title: Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region.
abstract: Carbapenems are increasingly being utilised owing to the escalating prevalence of antimicrobial-resistant Gram-negative bacteria from community and hospital settings. In this study, pharmacodynamic profiles of doripenem, imipenem and meropenem were evaluated against Gram-negative bacteria isolated from hospitalised patients. MICs for carbapenems were determined for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii obtained from the COMPACT II programme conducted in the Asia-Pacific region. Monte Carlo simulations were undertaken to assess the pharmacodynamic profile of carbapenems against each of the pathogens. All carbapenem regimens achieved optimal exposures [cumulative fraction of response (CFR) ≥90%] against E. coli and K. pneumoniae. Against P. aeruginosa, doripenem achieved 81.3-95.3% CFR, imipenem achieved 55.2-77.9% CFR and meropenem achieved 71.9-91.3% CFR; only doripenem regimens of 4-h infusion of 1000 mg every 8h (q8h) and 1-h and 4-h infusion of 2000 mg q8h and a meropenem regimen of 3-h infusion of 2000 mg q8h obtained optimal exposures; all carbapenem regimens showed slight (1-7%) improvement in CFRs in favour of isolates collected from ICU sources. Against A. baumannii, CFRs were much lower (25.9-46.7% CFR) and no carbapenem regimens achieved optimal exposure in or outside the ICU. Owing to the high potency of carbapenems against these Enterobacteriaceae populations, standard regimens are likely to perform well in the Asia-Pacific region. However, larger doses combined with prolonged infusions will be required to increase the CFR for these carbapenems against resistant non-fermenting Gram-negatives such as P. aeruginosa and A. baumannii that are prevalent in these countries.
authors.affiliation: Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Pattarachai
authors.initials: P
authors.lastname: Kiratisin
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Keel
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015780:Carbapenems / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077726:Doripenem; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D010139:Pacific Islands; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013845:Thienamycins; D015378:Imipenem; D000077726:Doripenem; D000077731:Meropenem