Worldwide experience with the use of doripenem against extended-spectrum-beta-lactamase-producing and ciprofloxacin-resistant Enterobacteriaceae: analysis of six phase 3 clinical studies - PubMed


Koné Kaniga 1 ,

Article Images

Worldwide experience with the use of doripenem against extended-spectrum-beta-lactamase-producing and ciprofloxacin-resistant Enterobacteriaceae: analysis of six phase 3 clinical studies

Koné Kaniga et al. Antimicrob Agents Chemother. 2010 May.

Abstract

The worldwide increase in fluoroquinolone-resistant and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae pathogens has led to doripenem and other carbapenems assuming a greater role in the treatment of serious infections. We analyzed data from 6 phase 3 multinational doripenem clinical trials on ciprofloxacin-resistant Enterobacteriaceae isolates consisting of all genera (CIPRE) and ESBL-producing Enterobacteriaceae isolates consisting of Escherichia coli, Klebsiella spp., and Proteus spp. with ceftazidime MICs of >or=2 microg/ml (ESBLE) for prevalence by geographic region and disease type, in vitro activities of doripenem and comparator agents, and clinical or microbiologic outcomes in doripenem- and comparator-treated patients across disease types (complicated intra-abdominal infection [cIAI], complicated urinary tract infection [cUTI], and nosocomial pneumonia [NP]). Of 1,830 baseline Enterobacteriaceae isolates, 88 (4.8%) were ESBLE and 238 (13.0%) were CIPRE. The incidence of ESBLE was greatest in Europe (7.8%); that of CIPRE was higher in South America (15.9%) and Europe (14.4%). ESBLE incidence was highest in NP (12.9%) cases; that of CIPRE was higher in cUTI (18.3%) and NP (14.9%) cases. Against ESBLE and CIPRE, carbapenems appeared more active than other antibiotic classes. Among carbapenems, doripenem and meropenem were most potent. Doripenem had low MIC(90)s for CIPRE (0.5 microg/ml) and ESBLE (0.25 microg/ml). Doripenem and comparators were highly clinically effective in infections caused by Enterobacteriaceae, irrespective of their ESBL statuses. The overall cure rates were the same for doripenem (82%; 564/685) and the comparators (82%; 535/652) and similar for ESBLE (73% [16/22] versus 72% [21/29]) and CIPRE (68% [47/69] versus 52% [33/64]). These findings indicate that doripenem is an important therapeutic option for treating serious infections caused by ESBLE and CIPRE.

Trial registration: ClinicalTrials.gov NCT00210938 NCT00210990 NCT00211003 NCT00211016 NCT00229021 NCT00229060.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.

MIC distributions of ESBLE (top panel) and CIPRE (bottom panel) for doripenem and comparator agents. ESBLE, extended-spectrum β-lactamase-producing Enterobacteriaceae isolates; CIPRE, ciprofloxacin-resistant Enterobacteriaceae isolates.

Similar articles

Cited by

References

    1. Chastre, J., R. Wunderink, P. Prokocimer, M. Lee, K. Kaniga, and I. Friedland. 2008. Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. Crit. Care Med. 36:1089-1096. - PubMed
    1. Clinical and Laboratory Standards Institute. 2006. Performance standards for antimicrobial susceptibility testing; 16th informational supplement, 19087-1898. Clinical and Laboratory Standards Institute, Wayne, PA.
    1. Kattan, J. N., M. V. Villegas, and J. P. Quinn. 2008. New developments in carbapenems. Clin. Microbiol. Infect. 14:1102-1111. - PubMed
    1. Keam, S. J. 2008. Doripenem: a review of its use in the treatment of bacterial infections. Drugs 68:2021-2057. - PubMed
    1. Lucasti, C., A. Jasovich, O. Umeh, J. Jiang, K. Kaniga, and I. Friedland. 2008. Efficacy and tolerability of IV doripenem versus meropenem in adults with complicated intra-abdominal infection: a phase III, prospective, multicenter, randomized, double-blind, noninferiority study. Clin. Ther. 30:868-883. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources