In vitro and in vivo potency of polymyxin B against IMP-type metallo-β-lactamase-producing Pseudomonas aeruginosa

• Published in: International journal of antimicrobial agents 2008-11, Vol.32 (5), p.437-440
• Main Authors: Miyajima, Yoshiko, Hiramatsu, Kazufumi, Mizukami, Eri, Morinaga, Ryotaro, Ishii, Hiroshi, Shirai, Ryo, Kishi, Kenji, Tokimatsu, Issei, Saikawa, Tetsunori, Kadota, Jun-ichi
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteremia - drug therapy; Bacteremia - microbiology; beta-Lactamases - biosynthesis; beta-Lactamases - genetics; Biological and medical sciences; Colistin - pharmacology; Colony Count, Microbial; Drug Resistance, Bacterial - drug effects; Drug Resistance, Bacterial - genetics; IMP-type metallo-β-lactamase; Infectious Disease; Male; Medical sciences; Mice; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Polymyxin B; Polymyxin B - pharmacology; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - metabolism; Pseudomonas Infections - drug therapy; Pseudomonas Infections - microbiology; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2008.05.006

Abstract Multidrug-resistant Pseudomonas aeruginosa , especially metallo-β-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 blaIMP -positive P. aeruginosa obtained from clinical specimens (94.6% of isolates demonstrated resistance to β-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 (MIC50 /MIC90 ) 4/4 mg/L), although COL was less potent (MIC50 /MIC90 8/16 mg/L). Cyclophosphamide-treated mice were intraperitoneally inoculated with blaIMP -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 blaIMP -positive P. aeruginosa.