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Evaluation of updated interpretative criteria for categorizing Klebsiella pneumoniae with reduced carbapenem susceptibility.

ABSTRACT: We studied the accuracy of various susceptibility testing methods, including the 2009, 2010, and updated 2010 CLSI recommendations, to identify Klebsiella pneumoniae isolates with reduced susceptibility to carbapenems associated with different mechanisms of resistance. Forty-three wild-type (WT) strains, 42 extended-spectrum ?-lactamase (ESBL) producers, 18 ESBL producers with outer membrane porin protein loss (ESBL/Omp strains), and 42 blaKPC-possessing K. pneumoniae (KPC-Kp) isolates were evaluated. Imipenem (IPM), meropenem (MEM), ertapenem (ERT), and doripenem (DOR) were tested by broth microdilution (BMD), Etest, and disk diffusion (DD), and the modified Hodge test (MHT) was performed using IPM and MEM disks. Results were interpreted according to original as well as recently updated interpretative criteria. MHT was positive for all 42 KPC-Kp isolates and 10 of 18 ESBL/Omp strains and therefore had poor specificity in differentiating between KPC-Kp and ESBL/Omp isolates. Based on the updated CLSI standards, phenotypic susceptibility testing by BMD and DD differentiated most carbapenem-susceptible from carbapenem-nonsusceptible K. pneumoniae isolates without the need for MHT, while the Etest method characterized many KPC-Kp isolates as susceptible, and breakpoints may need to be lowered for this method. However, both the original and updated CLSI criteria do not adequately differentiate between isolates in the KPC-Kp group, which are unlikely to respond to carbapenem therapy, and those in the ESBL/Omp group, which are likely to respond to carbapenem therapy if MICs are within pharmacokinetic/pharmacodynamic targets. Further studies are required to determine if there is a clinical need to differentiate between KPC-Kp and ESBL/Omp groups.

SUBMITTER: Endimiani A

PROVIDER: S-EPMC3008460 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Evaluation of updated interpretative criteria for categorizing Klebsiella pneumoniae with reduced carbapenem susceptibility.

Endimiani Andrea A Perez Federico F Bajaksouzian Saralee S Windau Anne R AR Good Caryn E CE Choudhary Yuvraj Y Hujer Andrea M AM Bethel Christopher R CR Bonomo Robert A RA Jacobs Michael R MR

Journal of clinical microbiology 20100929 12

We studied the accuracy of various susceptibility testing methods, including the 2009, 2010, and updated 2010 CLSI recommendations, to identify Klebsiella pneumoniae isolates with reduced susceptibility to carbapenems associated with different mechanisms of resistance. Forty-three wild-type (WT) strains, 42 extended-spectrum β-lactamase (ESBL) producers, 18 ESBL producers with outer membrane porin protein loss (ESBL/Omp strains), and 42 blaKPC-possessing K. pneumoniae (KPC-Kp) isolates were eval ...[more]

PMID: 20881179

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Project description:Carbapenem-resistantKlebsiella pneumoniae(CR-Kp) is significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract, where the bacterium is usually present at low density, but can bloom following antibiotic treatment, mostly in hospital settings. The impact of disturbances in the intestinal environment on the fitness, survival, expansion, and drug susceptibility of this pathogen is not well-understood. Nevertheless, gaining such knowledge could lead to innovative intervention strategies for addressing colonization and infection. Here, we adopted anin vivomodel to examine the transcriptional adaptation of a CR-Kp clinical isolate to immune activation in the intestine. We report that as early as 6 hours following host treatment with anti-CD3 antibody, CR-Kp underwent rapid transcriptional changes including downregulation of genes involved in sugar utilization and amino acid biosynthesis, and upregulation of genes involved in amino acid uptake and catabolism, antibiotic resistance, and stress response. In agreement with these findings, the concentration of oxidative species and amino acids was increased in the mouse intestine following treatment. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were particularly upregulated, however their deletion did not impair CR-Kp fitness in vivoupon immune activation. Transcription factor enrichment analysis identified the global regulator cAMP-Receptor Protein CRP as a potential orchestrator of the observed transcriptional signature. In keeping with the recognized role of CRP in regulating utilization of alternative carbon sources, CRP deletion in CR-Kp resulted in strongly impaired gut colonization, but this effect was not amplified by immune activation. Thus, following intestinal colonization, which occurs in a CRP-dependent manner, CR-Kp can rapidly respond to immune cues by implementing a well-defined and complex transcriptional program whose direct relevance towards bacterial fitness remains cryptic. Further analyses utilizing this model may identify key factors to tackle the intestinal stage of CR-Kp colonization.

Dataset Information

Evaluation of updated interpretative criteria for categorizing Klebsiella pneumoniae with reduced carbapenem susceptibility.

Publications

Evaluation of updated interpretative criteria for categorizing Klebsiella pneumoniae with reduced carbapenem susceptibility.

Similar Datasets

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