Vol.53 No.12 December 2005

Comparative basic study of carbapenems antibiotics against Pseudomonas aeruginosa

Chieko Shimauchi¹⁾, Kenichi Kaneko²⁾, Yoshinori Sato²⁾, Yuko Sato³⁾, Ryoichi Okamoto^2,3) and Matsuhisa Inoue⁴⁾

¹⁾Department of Environmental Infectious Diseases, Graduate School of Medical Sciences, Kitasato University (Present: Miyazaki Prefectural Nursing University)
²⁾Department of Environmental Infectious Diseases, Graduate School of Medical Sciences, Kitasato University,
³⁾Department of Microbiology, School of Medicine, Kitasato University
⁴⁾Department of Environmental Infectious Diseases, Graduate School of Medical Sciences, Kitasato University,
Department of Microbiology, School of Medicine, Kitasato University,
1-15-1 Kitasato, Sagamihara, Kanagawa, Japan

Abstract

Carbapenems antibiotics [imipenem/cilastatin (IPM/CS), meropenem (MEPM), biapenem (BIPM) and doripenem (DRPM)] were compared in terms of their antimicrobial activity against Pseudomonas aeruginosa, their growth inhibition ring during incubation, their bactericidal effect in the presence or absence of serum, morphological changes, their binding affinity to penicillin-binding proteins (PBPs), and the influence of human serum and the inducibility of AmpC β-lactamase. The MIC₅₀ and MIC₉₀ values of IPM/CS, MEPM, BIPM and DRPM against 50 strains of P. aeruginosa clinically isolated in 2003 were 2 and 16, 1 and 16, 1 and 16 and 1 and 8 μg/mL, respectively. The 1-hour bactericidal activity of carbapenem antibiotics that did not induce the formation of a double inhibition ring (IPM/CS and BIPM) was stronger than that of the drugs that induced a double ring formation (MEPM and DRPM). At the MIC of each drug, the bactericidal effect of IPM/CS and BIPM increased in the presence of human serum, but no increase was observed for MEPM or DRPM. This bactericidal activity was well reflected in the microbial conglobation (spherical forms) and bacteriolytic images observed in association with IPM/CS and BIPM. On the other hand, numerous microbes became filamentous after treatment with DRPM and MEPM, but no bacteriolytic images were seen. IPM/CS and BIPM exhibited the strongest binding affinity for PBP4, followed by 2, 1A≡3 and 1B. MEPM exhibited the strongest binding affinity for PBP4, followed by 3, 2, and 1A≡1B, and DRPM showed the strongest affinity for PBP4, followed by 3, 2, 1A and 1B. From the aspect of enzyme inducibility strong activity was observed for IPM/CS and BIPM, compared with MEPM and DRPM. These findings suggested that carbapenem antibiotics can be divided into two types: those with a strong bactericidal activity (IPM/CS, BIPM and perhaps panipenem) and those with a weak bactericidal activity (MEPM and DRPM).

Key word

Pseudomonas aeruginosa, carbapenem, penicillin binding proteins, class C β-lactamase, inducibility

Received

October 13, 2005

Accepted

November 9, 2005

Jpn. J. Chemother. 53 (12): 732-740, 2005