kaba
- Division of Medical Microbiology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa Institute for Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
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Wright LL, Turton JF, Livermore DM, Hopkins KL, Woodford N. Dominance of international 'high-risk clones' among metallo-β-lactamase-producing Pseudomonas aeruginosa in the UK. J Antimicrob Chemother 2014; 70:103-10. [PMID: 25182064 DOI: 10.1093/jac/dku339] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES Carbapenem-resistant isolates of Pseudomonas aeruginosa producing metallo-β-lactamases (MBLs) are increasingly reported worldwide and often belong to particular 'high-risk clones'. This study aimed to characterize a comprehensive collection of MBL-producing P. aeruginosa isolates referred to the UK national reference laboratory from multiple UK laboratories over a 10 year period. METHODS Isolates were referred to the UK national reference laboratory between 2003 and 2012 for investigation of resistance mechanisms and/or outbreaks. MBL genes were detected by PCR. Typing was carried out by nine-locus variable-number tandem repeat (VNTR) analysis and MLST. RESULTS MBL-producing P. aeruginosa isolates were referred from 267 source patients and 89 UK laboratories. The most common isolation sites were urine (24%), respiratory (18%), wounds (17%) and blood (13%). VIM-type MBLs predominated (91% of all MBLs found), but a few IMP- and NDM-type enzymes were also identified. Diverse VNTR types were seen, but 86% of isolates belonged to six major complexes. MLST of representative isolates from each complex showed that they corresponded to STs 111, 233, 235, 357, 654 and 773, respectively. Isolates belonging to these complexes were received from between 9 and 25 UK referring laboratories each. CONCLUSIONS The incidence of MBL-producing P. aeruginosa is increasing in the UK. The majority of these isolates belong to several 'high-risk clones', which have been previously reported internationally as host clones of MBLs.
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Affiliation(s)
- Laura L Wright
- Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, Colindale, London NW9 5EQ, UK Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK
| | - Jane F Turton
- Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, Colindale, London NW9 5EQ, UK
| | - David M Livermore
- Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, Colindale, London NW9 5EQ, UK Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK
| | - Katie L Hopkins
- Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, Colindale, London NW9 5EQ, UK
| | - Neil Woodford
- Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, Colindale, London NW9 5EQ, UK
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Sefraoui I, Berrazeg M, Drissi M, Rolain JM. Molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa clinical strains isolated from western Algeria between 2009 and 2012. Microb Drug Resist 2013; 20:156-61. [PMID: 24320688 DOI: 10.1089/mdr.2013.0161] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Infections caused by carbapenem-resistant Pseudomonas aeruginosa strains represent a major therapeutic and epidemiological problem. The aim of this study was to characterize carbapenem resistance in 89 clinical strains of P. aeruginosa isolated from three hospitals in western Algeria between October 2009 and November 2012. Minimum inhibitory concentrations (MICs) of imipenem were determined by the Etest method. Screening for metallo-β-lactamase (MβL) was performed using Etest MβL strips, and a PCR was conducted to detect carbapenemase-encoding genes. The amplification of the oprD gene followed by a sequencing reaction was performed for all strains resistant to imipenem. The clonality of 53 P. aeruginosa strains was demonstrated using multilocus sequence typing (MLST). Among the 89 isolates, 35 (39.33%) were found to be resistant to IMP (MICs ≥16 μg/ml). The blaVIM-2 gene was detected in two strains. The remaining imipenem-resistant isolates showed the presence of oprD mutations. The MLST analysis differentiated strains into various clones and the strains from the same clone had an identical sequence of the oprD gene. We report the second detection in 2010 of blaVIM-2 in Algerian P. aeruginosa strains. We also found that oprD mutations were the major determinant of high-level imipenem resistance. We demonstrate that these oprD mutations can be used as a tool to study the clonality in P. aeruginosa isolates.
