Tazpen Mechanism of Action

Pharmacology: Piperacillin, a broad spectrum, semisynthetic penicillin active against many Gram-positive and Gram-negative aerobic and anaerobic bacteria, exerts bactericidal activity by inhibition of both septum and cell wall synthesis. Tazobactam, a triazolylmethyl penicillanic acid sulfone, is a potent inhibitor of many β-lactamases, including the plasmid and chromosomally mediated enzymes that commonly cause resistance to penicillins. The presence of tazobactam in the TAZPEN formulation enhances and extends the antibiotic spectrum of piperacillin to include many β-lactamase producing bacteria normally resistant to it. Thus, TAZPEN combines the properties of a broad-spectrum antibiotic and a β-lactamase inhibitor.
Pharmacokinetics: Absorption: Peak plasma concentrations of piperacillin sodium and tazobactam sodium are attained immediately after completion of an intravenous infusion.
Distribution: Piperacillin and tazobactam are widely distributed into tissues and body fluids including intestinal mucosa, gallbladder, lung, female reproductive tissues (uterus, ovary, and fallopian tube), interstitial fluid and bile. Both piperacillin and tazobactam are approximately 30% bound to plasma proteins in adults.
Distribution of piperacillin and tazobactam into cerebrospinal fluid is low in adult subjects with non-inflamed meninges, as with other penicillins.
Both Piperacillin and Tazobactam cross the placenta. Piperacillin is distributed into milk. It is not known whether tazobactam is distributed into milk.
Elimination: Piperacillin is metabolized to a minor microbiologically active desethyl metabolite. Tazobactam is metabolized to a single metabolite that lacks pharmacological and antibacterial activities. Both piperacillin and tazobactam are eliminated via the kidney by glomerular filtration and tubular secretion.
Piperacillin is excreted rapidly as unchanged drug with 68% of the administered dose excreted in the urine. Tazobactam and its metabolite are eliminated primarily by renal excretion with 80% of the administered dose excreted as unchanged drug.
In adults, the plasma half-life of piperacillin and of tazobactam ranged from 0.7 to 1.2 hours.
Impaired liver function: The half-life of piperacillin and of tazobactam increases by approximately 25% and 18%, respectively, in patients with hepatic cirrhosis compared to healthy subjects.
Impaired renal function: The half-lives of piperacillin and of tazobactam increase with decreasing creatinine clearance. In adults with creatinine clearance below 20 mL/min, the increase in half-life is two-fold for piperacillin and four-fold for tazobactam compared to subjects with normal renal function.
Children: Piperacillin and tazobactam pharmacokinetics were studied in paediatric patients 2-9 months of age. The clearance of both compounds is slower in the younger patients compared to older children and adults.
Microbiology: Piperacillin and Tazobactam is active against most strains of the following β-lactamase producing and non β-lactamase producing microorganisms: Gram-negative bacteria: Escherichia coli, Citrobacter sp., Enterobacter sp. (including E. cloacae), Serratia sp. (including S. marcescens), Pseudomonas aeruginosa and other Pseudomonas sp., Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis, Acinetobacter sp., Haemophilus influenza, Shigella sp., Campylobacter sp.
Gram-positive bacteria: Streptococci (S. pneumoniae, S. pyogenes, S. agalactiae, S. viridans), Enterococci (E. faecalis), Staphylococcus aureus (not methicillin-resistant S. aureus), S. epidermidis (coagulase-negative staphylococci).
Anaerobic bacteria: Bacteroides spp. including Bacteroides fragilis group, Peptostreptococcus spp., Fusobacterium spp., Eubacterium group, Clostridia spp., Veillonella spp.