Vancomycin

Common indications

1. Treatment of Gram-positive infection, e.g. endocarditis, where infection is severe and/or penicillins cannot be used due to resistance (e.g. meticillin-resistant Staphylococcus aureus [MRSA]) or allergy.
2. Treatment of antibiotic-associated colitis caused by Clostridium difficile infection (usually second-line where metronidazole is ineffective or poorly tolerated).

 

Mechanisms of action

• Vancomycin inhibits growth and cross-linking of peptidoglycan chains, inhibiting synthesis of the cell wall of Gram-positive bacteria. 
• It therefore has specific activity against Gram-positive aerobic and anaerobic bacteria and is inactive against most Gram-negative bacteria, which have a different (lipopolysaccharide) cell wall structure. 
• Bacterial resistance to vancomycin is increasingly reported. One mechanism is modification of cell wall structure to prevent vancomycin binding.

 

Important adverse effects

• The most common adverse effect is pain and inflammation of the vein (thrombophlebitis) at the infusion site. 
• If vancomycin is infused rapidly, severe adverse reactions can occur. These include anaphylactoid reactions classically described as ‘red man syndrome’. This is characterised by generalised erythema and may be associated with hypotension and bronchospasm. Anaphylactoid reactions are not antigen-mediated (i.e. not true allergy), but are due to non-specific degranulation of mast cells. 
• However, true allergy to vancomycin (immediate or delayed hypersensitivity) can also occur. 
• Intravenous vancomycin can cause nephrotoxicity, including renal failure and interstitial nephritis, ototoxicity, with tinnitus and hearing loss, and blood disorders, including neutropenia and thrombocytopenia.

 

Warnings

• Vancomycin treatment requires careful monitoring of plasma drug concentrations and dose adjustment to avoid toxicity. 
• Particular caution including dose reduction should be taken when prescribing for people with renal impairment and the elderly (increased risk of hearing impairment).

 

Important interactions

• Vancomycin increases the risk of ototoxicity and/or nephrotoxicity when prescribed with aminoglycosides, loop diuretics or ciclosporin (an immunosuppressant drug).

 

Monitoring 

• Where IV therapy is used, pre-dose (trough) plasma vancomycin concentrations should be measured during treatment. 
• Vancomycin dosage should be adjusted to keep trough plasma concentrations above 10 mg/L to maintain therapeutic effect but below 15 mg/L to minimise toxicity. 
• Efficacy is assessed by monitoring symptoms, signs (e.g. pyrexia) and inflammatory markers (white cell count, C-reactive protein). 
• Safety monitoring should include daily renal function.  
• Platelet and leucocyte counts should be monitored in prolonged courses.