Part of this work was presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, MA, 2010.
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Rapid acquisition of decreased carbapenem susceptibility in a strain of Klebsiella pneumoniae arising during meropenem therapy
Article first published online: 11 JUL 2011
DOI: 10.1111/j.1469-0691.2011.03515.x
© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases
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How to Cite
Findlay, J., Hamouda, A., Dancer, S. J. and Amyes, S. G. B. (2012), Rapid acquisition of decreased carbapenem susceptibility in a strain of Klebsiella pneumoniae arising during meropenem therapy. Clinical Microbiology and Infection, 18: 140–146. doi: 10.1111/j.1469-0691.2011.03515.x
Publication History
- Issue published online: 20 JAN 2012
- Article first published online: 11 JUL 2011
- Accepted manuscript online: 23 MAR 2011 07:10AM EST
- Original Submission: 15 December 2010; Revised Submission: 2 February 2011; Accepted: 3 March 2011 Editor: M. Drancourt
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Keywords:
- CTX-M-15;
- efflux;
- ertapenem;
- Klebsiella pneumoniae;
- outer membrane proteins
Clin Microbiol Infect 2012; 18: 140–146
Abstract
A strain of Klebsiella pneumoniae (K1) was isolated from a catheterized patient with a urinary tract infection. The patient was subsequently treated with meropenem, after which K. pneumoniae (K2) was once again isolated from the patient’s urine. Susceptibility testing showed that strain K1 was fully susceptible to carbapenem antibiotics with the exception of ertapenem, to which it exhibited intermediate resistance, whilst K2 was resistant to ertapenem and meropenem. From pulsed-field gel electrophoresis profiling both strains exhibited identical banding patterns. Both contained CTX-M-15, OXA-1, SHV-1 and TEM-1 β-lactamase genes following PCR analyses. Outer membrane protein analysis demonstrated that K1 and K2 lacked an OMP of c. 40 kDa, with an additional OMP of c. 36 kDa missing from K2. Mutation studies showed that the K2 OMP phenotype could be selected by single-step carbapenem-resistant mutants of K1. Expression of transcriptional activator ramA and efflux pump component gene acrA were up-regulated in both strains by RT-PCR. Neither strain expressed ompK35, but ompK36 was found in both. Sequence analysis revealed gene sequences of ompK35, ompK36 and ramR in both strains; notably, ramR contained a mutation resulting in a premature stop codon. Transconjugation studies demonstrated transfer of a plasmid into E. coli encoding the CTX-M-15, TEM-1 and OXA-1 β-lactamases. We concluded that the carbapenem-resistant phenotype observed from this patient was attributable to a combination of CTX-M-15 β-lactamase, up-regulated efflux and altered outer membrane permeability, and that K2 arose from K1 as a direct result of meropenem therapy.