Doripenem activity tested against a global collection of Enterobacteriaceae, including isolates resistant to other extended-spectrum agents

The emergence and rapid dissemination of extended-spectrum β-lactamase (ESBL)-producing isolates among Enterobacteriaceae coupled with increasing prevalence of stably derepressed and plasmid-borne AmpC producers have rendered broad-spectrum cephalosporins and β-lactam/β-lactamase inhibitor combinations less effective. This scenario has required the use of carbapenems for treatment of infections caused by such organisms. In this study, the in vitro activities of doripenem and comparator agents against Enterobacteriaceae, including ESBL- and AmpC-producing strains, were evaluated. A total of 36 614 isolates collected from more than 60 medical centers (2000–2007) were included and tested for susceptibility using reference methods and interpretive criteria, except for doripenem (product package insert). Overall, doripenem inhibited 98.7% of all Enterobacteriaceae tested at ≤0.5 μg/mL. ESBL rates were higher among Klebsiella pneumoniae (from 7.7% to 44.0%, varied by geographic region), followed by Escherichia coli (3.6–14.0%) and Proteus mirabilis (0.8–34.8%). Derepressed AmpC production-mediated resistance rates were highest among Enterobacter cloacae (26.6–38.7%) compared with other species and generally higher for strains isolated in the Asia-Pacific and Latin American regions. Doripenem inhibited 94.3% and 93.7% of the ESBL phenotype and derepressed AmpC isolates, respectively, and these resistances had little adverse influence on doripenem MIC50 values (nil to 2-fold increases). The observed increase in AmpC- and ESBL-producing Enterobacteriaceae necessitates a greater confidence on carbapenem empiric therapy. Doripenem could represent a valuable choice for broad-spectrum coverage of contemporary Enterobacteriaceae isolates with widespread resistance mechanisms.