Pharmacology: Pharmacodynamics: Mechanism of action: Cefoperazone is a semi synthetic, broad-spectrum, third generation cephalosporin antibiotic. It acts by inhibiting biosynthesis of bacterial cell wall mucopeptide. Sulbactam acts as a beta-lactamase inhibitor, thus restoring Cefoperazone activity against beta-lactamase producing bacterial strains.
Pharmacokinetics: The mean serum concentration obtained at 30 min after 1 g I.V. Cefoperazone is 114 mcg/ml. The mean serum concentration obtained at 15 min after administration of 500 mg and 1000 mg IV Sulbactam are 21-40 mcg/ml and 48-88 mcg/ml respectively. The average peak plasma concentration at 5 minutes after administration of intravenous dose of 1 g is 81 mg/litre. The protein binding of Cefoperazone is 82-93% and that of Sulbactam is 38%. No significant quantity of metabolites of Cefoperazone has been found in the urine. The mean serum half-life of Cefoperazone and Sulbactam are about two hours and one hour respectively. Cefoperazone is excreted mainly in the bile. About 75-85% of Sulbactam is excreted in the urine during the first eight hours of administration. No significant changes are observed in patients with renal insufficiency compared to other patients. In patients with hepatic dysfunction, the serum half-life is prolonged and urinary excretion is increased. In patients with combined renal and hepatic insufficiency, Cefoperazone may accumulate in the serum.
The half-life of Cefoperazone in low birth weight neonates is 6-10 hours.
Microbiology: Spectrum of Antibacterial Activity: Cefoperazone is active in vitro against many Gram-negative bacteria including Pseudomonas aeruginosa, and Enterobacteriaceae (Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter, Proteus, Morganella, Providencia, Salmonella, Shigella, and Serratia spp.). Other susceptible Gram-negative bacteria include Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. It is slightly less active than other third-generation cephalosporins against some members of Enterobacteriaceae. It has good activity against Pseudomonas aeruginosa, but is less active than Ceftazidime. Cefoperazone is more susceptible than Cefotaxime to hydrolysis by certain beta-lactamases.
Sulbactam is a penicillanic acid sulfone with beta-lactamase inhibitory properties. It is active against Neisseriaceae and Acinetobacter baumanii, but generally has only weak antibacterial activity against other organisms. It is an irreversible inhibitor of most of the important β-lactamases and has a similar spectrum of beta-lactamase inhibition to clavulanic acid, although it is regarded as less potent. Sulbactam can therefore enhance the activity of penicillins and cephalosporins against many resistant strains of bacteria.