Abstract
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≤3μg/ml,(_??_) MIC>3-15μg/ml,(+) MIC>15-60μg/ml,(-) MIC>60μg/ml. In the 3 category system the classification used is as follows: susceptible MIC≤16μg/ml, moderately susceptible MIC>16-32μg/ml, resistant MIC>32μg/ml, or susceptible MIC ≤32μg/ml, moderately susceptible MIC>32-64μg/ml, resistant MIC>64μg/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 75μg. The MICs were determined using the agar dilution method at an inoculum level of 106 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 75μg 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 75μg discs, it was unable to subclassify strains against which MICs of CPZ were below 3μg/ml. However, with discs containing 1 to 10μg, it was possible to separate the strains against which MICs were less than 0.5μg/ml. The fact that most frequent values of MICs of CPZ against Escherichia colt, Klebsiella pneumoniae, Proteus spp., Haemophilus influenzae, Streptococcus pyogenes etc. were less than 0.5μg/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. Furthermore, the binding to serum proteins of antibiotics decreases their antimicrobial activity. Therefore, plasma levels of free, unbound CPZ as well as total amounts must be evaluated with respect to the antimicrobial activity.
Based on the antimicrobial activity and pharmacokinetic data obtained with recommended modest dose schedule (2-6g/day) of CPZ, MIC break points of 3 and 15μg/ml utilized in the 4 category system are more useful than those of 16 and 32μg/ml used in the 3 category system for evaluating the antimicrobial activity of free, unbound CPZ levels in blood. Use of low dose (1-10μg) discs in addition to 30 or 75μg discs enable us to more precisely evaluate plasma levels of CPZ with respect to its clinical efficacy.