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Affiliation(s)
- Imane Sefraoui
- 1 Aix-Marseille Université , Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes (URMITE), UM63, CNRS 7278, IRD 198, Inserm 1095, IHU Méditerranée Infection, Faculté de Médecine et de Pharmacie, Marseille, France
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Gomila M. Emergence of carbapenemases inPseudomonas aeruginosa: a worldwide problem. Expert Rev Anti Infect Ther 2013; 12:9-11. [DOI: 10.1586/14787210.2014.866037] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Multilocus sequence typing reveals genetic diversity of carbapenem- or ceftazidime-nonsusceptible Pseudomonas aeruginosa in China. Antimicrob Agents Chemother 2013; 57:5697-700. [PMID: 23939886 DOI: 10.1128/aac.00970-13] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
It is unclear whether the genetic background of drug-resistant Pseudomonas aeruginosa was disseminated from a certain clone. Thus, we performed MLST (multilocus sequence typing) of 896 P. aeruginosa isolates that were nonsusceptible to imipenem, meropenem, or ceftazidime. This revealed 254 sequence types (STs), including 104 new STs and 34 STs with novel alleles. Thirty-three clonal complexes and 404 singletons were found. In conclusion, drug-resistant P. aeruginosa clones can be developed from diverse genetic backgrounds.
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Jeannot K, Guessennd N, Fournier D, Müller E, Gbonon V, Plésiat P. Outbreak of metallo-β-lactamase VIM-2-positive strains of Pseudomonas aeruginosa in the Ivory Coast. J Antimicrob Chemother 2013; 68:2952-4. [PMID: 23887865 DOI: 10.1093/jac/dkt296] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Affiliation(s)
- Katy Jeannot
- Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France
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Identification of blaOXA-₅₁-like, blaOXA-₅₈, blaDIM-₁, and blaVIM carbapenemase genes in hospital Enterobacteriaceae isolates from Sierra Leone. J Clin Microbiol 2013; 51:2435-8. [PMID: 23658259 DOI: 10.1128/jcm.00832-13] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
We describe the results of a molecular epidemiological survey of 15 carbapenemase-encoding genes from a recent collection of clinical isolates from Mercy Hospital in Bo, Sierra Leone. The most salient findings revealed that (i) 60% of the isolates harbored multiple carbapenemase genes; (ii) the blaDIM-1 gene, which has previously only been reported in The Netherlands, is also circulating in this environment; and (iii) blaOXA-51-like and blaOXA-58 genes, which were thought to reside exclusively in Acinetobacter species, can also be found in members of the Enterobacteriaceae.
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Mudau M, Jacobson R, Minenza N, Kuonza L, Morris V, Engelbrecht H, Nicol MP, Bamford C. Outbreak of multi-drug resistant Pseudomonas aeruginosa bloodstream infection in the haematology unit of a South African Academic Hospital. PLoS One 2013; 8:e55985. [PMID: 23516393 PMCID: PMC3597724 DOI: 10.1371/journal.pone.0055985] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2012] [Accepted: 01/08/2013] [Indexed: 12/19/2022] Open
Abstract
Objective To describe an outbreak of multi-resistant Pseudomonas aeruginosa bloodstream infections (MRPA-BSI) that occurred in the haematology ward of a tertiary academic hospital in Cape Town, South Africa, and determine risk factors for acquisition of MRPA-BSI. Methods The outbreak investigation included a search for additional cases, review of patient records, environmental and staff screening, molecular typing using pulsed-field gel electrophoresis (PFGE) and Multi-locus sequencing (MLST) and a retrospective case-control study. Results Ten MRPA-BSI cases occurred in the haematology ward between January 2010 and January 2011. The case fatality rate was 80%. Staff screening specimens were negative for MRPA and an environmental source was not identified. PFGE showed that 9/10 isolates were related. MLST showed that 3 of these 9 isolates belonged to Sequence type (ST) 233 while the unrelated isolate belonged to ST260. Conclusion We have described an outbreak of MRPA-BSI occurring over an extended period of time among neutropenic haematology patients. Molecular typing confirms that the outbreak was predominantly due to a single strain. The source of the outbreak was not identified, but the outbreak appears to have been controlled following intensive infection control measures.
