More than 90% of community hospital-isolated strains of Staphylococcus (including methicillin-resistant isolates), Streptococcus, Haemophilus, Neisseria, Branhamella, Bacteroides, Escherichia coli, Klebsiella, Enterobacter aerogenes, Proteus, and Acinetobacter calcoaceticus were inhibited by the sulbactam/ampicillin (1:2) combination at concentrations of 8 micrograms/16 micrograms per ml. The peak serum level from a 15-min infusion of 1 g/2 g of sulbactam/ampicillin is more than seven times this 90% end point. Excellent bactericidal activity was demonstrated against ampicillin-resistant isolates. Ampicillin-resistant strains did not develop resistance to sulbactam/ampicillin when they were serially transferred in the presence of sublethal concentrations of the combination. In mice the combination was active against a variety of acute, fatal infections produced by ampicillin-resistant bacterial isolates, including methicillin-resistant strains of Staphylococcus aureus and mixed anaerobes. The in vitro and in vivo properties of sulbactam/ampicillin, coupled with its reliable pharmacokinetic performance, appear to make the combination ideally suited for the treatment of polymicrobial (aerobe-anaerobe) infections.

Acute Disease↗

PubMedDate not supplied

Activity of sulbactam/ampicillin in screening and discriminative animal models of infection.

The efficacy of sulbactam/ampicillin in the treatment of mice with fatal systemic infections produced by ampicillin-resistant Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, or Proteus vulgaris strains is well established. In this paper the demonstrations of efficacy for sulbactam/ampicillin have been extended to a number of clinically relevant models, including bacteremia and meningitis produced by H. influenzae in infant rats, experimental staphylococcal endocarditis in rabbits, localized lesions in mice, urinary tract infections in rats, and prophylaxis in a surgical wound model in mice. In these models, in which ampicillin-resistant organisms were used, sulbactam/ampicillin was either more effective than or as effective as appropriate control agents. Neither sulbactam nor ampicillin used separately displayed significant activity. The results of supportive pharmacokinetic studies, in which differential bioassays were used, demonstrated that sulbactam and ampicillin generally were delivered with equal efficiency to plasma and to extravascular fluids obtained by sampling the contents of implanted cylinders.

Ampicillin↗