Abstract
In vitro activities of ceftizoxime (CZX) against 328 clinical isolates were determined using the agar dilution method at an inoculum level of 108 cfu/ml. CZX was highly active against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Proteus vulgaris with MIC values below 0.20 μg/ml. It was also active against Serratia marcescens and Enterobacter aerogenes with MIC 85of 3.13 μg/ml. CZX was less active against Staphylococcus aureus and Staphylococcus epidermidis, showing inhibitory activities against only 47 and 78% of these clinical isolates, respectively, at a dose level of 12.5 μg/ml. CZX was not active against Pseudomonas aeruginosa and Enterococcus faecalis.
The reliability of CZX disc diffusion susceptibility tests for quantitative estimation of anti-microbial activities was also investigated using 8 mm diameter discs (Showa) and 6 mm diameter discs (Eiken), both of which contained 30 μg/disc of CZX. These disc susceptibility test results were well correlated with MICs, hence the CZX disc susceptibility test should be useful for the estimation of proper dose levels of CZX, except against P. aeruginosa and E. faecalis.
For the interpretation of CZX disc tests, a 3 category system has been used in USA and Europe, but a 4 category system is generally used in Japan. The 3 category system uses break points to classify bacteria into 3 categories of susceptibility according to MIC values as follows: resistant (R) MIC >32 μg/ml, moderately susceptible (MS) MIC 16-32 μg/ml, and susceptible (S) MIC ≤8 μg/ml. The 4 category system uses break points as follows (+++) MIC ≤3 μg/ml,(++) 3μg/ml ≤ MIC≤15 μg/ml,(+) 15 μg/ml ≤ MIC ≤60 μg/ml,(-) MIC ≥60 μg/ml.
Based on CZX pharmacokinetic data and the recommended modest dosage schedule (2-4g/day), MIC break points of 3 μg/ml and 15 μg/ml, appear to be more useful than & mak points of 8 μg/ml and 32 μg/ml for evaluating a proper dose level.
