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Prevalence of hypermutability in clinical isolates of Klebsiella pneumoniae and its role in ciprofloxacin resistance

Abstract number: P1481

Aathithan S., French G.L.

Objectives: To investigate the prevalence of hypermutability in clinical isolates of Klebsiella pneumoniae, and its possible role in the accumulation of mutations in the quinolone resistance-determining region (QRDR) and hence in ciprofloxacin resistance.

Methods: Sixty-four distinct clinical isolates of K. pneumoniae with widely differing ciprofloxacin MICs (range 0.016 to >512 mg/L) and known gyrA and parC QRDR sequences, were investigated for high frequency of mutations to rifampicin resistance using selective media containing 100 mg/L rifampicin. Twelve selected isolates with multiple, single or no QRDR mutations were also assessed for high frequency of mutation (or further mutation) to ciprofloxacin resistance, using selective media containing ciprofloxacin concentrations at 4× the MICs of the respective isolates.

Results: The rifampicin study identified three hypermutable isolates amongst the 64 tested (<5%); one was ciprofloxacin susceptible (1 of 12 such isolates), one ciprofloxacin resistant (1 of 28) and one high-level ciprofloxacin resistant (1 of 24). There was no association between ciprofloxacin MIC or gyrA and parC mutations and hypermutability.

The ciprofloxacin study identified only two of the hypermutant isolates found by the rifampicin study (one was the ciprofloxacin susceptible isolate with no mutations in the gyrA or parC QRDR; the other was the highly ciprofloxacin resistant isolate with double mutations in gyrA and a single mutation in parC QRDR). The ciprofloxacin study identified no other hypermutable isolates.

Conclusions: Hypermutation is uncommon in clinical isolates of K. pneumoniae and occurs randomly amongst ciprofloxacin resistant and susceptible isolates and in those with both no and multiple mutations in gyrA and parC. This suggests that hypermutation contributes to neither the accumulation of mutations in the QRDR nor directly to ciprofloxacin resistance.

Session Details

Date: 16/05/2009
Time: 00:00-00:00
Session name: 19th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Helsinki, Finland, 16 - 19 May 2009
Presentation type:
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