Antimicrobial activity of doripenem (S-4661): a global surveillance report (2003)

The spectrum of activity and potency of doripenem, a broad-spectrum parenteral carbapenem currently in clinical development, was evaluated using 16 008 clinical bacterial isolates collected as part of an international surveillance project during 2003. Using reference broth microdilution methods, doripenem was found to be highly active against oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci (2705 and 297 isolates, respectively; MIC90s 0.06 mg/L), with a potency greater than that of other carbapenem antibiotics. Against enterococci (1474 isolates), with the exception of Enterococcus faecium, doripenem displayed modest activity (MIC50 4). Doripenem was among the most potent agents tested against Streptococcus pneumoniae, viridans group streptococci and β-haemolytic streptococci (885, 140 and 397 isolates; MIC90s 0.5, 0.5 and 0.03 mg/L, respectively). For Enterobacteriaceae (> 6200 isolates), doripenem was four- to 32-fold more active than imipenem against wild-type isolates (MIC90s 0.03-0.5 mg/L). MIC90s for confirmed extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (121 and 155 isolates; 0.06 and 0.12 mg/L, respectively) were two-fold higher than for wild-type isolates. Doripenem was also active against Citrobacter spp., Enterobacter spp. and Serratia spp. (MIC90s 0.06-0.25 mg/L), including ceftazidime-resistant isolates. Doripenem and meropenem were the most active agents among all β-lactams against Pseudomonas aeruginosa (829 isolates; MIC50/90s 0.5/8 and 0.5/16 mg/L, respectively), whereas doripenem and imipenem were the most active agents against Acinetobacter spp. (155 isolates; MIC50/90s 0.5/4 and <0.5/2 mg/L, respectively). Doripenem was slightly more potent (MIC50 2 mg/L) than ertapenem and imipenem (MIC50 4 mg/L), and had a potency similar to that of meropenem (MIC50 2 mg/L), against Burkholderia cepacia (20 isolates). Both Haemophilus influenzae (1824 isolates) and Moraxella catarrhalis (108 isolates), including β-lactamase-positive isolates, were susceptible to doripenem (MIC90s 0.25 and 0.03 mg/L, respectively). Doripenem displays the favourable characteristics of other carbapenems, and appears to offer certain advantages in terms of potency, spectrum and β-lactamase stability when compared with some carbapenems used currently to treat nosocomial infections.