Core pharmacology

Class Group

ANTIBIOTIC:
PENICILLIN

Legacy Cicm Level

Level 1

Introduction

Piperacillin is a penicillin antibiotic combined with tazobactam to treat piperacillin-resistant, piperacillin/tazobactam¬ susceptible, β-lactamase generating strains of several bacteria.

Indications Uses

Piperacillin is used in the treatment of:
1. urinary and respiratory tract infections
2. intra-abdominal and biliary tract sepsis
3. gynaecological and obstetric infections
4. infections of skin, soft tissue, bone, and joints
5. septicaemia
6. meningitis and for
7. perioperative prophylaxis.

Chemical Pharmaceutics

A semi-synthetic penicillin.

Presentation

In vials containing 1/2 g and infusion bottles containing
4 g of piperacillin sodium. A fixed-dose combination with tazobactam is
also available.

The adult intravenous dose is 4 g
6 to 8 hourly (each gram should be infused over 3–5 minutes), and the
intramuscular dose 2 g 6 to 8 hourly.

Main Action

Bactericidal broad-spectrum antibiotic
that is effective against many beta-lactamase-producing organisms.

Mechanism of action

Piperacillin binds to cell wall PBPs and inhibits their activity

It affects
• PBP 1A/B which are involved in the crosslinking of cell wall peptidoglycans
• PBP 2 which is involved in the maintenance of the rod shape
PBP 3 which is involved in septal synthesis.

Physiological effects

Metabolic/other Piperacillin has a lower sodium content than other disodium penicillins and causes less fluid and electrolyte derangements; serum
potassium levels may decrease after the administration of the drug.

Antimicrobial Spectrum

In vitro, it shows activity against the Gram-negative organisms Escherichia
coli, Haemophilus influenzae, and Klebsiella, Neisseria, Proteus, Shigella, and
Serratia spp.; anaerobes, including Bacteroides and Clostridium spp.; and the
Gram-positive enterococci Staphylococcus, and Streptococcus spp.

It is particularly effective against Pseudomonas, indole-positive Proteus, Streptococcus faecalis, and Serratia marcescens.

Adverse Effects Toxicity

• Gastrointestinal upsets
• abnormalities of liver function tests
• allergic reactions
• transient leucopenia and neutropenia
Deterioration in renal function has
been reported in patients with pre-existent severe renal impairment

Absorption

Poorly absorbed when administered orally and is hydrolysed by gastric acids.

Distribution

High concentrations are found in most tissues and body fluids.

Protein binding

16% PB

Volume of distribution

Vd 0.32 L/kg

Metabolism

Not metabolized in man.

Excretion

Bile: 20%
Renal: Rest (by glomerular filtration and tubular secretion)

Half-life

Elimination half-life: 36–72 minutes

Special Points

The dose of piperacillin should be reduced in the presence of renal impairment; the drug is 30–50% removed by haemodialysis.