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.