[Clinical laboratory approach to evaluate efficacy of amikacin. Reevaluation of in vitro MIC break points in disc susceptibility test]

Abstract

Antimicrobial activities of amikacin (AMK) against 269 strains of various clinical isolates obtained in 1989 were determined and the reliability of the AMK disc susceptibility test in estimating approximate values of MICs was studied. In addition, clinical significance of various systems for the interpretation of the disc tests was evaluated to determine more useful method in the evaluation of clinical efficacy of AMK. Included in the study were a 3 category system of NCCLS, a 4 category system used in Japan, and the system proposed by the British Society for Antimicrobial chemotherapy. In this study, MICs were determined using the Mueller-Hinton agar containing 50 mg/L of Ca and 25 mg/L of Mg at an inoculum level of 10(3-4) CFU/ml. MIC80 values of AMK against Staphylococcus aureus and Staphylococcus epidermidis were 6.25 and 25 micrograms/ml, respectively. Those against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Enterobactor aerogenes, and Citrobacter spp. were less than 3.13 micrograms/ml. MIC values against Pseudomonas aeruginosa and Serratia marcescens were both less than or equal to 12.5 micrograms/ml. The disc susceptibility test was carried out according to the instruction in the Showa disc manual. Inhibition zones obtained with the disc method were compared with MIC values. The results of AMK disc susceptibility test obtained either with 30 micrograms discs or 10 micrograms discs were well correlated with MICs, indicating that the disc method was reliable in estimating approximate values of MICs (r = -0.807 to -0.897, P less than 0.01 in both instances). In the 4 category classification system currently used in Japan, the break points in MIC values of AMK proposed are (+3) MIC less than or equal to 3 micrograms/ml, (+2) MIC greater than 3-15 micrograms/ml, and (+) MIC greater than 15-60 micrograms/ml. The results obtained with Showa 30 micrograms discs and 30 micrograms discs prepared in this laboratory showed false positive results in 13% and 10.8% of the samples, and false negative results in 1.5% and 3.3%, respectively. In the 3 category classification system of NCCLS, the MIC break points proposed are defined sensitive (S) for MIC less than or equal to 16 micrograms/ml and resistant (R) for MIC greater than or equal to 32 micrograms/ml. In this study, the 30 micrograms disc tests using the above-mentioned 2 different types of discs resulted in false positive responses in 6.3% and 5.2% of the samples tested and false negative results in 1.1% and 1.9% of the samples, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)