Emergence of blaKPC carbapenemase genes in Australia

Partridge, Sally R.; Ginn, Andrew N.; Wiklendt, Agnieszka M.; Ellem, Justin A.; Wong, Jenny; Ingram, Paul R.; Guy, Stephen; Garner, Sarah; Iredell, Jonathan R.

doi:10.1016/j.ijantimicag.2014.10.006

Cited by 63 publications

(69 citation statements)

References 32 publications

(53 reference statements)

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“…The predominance of the GD duplication, also seen in association with bla KPC (43,46), and presumably excluding some large molecules, like ETP, without restricting smaller essential nutrients, is noteworthy. The complete loss of OmpK36 in K. pneumoniae also decreases ␤-lactam susceptibility but might have a greater impact on bacterial fitness, especially in those strains with defects in the other major porin, OmpK35 (38), which are commonly reported in clinical isolates (67).…”

Section: Discussionmentioning

confidence: 95%

“…Although detailed transcriptional and proteomic analyses are beyond the scope of this work, simple analysis of the association between MICs and the nucleotide sequences and apparent expression of the matrix porins OmpK35 (in K. pneumoniae) and OmpF (in E. coli) in SDS-PAGE revealed no apparent correlation of these proteins with MICs. Except for a low-level endemicity of bla IMP-4 , classic carbapenemase genes, such as bla NDM and bla KPC , have been seen as sporadic imports to Australia (16,19,46), although a recent KPC outbreak (64) may now result in KPC becoming endemic in some Victorian hospitals. A surprising finding is that a high percentage of ETP nonsusceptibility in K. pneumoniae in our region is due to the combination of common bla CTX-M (ESBL) genes with an OmpK36 variation (21 out of 70 K. pneumoniae isolates carrying a bla CTX-M gene had a mutation in OmpK36).…”

Section: Discussionmentioning

confidence: 99%

“…S1 in the supplemental material). A Gly134Asp135 (GD) duplication in OmpK36 loop 3, commonly seen in sequence type 258 (ST258) isolates carrying bla KPC (43,46) and predicted to functionally constrict the inner channel of the porin, was present in the other 11 isolates (Table 1; see also Fig. S1 in the supplemental material).…”

Section: Detection Of Genes Encoding ␤-Lactamases and Plasmid Typingmentioning

confidence: 99%

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Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae

et al. 2016

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cThe minimal concentration of antibiotic required to inhibit the growth of different isolates of a given species with no acquired resistance mechanisms has a normal distribution. We have previously shown that the presence or absence of transmissible antibiotic resistance genes has excellent predictive power for phenotype. In this study, we analyzed the distribution of six ␤-lactam antibiotic susceptibility phenotypes associated with commonly acquired resistance genes in Enterobacteriaceae in Sydney, Australia. Escherichia coli (n ‫؍‬ 200) and Klebsiella pneumoniae (n ‫؍‬ 178) clinical isolates, with relevant transmissible resistance genes (bla TEM , n ‫؍‬ 33; plasmid AmpC, n ‫؍‬ 69; extended-spectrum ␤-lactamase [ESBL], n ‫؍‬ 116; and carbapenemase, n ‫؍‬ 100), were characterized. A group of 60 isolates with no phenotypic resistance to any antibiotics tested and carrying none of the important ␤-lactamase genes served as comparators. The MICs for all drug-bacterium combinations had a normal distribution, varying only in the presence of additional genes relevant to the phenotype or, for ertapenem resistance in K. pneumoniae, with a loss or change in the outer membrane porin protein OmpK36. We demonstrated mutations in ompK36 or absence of OmpK36 in all isolates in which reduced susceptibility to ertapenem (MIC, >1 mg/liter) was evident. Ertapenem nonsusceptibility in K. pneumoniae was most common in the context of an OmpK36 variant with an ESBL or AmpC gene. Surveillance strategies to define appropriate antimicrobial therapies should include genotype-phenotype relationships for all major transmissible resistance genes and the characterization of mutations in relevant porins in organisms, like K. pneumoniae. E scherichia coli and Klebsiella pneumoniae are among the most important pathogens in community and hospital settings, and their increasing resistance to extended-spectrum (third-and fourth-generation) cephalosporin and carbapenem antibiotics is a major health threat. In Gram-negative bacteria, such as these, a variety of mechanisms may confer ␤-lactam resistance (1), but the spread of transmissible genes encoding extended-spectrum ␤-lactamases (ESBLs) (2), plasmid-mediated AmpC ␤-lactamases (pAmpCs) (3), and carbapenemases (4) is particularly significant. Carbapenems have been the antibiotics of choice for treating ESBLs and other multidrug-resistant strains, but carbapenem resistance is increasingly common (5). This is mostly attributed to the production of specific carbapenemases (6), but the expression of AmpC or ESBL enzymes in isolates with altered outer membrane porins is also associated with decreased susceptibility to carbapenems (7-9). Mutations in major outer membrane porins may be required for clinically relevant carbapenem resistance in K. pneumoniae isolates expressing carbapenemases, such as KPC and OXA-48-like enzymes, which rarely elicit clinically important antibiotic resistance in E. coli (6).The clinical definitions of antibiotic susceptibility are developed by the collection and analysis of...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Detection Of Genes Encoding ␤-Lactamases and Plasmid Typingmentioning

confidence: 99%

See 1 more Smart Citation

Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae

et al. 2016

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“…It is important to note that pathogenic K pneumoniae subtypes that carry the KPC gene 133-136 have often not only lost a functional OmpK35 "matrix" porin but also have a potentially important variation in the OmpK36 outer membrane "osmo" porin that is expected to augment the resistance phenotype. 134 137 E coli carrying the KPC gene are much less resistant than K pneumoniae ST258 with the same gene when both are present together. 134 KPC gene transmission between strains, species, and patients may therefore go undetected by phenotypic screening methods, as discussed later, although the spread of KPC probably relates primarily to its successful association with the Klebsiella strains in which the carbapenem resistance phenotype is marked.…”

Section: K Pneumoniae St258 and The Kpc Carbapenemasementioning

confidence: 99%

Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications

Iredell

Brown

Tagg

2016

BMJ

277

177

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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.

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“…K. pneumoniae strains harboring this gene are involved in outbreaks throughout the world (Partridge et al, 2015;Liu et al, 2014). The use of a strain not carrying many antibiotic resistance mechanisms for the development of a first generation vaccine provides increased safety and can prevent the development of some outbreaks of infections worldwide.…”

Section: Resultsmentioning

confidence: 99%

Intradermal Immunization of BALB/C Mice with Heat Killed Klebsiella pneumoniae ATCC BAA1706 Leads to the Production of both IgG1 and IgG2a

Pereira¹,

Galantine²,

Muniz³

et al. 2017

Int.J.Curr.Microbiol.App.Sci

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Emergence of blaKPC carbapenemase genes in Australia

Cited by 63 publications

References 32 publications

Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae

Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae

Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications

Intradermal Immunization of BALB/C Mice with Heat Killed Klebsiella pneumoniae ATCC BAA1706 Leads to the Production of both IgG1 and IgG2a

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