<i>Klebsiella pneumoniae</i>Carbapenemase, Canada

Pillai, Dylan R.; Melano, Roberto G.; Rawte, Prasad; Lo, Stephen; Tijet, Nathalie; Fuksa, M; Roda, Nancy; Farrell, David J.; Krajden, Sigmund

doi:10.3201/eid1505.081536

Cited by 37 publications

(23 citation statements)

References 6 publications

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“…3,4 At present, infections with carbapenemase -producing organisms are rare in Canada, but at least one infection with a K. pneumoniae carbapenemase-producing organism apparently acquired in Canada has been described. 5,6 A review of K. pneumoniae carbapenemase in Canada was recently published in this journal. …”

Section: Methodsmentioning

confidence: 99%

New Delhi metallo- -lactamase-1 in Enterobacteriaceae: emerging resistance

Pillai¹,

McGeer²,

Low³

2011

Canadian Medical Association Journal

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Let us consider the following hypothetical scenario. A 48-year-old man with a history of type 2 diabetes mellitus was recently on vacation in Calcutta, India. Three days into his stay, he was involved in a motor vehicle accident, for which he was admitted to the local general hospital. He underwent open reduction and internal fixation of a comminuted fracture of the left tibia. His postoperative care was unremarkable except for a urinary tract infection. He was given cefazolin intravenously for five days. After 12 days in hospital, he was discharged and was assessed by an orthopedic surgeon upon his return to Canada. Radiographic examination showed loosening of the prosthetic hardware. He was admitted to hospital for revision of the hardware. Intraoperative cultures grew Klebsiella pneumoniae that showed resistance to β -lactam antibiotics, fluoroquinolones, cephalosporins and carbapenems. A modified Hodge test to detect carbapenemase gave a positive result. The isolate was forwarded to the local public health laboratory, where the presence of the gene for New Delhi metallo-β-lactamase-1 (NDM-1) was confirmed by polymerase chain reaction and DNA sequencing.T he carbapenem class of antimicrobials, which comprises imipenem, meropenem, ertapenem and doripenem, are often the last resort for the safe and effective treatment of infections caused by multidrug -resistant gramnegative bacteria. Resistance to carbapenems occurs through several mechanisms, including the production of carbapenemases. One such example is the newly described NDM-1, which is found on mobile genetic elements and confers resistance to all β-lactam antibiotics available in Canada.1 These mobile genetic elements (strands of DNA able to transfer from one bacterium to another, such as a plasmid or transposon) typically carry genes that confer resistance to fluoroquinolones, aminoglycosides and trimethoprim-sulfamethoxazole. MethodsWe searched PubMed using the term "NDM-1" for all relevant scientific articles published up to and including October 2010. Twenty-three research articles were identified, most of which were case reports or case series. Four of these articles were used in this review, and 19 articles were excluded because they lacked new information or because they were not available in English. Each of the included articles was reviewed by at least two of the authors. A Google News search of the lay press using the terms "NDM-1" or "medical tourism" was also conducted. Given the recent emergence of NDM-1, we included all articles that were deemed credible by the authors. Additional information was obtained through personal communication with relevant experts. Emergence of carbapenem resistanceCarbapenems are increasingly used because of the emergence of extended-spectrum β -lactamases in Enterobacteriaceae, particularly in Escherichia coli and K. pneumoniae. Review CMAJ • New Delhi metallo-β-lactamase-1 is a bacterial enzyme that renders all current β-lactam antibiotics inactive.

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Section: Methodsmentioning

confidence: 99%

New Delhi metallo- -lactamase-1 in Enterobacteriaceae: emerging resistance

Pillai¹,

McGeer²,

Low³

2011

Canadian Medical Association Journal

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“…In 2008, 10 isolates of K. pneumoniae were referred to the Ontario Public Health Laboratories for further testing. 11,12 The initial results of susceptibility testing of 1 of the 10 isolates using an automated method suggested that the organism was susceptible to meropenem. However, the initial results of testing using routine clinical laboratory methods showed general resistance to all lactams, with complete or intermediate resistance to meropenem, which raised the possibility of KPC production.…”

