In vitro activity of colistin or sulbactam in combination with fosfomycin or imipenem against clinical isolates of carbapenem-resistant Acinetobacter baumannii producing OXA-23 carbapenemases.
This study investigated the in vitro activity of colistin or sulbactam in combination with fosfomycin or imipenem against eight strains of carbapenem-resistant A. baumannii (CRAB). The eight CRAB clinical isolates were collected from hospitalized patients admitted to Songklanagarind Hospital in southern Thailand during January-December 2008. The isolates were divided into 4 different patterns of clonal relationships using the Repetitive Extragenic Palindromic-Polymerase Chain Reaction method (REP-PCR). The in vitro activity of combination antibacterial agents against theses isolates were determined by chequerboard and time-kill methods. All isolates producing OXA-23 carbapenemases were universally susceptible to colistin but intermittently susceptible to other antimicrobial agents. A chequerboard assay showed the synergistic effects of sulbactam plus fosfomycin and colistin plus fosfomycin in 75% and 12.5% of isolates, respectively. Sulbactam at a concentration of 1 x MIC plus fosfomycin at 1 x MIC or at 1/4 x MIC showed synergism in 75% and 37.5% of clinical isolates, respectively. Bactericidal activity was observed for up to 12 hours of incubation. There was no synergism between colistin and sulbactam, sulbactam and imipenem, and colistin and imipenem, against the tested isolates. Combined use of sulbactam and fosfomycin may provide an alternative therapeutic option for CRAB infections.
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, Thailand. wichai1234@gmail.com
Wichai
W
Santimaleeworagun
Payom
P
Wongpoowarak
Pantip
P
Chayakul
Sutthiporn
S
Pattharachayakul
Pimpimon
P
Tansakul
Kevin W
KW
Garey
D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D015780:Carbapenems / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005578:Fosfomycin / Q000494:pharmacology; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D013785:Thailand; D013997:Time Factors; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D005578:Fosfomycin; D015378:Imipenem; D001618:beta-Lactamases; C063912:carbapenemase; D003091:Colistin