Antimicrobials · Glycopeptides
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Vancomycin inhibits bacterial cell wall synthesis by binding to the D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptides.
The primary clinical indication for intravenous vancomycin is the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections.
Oral vancomycin is the first-line treatment for Clostridioides difficile infection (CDI) because it is not systemically absorbed and achieves high fecal concentrations.
Rapid intravenous infusion of vancomycin causes Red Man Syndrome, a non-IgE-mediated histamine release characterized by flushing and pruritus.
Vancomycin is associated with nephrotoxicity, particularly when administered concurrently with other nephrotoxic agents like aminoglycosides or piperacillin-tazobactam.
Therapeutic drug monitoring via trough levels is required to ensure efficacy and minimize the risk of ototoxicity and renal injury.
Resistance to vancomycin occurs via the modification of the peptidoglycan binding site, specifically the substitution of D-Ala-D-Ala with D-Ala-D-Lac.
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A 62-year-old male is hospitalized for a severe skin and soft tissue infection. He is started on intravenous vancomycin. Shortly after the infusion begins, he develops diffuse erythematous flushing of the face, neck, and upper torso accompanied by intense pruritus. His blood pressure is 128/82 mmHg and his heart rate is 88 bpm. He has no history of allergies.
What is the most appropriate next step in management?
Slow the infusion rate and administer an antihistamine.
The patient is exhibiting classic signs of Red Man Syndrome, a dose-dependent infusion reaction caused by rapid histamine release, which is addressed by slowing the infusion rather than discontinuing the medication.
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Classification
Glycopeptide antibiotic; bactericidal inhibitor of cell wall synthesis.
Indications
MRSA infections, C. difficile (oral), and empiric coverage for gram-positive sepsis.
Mechanism of Action
Binds D-Ala-D-Ala terminus of peptidoglycan precursors, preventing cross-linking.
Side Effects
Red man syndrome (infusion-related), nephrotoxicity, and ototoxicity.
Contraindications / Monitoring
Hypersensitivity; monitor trough levels and serum creatinine.
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Mechanism of Action
Vancomycin inhibits bacterial cell wall synthesis by binding with high affinity to the D-alanyl-D-alanine terminus of cell wall precursor units. This steric hindrance prevents the action of transglycosylase and transpeptidase enzymes. The resulting failure of peptidoglycan polymerization leads to cell lysis and death in susceptible gram-positive organisms.
Unique Properties
It is a large, hydrophilic molecule with poor oral bioavailability, making it the gold standard for systemic MRSA when given IV. Conversely, oral administration is reserved exclusively for Clostridioides difficile colitis because it remains confined to the gastrointestinal lumen.
Indications
Primary treatment for MRSA-related skin/soft tissue infections, pneumonia, and osteomyelitis. It is the empiric choice for infective endocarditis and meningitis when combined with other agents. Oral vancomycin is the preferred treatment for severe C. difficile infection.
Pharmacokinetics
Excreted primarily via glomerular filtration in the kidneys, necessitating dose adjustments in patients with renal impairment. It does not undergo significant hepatic metabolism. Poor tissue penetration into the cerebrospinal fluid requires higher dosing or adjunctive therapy for meningitis.
Side Effects & Adverse Events
Red man syndrome is a non-allergic histamine release caused by rapid infusion, managed by slowing the rate. Nephrotoxicity is dose-dependent and increased when combined with other nephrotoxic agents like aminoglycosides. Ototoxicity is a rare but serious risk associated with high serum concentrations.
Contraindications
Hypersensitivity to vancomycin is the only absolute contraindication. Use with extreme caution in patients with pre-existing renal failure or hearing loss, as the drug may exacerbate these conditions.
Monitoring
Therapeutic drug monitoring is required for serious infections. Current consensus (2020 ASHP/IDSA/PIDS/SIDP) favors AUC/MIC-guided dosing (target AUC/MIC 400-600) for serious MRSA infections; trough-based monitoring (target 10-15 mcg/mL) remains acceptable for less severe infections, while the older 15-20 mcg/mL trough target is no longer recommended. Serum creatinine must be monitored frequently to detect early signs of acute kidney injury.
Clinical Pearls
If a patient develops flushing and hypotension during infusion, the classic board answer is to stop the infusion and restart at a slower rate. Remember that oral vancomycin is not absorbed and will not treat systemic infections; it is strictly for C. difficile.