Journal
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Volume 39, Issue 3, Pages 251-254Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijantimicag.2011.10.012
Keywords
Carbapenemase; Enterobacteriaceae; Multidrug resistance; Colistin; Tigecycline
Funding
- Ministerio de Ciencia e Innovacion, Instituto de Salud Carlos III
- European Development Regional Fund 'A way to achieve Europe' ERDF
- Spanish Network for the Research in Infectious Diseases [REIPI RD06/0008/0000]
- INSERM (Paris, France) [U914]
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New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an experimental model of pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella pneumoniae. The susceptibilities of K. pneumoniae NDM, E. coli NDM and K. pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an experimental model of pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 (K. pneumoniae NDM) and 37 (K. pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. pneumoniae NDM and K. pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 log CFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. pneumoniae NDM and K. pneumoniae ATCC 29665 load by 2.67 log CFU/g and 4.62 log CFU/g (P < 0.05). Colistin and tigecycline decreased lung concentrations of E. coli NDM by 2.27 log CFU/g and 4.15 log CFU/g (P < 0.05), respectively, compared with controls, and was more active than colistin (P < 0.05). In conclusion, these results suggest that colistin is inappropriate for treating pneumonia due to NDM-1-producing K. pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli. A high tigecycline dose was efficacious for treating experimental pneumonia due to NDM-1-producing E. coli and K. pneumoniae. (C) 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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