Ampimax Mechanism of Action

Pharmacotherapeutic group: Antibacterial for systemic use.
Pharmacology: Pharmacodynamics: Mechanism of action: Ampicillin acts through the inhibition of the biosynthesis of the cell wall mucopeptide. Ampicillin has a broad spectrum of bactericidal action against many Gram-positive and Gram-negative aerobic and anaerobic bacteria, but is degraded by β-lactamases. Many β-lactamases found in microorganisms resistant to penicillins and to cephalosporins are irreversibly inhibited by Sulbactam, which alone has a little useful bactericidal activity. Beta-lactamase inhibition by Sulbactam is a two-step process. Initially, Sulbactam reversibly forms an inactive enzyme-inhibitor complex with beta-lactamase. In a time- and concentration-dependent manner, this complex evolves into one, or more, irreversibly inactivated proteins. Sulbactam's ability to protect resistant microorganisms against their degradation by penicillins and cephalosporins has been confirmed in all in vivo studies using resistant strains. In these studies Sulbactam showed a synergic activity with penicillins and cephalosporins. Since Sulbactam is bound to certain equal binding sites of penicillin-binding proteins, some susceptible strains are even more susceptible to this combination than to beta-lactam antibiotics alone. Pharmacodynamic effects, Ampicillin and Sulbactam is a combination of a beta-lactam antibiotic (Ampicillin) and an irreversible beta-lactamase inhibitor (Sulbactam). Sulbactam alone has a very poor antibacterial activity which is of very little utility except against the Neisseriaceae, Acinetobacter calcoaceticus, Bacteroides spp, Branhamella catarrhalis and Pseudomonas cepacia but the combination with Ampicillin restores the activity of Ampicillin against β-lactamase producing strains. The combination, for parenteral use only, has a broad spectrum antibacterial activity against gram-positive and gram-negative aerobic and anaerobic bacteria including beta-lactamase producing strains.
Pharmacokinetics: General: Peak serum levels are achieved within 15 minutes after completion of I.V. infusion or after 30-60 minutes following I.M. administration. Serum concentrations are dependent upon the dose of the drug used, the route and body weight of the patient. The mean serum half-life of both drugs is approximately one hour in healthy volunteers. Approximately 75 to 85% of both Sulbactam and Ampicillin are excreted unchanged in the urine during the first 8 hours after administration to individuals with normal renal function. In patients with impaired renal function, the elimination kinetics of Sulbactam and Ampicillin are similarly affected, hence the ratio of one to the other remains constant whatever the renal function is. The dose of Sulbactam Sodium/Ampicillin Sodium in such patients should be administered in accordance with the usual practice for Ampicillin. Ampicillin is approximately 28% reversibly bound to human serum protein and Sulbactam is approximately 38% reversibly bound. It penetrates readily into the various tissues and body fluids like peritoneal fluid, intestinal mucosa, appendix etc. and offers synergistic bactericidal concentration. Penetration of both Sulbactam and Ampicillin into cerebrospinal fluid in the presence of inflamed meninges has been demonstrated after IV administration.
Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential.
Microbiology: A wide range of beta-lactamase found in microorganisms resistant to penicillins and cephalosporins have been shown to be irreversibly inhibited by Sulbactam. Although Sulbactam alone possesses little useful antibacterial activity, it is effective against the Neisseriaceae. Whole organism studies have shown that Sulbactam restores Ampicillin's activity against beta-lactamase producing strains. In particular, Sulbactam has good inhibitory activity against the clinically important plasmid mediated beta-lactamase most frequently responsible for transferred drug resistance. Sulbactam has no deleterious effect on the activity of Ampicillin against Ampicillin susceptible strains.
The presence of Sulbactam in the formulation effectively extends the antimicrobial spectrum of ampicillin to include many bacteria normally resistant to it and to other beta-lactam antibiotics. Thus, it possesses the synergistic properties of broad-spectrum antibiotic and beta-lactamase inhibitor.
The bacterial activity of Ampicillin has a broad spectrum bactericidal activity against many Gram-positive and Gram-negative aerobic and anaerobic bacteria. Ampicillin is, however, degraded by beta-lactamase and therefore, the spectrum of activity does not normally include beta-lactamase producing organisms.
Susceptible microorganisms: Gram-positive Bacteria: Staphylococcus aureus (beta-lactamase and non-beta-lactamase producing), Streptococcus epidermis (beta-lactamase and non-beta-lactamase producing), Streptococcus saprophyticus (beta-lactamase and non-beta-lactamase producing), Streptococcus faecalis* (Enterococcus), Streptococcus pneumoniae* (formerly D. pneumoniae), Streptococcus pyogenes*, Streptococcus viridans*.
Gram-negative Bacteria: Haemophilus influenzae (beta-lactamase and non-beta-lactamase producing), Branhamella catarrhalis (formerly Neisseria catarrhalis) (beta-lactamase and non-beta-lactamase producing), Klebsiella species (all known strains are beta-lactamase producing), Proteus vulgaris, Morganella morganii and Neisseria gonorrhoeae (beta-lactamase and non-beta-lactamase producing).
Anaerobic: Bacteroides species, including B. fragilis. (*These are not beta-lactamase producing strains and therefore, are susceptible to ampicillin alone).