A pharmacodynamic model to support a 12-hour dosing interval for amoxicillin/sulbactam, a novel oral combination, in the treatment of community-acquired lower respiratory tract infections

We evaluated, by time-kill studies, the pharmacodynamics of amoxicillin/sul bactam (AMX/SUL, 875 mg/125 mg), a novel oral combination, against the majo r respiratory pathogens in 12 Volunteers receiving a single dose. The sera corresponding to 50% of a 12-h dosing interval displayed either bactericida l or inhibitory activity against both a penicillin-susceptible and a penici llin-intermediate Streptococcus pneumoniae strain (penicillin MIC of 0.03 a nd 0.25 pig/ml, respectively), as well as against a beta-lactamase-positive Moraxella catarrhalis and a beta-lactamase-negative Haemophilus influenzae strain. Both the peak samples and those corresponding to 4 h after dose (i .e. 33% of a 12-h dosing interval) proved active against both a penicillin- resistant S, pneumoniae (MIC, 2 mu g/ml) and a beta-lactamase-positive H. i nfluenzae strain. The AMX-SUL formulation evaluated in this study showed ph armacodynamic features that support clinical trials to assess its efficacy in the treatment of lower respiratory tract infections with a 12-h dosing i nterval regimen.