Core pharmacology

Class Group

ANTIBIOTIC:
GLYCOPEPTIDE

Legacy Cicm Level

Level 1

Introduction

Tricyclic glycopeptide antibiotic produced by streptococcus orientalis

Indications Uses

It possesses a broad spectrum of activity against gram positive bacteria including MRSA.
Acts synergistically with aminoglycosides, cephalosporins and rifampicin (although synergy testing required as vancomycin + cephalosporin may act antagonistically against some strains of staph epidermis)

Presentation

Store at 2-8 degrees, clear solution. Slowly due to vessel irritation (& risk of red man syndrome).
Monitoring required to avoid toxic levels (aiming serum conc 15+/-3).

Mechanism of action

Inhibits Glycopeptide synthetase  prevents peptidoglycan formation in bacterial cell well
(Unlike penicillins, prevents the transfer and addition of the muramylpentapeptide
building blocks that make up the peptidoglycan molecule itself.)
May also alter membrane permeability and selectively inhibit RNA synthesis.
Antimicrobial activity Dependent on Duration above MIC, not concentration

Antimicrobial Spectrum

active against most gram positive bacteria (including staphlycocci, streptococci, enterococci, listeria monocytogenes, clostridium sp, and Bacillus sp.), with limited gram negative activity.

Resistance Mechanism

VanA resistance – gene mutation leading to decreased affinity of peptidoglycan precursors for vancomycin.
Induced by exposure to vanc / teicoplanin
Van B resistance – similar but only induced by vancomycin; strains may remain susceptible to teicoplanin

Adverse Effects Toxicity

Hypersensitivity reactions including anaphylaxis.
Rapid infusion is associated with histamine release - red-man syndrome.
Ototoxicity rare, dose related. Nephrotoxicity has declined with improved formulations, usually resolves with cessation of drug

Absorption

bioavailabilty Oral: Poor; I.M.: Erratic; Intraperitoneal: ~38%
IV. dose loading 20mg/kg then 1-1.5g daily based on levels

Distribution

Distributes widely in
body tissue and fluids, except for CSF, improved CSF penetration with inflamed meninges

Protein binding

~50% PB

Volume of distribution

Vd: 0.4-1 L/kg

Metabolism

Little or no metabolism

Excretion

excretion via kidneys unchanged
Not effectively removed by dialysis

Half-life

half life Biphasic half life, prolonged in renal fail. Mean t1/2 4-6hrs