CLINICAL LABORATORY APPROACH TO EVALUATE ADMINISTRATION DOSE OF ARBEKACIN: REEVALUATION OF IN VITRO MIC BREAK POINTS IN THE DISK SUSCEPTIBILITY TEST

Antimicrobial activities of arbekacin (ABK) against various clinical isolates, 335 strains obtained in 1991, were determined and the reliability of the ABK disk susceptibility test in estimating approximate values of MICs was studied. In addition, clinical significance of two different systems for the interpretation of the disk tests was evaluated as to which system would be more useful for the evaluation of clinical efficacy of ABK. The 4 category system used in Japan, and the system proposed by the Japanese Society for Antimicrobial Chemotherapy were studied. In this study, MICs were determined using the Mueller-Hinton agar containing 50mg/L of Ca and 25mg/L of Mg at an inoculum level of 106 CFU/ml. MIC90 values of ABK against Staphylococcus aureus (MSSA and MRSA) and Staphylococcus epidermidis were both 3.13μg/ml. Those against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris, Enterobacter spp., and Citrobacter spp., were also≤3.13μg/ml. MIC90values against Pseudomonas aeruginosa and Serratia spp. were both 50μg/ml. The disk susceptibility test was carried out according to the instruction in the Showa disk manual. The inhibition zones obtained with the disk method were compared with MICs. Results of ABK disk susceptibility test with 30, 10, 5 or 2μg disks were well correlated with MICs, showing the reliability of the disk method in estimating approximate values of MICs (r=-0.627-0.724, P10-50μug/ml and (-) MIC>50μg/ml. The results obtained with Showa 30μg disks showed false positive in 13.4%, and false negative in 3.9% of the samples. With 10μg disks, false positive and false negative were 8.1%, and 3.9%, respectively. Similarly, those with 5μg and 2μg disks were 6.9% and 7.2%, and 3.0% and 14.6%, respectively. In the break point classification system of Japanese Society for Antimicrobial Chemotherapy, the MIC break point for ABK proposed is 2μg/ml. It appeared to be difficult to make out this break point on the inhibition zone diameters obtained with various disks used, since there were nosignificant difference in the inhibition zone diameters against strains with MIC values ranging 0.39-3.13μg/ml. A pharmacokinetic examination with the recommended dose schedule for ABK (100mg IM or IV) showed that plasma levels of ABK reached 3.7-11.3μg/ml. Based on the pharmacokinetic