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Affiliation(s)
- Maanda Mudau
- Centre for Tropical, Opportunistic and Hospital Infections, National Institute for Communicable Diseases, Johannesburg, South Africa
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Dissemination of a class I integron carrying VIM-2 carbapenemase in Pseudomonas aeruginosa clinical isolates from a hospital intensive care unit in Annaba, Algeria. Antimicrob Agents Chemother 2013; 57:2426-7. [PMID: 23459493 DOI: 10.1128/aac.00032-13] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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Bonnin RA, Poirel L, Nordmann P, Eikmeyer FG, Wibberg D, Pühler A, Schlüter A. Complete sequence of broad-host-range plasmid pNOR-2000 harbouring the metallo-β-lactamase gene blaVIM-2 from Pseudomonas aeruginosa. J Antimicrob Chemother 2013; 68:1060-5. [PMID: 23354281 DOI: 10.1093/jac/dks526] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVES Metallo-β-lactamases (MBLs) are increasingly reported not only in Enterobacteriaceae but also in Pseudomonas spp. These enzymes hydrolyse all β-lactams, including carbapenems, and are not inhibited by β-lactamase inhibitors. The aim of this study was to fully characterize a plasmid bearing the blaVIM-2 MBL gene identified in a Pseudomonas aeruginosa isolate. METHODS This plasmid was fully sequenced by high-density pyrosequencing and annotated using the GenDB version 2.0 annotation tool. The evaluation of the broad-host-range replication of the pNOR-2000 replication initiation gene was assessed using electro-transformation and conjugation assays and the distribution of this replicase gene was evaluated using an international collection of VIM-producing Pseudomonas spp. RESULTS Analysis of the 21 880 bp sequence of pNOR-2000 revealed a truncated and non-functional transfer operon, in addition to novel genes encoding a serine protease and toxin/antitoxin addiction systems. This broad-host-range plasmid shares high gene synteny with part of the mobile genomic island pKLC102 identified in P. aeruginosa strain C. CONCLUSIONS We report here the complete nucleotide sequence of plasmid pNOR-2000 from a P. aeruginosa clinical isolate harbouring the integron-located MBL gene blaVIM-2.
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Affiliation(s)
- Rémy A Bonnin
- Service de Bactériologie-Virologie, INSERM U914, Emerging resistance to antibiotics, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine et Université Paris Sud, K-Bicêtre, France
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Gabani P, Prakash D, Singh OV. Emergence of antibiotic-resistant extremophiles (AREs). Extremophiles 2012; 16:697-713. [PMID: 22907125 DOI: 10.1007/s00792-012-0475-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2012] [Accepted: 08/02/2012] [Indexed: 12/14/2022]
Abstract
Excessive use of antibiotics in recent years has produced bacteria that are resistant to a wide array of antibiotics. Several genetic and non-genetic elements allow microorganisms to adapt and thrive under harsh environmental conditions such as lethal doses of antibiotics. We attempt to classify these microorganisms as antibiotic-resistant extremophiles (AREs). AREs develop strategies to gain greater resistance to antibiotics via accumulation of multiple genes or plasmids that harbor genes for multiple drug resistance (MDR). In addition to their altered expression of multiple genes, AREs also survive by producing enzymes such as penicillinase that inactivate antibiotics. It is of interest to identify the underlying molecular mechanisms by which the AREs are able to survive in the presence of wide arrays of high-dosage antibiotics. Technologically, "omics"-based approaches such as genomics have revealed a wide array of genes differentially expressed in AREs. Proteomics studies with 2DE, MALDI-TOF, and MS/MS have identified specific proteins, enzymes, and pumps that function in the adaptation mechanisms of AREs. This article discusses the molecular mechanisms by which microorganisms develop into AREs and how "omics" approaches can identify the genetic elements of these adaptation mechanisms. These objectives will assist the development of strategies and potential therapeutics to treat outbreaks of pathogenic microorganisms in the future.
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Affiliation(s)
- Prashant Gabani
- Division of Biological and Health Sciences, University of Pittsburgh, 300 Campus Drive, Bradford, PA 16701, USA
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