Unasyn IM/IV Mechanism of Action

Pharmacologic Category: Antibacterial (Penicillin-Beta-Lactamase Inhibitor Combination).
Pharmacology: Pharmacodynamics: Biochemical studies with cell-free bacterial systems have shown sulbactam to be an irreversible inhibitor of most important β-lactamases that occur in penicillin-resistant organisms. While sulbactam's 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 β-lactam antibiotic alone.
The bactericidal component of the combination 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.
Ampicillin sodium/sulbactam sodium IM/IV is effective against a wide range of Gram-positive and Gram-negative bacteria including: Staphylococcus aureus and epidermidis (including penicillin-resistant and some methicillin-resistant strains); Streptococcus pneumoniae, Streptococcus faecalis and other Streptococcus species; Haemophilus influenzae and parainfluenzae (both β-lactamase positive and negative strains); Branhamella catarrhalis; anaerobes, including Bacteroides fragilis and related species; Escherichia coli, Klebsiella species, Proteus species (both indole-positive and indole-negative), Morganella morganii, Citrobacter species, Enterobacter species, Neisseria meningitidis and Neisseria gonorrhoeae.
Pharmacokinetics: Ampicillin sodium/sulbactam sodium IM/IV diffuses readily into most body tissues and fluids in the human. Penetration into brain and spinal fluid is low except when meninges are inflamed. High concentrations of ampicillin and sulbactam are achieved in the blood following intravenous or intramuscular administration and both components have a half-life of approximately 1 hour. Most of the ampicillin sodium/sulbactam sodium IM/IV is excreted unchanged in the urine.
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 the carcinogenic potential. The individual components, ampicillin and sulbactam, tested negative for mutagenicity.
Reproduction studies have been performed in mice and rats with sultamicillin, an oral prodrug that hydrolyzes in vivo to release ampicillin and sulbactam, at doses in excess of the human dose and have revealed no evidence of impaired fertility or harm to the fetus.