VALIDATION OF NCCLS MACROLIDE (AZITHROMYCIN, CLARITHROMYCIN, AND ERYTHROMYCIN) INTERPRETIVE CRITERIA FOR HAEMOPHILUS-INFLUENZAE TESTED WITHTHE HAEMOPHILUS TEST MEDIUM

Some recently marketed macrolide antimicrobial agents possess physioch emical, antimicrobial, and pharmacokinetic advantages that enable thei r wider clinical use against Haemophilus influenzae infections. A five -laboratory study assessed the validity of existing or proposed azithr omycin, clarithromycin, and erythromycin interpretive criteria for tes ts with H. influenzae isolates. National Committee for Clinical Labora tory Standards (NCCLS) methods, criteria, and quality-control guidelin es were used. A total of 350 H. influenzae strains were processed, inc luding fresh clinical isolates (250 strains) and replicate tests of 10 0 stock cultures sampling strains isolated from 1984 to 91. Azithromyc in interpretive criteria (susceptible at less than or equal to 4 mu g/ ml, greater than or equal to 12 mm) produced a 99.8% absolute agreemen t between the minimum inhibitory concentrations and disk diffusion res ults (0.2% false-susceptible error) Clarithromycin breakpoint criteria (susceptible at less than or equal to 8 mu g/ml, greater than or equa l to 13 mm; and resistant at greater than or equal to 32 mu g/ml, less than or equal to 10 mm) produced high minor interpretive error, but l ess than or equal to 1% combined false-susceptible and false-resistant discrepancies. Erythrmycin interpretive guidelines were initially pro posed for susceptible at less than or equal to 0.5 mu g/ml, greater th an or equal to 26 mm. This categorizes nearly all H. influenzae strain s as resistant to this older macrolide. The NCCLS should consider the proposed erythromycin criteria for publication in appropriate tables, and a class drug should also be selected (azithromycin) that would bes t predict macrolide-class susceptibility for those agents indicated by the US Food and Drug Administration for H. influenzae infection chemo therapy (azithromycin and clarithromycin). No serious interpretive pro blems were observed with the current NCCLS criteria using Haemophilus test medium.