Pharmacology: Pharmacodynamics: Biochemical studies with cell-free bacterial systems have shown sulbactam to be an irreversible inhibitor of most important beta-lactamases that occur in penicillin-resistant organisms. While sulbactam antibacterial activity is mainly limited to Neisseriaceae, the potential for sulbactam sodium in preventing the destruction of penicillins and cephalosporins by resistant organisms was confirmed in whole organism studies using resistant strains, in which sulbactam sodium exhibited marked synergistic effects with penicillins and cephalosporins. Since sulbactam also binds to some penicillin-binding proteins, some sensitive strains are rendered more susceptible to the combination than to the beta-lactam antibiotic alone.
The bactericidal component of this product is ampicillin which, like benzyl penicillin, acts against sensitive organisms during the stage of active multiplication by the inhibition of biosynthesis of cell wall mucopeptide.
Sultamicillin is effective against a wide range of gram-positive and gram-negative bacteria including: Staphylococcus aureus and Staphylococcus epidermidis (including penicillin-resistant and some methicillin resistant strains); Streptococcus pneumoniae, Streptococcus faecalis and other Streptococcus species; Haemophilus influenzae and Haemophilus parainfluenzae (both beta-lactamase positive and negative strains); Moraxella catarrhalis; anaerobes including Bacteroides fragilis and related species; Escherichia coli; Klebsiella species; Proteus species (both indole-positive and indole-negative); Enterobacter species; Morganella morganii; Citrobacter species; Neisseria meningitidis and Neisseria gonorrhoeae.
Pharmacokinetics: Following oral administration in humans, sultamicillin is hydrolyzed during absorption to provide sulbactam and ampicillin in a 1:1 molar ratio in the systemic circulation. The bioavailability of an oral dose is 80% of an equal intravenous dose of sulbactam and ampicillin. Administration following food does not affect the systemic bioavailability of sultamicillin. Peak serum levels of ampicillin following administration of sultamicillin are approximately twice those of an equal dose of oral ampicillin. Elimination half-lives are approximately 0.75 and 1 hour for sulbactam and ampicillin respectively in healthy volunteers, with 50%-75% of each agent being excreted unchanged in the urine. Elimination half-lives are increased in the elderly and in patients with renal dysfunction. Probenecid decreases the renal tubular secretion of both ampicillin and sulbactam. Concurrent use of probenecid with sultamicillin results in increased and prolonged blood levels of ampicillin and sulbactam (see Interactions).
Toxicology: Preclinical Safety Data: While reversible glycogenosis was observed in laboratory animals, this phenomenon was dose- and time-dependent and is not expected to develop at the therapeutic doses and corresponding plasma levels attained during the relatively short periods of combined ampicillin/sulbactam therapy in humans.
Long-term studies in animals have not been performed to evaluate carcinogenic potential. The individual components of sultamicillin (ampicillin/sulbactam) tested negative for mutagenicity.
Reproduction studies have been performed in mice and rats at doses in excess of the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to sultamicillin.