Core pharmacology

Class Group

ANTIBIOTIC:
PENICILLIN

Legacy Cicm Level

Level 1

Introduction

Antipseudomonal penicillin

Indications Uses

used to treat a variety of infections, including those caused by aerobic and facultative gram-positive and gram-negative bacteria, in addition to gram-positive and gram-negative anaerobes.
E.g: cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis infections.

Mechanism of action

β lactam antibiotic
Binds to penicillin binding protein (transpeptidase) and
prevents crosslinking of bacterial peptidoglycan
impairs cell wall synthesis

Antimicrobial Spectrum

Pseudomonas
Beta-lactamase producing bacteria
Gram negatives
Anaerobes

Resistance Mechanism

Certain gram-negative bacilli infections with beta-lactamase producing organisms cannot be treated with piperacillin-tazobactam, due to a gene mutation conferring antibiotic resistance

Adverse Effects Toxicity

1. Hypokalaemia (lower sodium concentration so hypernatraemia less likely)
2. Piptaz + vancomycin associated with increased AKI
3. LFT derangement
Neutropenia

Absorption

Poorly absorbed orally
Peak plasma concentrations occur immediately after the completion of intravenous infusion. Following several doses of piperacillin-tazobactam infusions every 6 hours, peak concentrations were similar to those that were measured after the initial dose.

Distribution

Widely distributed in body tissues and fluids.

Meningeal distribution of piperacillin-tazobactam increases with inflammation, but is otherwise low

Protein binding

30% PB

Volume of distribution

Vd <1L/kg

Metabolism

Piperacillin is not metabolized in man.

Tazobactam is mainly metabolized to M1, an inactive metabolite.

Excretion

Renal: 80% unchanged + metabolite

Half-life

Half-life of Piperacillin-tazobactam: 0.7 to 1.2 hours

Special Points

Removed by haemodialysis