Intercontinental spread of OXA-48 beta-lactamase-producing Enterobacteriaceae over a 11-year period, 2001 to 2011.
01 Aug 2013-Eurosurveillance (European Centre for Disease Prevention and Control)-Vol. 18, Iss: 31, pp 20549
TL;DR: The molecular epidemiology of a collection of OXA-48 beta-lactamase-positive enterobacterial isolates recovered from European and north-African countries between January 2001 and December 2011 is reported, and multiple cases of importation and spread are identified at least in Europe.
Abstract: OXA-48 beta-lactamase producers are emerging as an important threat mostly in the Mediterranean area. We report here the molecular epidemiology of a collection of OXA-48 beta-lactamase-positive enterobacterial isolates (n=107) recovered from European and north-African countries between January 2001 and December 2011. This collection included 67 Klebsiella pneumoniae, 24 Escherichia coli and 10 Enterobacter cloacae. Using the EUCAST breakpoints, ninety-eight isolates (91.6%) were of intermediate susceptibility or resistant to ertapenem, whereas 66% remained susceptible to imipenem. Seventy-five per cent of the isolates co-produced an extended-spectrum beta-lactamase, most frequently CTX-M-15 (77.5%). Susceptibility testing to non-beta-lactam antibiotics showed that colistin, tigecycline, amikacin, and fosfomycin remain active against most of the isolates. Multilocus sequence typing indicated that the most common sequence types (ST) were ST101 and ST38 for K. pneumoniae and E. coli, respectively. The bla(OXA-48) gene was located on a 62 kb IncL/M plasmid in 92.5% of the isolates, indicating that a single plasmid was mainly responsible for the spread of that gene. In addition, this study identified multiple cases of importation of OXA-48 beta-lactamase producers at least in Europe, and spread of OXA-48 beta-lactamase producers giving rise to an endemic situation, at least in France.
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TL;DR: The emergence of OXA enzymes that can confer resistance to carbapenems, particularly in A. baumannii, has transformed these β-lactamases from a minor hindrance into a major problem set to demote the clinical efficacy of thecarbapenem resistance.
Abstract: The OXA β-lactamases were among the earliest β-lactamases detected; however, these molecular class D β-lactamases were originally relatively rare and always plasmid mediated. They had a substrate profile limited to the penicillins, but some became able to confer resistance to cephalosporins. From the 1980s onwards, isolates of Acinetobacter baumannii that were resistant to the carbapenems emerged, manifested by plasmid-encoded β-lactamases (OXA-23, OXA-40, and OXA-58) categorized as OXA enzymes because of their sequence similarity to earlier OXA β-lactamases. It was soon found that every A. baumannii strain possessed a chromosomally encoded OXA β-lactamase (OXA-51-like), some of which could confer resistance to carbapenems when the genetic environment around the gene promoted its expression. Similarly, Acinetobacter species closely related to A. baumannii also possessed their own chromosomally encoded OXA β-lactamases; some could be transferred to A. baumannii, and they formed the basis of transferable carbapenem resistance in this species. In some cases, the carbapenem-resistant OXA β-lactamases (OXA-48) have migrated into the Enterobacteriaceae and are becoming a significant cause of carbapenem resistance. The emergence of OXA enzymes that can confer resistance to carbapenems, particularly in A. baumannii, has transformed these β-lactamases from a minor hindrance into a major problem set to demote the clinical efficacy of the carbapenems.
578 citations
TL;DR: Although, combination therapy has been recommended for the treatment of severe carbapenemase-producing K. pneumoniae infections, the clinical evidence for this strategy is currently limited, and more accurate randomized controlled trials will be required to establish the most effective treatment regimen.
