VARIABILITY IN SUSCEPTIBILITIES OF HAEMOPHILUS-INFLUENZAE TO CLARITHROMYCIN AND AZITHROMYCIN DUE TO MEDIUM PH

The National Committee for Clinical Laboratory Standards (NCCLS) metho ds for susceptibility testing of Haemophilus influenzae in Haemophilus test medium allow a pH range of 7.2 to 7.4. However, it is known that bacteria may appear to he less susceptible to macrolides at lower pHs . Forty-four strains of H. influenzae were tested for their susceptibi lities to clarithromycin and azithromycin by the disk diffusion and br oth microdilution methods, The isolates appeared to be less susceptibl e at pH 7.2 than at pH 7.4 by both methods, Clarithromycin was less ac tive at pH 7.2 against 43% of the isolates by the disk diffusion metho d and against 52% of the isolates by the broth microdilution method, S imilarly, azithromycin was less active at pH 7.2 against 41 and 45% of the isolates by the disk diffusion and broth microdilution methods, r espectively, Forty-two isolates were classified as clarithromycin susc eptible and all isolates were classified as azithromycin susceptible b y the disk diffusion method, regardless of the medium pH, However, onl y 21 isolates were clarithromycin susceptible at pH 7.2 and 34 isolate s were susceptible at pH 7.4 by the broth microdilution method, even t hough quality control results indicated valid testing at both pHs. Thi s study indicated that the results of tests of the susceptibility of H . influenzae with clarithromycin and azithromycin are highly dependent on the pH of the medium, Test results and their interpretations varie d even when the medium pH was within the NCCLS-approved range and, cou pled with the current NCCLS breakpoint of 8 mu g/ml in the case of cla rithromycin, may explain some of the observed discordances between the disk diffusion and broth microdilution methods.