The activity of clarithromycin and its 14-hydroxy metabolite against Haemophilus influenzae, determined by in-vitro and serum bactericidal tests

Abstract

The in-vitro activity of clarithromycin and its main metabolite 14-hydroxy clarithromycin against Haemophilus influenzae was evaluated by determining minimum inhibitory and minimum bactericidal concentrations. The 14-hydroxy metabolite was more active than the parent compound against H. influenzae. The activity of the parent compound/metabolite combination was evaluated against 20 strains of H. influenzae by the chequerboard technique. The combination was synergistic against seven isolates in terms of fractional bactericidal concentration index and against five isolates in terms of fractional inhibitory concentration index; the combination demonstrated additive activity against the remaining strains. Serum bactericidal activity against H. influenzae was measured in sera from six healthy volunteers who had received 250 mg clarithromycin by mouth. The area under the serum bactericidal activity curve correlated with the area under the curves for clarithromycin and 14-hydroxy clarithromycin, and with the in-vitro susceptibility of the strains tested. Serum bactericidal activity was detected at 30 min after dosing and lasted for 5-6 h.