Piptaz 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 multidrug efflux pumps, may cause or contribute to bacterial resistance to Piperacillin/Tazobactam, especially in Gram-negative bacteria.
Pharmacokinetics: Both Piperacillin and Tazobactam are not well absorbed in the GIT but have good bioavailability after an IM injection. They are both widely distributed into different body compartments but penetration into the meninges of Tazobactam is poor when meninges are not inflamed. Tazobactam is metabolized to a single inactive metabolite while Piperacillin is metabolized to the desethyl metabolite, which has minor activity. Approximately 68% and 80% of an administered dose of Piperacillin and Tazobactam, respectively are excreted unchanged in the urine.