Abstract

Infections caused by multidrug resistant Klebsiella pneumoniae have been increasingly reported in many parts of the world. A total of 93 Malaysian multidrug resistant K. pneumoniae isolated from patients attending to University of Malaya Medical Center, Kuala Lumpur, Malaysia from 2010-2012 were investigated for antibiotic resistance determinants including extended-spectrum beta-lactamases (ESBLs), aminoglycoside and trimethoprim/sulfamethoxazole resistance genes and plasmid replicons. CTX-M-15 (91.3%) was the predominant ESBL gene detected in this study. aacC2 gene (67.7%) was the most common gene detected in aminoglycoside-resistant isolates. Trimethoprim/sulfamethoxazole resistance (90.3%) was attributed to the presence of sul1 (53.8%) and dfrA (59.1%) genes in the isolates. Multiple plasmid replicons (1-4) were detected in 95.7% of the isolates. FIIK was the dominant replicon detected together with 13 other types of plasmid replicons. Conjugative plasmids (1-3 plasmids of ~3-100 kb) were obtained from 27 of 43 K. pneumoniae isolates. An ESBL gene (either CTX-M-15, CTX-M-3 or SHV-12) was detected from each transconjugant. Co-detection with at least one of other antibiotic resistance determinants [sul1, dfrA, aacC2, aac(6ˊ)-Ib, aac(6ˊ)-Ib-cr and qnrB] was noted in most conjugative plasmids. The transconjugants were resistant to multiple antibiotics including β-lactams, gentamicin and cotrimoxazole, but not ciprofloxacin. This is the first study describing the characterization of plasmids circulating in Malaysian multidrug resistant K. pneumoniae isolates. The results of this study suggest the diffusion of highly diverse plasmids with multiple antibiotic resistance determinants among the Malaysian isolates. Effective infection control measures and antibiotic stewardship programs should be adopted to limit the spread of the multidrug resistant bacteria in healthcare settings.

Highlights

  • Klebsiella pneumoniae is a major cause of community and healthcare associated infections [1]

  • CTX-M-15 was the prevalent extended-spectrum beta-lactamases (ESBLs) gene detected among 91.3% of Malaysian multidrug-resistant K. pneumoniae isolates

  • The dramatic shift of ESBL gene types from SHV to CTX-M has been noted globally as ESBL-SHV types are currently less common compared to CTX-M types [25, 26]

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Summary

Introduction

Klebsiella pneumoniae is a major cause of community and healthcare associated infections [1]. Infections caused by multidrug resistant K. pneumoniae, have been increasingly reported in many clinical settings [1,2,3]. Besides extended-spectrum β-lactamase (ESBL) production, K. pneumoniae is frequently known to be resistant to multiple antimicrobial agents including fluoroquinolones, aminoglycosides and trimethoprim/sulfamethoxazole [4]. These infections are usually associated with high morbidity and mortality, long hospital stay and high healthcare costs [4,5]. FIIK plasmids with multiple antibiotic resistance genes including CTX-M-15 have been identified in K. pneumoniae [11]

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