Abstract
Reliability of the cefamandole (CMD) disc susceptivility test in estimating approximate values of MICs was studied using various clinical isolates totaling 246 strains with Showa discs (8 mm diameter containing 30μ g of CMD). Clinical significance of a 4 category system for the interpretation of the CMD disc tests, which is normally used in Japan, was also evaluated to determine whether this system would be suitable or not for the evaluation of a proper dose of administration.
The results obtained with the disc method were compared with MICs determined using the agar dilution method at an inoculum level of 108 CFU/ml. The results of the CMD disc susceptibility test were well correlated with MICs, showing the reliability of the disc method to estimate approximate values of MICs. Break points in MIC values proposed for the classification ofbacteria into 4 categories of susceptibility are (+++) MIC ≤ 3μ g/ml,(++) MIC > 3-15μ g/ml, MIC > 15-60 μ g/ml,(-) MIC > 60 μ g/ml. Only 4 (1.6%) out of the 246 strains tested showed false positive results and 11 (4.5%) showed false negative results, showing the excellent reliability of this test.
In this study, approximately 90% of strains of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolated from clinical materials randomely were inhibited by CMD at concentrations less than 3. 13 μ g/ml. Proteus vulgaris and Enterobacter aerogenes were sensitive to CMD at 67 and 69% of strains, respectively, at concentrations below 6. 25 μ g/ml. CMD was not active against Pseudomonas aeruginosa, Serratia marcescens and Enterococcus faecalis. About 90% of Staphylococcus aureus were inhibited at dose levels smaller than 6. 25 μ g/ml and 70% of the strains at levels less than 3. 13 μ g/ml.
Susceptibilities to 15 μ g/ml CMD of highly methicillin-resistant strains (MIC > 30 μ g/ml)of S. aureus were examined. Ten of 12 strains examined were found susceptible to CMD, but only 6 of the 12 to cefmetazole. Imipenem/cilastatin was effective to 5 of the 12 strains at levels lower than 3 μ g/ml and to one at a level less than 15 μ g/ml. Minocycline was effective against 11 strains at concentrations below 2 μ g/ml.
Based on the antimicrobial activity and pharmacokinetic data of the recommended dosage schedule of CMD (less than 4 g a day) MIC break points of < 3 μ g/ml and < 15 μ g/ml in a 4 category system appear to be more useful than those of < μ g/ml and < 32 μ g/ml utilized in a 3 category system for evaluation of a proper administrative dose.
