Comparative activity of doripenem and three other carbapenems tested against Gram-negative bacilli with various β-lactamase resistance mechanisms

Doripenem (formerly S-4661), a novel carbapenem antimicrobial, was compared with ertapenem, imipenem, and meropenem using reference broth microdilution test methods against wild-type and various resistant microbial subsets (380 strains). Doripenem and meropenem were consistently more potent than ertapenem or imipenem when tested against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. Ertapenem exhibited minimum inhibitory concentration (MIC) elevations for some isolates producing AmpC and extended-spectrum β-lactamases, in contrast to greater enzyme stability for doripenem and other carbapenems tested. Multiple β-lactamase (TEM, SHV, CTX-M, OXA, CMY types)-producing Escherichia coli had doripenem MIC values at ≤0.016 μg/mL (with higher values for ertapenem). Doripenem appears to be a promising, potent carbapenem for parenteral use against contemporary Gram-negative bacilli producing various β-lactamases.