Tazolitt Mechanism of Action

Pharmacotherapeutic group: Antibacterials for systemic use, Combinations of penicillins, including beta-lactamase inhibitors.
Pharmacology: Pharmacodynamics: Mechanism of action: Piperacillin, a broad spectrum, semisynthetic penicillin exerts bactericidal activity by inhibition of both septum and cell wall synthesis.
Tazobactam, a beta-lactam structurally related to penicillins, is an inhibitor of many beta-lactamases, which commonly cause resistance to penicillins and cephalosporins but it does not inhibit AmpC enzymes or metallo beta-lactamases.
Tazobactam extends the antibiotic spectrum of piperacillin to include many beta-lactamase-producing bacteria that have acquired resistance to piperacillin alone.
Mechanism of resistance: The two main mechanisms of resistance to Piperacillin/Tazobactam are: Inactivation of the piperacillin component by those beta-lactamases that are not inhibited by tazobactam: beta-lactamases in the Molecular class B, C and D. In addition, tazobactam does not provide protection against extended-spectrum beta-lactamases (ESBLs) in the Molecular class A and D enzyme groups.
Alteration of penicillin-binding proteins (PBPs), which results in the reduction of the affinity of piperacillin for the molecular target in bacteria.
Additionally, alterations in bacterial membrane permeability, as well as expression of multi-drug efflux pumps, may cause or contribute to bacterial resistance to piperacillin/tazobactam, especially in Gram-negative bacteria.
Pharmacokinetics: Absorption: The peak piperacillin and tazobactam concentrations after 4 g/500 mg administered over 30 minutes by intravenous infusion are 298 μg/mL and 34 μg/mL respectively.
Distribution: Both piperacillin and tazobactam are approximately 30% bound to plasma proteins. The protein binding of either piperacillin or tazobactam is unaffected by the presence of the other compound. Protein binding of the tazobactam metabolite is negligible.
Piperacillin/Tazobactam is widely distributed in tissue and body fluids including intestinal mucosa, gallbladder, lung, bile and bone. Mean tissue concentrations are generally 50 to 100% of those in plasma. Distribution into cerebrospinal fluid is low in subjects with non-inflamed meninges, as with other penicillins.
Biotransformation: Piperacillin is metabolised to a minor microbiologically active desethyl metabolite. Tazobactam is metabolised to a single metabolite, which has been found to be micro-biologically inactive.
Elimination: Piperacillin and tazobactam are eliminated by the kidney via glomerular filtration and tubular secretion. Piperacillin is excreted rapidly as unchanged drug with 68% of the administered dose appearing in the urine. Tazobactam and its metabolite are eliminated primarily by renal excretion with 80% of the administered dose appearing as unchanged drug and the remainder as the single metabolite.
Piperacillin, tazobactam, and desethyl piperacillin are also secreted into the bile.
Following single or multiple doses of Piperacillin/Tazobactam to healthy subjects, the plasma half-life of piperacillin and tazobactam ranged from 0.7 to 1.2 hours and was unaffected by dose or duration of infusion. The elimination half-lives of both piperacillin and tazobactam are increased with decreasing renal clearance.
There are no significant changes in piperacillin pharmacokinetics due to tazobactam. Piperacillin appears to reduce the clearance of tazobactam.