Efficacy of Panipenem versus Imipenem against Clinical Isolate of Pseudomonas aeruginosa in a Two-Compartment Artificial Capillary Model

Lee, Dong Gun; Chun, Hye Sun; Choi, Su Mi; Choi, Jung Hyun; Yoo, Jin Hong; Shin, Wan Shik

Abstract

BACKGROUND: Panipenem (PAPM) is a new carbapenem which has an enhanced broad spectrum activity against both gram-positive and negative organisms. However, its activities in vitro against Pseudomonas aeruginosa are still under controversy. The aim of this study was to compare the activity of PAPM with those of imipenem (IMPM) against clinical isolates of P. aeruginosa using in vitro kinetic model and to evaluate the differences according to the quantity of basic amino acid in media.
MATERIALS AND METHODS
Using a clinical isolate of P. aeruginosa (SGP14) from blood, an in vitro 2-compartment artificial capillary model based on a dialyzer unit was prepared. Antibiotics were given as a bolus q12 hrs for 48 hrs. Simulated doses and frequencies of PAPM and IMPM were 500 mg q12 hrs as approved by Korea Food and Drug Administration. Muller-Hinton broth (MHB) and minimal broth Davis (MBD) were used as culture media and we divided the experiments into 4 groups [PAPM (MHB), PAPM (MBD), IMPM (MHB), IMPM (MBD)]. At 0, 1, 2, 4, 6, 8, 12, 24, 32, and 48 h, samples were removed from peripheral compartment and viable bacterial counts were measured.
RESULTS
The susceptibility of PAPM and IMPM for SGP14 were 64 and 2 ug/mL in MHB and 4 and 2 ug/mL in MBD, respectively. Up until 12 hours, changes in bacterial colony counts were not significantly different (P=0.073) for each group. However among the four groups, PAPM (MHB) showed the least changes compared with PMPM (MBD), IMPM (MBD). The largest decrement of colony during 48 hours was observed with PMPM (MBD), followed by IMPM (MHB) or IMPM (MBD), and PAPM (MHB) in decreasing order (P=0.00). There were no differences between IMPM (MHB) and IMPM (MBD) as for the change in colony counts.
CONCLUSIONS
The bactericidal activities of panipenem against the clinical isolate of P. aeruginosa was similar (at 12 h) or superior (at 48 h) to that of imipenem in an in vitro 2-compartment artificial capillary model using minimal broth to simulate human serum drug concentrations.