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Drug Reference

vancomycin

glycopeptide antibiotic· Brands: Vancocin, FirvanqIVPO

Mechanism of action
Vancomycin is a glycopeptide antibiotic that inhibits bacterial cell wall synthesis. It binds with high affinity to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus of peptidoglycan precursors on the outer surface of the cytoplasmic membrane. This binding prevents the transglycosylation and transpeptidation steps required for cross-linking of the peptidoglycan network, leading to osmotic lysis of susceptible bacteria. Vancomycin is bactericidal against many Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA), meticillin-susceptible S. aureus, streptococci, and enterococci (except VanA/VanB phenotypes). It is not active against Gram-negative bacteria because its large molecular size prevents penetration of the outer membrane. Some organisms, such as vancomycin-resistant enterococci (VRE) and vancomycin-resistant S. aureus (VRSA), have acquired resistance through alteration of the D-Ala-D-Ala target to D-Ala-D-Lac or D-Ala-D-Ser.
Pharmacokinetics
Vancomycin is poorly absorbed from the gastrointestinal tract; oral administration results in high faecal concentrations but negligible systemic absorption, so it is used orally only for Clostridioides difficile infection. For systemic infections, it must be given intravenously. After IV administration, vancomycin distributes widely into most body tissues and fluids, although penetration into cerebrospinal fluid is poor unless the meninges are inflamed. It is approximately 50% protein-bound. The volume of distribution is about 0.4 to 1 L/kg. Vancomycin is eliminated primarily unchanged by glomerular filtration, with a half-life of about 4 to 6 hours in patients with normal renal function. In renal impairment, the half-life is prolonged and accumulation occurs, so dose adjustment is required. Therapeutic drug monitoring is recommended for serious infections, typically by measuring trough serum concentrations (targeting 10 to 20 mg/L depending on indication) or, increasingly, by AUC-guided dosing (AUC/MIC ratio of 400 to 600). Oral vancomycin is not systemically absorbed and does not require serum level monitoring.
Indications & dosing

Serious MRSA infection (bacteraemia, pneumonia, skin and soft tissue, bone and joint)

Dose by actual body weight; target AUC/MIC 400-600 or trough 10-20 mg/L; adjust in renal impairment.

  • adult · IV: 15–20 mg/kg q8-12h · Dose by actual body weight; target AUC/MIC 400-600 or trough 10-20 mg/L; adjust in renal impairment.

MRSA bacteraemia and infective endocarditis

Consider infectious diseases input; target AUC/MIC 400-600 or trough 10-20 mg/L.

  • adult · IV: 15–20 mg/kg q8-12h · Consider infectious diseases input; target AUC/MIC 400-600 or trough 10-20 mg/L.

Meningitis (empirical or MRSA)

Target trough 15-20 mg/L; combine with appropriate beta-lactam when indicated.

  • adult · IV: 15–20 mg/kg q8-12h · Target trough 15-20 mg/L; combine with appropriate beta-lactam when indicated.

Clostridioides difficile infection

Oral vancomycin is not absorbed; use for severe or recurrent CDI as per local guidance.

  • adult · PO: 125 mg q6h · Oral vancomycin is not absorbed; use for severe or recurrent CDI as per local guidance.

Surgical prophylaxis in patients with beta-lactam allergyoff-label

Give within 120 minutes before incision; maximum 2 g per dose; local protocols vary.

  • adult · IV: 15 mg/kg once · Give within 120 minutes before incision; maximum 2 g per dose; local protocols vary.

Neonatal sepsis (resistant gram-positive)

Interval guided by postmenstrual age and renal function; monitor levels.

  • neonatal · IV: 10–15 mg/kg q8-24h · Interval guided by postmenstrual age and renal function; monitor levels.

Paediatric serious gram-positive infection

Target AUC/MIC 400-600; adjust for renal impairment.

  • pediatric · IV: 15–20 mg/kg q6-8h · Target AUC/MIC 400-600; adjust for renal impairment.

Paediatric Clostridioides difficile infection

Maximum 125 mg per dose; oral route not absorbed; local guidance may vary.