Abstract: The emergence of carbapenem-resistant Gram-negative pathogens poses a serious threat to public health worldwide. In particular, the increasing prevalence of carbapenem-resistant Klebsiella pneumoniae is a major source of concern. Klebsiella pneumoniae carbapenemases (KPC) and carbapenemases of the oxacillinase-48 (OXA-48) type have been reported worldwide. New Delhi metallo--lactamase (NDM) carbapenemases were originally identified in Sweden in 2008 and have spread worldwide rapidly. In this review, we summarize the epidemiology of K. pneumoniae producing three carbapenemases (KPCs, NDMs, and OXA-48-like). Although the prevalence of each resistant strain varies geographically, K. pneumoniae producing KPCs, NDMs, and OXA-48-like carbapenemases have become rapidly disseminated. In addition, we used recently published molecular and genetic studies to analyze the mechanisms by which these three carbapenemases, and major K. pneumoniae clones, such as ST258 and ST11, have become globally prevalent. Because carbapenemase-producing K. pneumoniae are often resistant to most -lactam antibiotics and many other non--lactam molecules, the therapeutic options available to treat infection with these strains are limited to colistin, polymyxin B, fosfomycin, tigecycline, and selected aminoglycosides. Although combination therapy has been recommended for the treatment of severe carbapenemase-producing K. pneumoniae infections, the clinical evidence for this strategy is currently limited, and more accurate randomized controlled trials will be required to establish the most effective treatment regimen. Moreover, because rapid and accurate identification of the carbapenemase type found in K. pneumoniae may be difficult to achieve through phenotypic antibiotic susceptibility tests, novel molecular detection techniques are currently being developed.
508 citations
Cites background from "Intercontinental spread of OXA-48 b..."
...The molecular epidemiology of OXA-48 in European and North African countries showed that in 92.5% of the isolates, the blaOXA−48 gene was located on this self-conjugative IncL/M type plasmid (Potron et al., 2013)....
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...Other OXA-48-derivatives, such as OXA-204 (Potron et al., 2013), OXA-232 (Potron et al., 2013), and OXA-163 (Poirel et al., 2011b), were recently identified in Tunisia, France, and Argentina, respectively, and OXA-244 and Frontiers in Microbiology | www.frontiersin.org 14 June 2016 | Volume 7 | Article 895 OXA-245 were first reported in Spain (Oteo et al., 2013a)....
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...…isolates collected from European and north-African countries between 2001 and 2011 indicated that ST101 was the most commonly observed sequence type in K. pneumoniae isolates, accounting for 17 out of 67 isolates (25.4%), followed by ST395 and ST15 (each seven isolates, 10.5%; Potron et al., 2013)....
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...Other OXA-48-derivatives, such as OXA-204 (Potron et al., 2013), OXA-232 (Potron et al., 2013), and OXA-163 (Poirel et al., 2011b), were recently identified in Tunisia, France, and Argentina, respectively, and OXA-244 and Frontiers in Microbiology | www.frontiersin.org 14 June 2016 | Volume 7 |…...
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TL;DR: The purpose of this review is to provide an overview of all known AMR-related plasmid families in Enterobacteriaceae, the resistance genes they carry and their geographical distribution.
Abstract: Bacterial antimicrobial resistance (AMR) is constantly evolving and horizontal gene transfer through plasmids plays a major role. The identification of plasmid characteristics and their association with different bacterial hosts provides crucial knowledge that is essential to understand the contribution of plasmids to the transmission of AMR determinants. Molecular identification of plasmid and strain genotypes elicits a distinction between spread of AMR genes by plasmids and dissemination of these genes by spread of bacterial clones. For this reason several methods are used to type the plasmids, e.g. PCR-based replicon typing (PBRT) or relaxase typing. Currently, there are 28 known plasmid types in Enterobacteriaceae distinguished by PBRT. Frequently reported plasmids [IncF, IncI, IncA/C, IncL (previously designated IncL/M), IncN and IncH] are the ones that bear the greatest variety of resistance genes. The purpose of this review is to provide an overview of all known AMR-related plasmid families in Enterobacteriaceae, the resistance genes they carry and their geographical distribution.
485 citations
TL;DR: Enterobacter aerogenes and E. cloacae have been reported as important opportunistic and multiresistant bacterial pathogens for humans during the last three decades in hospital wards and questions about the horizontal transmission of mobile elements containing antibiotic resistance genes are raised.
