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

Abstract

We evaluated, by time-kill studies, the pharmacodynamics of amoxicillin/sul-bactam (AMX/SUL, 875 mg/125 mg), a novel oral combination, against the major respiratory pathogens in 12 volunteers receiving a single dose. The sera corresponding to 50% of a 12-h dosing interval displayed either bactericidal or inhibitory activity against both a penicillin-susceptible and a penicillin-intermediate Streptococcus pneumoniae strain (penicillin MIC of 0.03 and 0.25 μg/ml, respectively), as well as against a β-lactamase-positive Moraxella catarrhalis and a β-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 μg/ml) and a β-lactamase-positive H. influenzae strain. The AMX-SUL formulation evaluated in this study showed pharmacodynamic features that support clinical trials to assess its efficacy in the treatment of lower respiratory tract infections with a 12-h dosing interval regimen.