Potency of Carbapenems for the Prevention of Carbapenem-Resistant Mutants of Pseudomonas aeruginosa

The High Potency of a New Carbapenem Doripenem

Shihomi Sakyo, Haruyoshi Tomita, Koichi Tanimoto, Shuhei Fujimoto, Yasuyoshi Ike

Received: February 2, 2006 / Accepted: March 29, 2006
© Japan Antibiotics Research Association

Abstract The potencies of the carbapenems; doripenem (DRPM), meropenem (MEPM) and imipenem (IPM) in preventing the emergence of carbapenem-resistant mutants were examined in Pseudomonas aeruginosa strains. The carbapenems predominantly selected carbapenem-resistant mutants or carbapenem mutants with reduced susceptibilities that were specifically resistant to carbapenems and had arisen as a result of the reduced level of expression of the outer membrane protein with a molecular weight of about 48,000 (OprD). The potency of carbapenems in preventing the growth of the mutants differed for DRPM, MEPM and IPM. The isolation frequency of the mutant was examined on agar plates containing each of the carbapenems at a concentration of 1/2 or 1/4 MIC of each carbapenem for that mutant. Mutants were not selected on agar containing DRPM at a frequency of greater than 10−9 per cell per generation, whereas mutants of each strain were selected on agar containing MEPM or IPM at frequencies of 10−7 to 10−9 per cell per generation. The drug concentrations and the drug concentration range for the selective increase of carbapenem resistant mutants in the broth culture containing each carbapenem differed for each carbapenem. DRPM exhibited both the lowest drug concentration and the narrowest range of drug concentration for selection of the carbapenem-resistant mutants. The results shown in this report indicated that DRPM exhibited the greatest ability to prevent the emergence of the mutant.

Keywords carbapenem, doripenem, carbapenem-resistant mutant, outer membrane protein, prevention of mutation

Y. Ike (Corresponding author), S. Sakyo, H. Tomita, S. Fujimoto: Department of Bacteriology and Bacterial Infection Control, Gunma University Graduate School of Medicine, Showa-machi 3-39-22, Maebashi, Gunma 371-8511, Japan,
E-mail: yasuike@med.gunma-u.ac.jp
K. Tanimoto, Y. Ike: Laboratory of Bacterial drug Resistance, Gunma University Graduate School of Medicine, Showa-machi 3-39-22, Maebashi, Gunma 371-8511, Japan