[Clinical laboratory approach for estimating effective administrative dose of cefoperazone. Evaluation of disc...

To interpret of the cefoperazone (CPZ) disc susceptibility test, a 4 category system is used in Japan, but a 3 category system is used in the U.S.A. and Europe. In the 4 category interpretation system of Showa CPZ disc the following classification is used: ( ) MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3 approximately 15 micrograms/ml, (+) MIC greater than 15 approximately 60 micrograms/ml, (-) MIC greater than 60 micrograms/ml. In the 3 category system the classification used is as follows: susceptible MIC less than or equal to 16 micrograms/ml, moderately susceptible MIC greater than 16 approximately 32 micrograms/ml, resistant MIC greater than 32 micrograms/ml, or susceptible MIC less than or equal to 32 micrograms/ml, moderately susceptible MIC greater than 32 approximately 64 micrograms/ml, resistant MIC greater than 64 micrograms/ml, depending on dose levels, 1 or 2 g. Reliability of the CPZ disc susceptibility test in estimating approximate MICs by classifying the test results into 4 categories was studied using discs containing 1, 2, 5, 10, 30 and 75 micrograms. The MICs were determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. A good negative correlation was observed between inhibitory zone diameters and MICs, showing reliability of the test using these discs. The results obtained with discs containing 30 or 75 micrograms of CPZ were well categorized into the 4 groups mentioned above. Some strains of Pseudomonas aeruginosa and Enterococcus faecalis, however, showed false positive results. When different break points of inhibitory zone diameters than those used for other bacteria were used for P. aeruginosa, and E. faecalis was excluded from the test, an excellent correlations were obtained. With 30 or 75 micrograms discs, it was unable to subclassify strains against which MICs of CPZ were below 3 micrograms/ml. However, with discs containing 1 to 10 micrograms, it was possible to separate the strains against which MICs were less than 0.5 microgram/ml. The fact that most frequent values of MICs of CPZ against Escherichia coli, Klebsiella pneumoniae, Proteus spp., Haemophilus influenzae, Streptococcus pyogenes etc. were less than 0.5 microgram/ml supports the usefulness of low dose discs. According to recently ongoing concepts on the pharmacokinetics of antibiotics and their penetration into tissues and inflammatory fluids, serum protein binding appear to be one of the important determinants of drug distribution in the body. Only free, unbound drug molecules can readily pass through capillary pores into tissue fluids except into hepatic biliary system.(ABSTRACT TRUNCATED AT 400 WORDS)