Patterns of Resistance Associated with Integrons, the Extended-Spectrum β-Lactamase SHV-5 Gene, and a Multidrug Efflux Pump of Klebsiella pneumoniae Causing a Nosocomial Outbreak

Abstract

Multiresistant Klebsiella pneumoniae caused a nosocomial outbreak. Resistance patterns of the presumed outbreak isolates varied among and within patients. In order to control the outbreak, screening for extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae was commenced. A number of susceptible K. pneumoniae strains were stored to serve as controls in genetic strain typing. Typing by pulsed-field gel electrophoresis proved the clonality of the strains in the recognized outbreak patients. Typing of the control strains by pulsed-field gel electrophoresis showed that at least one patient had been missed by the ESBL screening procedure. Further genetic typing confirmed the presence of the SHV-5 ESBL gene in all but one of the outbreak strains. Variable presence of integrons that carried the aminoglycoside resistance genes aadB and aadA2 was found. A gyrA mutation in codon 83 was present in all outbreak strains tested, despite considerable differences in ciprofloxacin MICs. The MICs of ciprofloxacin and the chemically unrelated drug cefoxitin were correlated ( r = 0.86, P < 0.01) and were compatible with the overexpression of an efflux pump in a subset of the outbreak strains. We conclude that outbreak strains that express an ESBL gene only at a low level may pass unnoticed in a screening procedure, when the laboratory is unaware of variable ESBL expression. In this particular outbreak, screening for strains for which ciprofloxacin MICs were ≥0.25 μg/ml would in retrospect have been the most sensitive method for detection of the K. pneumoniae outbreak strain.