title: Comparative in vitro susceptibility of Burkholderia pseudomallei to doripenem, ertapenem, tigecycline and moxifloxacin.
abstract: Burkholderia pseudomallei, the causative agent of melioidosis, continues to present therapeutic challenges in endemic areas. A number of clinical issues have prompted consideration of alternative antimicrobial therapies. These include stability in 24-h infusion pumps, broad-spectrum coverage in the empirical treatment of community-acquired pneumonia, cost, the need for effective oral agents and rare reports of emerging resistance. This study aimed to examine the in vitro susceptibility of B. pseudomallei to four new antimicrobial agents, namely moxifloxacin, tigecycline, ertapenem and doripenem. A total of 100 clinical isolates were tested by Etest and disk diffusion. As there are no interpretative standards for these antimicrobials, MIC(90) values (minimum inhibitory concentrations for 90% of the isolates) were compared with those for meropenem. MIC values for each agent were correlated with zone of inhibition diameters. MICs for doripenem were broadly similar to those for meropenem, with a MIC(90) of 1.5 μg/mL (range 0.38-4 μg/mL). There was good correlation (r=-0.71; P<0.001) between the MIC and disk diffusion for doripenem. Ertapenem, tigecycline and moxifloxacin had limited in vitro activity in this study, although no interpretative criteria exist for these agents. Further in vitro, animal and clinical studies are suggested to validate the efficacy of doripenem in the management of melioidosis.
authors.affiliation: Pathology Queensland, Townsville Hospital, 100 Angus Smith Drive, Douglas, Queensland 4814, Australia. padstock@hotmail.com
authors.forename: Patrick
authors.initials: P
authors.lastname: Harris
authors.forename: Cathy
authors.initials: C
authors.lastname: Engler
authors.forename: Robert
authors.initials: R
authors.lastname: Norton
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology; D016957:Burkholderia pseudomallei / Q000187:drug effects* / Q000302:isolation & purification; D015780:Carbapenems / Q000494:pharmacology; D000077726:Doripenem; D000077727:Ertapenem; D024841:Fluoroquinolones; D006801:Humans; D008554:Melioidosis / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D000077266:Moxifloxacin; D011804:Quinolines / Q000494:pharmacology; D000078304:Tigecycline; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D015780:Carbapenems; D024841:Fluoroquinolones; D011804:Quinolines; D047090:beta-Lactams; D000078304:Tigecycline; D000077726:Doripenem; D008911:Minocycline; D000077727:Ertapenem; D000077266:Moxifloxacin