Abstract: Enterobacter aerogenes and E. cloacae have been reported as important opportunistic and multiresistant bacterial pathogens for humans during the last three decades in hospital wards. These Gram-negative bacteria have been largely described during several outbreaks of hospital-acquired infections in Europe and particularly in France. The dissemination of Enterobacter sp. is associated with the presence of redundant regulatory cascades that efficiently control the membrane permeability ensuring the bacterial protection and the expression of detoxifying enzymes involved in antibiotic degradation/inactivation. In addition, these bacterial species are able to acquire numerous genetic mobile elements that strongly contribute to antibiotic resistance. Moreover, this particular fitness help them to colonize several environments and hosts and rapidly and efficiently adapt their metabolism and physiology to external conditions and environmental stresses. Enterobacter is a versatile bacterium able to promptly respond to the antibiotic treatment in the colonized patient. The balance of the prevalence, E. aerogenes versus E. cloacae, in the reported hospital infections during the last period, questions about the horizontal transmission of mobile elements containing antibiotic resistance genes, e.g., the efficacy of the exchange of resistance genes Klebsiella pneumoniae to Enterobacter sp. It is also important to mention the possible role of antibiotic use in the treatment of bacterial infectious diseases in this E. aerogenes/E. cloacae evolution.
386 citations
Cites background or result from "Intercontinental spread of OXA-48 b..."
...The OXA48 type serine carbapenemase is the most prevalent because its gene is located on a plasmid, associated to the bla-CTXM-15 gene coding ESBL, thus explaining its spread and the associated resistance (Potron et al., 2013; Torres et al., 2014)....
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...These characteristics, associated with the frequent endogenous intestinal carriage of E. cloacae, may result in abnormally high levels in the bowels of hospitalized patients, especially those who have received cephalosporins (Potron et al., 2013)....
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...…of most frequent extended spectrum β-lactamases (ESBL) and carbapenemases in this species, E. cloacae has now become the third broad spectrum Enterobacteriaceae species involved in nosocomial infections after Escherichia coli and K. pneumoniae (Potron et al., 2013; Jarlier and INVS, 2014)....
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...Regarding Enterobacter, we can note the successive waves of E. cloacae, followed by E. aerogenes and now again E. cloacae reported in hospital wards (Potron et al., 2013)....
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TL;DR: In the present review, an update of the knowledge about the pathogenicity, antimicrobial resistance and clinical aspects of this ‘old friend’ was presented.
Abstract: Escherichia coli is one of the most-studied microorganisms worldwide but its characteristics are continually changing. Extraintestinal E. coli infections, such as urinary tract infections and neonatal sepsis, represent a huge public health problem. They are caused mainly by specialized extraintestinal pathogenic E. coli (ExPEC) strains that can innocuously colonize human hosts but can also cause disease upon entering a normally sterile body site. The virulence capability of such strains is determined by a combination of distinctive accessory traits, called virulence factors, in conjunction with their distinctive phylogenetic background. It is conceivable that by developing interventions against the most successful ExPEC lineages or their key virulence/colonization factors the associated burden of disease and health care costs could foreseeably be reduced in the future. On the other hand, one important problem worldwide is the increase of antimicrobial resistance shown by bacteria. As underscored in the last WHO global report, within a wide range of infectious agents including E. coli, antimicrobial resistance has reached an extremely worrisome situation that ‘threatens the achievements of modern medicine’. In the present review, an update of the knowledge about the pathogenicity, antimicrobial resistance and clinical aspects of this ‘old friend’ was presented.
242 citations
References
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TL;DR: In this paper, a simple and rapid phylogenetic grouping technique based on triplex PCR was proposed, which uses a combination of two genes (chuA and yjaA) and an anonymous DNA fragment, was tested with 230 strains and showed excellent correlation with reference methods.
Abstract: Phylogenetic analysis has shown that Escherichia coli is composed of four main phylogenetic groups (A, B1, B2, and D) and that virulent extra-intestinal strains mainly belong to groups B2 and D. Actually, phylogenetic groups can be determined by multilocus enzyme electrophoresis or ribotyping, both of which are complex, time-consuming techniques. We describe a simple and rapid phylogenetic grouping technique based on triplex PCR. The method, which uses a combination of two genes (chuA and yjaA) and an anonymous DNA fragment, was tested with 230 strains and showed excellent correlation with reference methods.
