The in-vitro and disc susceptibility testing of clarithromycin and its 14-hydroxy metabolite

The in-vitro antibacterial activity of clarithromycin, its 14-hydroxy metabolite and a combination containing clarithromycin and the 14-hydroxy metabolite in a ratio of three parts of the former to one part of the latter were compared with erythromycin by determination of MICs. Disc susceptibility testing was also performed using discs containing 6 micrograms clarithromycin, 6 micrograms clarithromycin with 2 micrograms 14-hydroxy-clarithromycin, 3 micrograms clarithromycin and 3 micrograms clarithromycin with 1 microgram 14-hydroxy-clarithromycin. This was to determine a suitable disc content and minimum zone diameter to distinguish between sensitive and resistant strains using a breakpoint of 4 mg/l clarithromycin. Clarithromycin showed similar activity to erythromycin against Streptococcus pneumoniae and Haemophilus influenzae, although the 14-hydroxy metabolite was more active against H. influenzae. The clarithromycin/14-hydroxy metabolite combination was most active against beta-haemolytic streptococci (Groups A-C) (mode MIC 0.06 mg/l). The parent compound and the combination were similarly active against Staphylococcus aureus (MIC50 0.12 mg/l). Branhamella catarrhalis was more susceptible to clarithromycin (MIC90 0.06) than to erythromycin (MIC90 0.25 mg/l). Activities of all compounds against S. epidermidis and enterococci were similar but against Neisseria species erythromycin was the more active compound. The 6 micrograms clarithromycin disc strength was found to give the most consistent results for all isolates. Using a breakpoint of 4 mg/l, minimum zone diameters indicative of sensitivity were as follows: 16 mm for staphylococci, 17 mm for respiratory pathogens and 11 mm for streptococci and Neisseria spp.