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.
Logan
M N
MN
Department of Medical Microbiology, Dudley Road Hospital, Birmingham, UK.
Ashby
J P
JP
Andrews
J M
JM
Wise
R
R
D001419:Bacteria / Q000187:drug effects*; D001798:Blood Proteins / Q000378:metabolism*; D017291:Clarithromycin / Q000031:analogs & derivatives; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination / Q000494:pharmacology; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011485:Protein Binding
D001798:Blood Proteins; C056228:14-hydroxyclarithromycin; D004917:Erythromycin; D017291:Clarithromycin