Time-kill kinetic studies of ampicillin/sulbactam for β-Lactamase-producing enterococci☆

Abstract β-Lactamase-producing (Bla + enterococci have now been reported from several geographic areas. Most of these strains also demonstrate high-level aminoglycoside resistance, making therapy of serious infections due to Bla + enterococci difficult. Using time-kill kinetic studies, we evaluated the activity of ampicillin-sulbactam (Am/SB) against five clinical Bla + Enterococcus faecalis isolates from three geographically distinct areas. Am at fourfold minimum inhibitory concentrations (MIC) concentrations did not achieve bactericidal activity as determined by time-kill kinetic studies. Am/SB achieved 99.9% reduction in growth at 24 hr at twofold MIC concentrations without an aminoglycoside in four of five strains. SB alone had little independent activity against any of the strains, but synergy of killing was achieved in all five strains with a combination of Am + SB. No synergy was shown in a Bla − control strain. Am/SB may be useful for serious infections due to Bla + enterococci.