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JAC Advance Access published online on May 25, 2005

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki175
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org
Received February 16, 2005
Revised March 31, 2005
Accepted April 26, 2005

Original article

Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: molecular epidemiology and in vitro activity of polymyxin B and other agents

Simona Bratu 1, Pooja Tolaney 1, Usha Karumudi 1, John Quale 1, Mohamad Mooty 1, Satyen Nichani 1, and David Landman 1*

1 Department of Medicine, SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 77, Brooklyn, NY 11203, USA

* To whom correspondence should be addressed.
David Landman, E-mail: dlandman{at}downstate.edu


   Abstract

Objectives: To describe the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in Brooklyn, NY and assess the in vitro activity of various antibiotic combinations.

Methods: Clinical isolates with suspected carbapenem resistance were referred to the central research laboratory from August 2003 to June 2004. Isolates underwent MIC testing, ribotyping, and were analysed for the presence of KPC carbapenemases. Time-kill studies using various antibiotic(s) were performed on selected isolates.

Results: Ninety-six isolates were referred from 10 Brooklyn hospitals. All isolates were resistant to the carbapenems with most having MICs >32 mg/L. Few were susceptible to fluoroquinolones and cephalosporins; approximately half were susceptible to aminoglycosides, and 90% to polymyxin B. Two-thirds were susceptible to doxycycline, and all were considered susceptible to the investigational glycylcycline antibiotic tigecycline. Virtually all possessed blaKPC, and over 80% belonged to one ribotype. In time-kill studies involving 16 isolates, tigecycline demonstrated bacteriostatic activity and polymyxin B concentration-dependent bactericidal activity. The combination of polymyxin B at 0.5 x MIC plus rifampicin had synergic activity against 15/16 isolates, including two polymyxin-resistant strains. The combination of polymyxin B plus imipenem had synergic bactericidal activity against 10/16 isolates, but was antagonistic for three isolates.

Conclusions: Multiresistant K. pneumoniae with blaKPC are present in multiple hospitals in New York City. The most consistently active agents in vitro were tigecycline and polymyxin B, particularly when the latter was combined with rifampicin. The clinical efficacy of these agents remains to be determined.

Keywords: antibiotic resistance; {beta}-lactamases; imipenem; tigecycline.
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