  • pediatric · PO: 10 mg/kg q6h · Maximum 125 mg per dose; oral route not absorbed; local guidance may vary.
Contraindications & precautions
  • Known hypersensitivity to vancomycin or another glycopeptide (for example teicoplanin) · Avoid all routes. Cross-reactivity within the glycopeptide class is possible; document the reaction and select an alternative agent.
  • Previous severe cutaneous adverse reaction attributed to vancomycin (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS) · Do not rechallenge. Re-exposure risks a severe, potentially fatal reaction.
  • Significant pre-existing renal impairment or anuria · Not an absolute bar when the drug is essential, but accumulation occurs. Use weight-based loading, extend intervals, monitor levels and renal function closely, and involve pharmacy.
  • Pre-existing hearing loss or concurrent ototoxic therapy · Baseline audiometry is sensible in prolonged therapy. Stop or review the drug if tinnitus or new hearing loss develops.
  • Concurrent nephrotoxic drugs (aminoglycosides, amphotericin B, ciclosporin, tacrolimus, NSAIDs, contrast media) · Combined nephrotoxicity is additive. Monitor renal function daily and consider therapeutic drug monitoring for both agents.
  • Pregnancy and breastfeeding · Use when a serious Gram-positive infection justifies it; vancomycin is generally considered acceptable in pregnancy when alternatives are unsuitable. Practice and local guidance vary.
  • Infuse intravenously over at least 60 minutes, or no faster than about 10 mg/kg per hour in adults. Rapid injection is unsafe. Slow or stop the infusion if flushing, rash or hypotension appears; this is a histamine reaction, not true allergy.
  • Doses are teaching examples only: adult dosing is weight-based and must be individualised to renal function, infection site and severity. Prescribing decisions rest with the treating team and local protocols.
  • Monitor serum creatinine and urine output before and during therapy. In renal impairment or obesity, use therapeutic drug monitoring, either trough levels or AUC-guided dosing, as local policy dictates; targets vary between guidelines and formularies.
  • Avoid or minimise concurrent nephrotoxic and ototoxic drugs. Review the medicines chart at initiation and daily, and consider an alternative where one exists.
  • Oral vancomycin is not absorbed and is used only for Clostridioides difficile infection or staphylococcal enterocolitis. Do not use the oral route to treat systemic infection.
  • Counsel patients to report tinnitus, hearing change, reduced urine output, rash or infusion-related flushing. Baseline audiometry is reasonable for prolonged courses or prior hearing loss.
Adverse effects
  • Vancomycin infusion reaction (red man syndrome): flushing, pruritus, rash, often of the face, neck and upper trunk
  • Nephrotoxicity, including acute kidney injury and rising serum creatinineserious
  • Phlebitis and pain at the infusion site; tissue necrosis if extravasation occurs
  • Hypotension during or shortly after a rapid infusionserious
  • Ototoxicity: tinnitus, hearing loss, vertigo, particularly with high levels or renal impairmentserious
  • Neutropenia or leukopenia, mainly with prolonged courses (weeks)serious
  • Thrombocytopenia
  • Anaphylaxisserious
  • Severe cutaneous adverse reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESSserious
Interactions
  • gentamicinmajorAvoid the combination if possible. If co-prescription is necessary, monitor renal function (serum creatinine, urea, electrolytes, urine output) at least daily. Consider therapeutic drug monitoring for both agents, and adjust doses according to renal function. Ensure adequate hydration and consider alternative antibiotics, extended-interval aminoglycoside dosing, or shorter courses of therapy.
Renal & hepatic adjustment
  • eGFR 50+: Usual initial dosing, for example 15 to 20 mg/kg IV every 8 to 12 hours, guided by indication, actual body weight and local policy. Monitor trough or AUC and renal function.
  • eGFR 20–49.9: Give a loading dose based on actual body weight, then extend the interval, for example every 24 hours, and adjust subsequent doses using serum levels. Consult pharmacy or local guidance.
  • eGFR 10–19.9: Give a loading dose, then redose based on serum levels, often every 24 to 48 hours or less frequently. Monitor levels and renal function closely.
  • eGFR 0–9.9: Give a loading dose and then use level-guided dosing, often with intervals of 48 hours or more. In dialysis or CRRT, dosing is complex and requires specialist advice; monitor levels frequently.
