Vancomycin (Vancocin)

This glycopeptide antibiotic has bactericidal activity against aerobic and anaerobic Gram + ve bacteria, including MRSA. It is only bacteriostatic for most enterococci. It is used for therapy of Clostridium difficileassociated diarrhoea unresponsive to metronidazole, for which it has to be given by mouth. It is not significantly absorbed from the gut.

Serum level monitoring is required to ensure therapeutic levels are achieved and to limit toxicity. Successful treatment of MRSA infections requires levels above the traditionally recommended range. Underdosing and problems associated with the sampling and the timing of serum level monitoring are problems that may result in decreased efficacy of vancomycin in the treatment of infection.The efficacy of vancomycin depends on the time for which the serum level exceeds the MIC (minimum inhibitory concentration) for the micro-organism rather than the attainment of high peak levels. Administration of vancomycin as a continuous IV infusion is therefore an ideal method of administration for optimum efficacy. Once the infusion reaches a steady state, the timing for serum level monitoring is not crucial, and samples can be taken at any time.

Vancomycin-resistant strains of enterococcus (VRE) are well recognized in the UK. Resistance also occurs less commonly in coagulase-negative staphylococci and is starting to emerge in rare isolates of Staphylococcus aureus.

Uses
C. difficile-associated diarrhoea via the oral route
Serious Gram + ve infections:
• prophylaxis and treatment of infective endocarditis (usually combined with gentamicin)
• dialysis-associated peritonitis
• infection caused by MRSA
• prosthetic device infections due to coagulase-negative staphylococci
• alternative to penicillins and cephalosporins where patients are allergic

Contraindications
Hypersensitivity

Administration
• C. difficile-associated diarrhoea
Orally: 125 mg 6 hourly for 7–10 days
For NG administration, the 500-mg reconstituted vial can be used nasogastrically for the four daily doses, otherwise 125-mg capsules can be used.

• Infective endocarditis and other serious Gram + ve infections including those caused by MRSA

IV infusion: 1 g 12 hourly, given over at least 100 min or 500 mg 6 hourly, given over at least 60 min

Duration of therapy is determined by severity of infection and clinical response. In staphylococcal endocarditis, treatment for at least 4 weeks is recommended.If pre-dose (trough) level is consistently less than 10 mg/l, (or 15–20 mg/l for less sensitive strains of MRSA), decrease the dose interval to 8 hourly or 6 hourly. If the post-dose (peak) level is >30 mg/l, decrease the dose (see therapeutic drug monitoring).

Vancomycin must be initially reconstituted by adding WFI:
• 250-mg vial – add 5 ml WFI
• 500-mg vial – add 10 ml WFI
• 1-g vial – add 20 ml WFI

The liquid in each reconstituted vial will contain 50 mg/ml vancomycin. Further dilution is required:
• reconstituted 250-mg vial – dilute with at least 50 ml diluent
• reconstituted 500-mg vial – dilute with at least 100 ml diluent
• reconstituted 1-g vial – dilute with at least 200 ml diluent

Suitable diluent: sodium chloride 0.9% or glucose 5% Continuous IV infusion

Monitor: Renal function
Serum vancomycin levels

How not to use vancomycin
Rapid IV infusion (severe hypotension, thrombophlebitis)
Not for IM administration

Adverse effects
Following IV use:
• severe hypotension
• flushing of upper body (‘red man’ syndrome)
• ototoxic and nephrotoxic
• blood disorders
• hypersensitivity
• rashes

Cautions
Concurrent use of:
• aminoglycosides – ↑ototoxicity and nephrotoxicity
• loop diuretics – ↑ototoxicity

Organ failure
Renal: reduce dose

Renal replacement therapy
CVVH dialysed, dose as in CC 10–20 ml/min, i.e. 1 g IV dose then monitor plasma levels every 24 hours until 10–15 mg/l, then give another 1 g dose and repeat this process. For continuous vancomycin infusions, consult local guidance for dosing in CVVH. HD/PD not dialysable, dose as in CC <10 ml/min, i.e. 500 mg–1 g IV every 48–96 hours. For oral/enteral treatment, no dose adjustment is needed in renal replacement therapy as insignificant absorption occurs.