IN-VITRO ACTIVITY OF CLARITHROMYCIN ALONE AND IN COMBINATION WITH CIPROFLOXACIN OR LEVOFLOXACIN AGAINST LEGIONELLA SPP - ENHANCED EFFECT BYTHE ADDITION OF THE METABOLITE 14-HYDROXY CLARITHROMYCIN

Clarithromycin is metabolized to an active metabolite, 14-hydroxy clar ithromycin. These compounds have demonstrated excellent in vitro activ ity against Legionella species, with both agents having significantly lower MICs than erythromycin. Using a checkerboard assay, the activity of clarithromycin and its hydroxy metabolite, alone and in combinatio n, was examined against 41 Legionella organisms. The activity of clari thromycin and 14-hydroxy clarithromycin, in a 2:1 ratio, plus ciproflo xacin or levofloxacin was also determined. Activity of the antibiotic combinations was determined by calculating the fractional inhibitory c oncentration index. An agar dilution method using buffered charcoal ye ast extract media was used for susceptibility and synergy testing. An inoculum of 10(4) CFU/spot was used, with all plates incubated at 35 d egrees C for 48 h. The MICs90 for clarithromycin or 14-hydroxy clarith romycin alone was 0.5, versus 0.25 mu g/mL for the combination. Additi ve effects were observed with clarithromycin and its hydroxy metabolit e for 61% of the Legionella species, with fractional inhibitory concen tration indices ranging from 0.63 to 1.25. The 14-hydroxy metabolite s ignificantly increased the activity of both fluoroquinolone/clarithrom ycin combinations. Based on these data, in vitro susceptibility testin g of agents for the activity of active metabolites. (C) 1997 Elsevier Science Inc.