[Evaluation of antibiotics by the method of initial bactericidal activity]

Minimum inhibitory concentration (MIC) has been generally used to evaluate the activity of antimicrobial agents. However, there is some discrepancy between clinical efficacy and the MIC value. We studied the relationship between initial bactericidal activity of imipenem (IPM), panipenem (PAPM), meropenem (MEPM), ceftazidime (CAZ) and amikacin (AMK) and the respective MIC values against Pseudomonas aeruginosa PAO1. Initial bactericidal activity was defined as percent reduction of initial bacterial cell concentration (10(6) cells/ml) after 1 hour incubation following addition of antibiotic. The concentration of antibiotic used in this experiment was the blood level of each antibiotic at 3 hours after administration by drip infusion of the usual dose (IPM, PAPM and CAZ were 1 g for 1 hour drip infusion, MEPM was 1 g for 0.5 hours drip infusion and AMK was 200 mg for 1 hour drip infusion, respectively). The antibiotic concentration of IPM, PAPM, MEPM, CAZ and AMK were 8.77 micrograms/ml, 6.37 micrograms/ml, 4.12 micrograms/ml, 12.0 micrograms/ml and 5.18 micrograms/ml, respectively. MICs of IPM, PAPM, MEPM, CAZ and AMK were 2 micrograms/ml, 64 micrograms/ml, 1 microgram/ml, 1 microgram/ml and 2 micrograms/ml, respectively. Initial bactericidal activity of IPM, PAPM, MEPM, and CAZ against P. aeruginosa PAO1 was 98.2%, 86.1%, 48.1%, and 43.4% reduction in bacterial concentration, respectively. AMK shows the strongest initial bactericidal activity with more than 99.9%. The killing speed of IPM was obviously the most rapid among the three carbapenems. The MIC of PAPM was significantly higher than the other antibiotics, and the initial bactericidal activity of PAPM was second to IPM. We can classify antibiotics into two groups based on initial bactericidal activity against P. aeruginosa; one class is antibiotics having rapid initial killing such as AMK, IPM and PAPM, the other is CAZ, MEPM showing slow initial killing.