Glycopeptide Antibiotics (Vancomycin and Teicoplanin)

They work by binding to the terminal end of peptidoglycan precursors, which are the building blocks of bacterial cell walls. This prevents the cross-linking, which forms the cell wall. They also inhibit RNA synthesis. This is a very slow method of killing bacteria and it is a time-dependent killing. They exhibit a synergistic effect with aminoglycosides, as they facilitate penetration of the latter into bacterial cells.
They are effective against Gram positive organisms only. These include:

• Staphylococcus spp.
• Streptococcus spp.
• Enterococcus faecalis
• E.faecium
• Listeria monocytogenes
• Clostridium difficile and other Clostridia
• Bacillus cereus and B. subtilis
• Corynebacterium
• Actinomyces

• Vancomycin
• Teicoplanin

Vancomycin

Administration is intravenous. However, it can be given orally for C. difficile related diarrhoea. It penetrates most body tissues and fluids, but unless meninges are inflamed there is little diffusion into CSF. Excretion is mainly renal. 80% of a dose is excreted within 24h in urine. A small amount is excreted in faeces.

Teicoplanin

Very similar to vancomycin, but has a longer duration of action, allowing it to be given once daily. Can be administered intravenously or intramuscularly. Absorption after IM injection equivalent to that after IV injection. It is poorly absorbed in to the CSF. It is excreted almost entirely renally. It is not cleared from circulation by haemodialysis.

• Dosage is reduced in renal failure and also in severe hepatic failure.
  • For Vancomycin the starting dose in patients with impaired renal function should be no greater than 15mg/kg body weight with subsequent doses based mainly on renal function (according to creatinine clearance) and serum concentrations of the drug. A normogram is available to help with dose adjustments.¹¹
  • For teicoplanin if creatinine clearance is between 40-60ml/min, halve the dose. If creatinine clearance is less than 40ml/min give one third of the dose.
• Concentration should be monitored after 3-4 days in patients with normal renal function. If renal function is poor measure after 24 hours.
• The trough concentration is taken 1 hour before the next dose.
  • For vancomycin the trough concentration should be approximately 5-10mg/l. When treating endocarditis, a normal level could be as high as 10-15mg/l.
  • For teicoplanin trough concentration should not be less than 10mg/l.
• For vancomycin peak serum concentrations, measured 2 hours after infusion is complete, range from 18-26mg/l.
• For teicoplanin peak serum concentrations, measured 1 hour after infusion, range from 20-50mg/l.
• Also monitor auditory function, blood counts and renal function.
• Avoid rapid infusion-see below.
• Rotate infusion sites.
• Avoid if patient has a history of deafness.
• Avoid if patient has history of previous hypersensitivity

• Histamine may be released if the infusion is too rapid. This results in anaphylactic reaction, muscular spasms, and sometimes hypotension ("red man syndrome", or erythroderma).
• Anaesthetic agents and vancomycin use at the same time has been associated with erythema, histamine-like flushing and anaphylactic reactions.
• Glycopeptides may cause drug rash, eosinophilia and systemic symptoms - DRESS syndrome. This has a 10% mortality rate.¹²
• Glycopeptides have a risk of nephrotoxicity, especially in combination with other renal insults.
• Incidence of renal impairment with teicoplanin (especially in combination with an aminoglycoside) lower than that associated with vancomycin.
• Teicoplanin has a lower risk causing, anaphylactic-type reactions (red man syndrome), than vancomycin. Occurence with vancomycin use does NOT contraindicate teicoplanin use.
• Glycopeptides may cause pyrexia. Incidence is approximately 8 cases per 1000
• Glycopeptides may cause ototoxicity. Incidence is approximately 3 cases per 1000