title: In vitro activity of various combinations of antimicrobials against carbapenem-resistant Acinetobacter species in Singapore.
abstract: Outbreaks of carbapenem-resistant Acinetobacter species have emerged, especially in Singapore. Combination therapy may be the only viable option until new antibiotics are available. The objective of this study was to identify potential antimicrobial combinations against carbapenem-resistant Acinetobacter baumannii and Acinetobacter species in Singapore. From an ongoing surveillance program, two isolates of A. baumannii and an isolate of Acinetobacter species that were multidrug resistant were selected on the basis of their unique resistance mechanisms. The two A. baumannii isolates carried the carbapenemase bla(OXA-23)-like gene and the Acinetobacter species carried a metallo-beta-lactamase IMP-4 gene. Time-kill studies were conducted with approximately 10(5) CFU ml(-1) at baseline with 0.5 times minimum inhibitory concentrations (MICs) of polymyxin B and tigecycline, and at a maximally achievable clinical concentration of meropenem(64 microg ml(-1)) and rifampicin(2 microg ml(-1)), alone and in combinations. The MICs (microg ml(-1)) of Acinetobacter species A105, A. baumannii AB112 and A. baumannii AB8879 to polymyxin B/tigecycline/rifampicin/meropenem were found to be 1/0.5/4/64, 1/4/4/32 and 2/2/2/64, respectively. In time-kill studies, enhanced combined killing effects were observed in the tigecycline-rifampicin combination; the tigecycline-rifampicin and rifampicin-polymyxin B combination; and the rifampicin-polymyxin B combination for Acinetobacter species A105, A. baumannii AB112 and A. baumannii AB8879, respectively, with >5 log kill at 24 h suggesting synergism, with no regrowth observed at 72 h. These findings demonstrate that in vitro synergy of antibiotic combinations in carbapenem-resistant Acinetobacter species may be strain dependent. It may guide us in choosing a preemptive therapy for carbapenem-resistant Acinetobacter species infections and warrants further investigations.
authors.affiliation: Department of Pharmacy, Singapore General Hospital, Singapore.
authors.forename: Tze-Peng
authors.initials: TP
authors.lastname: Lim
authors.forename: Thean-Yen
authors.initials: TY
authors.lastname: Tan
authors.forename: Winnie
authors.initials: W
authors.lastname: Lee
authors.forename: Suranthran
authors.initials: S
authors.lastname: Sasikala
authors.forename: Thuan-Tong
authors.initials: TT
authors.lastname: Tan
authors.forename: Li-Yang
authors.initials: LY
authors.lastname: Hsu
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Kwa
mesh_terms: D000150:Acinetobacter / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D000151:Acinetobacter Infections / Q000382:microbiology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015780:Carbapenems / Q000494:pharmacology*; D015169:Colony Count, Microbial; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D012846:Singapore; D013997:Time Factors; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D001618:beta-Lactamases