Cefpar SB Mechanism of Action

Pharmacology: Pharmacodynamics: The antibacterial component is cefoperazone, a 3rd generation cephalosporin, which acts against sensitive organisms during the stage of active multiplication by inhibiting biosynthesis of cell wall mucopeptide. Sulbactam does not possess any useful antibacterial activity, except against Neisseriaceae and Acinetobacter. However, biochemical studies with cell-free bacterial systems have shown it to be an irreversible inhibitor of most important β-lactamases produced by β-lactam antibiotic-resistant organisms.
The potential for sulbactam preventing the destruction of penicillins and cephalosporins by resistant organisms was confirmed in whole-organism studies using resistant strains in which sulbactam exhibited marked synergy with penicillins and cephalosporins. As sulbactam also binds with some penicillin-binding proteins, sensitive strains are also often rendered more susceptible to sulbactam/cefoperazone than to cefoperazone alone.
The combination of sulbactam and cefoperazone is active against all organisms sensitive to cefoperazone. In addition, it demonstrates synergistic activity (up to 4-fold reduction in minimum inhibitory concentrations for the combination versus those for each component) in a variety of organisms, most markedly the following: Haemophilus influenzae, Bacteroides sp, Staphylococcus sp, Acinetobacter calcoaceticus, Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter diversus.
Sulbactam/cefoperazone is active in vitro against a wide variety of clinically significant organisms: Gram-Positive Organisms: Staphylococcus aureus (penicillinase- and nonpenicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pneumoniae (formerly Diplococcus pneumoniae), Streptococcus pyogenes (Group A β-hemolytic streptococci), Streptococcus agalactiae (Group B β-hemolytic streptococci), most other strains of β-hemolytic streptococci, many strains of Streptococcus faecalis (enterococcus).
Gram-Negative Organisms: Escherichia coli, Klebsiella sp, Enterobacter sp and Citrobacter sp, Haemophilus influenzae, Proteus mirabilis, Proteus vulgaris, Morganella morganii (formerly Proteus morganii), Providencia rettgeri (formerly Proteus rettgeri), Providencia sp, Serratia sp (including S. marcescens), Salmonella sp, Shigella sp, Pseudomonas aeruginosa and some other Pseudomonas sp, Acinetobacter calcoaceticus, Neisseria gonorrhoeae, Neisseria meningitidis, Bordetella pertussis and Yersinia enterocolitica.
Anaerobic Organisms: Gram-negative bacilli (including Bacteroides fragilis, other Bacteroides sp, and Fusobacterium sp).
Gram-positive and gram-negative cocci (including Peptococcus, Peptostreptococcus and Veillonella sp).
Gram-positive bacilli (including Clostridium, Eubacterium and Lactobacillus sp).
Pharmacokinetics: Approximately 84% of the sulbactam dose and 25% of the cefoperazone dose administered with sulbactam/cefoperazone is excreted by the kidney. Most of the remaining dose of cefoperazone is excreted in the bile. After sulbactam/cefoperazone administration, the mean half-life for sulbactam is about 1 hr while that for cefoperazone is 1.7 hrs. Serum concentrations have been shown to be proportional to the dose administered. These values are consistent with previously published values for the agents when given alone.
Mean peak sulbactam and cefoperazone concentrations after the administration of 2 g of sulbactam/cefoperazone (1 g sulbactam, 1 g cefoperazone) IV over 5 min were 130.2 and 236.8 mcg/mL, respectively. This reflects the larger volume of distribution for sulbactam (Vd=18-27.6 L) compared to cefoperazone (Vd=10.2-11.3 L).
After IM administration of 1.5 g sulbactam/cefoperazone (0.5 g sulbactam, 1 g cefoperazone) peak serum concentrations of sulbactam and cefoperazone are seen from 15 min to 2 hrs after administration. Mean peak serum concentrations were 19 and 64.2 mcg/mL for sulbactam and cefoperazone, respectively.
After multiple dosing, no significant changes in the pharmacokinetics of either component of sulbactam/cefoperazone have been reported and no accumulation has been observed when administered every 8-12 hrs.
Renal Dysfunction: In patients with different degrees of renal function administered sulbactam/cefoperazone, the total body clearance of sulbactam was highly correlated with estimated creatinine clearance. Patients, who are functionally anephric, show a significantly longer half-life of sulbactam (mean 6.9 and 9.7 hrs in separate studies). Hemodialysis significantly altered the half-life, total body clearance and volume of distribution of sulbactam. No significant differences have been observed in the pharmacokinetics of cefoperazone in renal failure patients.
Elderly: The pharmacokinetics of sulbactam/cefoperazone have been studied in elderly individuals with renal insufficiency and compromised hepatic function. Both sulbactam and cefoperazone exhibited longer half-life, lower clearance and larger volumes of distribution when compared to data from normal volunteers. The pharmacokinetics of sulbactam correlated well with the degree of renal dysfunction while for cefoperazone there was a good correlation with the degree of hepatic dysfunction.
Children: Studies conducted in pediatrics have shown no significant changes in the pharmacokinetics of the components of Cefoperazon Sulbactam compared to adult values. The mean half-life in children has ranged from 0.91-1.42 hrs for sulbactam and from 1.44-1.88 hrs for cefoperazone.