2,564 citations
TL;DR: Results indicated that the inc/rep PCR method demonstrates high specificity and sensitivity in detecting replicons on reference plasmids and also revealed the presence of recurrent and common plasmid in epidemiologically unrelated Salmonella isolates of different serotypes.
2,163 citations
"Intercontinental spread of OXA-48 b..." refers background or methods in this paper
...Replicon and transposon typing PCR-based replicon typing (PBRT) of the main plasmid incompatibility groups reported in Enterobacteriaceae was performed as described [27] and using the specific primers designed from plasmid pOXA-48a [28]....
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...pneumoniae 11978 [27] to amplify its replicase gene, 99 of the 107 isolates (92....
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TL;DR: These resistance traits have been identified among nosocomial and community-acquired infections and are being investigated for use in drug discovery and development.
Abstract: Carbapenemases increasingly have been reported in Enterobacteriaceae in the past 10 years. Klebsiella pneumoniae carbapenemases have been reported in the United States and then worldwide, with a marked endemicity at least in the United States and Greece. Metallo-enzymes (Verona integron–encoded metallo-β-lactamase, IMP) also have been reported worldwide, with a higher prevalence in southern Europe and Asia. Carbapenemases of the oxacillinase-48 type have been identified mostly in Mediterranean and European countries and in India. Recent identification of New Delhi metallo-β-lactamase-1 producers, originally in the United Kingdom, India, and Pakistan and now worldwide, is worrisome. Detection of infected patients and carriers with carbapenemase producers is necessary for prevention of their spread. Identification of the carbapenemase genes relies mostly on molecular techniques, whereas detection of carriers is possible by using screening culture media. This strategy may help prevent development of nosocomial outbreaks caused by carbapenemase producers, particularly K. pneumoniae.
2,044 citations
"Intercontinental spread of OXA-48 b..." refers background in this paper
...Introduction Currently, an emergence of carbapenem resistance in Enterobacteriaceae is reported, mostly related to the spread of carbapenemases [1]....
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...IMP, VIM and NDM) [1], and class D (e....
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...All isolates were screened by PCR for the Ambler class A and B carbapenemase-encoding genes blaKPC, blaIMP, blaVIM, blaNDM [19-20]....
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...That sequence type corresponds to an internationally occurring clone and has been associated with different ESBL genes, but also with the metallo-beta-lactamase genes coding for NDM and VIM [36,37]....
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...Those carbapenemhydrolysing beta-lactamases belong to the Ambler class A (e.g. KPC), class B (e.g. IMP, VIM and NDM) [1], and class D (e.g. OXA-48 and its variants possessing weaker but significant carbapenemase activity) [2]....
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Book•
01 Jan 2010
TL;DR: The tabular information presented here represents the most current information for drug selection, interpretation, and quality control using the procedures standardized in M02 and M07, and users should replace the tables published earlier with these new tables.
Abstract: The supplemental information presented in this document is intended for use with the antimicrobial susceptibility testing procedures published in the following Clinical and Laboratory Standards Institute (CLSI)–approved standards: M02-A10—Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard—Tenth Edition; and M07-A8—Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Eighth Edition. The standards contain information about both disk (M02) and dilution (M07) test procedures for aerobic bacteria. Clinicians depend heavily on information from the clinical microbiology laboratory for treatment of their seriously ill patients. The clinical importance of antimicrobial susceptibility test results requires that these tests be performed under optimal conditions and that laboratories have the capability to provide results for the newest antimicrobial agents. The tabular information presented here represents the most current information for drug selection, interpretation, and quality control using the procedures standardized in M02 and M07. Users should replace the tables published earlier with these new tables. (Changes in the tables since the most current edition appear in boldface type.) Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-First Informational Supplement. CLSI document M100-S21 (ISBN 1-56238-742-1). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087 USA, 2011. The data in the interpretive tables in this supplement are valid only if the methodologies in M02-A10—Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard—Tenth Edition; and M07-A8—Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Eighth Edition are followed. January 2011 M100-S21
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TL;DR: A rapid and reliable PCR-based technique was developed for detection of genes encoding carbapenemases belonging to different classes using optimized conditions, with PCR giving distinct amplicon sizes corresponding to the different genes for each mixture.
1,438 citations