In vitro and in vivo potency of polymyxin B against IMP-type metallo-beta-lactamase-producing Pseudomonas aeruginosa.
Multidrug-resistant Pseudomonas aeruginosa, especially metallo-beta-lactamase (MBL)-producing P. aeruginosa, is an important pathogen in nosocomial infection and emergence of this pathogen has revived interest in polymyxin B (PMB) and colistin (COL). In this study, we evaluated the efficacies of PMB, COL and other antipseudomonal agents against IMP-type MBL-producing P. aeruginosa both in vitro and in vivo. A total of 75 isolates of bla(IMP)-positive P. aeruginosa obtained from clinical specimens (94.6% of isolates demonstrated resistance to beta-lactam, fluoroquinolone and aminoglycoside agents) were evaluated in the in vitro study. More than 90% of the examined isolates were susceptible to PMB (minimum inhibitory concentration for 50/90% of the isolates (MIC(50)/MIC(90)) 4/4 mg/L), although COL was less potent (MIC(50)/MIC(90) 8/16 mg/L). Cyclophosphamide-treated mice were intraperitoneally inoculated with bla(IMP)-positive P. aeruginosa. Treatment with PMB, but not COL, imipenem/cilastatin or aztreonam, significantly improved the survival rate and decreased the number of bacteria in the blood in a dose-dependent manner. Our results indicate that, among the agents studied, PMB is the most effective agent against bla(IMP)-positive P. aeruginosa.
Miyajima
Yoshiko
Y
Department of Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, 879-5593, Japan.
Hiramatsu
Kazufumi
K
Mizukami
Eri
E
Morinaga
Ryotaro
R
Ishii
Hiroshi
H
Shirai
Ryo
R
Kishi
Kenji
K
Tokimatsu
Issei
I
Saikawa
Tetsunori
T
Kadota
Jun-Ichi
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D003091:Colistin / Q000494:pharmacology; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D011112:Polymyxin B / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
D000900:Anti-Bacterial Agents; D001618:beta-Lactamases; D011112:Polymyxin B; D003091:Colistin