Ex vivo 12 h bactericidal activity of oral co-amoxiclav (1.125 g) against beta-lactamase-producing Haemophilus influenzae

The aim of the study was to evaluate the in vitro/ex vivo bactericidal acti vity of a new co-amoxiclav single-dose sachet formulation (1 g amoxicillin + 0.125 g clavulanic acid) against a beta -lactamase-producing strain of Ha emophilus influenzae. The evaluation covered the 12 h period after antibiot ic administration. Serum specimens from the 12 healthy volunteers included in the pharmacokinetic study were pooled by time point and in equal volumes . Eight of 12 pharmacokinetic sampling time points were included in the stu dy. At time points 0.5, 0.75, 1, 1.5, 2.5, 5, 8 and 12 h post-dosing, the k inetics of bactericidal activity were determined for each of the serial dil utions. Each specimen was serially diluted from 1:2 to 1:256. The index of surviving bacteria (ISB) was subsequently determined for each pharmacokinet ic time point. For all the serum samples, bactericidal activity was fast (3 -6 h), marked (3-6 log(10) reduction in the initial inoculum) and sustained over the 12 h between-dosing interval. The results obtained also confirmed that the potency of the amoxicillin plus clavulanic acid combination was t ime dependent against the species under study and that the time interval ov er which the concentrations were greater than the MIC (t > MIC) was 100% fo r the strain under study. The data thus generated constitute an interesting prerequisite with a view to using co-amoxiclav 1.125 g in a bd oral regime n.