Cefsul IV Mechanism of Action

Pharmacotherapeutic group: Combinations of Cephalosporin and beta-lactamase inhibitors.
Pharmacology: Ceftriaxone sodium + Sulbactum sodium (Cefsul IV) 1 g/500 mg Powder for injection (I.M./I.V.) is an anti-infective combination of Ceftriaxone with Sulbactam. Ceftriaxone is a broad spectrum semi-synthetic third generation cephalosporin with a potent bactericidal activity against a wide range of Gram-positive and Gram negative-bacteria. Sulbactams is β-lactamase inhibitor.
Pharmacodynamics: Mode of action: Ceftriaxone is a beta-lactam antibiotic like the penicillin with bactericidal action. Penicillin-binding proteins (PBPs) are responsible for several steps in the synthesis of the cell wall of bacteria and are found in large quantities (several hundred to several thousand molecules/bacterial cell). Ceftriaxone inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to the specific PBPS located inside the bacterial cell wall. Ceftriaxone interferes with PBP-mediated cell wall synthesis leading to cell lysis, which is mediated by bacterial cell wall autolytic enzymes (autolysins), possibly through interference with an autolysin inhibitor. The presence of an aminothiazolylacetyl side chain with an alpha methoxyimino group at the 7-position of the beta-lactam ring provides Ceftriaxone with enhanced antibacterial activity, particularly against the Enterobacteriaceae (e.g., E. coli, Klebsiella, Proteus, and Serratia) and increased stability against many of the beta lactamases. Many strains of Pseudomonas aeruginosa are susceptible to Ceftriaxone. Other susceptible gram-negative organisms include Enterobacter, Citrobacter, Morganella, Providencia, Moraxella (Branhamella) catarrhalis, and N. meningitidis. Ceftriaxone has exceptional activity against H. influenzae and N. gonorrhoeae and is the drug of choice for uncomplicated N. gonorrhoeae infections. It has no activity against B. fragilis but is active against many other anaerobes.
However, recently it has been observed that the bacteria, through formation of beta lactamases hydrolyze the beta-lactam ring of cephalosporins to inactivate them, thereby developing resistance to the drug. Recently, such a development of resistance to ceftriaxone has been observed, which can be judged by an increase in the MIC. Sulbactam, by irreversibly binding to the beta-lactamases produced by the common gram-positive or negative bacteria protects the beta-lactam ring of ceftriaxone, and conserves the activity. Thus on combining ceftriaxone with sulbactam, the combination product Ceftriaxone & Sulbactam for Injection extends its utility in the treatment of broad range of infections caused by organism's resistant to the antibiotic alone, making them susceptible, possibly through lowering of MIC.
Pharmacokinetics: Following intramuscular administration, peak serum concentrations of Ceftriaxone and Sulbactam are seen between 15 minutes to 2 hrs. The area under curve (AUC) after IM administration is equivalent to that after IV administration of an equivalent dose, indicating 100% bioavailability of intramuscularly administered Ceftriaxone sodium. Ceftriaxone is highly bound to human serum protein by about 83-90%. Ceftriaxone sodium penetrates well into the extravascular spaces, tissue fluid and the synovial fluid of inflamed joints.
Ceftriaxone crosses the placenta and is distributed in the amniotic fluid. It is also distributed in the milk.
Ceftriaxone is eliminated unchanged via two pathways, urine and bile. Metabolism of sulbactams is less than 25%. 70-80% of Sulbactam is excreted by the kidney & biliary excretion is minimal.