title: Comparative activity of doripenem and three other carbapenems tested against Gram-negative bacilli with various beta-lactamase resistance mechanisms.
abstract: 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 beta-lactamases, in contrast to greater enzyme stability for doripenem and other carbapenems tested. Multiple beta-lactamase (TEM, SHV, CTX-M, OXA, CMY types)-producing Escherichia coli had doripenem MIC values at </=0.016 mug/mL (with higher values for ertapenem). Doripenem appears to be a promising, potent carbapenem for parenteral use against contemporary Gram-negative bacilli producing various beta-lactamases.
authors.affiliation: The JONES Group/JMI Laboratories, North Liberty, IA 52317, USA. ronald-jones@jmilabs.com
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fritsche
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000737:chemistry / Q000494:pharmacology*; D000077726:Doripenem; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008826:Microbial Sensitivity Tests; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem; D001618:beta-Lactamases