Open AccessWorldwide Experience with the Use of Doripenem against Extended-Spectrum-β-Lactamase-Producing and Ciprofloxacin-Resistant Enterobacteriaceae : Analysis of Six Phase 3 Clinical Studies
Author(s) -
Koné Kaniga,
Robert K. Flamm,
Shin-Yir Tong,
Michael Lee,
Ian R. Friedland,
Rebecca Redman
Publication year - 2010
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01450-09
Subject(s) - doripenem , meropenem , enterobacteriaceae , microbiology and biotechnology , ciprofloxacin , medicine , carbapenem , ceftazidime , ceftazidime/avibactam , antibiotics , biology , antibiotic resistance , escherichia coli , bacteria , pseudomonas aeruginosa , biochemistry , genetics , gene
The worldwide increase in fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-producingEnterobacteriaceae 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-resistantEnterobacteriaceae isolates consisting of all genera (CIPRE) and ESBL-producingEnterobacteriaceae isolates consisting ofEscherichia coli ,Klebsiella spp., andProteus spp. with ceftazidime MICs of ≥2 μg/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 baselineEnterobacteriaceae 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 MIC90 s for CIPRE (0.5 μg/ml) and ESBLE (0.25 μg/ml). Doripenem and comparators were highly clinically effective in infections caused byEnterobacteriaceae , 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.