  • Hepatic impairment (mild): No specific hepatic dose adjustment is required. Vancomycin is eliminated mainly by the kidneys. Monitor renal function and vancomycin levels as usual.
  • Hepatic impairment (moderate): No specific hepatic dose adjustment is required. If ascites or hepatorenal syndrome alters renal function, dose by renal function and serum levels.
  • Hepatic impairment (severe): No specific hepatic dose adjustment is required. Use standard renal-based dosing and monitor levels; consider specialist advice if severe liver disease is accompanied by renal impairment.
Monitoring, pregnancy & toxicity
  • Serum vancomycin concentration (trough or AUC) · Before the fourth dose or at steady state, then at least weekly or more often if renal function changes or high doses are used.
  • Serum creatinine and eGFR · Baseline and at least every 24 to 48 hours during therapy, more often if unstable or receiving nephrotoxic drugs.
  • Infusion site and infusion rate · During each infusion; observe for flushing, rash or hypotension.
  • Renal and auditory function · Assess baseline; ask about tinnitus or hearing loss and monitor if prolonged therapy, high levels or other ototoxic drugs.
  • Full blood count · Baseline and weekly during prolonged therapy, as neutropenia and thrombocytopenia can occur.
  • Signs of superinfection · During and after therapy, especially with prolonged broad-spectrum use.
  • Pregnancy: Vancomycin is generally considered acceptable when needed for serious gram-positive infections in pregnancy, including MRSA. It crosses the placenta but has not been associated with a clear pattern of major birth defects. Use the lowest effective dose guided by serum levels, because renal clearance changes in pregnancy. Specialist advice is advised for prolonged therapy or in the first trimester.
  • Toxicity: Nephrotoxicity and ototoxicity: rising serum creatinine, reduced urine output, tinnitus, hearing loss or vertigo. Risk is higher with high trough levels, prolonged therapy, concurrent nephrotoxic or ototoxic drugs, and pre-existing renal impairment. · Stop or adjust vancomycin, monitor renal function and levels daily, maintain hydration, and consider alternative agents. Perform audiometry if hearing symptoms. Renal replacement therapy may be needed in severe renal failure.
  • Toxicity: Vancomycin infusion reaction (formerly red man syndrome): flushing, erythema, pruritus, hypotension and tachycardia during or soon after infusion. · Stop or slow the infusion, give an antihistamine if needed, and restart at a slower rate once stable. It is not a true allergy.
  • Toxicity: Haematological toxicity: neutropenia, agranulocytosis or thrombocytopenia, typically with prolonged therapy (more than 1 to 2 weeks). · Check full blood count, stop vancomycin if counts fall, and provide supportive care. Counts usually recover after withdrawal.
  • Toxicity: Overdose: no specific antidote; features may include nausea, hypotension, flushing, acute kidney injury and ototoxicity. · Supportive care, stop the drug, monitor renal function, levels and full blood count. Haemodialysis or haemofiltration may remove vancomycin in severe cases.
Clinical notes
Vancomycin is used for serious infections caused by Gram-positive bacteria, including MRSA bacteraemia, endocarditis, pneumonia, bone and joint infections, and skin and soft tissue infections. Oral vancomycin is first-line treatment for severe Clostridioides difficile infection. It is also used for surgical prophylaxis in patients with documented beta-lactam allergy or known MRSA colonisation, although local protocols vary. Adverse effects include nephrotoxicity, particularly when combined with other nephrotoxins such as aminoglycosides or piperacillin-tazobactam, and ototoxicity, which is rare with modern formulations but may occur with high serum levels. Rapid intravenous infusion can cause vancomycin flushing syndrome (formerly called red man syndrome), a histamine-mediated reaction characterised by flushing, pruritus, and hypotension; it is managed by slowing the infusion and, if needed, premedication with an antihistamine. Vancomycin should be infused over at least 60 minutes (or longer for higher doses) to reduce this risk. Dosing is weight-based and adjusted for renal function; monitoring of serum creatinine and vancomycin levels is essential. Practice varies by region and formulary regarding target levels, monitoring frequency, and the use of continuous versus intermittent infusion. Vancomycin is not effective against Gram-negative bacteria, so empirical therapy must cover these organisms when appropriate.

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BNF; local antimicrobial formulary; summary of product characteristics