Section: Diagnosismentioning

confidence: 99%

Carbapenem resistance in Canada

Toye¹,

Krajden²,

Fuksa³

et al. 2009

Canadian Medical Association Journal

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“…KPC enzymes efficiently hydrolyze all ␤-lactam molecules (1, 22), conferring various levels of resistance to all ␤-lactam compounds, including carbapenems (13). However, KPC-producing K. pneumoniae may appear susceptible to carbapenems, mainly meropenem (2, 13), by reference CLSI agar dilution or broth microdilution methods as well as by automated systems (6,15,17). Characteristically, it has been reported that automated systems may identify as many as 87% of KPC-KP isolates to be susceptible to meropenem (13).…”

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confidence: 99%

“…Carbapenem heteroresistance has been characterized previously in several Gram-negative rods, such as Acinetobacter baumannii and P. aeruginosa (8,15). KPC-producing Enterobacteriaceae commonly exhibit a heterogeneous mode of growth to carbapenems, rendering difficult their detection and the estimation of their susceptibility levels (18).…”

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confidence: 99%

Characteristics of Meropenem Heteroresistance in Klebsiella pneumoniae Carbapenemase (KPC)-Producing Clinical Isolates of K. pneumoniae

et al. 2010

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Meropenem heteroresistance was investigated in six apparently meropenem-susceptible, Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) clinical isolates, compared with that in carbapenemase-negative, meropenem-susceptible controls. In population analyses, the KPC-KP isolates grew at meropenem concentrations of 64 to 256 g/ml. Heteroresistant colonies had significantly elevated expression of the bla KPC gene compared with the native populations but did not retain heteroresistance when subcultured in drug-free media. Time-kill assays indicated that meropenem alone was not bactericidal against KPC-KP but efficiently killed the control strains.Since the beginning of the last decade, Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) isolates have been increasingly detected in the United States and subsequently in several regions worldwide (3,4,13,17,21). KPC enzymes efficiently hydrolyze all ␤-lactam molecules (1, 22), conferring various levels of resistance to all ␤-lactam compounds, including carbapenems (13). However, KPC-producing K. pneumoniae may appear susceptible to carbapenems, mainly meropenem (2, 13), by reference CLSI agar dilution or broth microdilution methods as well as by automated systems (6,15,17). Characteristically, it has been reported that automated systems may identify as many as 87% of KPC-KP isolates to be susceptible to meropenem (13). The detection of the susceptibility level of KPC-KP isolates to carbapenems has been shown to be difficult due to the phenotypic heterogeneity that they commonly exhibit (3, 10, 13). For instance, in agar diffusion methods such as disk diffusion or Etest, the heterogeneous growth to carbapenems of KPC-KP results in the appearance of scattered colonies within the inhibition zones (9, 13).These issues raise the need for cautious evaluation of susceptibility testing in KPC-KP isolates that are recovered in clinical laboratories. In our clinical laboratories, several KPC-KP isolates that appear susceptible by automated susceptibility assays or reference dilution assays contain heterogeneous subpopulations (D. Sofianou and K. Themeli-Digalaki, personal communications). It has been also shown that among Greek KPC-KP isolates, meropenem tends to exhibit lower MICs than imipenem or ertapenem (17,20). In that respect, the aim of the present study was to characterize the heterogeneous mode of growth of apparently meropenem-susceptible KPC-KP clinical isolates by population analyses and bactericidal assays.Bacterial strains, susceptibility studies, and macrorestriction analysis. Six KPC-2-producing K. pneumoniae clinical isolates from our laboratory collection were randomly selected for the study among those that were meropenem susceptible by agar dilution (MIC Յ 4 g/ml) (5) but exhibited scattered heterogeneous colonies around carbapenem discs. The isolates were recovered from separate patients hospitalized in four hospitals located in different Greek regions. K. pneumoniae ATCC 13883, Pseudomonas aeruginosa ATCC 27853, ...

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Klebsiella pneumoniaeCarbapenemase, Canada

Cited by 37 publications

References 6 publications

New Delhi metallo- -lactamase-1 in Enterobacteriaceae: emerging resistance

New Delhi metallo- -lactamase-1 in Enterobacteriaceae: emerging resistance

Carbapenem resistance in Canada

Characteristics of Meropenem Heteroresistance in Klebsiella pneumoniae Carbapenemase (KPC)-Producing Clinical Isolates of K. pneumoniae

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