In vitro antimicrobial effects of aztreonam, colistin, and the 3-drug combination of aztreonam, ceftazidime and amikacin on metallo-beta-lactamase-producing Pseudomonas aeruginosa.
BACKGROUND
There are limited choice of antimicrobial agents to treat infection with metallo-beta-lactamase-producing Pseudomonas aeruginosa. We evaluate the antimicrobial effects of aztreonam alone, colistin alone and the 3-drug combination of aztreonam, ceftazidime and amikacin on 23 strains of metallo-beta-lactamase-producing P. aeruginosa by time-killing tests.


METHODS
Strains used were from different hospitals in Japan and had different pulse-field gel electrophoresis patterns by restriction with SpeI. The minimum inhibitory concentrations of 11 antimicrobial agents (piperacillin, piperacillin/tazobactam, imipenem, meropenem, aztreonam, ceftazidime, amikacin, tobramycin, arbekacin, ciprofloxacin and colistin) were determined using the agar dilution test. The effects of aztreonam, colistin and the combination of aztreonam, ceftazidime and amikacin were determined by time-killing studies.


RESULTS
Bacteriostatic effects after 6 hours of drug exposure were observed in 12 strains (52.2%) of 23 strains of metallo-beta-lactamase-producing P. aeruginosa with 48 mg/l aztreonam, in 19 strains (82.6%) with the 3-drug combination of 16 mg/l aztreonam, 16 mg/l ceftazidime, and 4 mg/l amikacin, and in 23 strains (100%) with 2 mg/l colistin. Bactericidal effects after 6 h drug exposure were observed in 1 strain (4.3%) with 48 mg/l aztreonam, in 8 strains (30.4%) with the 3-drug combination and in all 23 strains (100%) with 2 mg/l colistin.


CONCLUSIONS
Evaluation of in vitro antimicrobial effects on metallo-beta-lactamase-producing P. aeruginosa revealed relatively good effects of the 3-drug combination of aztreonam, ceftazidime and amikacin and marked effects of colistin.
Oie
Shigeharu
S
Department of Pharmacy, Yamaguchi University Hospital, Ube, Japan. oie-ygc@umin.ac.jp
Fukui
Yumi
Y
Yamamoto
Masaya
M
Masuda
Yuki
Y
Kamiya
Akira
A
D000583:Amikacin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001398:Aztreonam / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000583:Amikacin; D002442:Ceftazidime; D001618:beta-Lactamases; D001398:Aztreonam; D003091:Colistin