Vancomycin

Vancomycin is a nonribosomally synthesised heptapeptide from Amycolatopsis orientalis whose rigid cup-shaped aglycone forms five hydrogen bonds with the terminal D-alanyl-D-alanine of lipid II. Because it sequesters the substrate rather than inhibiting an enzyme, it is essentially immune to the beta-lactamase resistance mechanisms that defeat penicillins. It is too large to cross the gram-negative outer membrane, which is why its spectrum is strictly gram-positive. Resistance in enterococci and, rarely, S. aureus comes from vanA/vanB gene clusters that remodel the precursor terminus to D-Ala-D-Lac, reducing binding affinity roughly a thousandfold. Killing is slow and time-dependent, which is why exposure is now targeted by 24-hour AUC rather than peak concentration.

Targets: Lipid II D-Ala-D-Ala terminus, Peptidoglycan transglycosylase, Bacterial cell wall synthesis

• · The real rule is weight-based: 15-20 mg/kg of actual body weight per dose. For a 75 kg adult that lands at roughly 1000-1500 mg every 12 hours. Current IDSA guidance targets an AUC24/MIC of 400-600 mg·h/L rather than a trough, though many centres still use a 15-20 mcg/mL trough as a surrogate.
• · 20-35 mg/kg, capped at 3000 mg. Loading matters because vancomycin has a large volume of distribution and unloaded patients sit sub-therapeutic for the first 24-48 hours.
• · Oral vancomycin is essentially unabsorbed and acts entirely in the colonic lumen — systemic levels and kidney monitoring are irrelevant here. Fulminant colitis uses 500 mg four times daily, sometimes with rectal instillation if ileus is present.

Work out your exact syringe units →

• very commonVancomycin infusion reaction (red man syndrome)— Direct mast-cell histamine release from fast infusion — flushing, itching and rash over the face, neck and torso. Slow the infusion and pre-treat with an antihistamine; it is not an allergy.
• commonNephrotoxicity— Risk climbs sharply with AUC above 600 mg·h/L, troughs above 20 mcg/mL, concurrent piperacillin-tazobactam, and courses longer than 7 days.
• commonPhlebitis and infusion-site pain— The main reason long courses get a PICC or central line.
• uncommonNeutropenia— Typically after two or more weeks of therapy and reversible on stopping.
• rareOtotoxicity— Usually with very high sustained levels or combined aminoglycoside exposure; hearing loss can be permanent.
• rareDRESS and linear IgA bullous dermatosis— Genuine drug hypersensitivity reactions, distinct from the infusion reaction, requiring immediate discontinuation.

• Known true IgE-mediated hypersensitivity to vancomycin or previous DRESS reaction to it.
• Not a substitute for a beta-lactam in methicillin-susceptible S. aureus — vancomycin performs measurably worse and is associated with higher mortality in MSSA bacteraemia.
• Oral vancomycin does nothing for systemic infection; IV vancomycin does nothing for C. difficile colitis. The routes are not interchangeable.

• cautionpiperacillin-tazobactam — The combination roughly doubles the incidence of acute kidney injury compared with vancomycin plus cefepime or meropenem. It is one of the best-documented nephrotoxic drug pairings in hospital medicine.
• cautionaminoglycosides — Additive nephrotoxicity and ototoxicity.
• redundantdaptomycin — Both cover MRSA; combining them is done only in specific salvage scenarios such as persistent bacteraemia, not routinely.
• cautionloop diuretics — Volume depletion and additive ototoxicity raise the renal and auditory risk.

• · Serum creatinine and eGFR at baseline and at least every 2-3 days during therapy.
• · Vancomycin AUC24 (Bayesian estimation from one or two levels) targeting 400-600 mg·h/L, or a trough of 15-20 mcg/mL if AUC monitoring is unavailable.
• · CBC weekly on courses beyond 7 days to catch neutropenia.
• · Audiometry only in prolonged high-dose therapy or with concurrent aminoglycosides.

Prescription-only medicine, approved in effectively every country. Hospital-administered for IV use; oral capsules and solution are dispensed by community pharmacies.

• Rybak et al. 2020, ASHP/IDSA/PIDS/SIDP consensus guideline on therapeutic monitoring of vancomycin (guideline)
• Liu et al., IDSA clinical practice guidelines for MRSA infections in adults and children (guideline)
• Johnson et al. 2021, IDSA/SHEA clinical practice guideline update for Clostridioides difficile infection (guideline)

Binds the D-Ala-D-Ala terminus of peptidoglycan precursors, physically blocking transglycosylation and transpeptidation. Because it occupies the substrate rather than an enzyme, resistance requires remodelling the target itself - the vanA operon swaps the terminal D-Ala for D-lactate, which drops affinity roughly a thousandfold. That is also why vancomycin is bactericidal but slowly so: it cannot act on organisms that are not actively building wall.

Two failures dominate. The first is confusing the routes: oral vancomycin does not treat bacteraemia, and intravenous vancomycin does not treat C. difficile colitis, because the drug goes where the route puts it. The second is the infusion reaction - flushing and torso erythema from direct mast-cell histamine release, historically called red man syndrome. It is rate-dependent, not an allergy, and the correct response is to slow the infusion rather than to label the patient allergic and lose the drug for life.

• D-Ala-D-Ala peptidoglycan terminus — High; falls ~1000-fold against vanA D-Ala-D-Lac

  Blocks cell wall cross-linking in Gram-positive organisms

Bactericidal but slowly, so clinical response is judged over 48-72 hours rather than hours. Steady state is reached after roughly four doses in normal renal function, which is why levels are drawn then.

Combining with piperacillin-tazobactam raises measured nephrotoxicity substantially; cefepime or meropenem are the usual alternatives when broad Gram-negative cover is needed alongside.

Daptomycin is the usual alternative for MRSA bacteraemia and is faster-acting, but cannot be used in pneumonia because pulmonary surfactant inactivates it. Linezolid reaches lung tissue well but is bacteriostatic and carries a serotonergic interaction.

• ?The AUC-guided versus trough-guided monitoring debate is settled in guidelines but not in universal practice, and many centres still dose on troughs alone.
• ?Whether the piperacillin-tazobactam nephrotoxicity signal reflects true injury or an artefact of creatinine secretion interference remains argued in the literature.