https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-0691.2012.03821.x

Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)60007-0/pdf

ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant Gram-negative bacteria in hospitalized patients

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.

/pdf/global-dissemination-of-carbapenemase-producing-klebsiella-4qyejl7z34.pdf

Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods

Resistance of the Enterobacteriaceae to antibiotics, especially of the β lactam type, is increasingly dominated by the mobilization of continuously expressed single genes that encode efficient drug modifying enzymes. Strong and ubiquitous selection pressure has seemingly been accompanied by a shift from "natural" resistance, such as inducible chromosomal enzymes, membrane impermeability, and drug efflux, to the modern paradigm of mobile gene pools that largely determine the epidemiology of modern antibiotic resistance. In this way, antibiotic resistance is more available than ever before to organisms such as Escherichia coli and Klebsiella pneumoniae that are important causes of major sepsis. Modulation of the phenotype by host bacteria makes gene transmission less obvious and may in part explain why tracking and control of carbapenem resistance has been particularly problematic in the Enterobacteriaceae. This review discusses the underlying principles and clinical implications of the mobility and fixation of resistance genes and the exploitable opportunities and potential threats arising from apparent limitations on diversity in these mobile gene pools. It also provides some illustrative paradoxes and clinical corollaries, as well as a summary of future options.

Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications.

Objectives Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae has spread rapidly in China. In this study, we aimed to investigate the molecular epidemiology of KPC-producing K. pneumoniae isolates in China. Methods Ninety-five carbapenem-resistant K. pneumoniae isolates from 13 hospitals in nine cities covering five provinces in China were analysed. Antibiotic susceptibility was determined by the Etest. Multilocus sequence typing (MLST) and PFGE were used for epidemiological analysis. The genetic structure around bla(KPC) and the encoding genes of extended-spectrum β-lactamases and plasmid-mediated AmpC enzymes were detected by PCR and sequencing. Plasmids were analysed by transformation, restriction and Southern blot. Results All isolates harboured the bla(KPC-2) gene. Seven sequence types (STs) were obtained. The dominant clone was ST11 (61/95), which was identified in isolates from Zhejiang province (four hospitals in Hangzhou and one hospital in Ningbo), Jiangsu province (one hospital in Nanjing) and Anhui province (one hospital in Hefei). Isolates with ST11 showed >80% similarity in PFGE patterns. Plasmids from 14 selected transformants, their original isolates representing different STs and/or regions, had a diversity of HindIII restriction maps. Conclusions The dominant clone of KPC-producing K. pneumoniae in China is ST11, which is closely related to ST258, which has been reported worldwide.

/pdf/st11-the-dominant-clone-of-kpc-producing-klebsiella-lntprwo5hk.pdf

ST11, the dominant clone of KPC-producing Klebsiella pneumoniae in China

We report the first outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in Germany. The presence of KPC was confirmed by polymerase chain reaction (PCR). The KPC-encoding plasmid was analysed by transconjugation experiments, DNA sequencing, Southern blotting and isoelectric focussing. Typing was performed by pulsed-field gel electrophoresis (PFGE). An ertapenem-resistant K. pneumoniae with low minimum inhibitory concentrations (MIC) to other cabapenems (tested by the Vitek system) was isolated from the index patient in January 2008. A KPC-2 was identified after K. pneumoniae with identical susceptibility patterns had been isolated from two more patients. Despite the introduction of infection control measures, transmission occurred in five additional patients and three of the patients died from infections. The source of the outbreak strain remained unclear; however, the Tn4401-containing blaKPC-2 gene was similar to previously described isolates from Greece. Five months after the end of the outbreak, a KPC-K. pneumoniae was isolated from a patient who had been treated in Greece previously. Retrospectively, this patient was treated in November 2007 on the same unit as the index case. Typing revealed that all patients were colonised by the same strain. KPC-K. pneumoniae has been introduced to Germany possibly from Greece and transmission to other institutions is likely.

https://hal.archives-ouvertes.fr/hal-00574008/document

First outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in Germany.

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First outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in Germany.