Vancomycin

Usage

Vancomycin is a glycopeptide antibiotic prescribed for serious infections caused by Gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). It is indicated for conditions such as: infective endocarditis, septicemia, skin and skin structure infections, bone infections, lower respiratory tract infections, bacterial meningitis, Clostridium difficile-associated diarrhea (CDAD), and staphylococcal enterocolitis. Its pharmacological classification is antibiotic. Vancomycin inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of peptidoglycan precursors, preventing their incorporation into the cell wall.

Alternate Names

Vancomycin is also known as Vancocin and Firvanq.

How It Works

Pharmacodynamics: Vancomycin exerts its bactericidal action primarily against Gram-positive bacteria by hindering cell wall biosynthesis. It binds to the D-Ala-D-Ala termini of cell wall precursor units, preventing cross-linking and subsequent cell wall assembly. This leads to bacterial cell death.

Pharmacokinetics: Vancomycin is poorly absorbed orally and is typically administered intravenously (IV) for systemic infections. For CDAD, it is given orally. After IV administration, it distributes widely into tissues, including the lungs, kidneys, and heart. Vancomycin is primarily eliminated by renal excretion, with minimal hepatic metabolism. The half-life is around 4-6 hours in individuals with normal renal function but can be prolonged in patients with renal impairment.

Dosage

Standard Dosage

Adults:

• Standard Dose: 15-20 mg/kg (actual body weight) every 8-12 hours, infused IV over at least 60 minutes for 1g or 120 mins for doses >1g. Loading dose: 25–30 mg/kg (actual body weight, maximum 2.5g). Maximum daily dose generally 2g, but doses up to 4g have been used for severe infections. *Critically ill adults: 25-30 mg/kg (rounded to the nearest 250mg, Max 2.5g) loading dose is recommended due to correlation between volume of distribution, clearance, and body weight.

Children:

• Pediatric Dose: Initial Dose: 15 mg/kg. Neonates (<1 week): 10 mg/kg every 12 hours. Neonates (1-4 weeks): 10 mg/kg every 8 hours. Infants and Children (≥4 weeks): 10–15 mg/kg/dose (max 750mg/dose) every 6 hours

Special Cases:

• Elderly Patients: Dose adjustment is required based on renal function, which often declines with age.
• Patients with Renal Impairment: Dose reduction and/or increased dosing interval is necessary based on creatinine clearance (CrCl). CrCl <20 mL/min: Initial dose 15mg/kg, monitor levels after 4-5 days, redose only when level <12mg/L.
• Patients with Hepatic Dysfunction: Although hepatic impairment does not significantly alter vancomycin’s pharmacokinetics, caution is advised.

Clinical Use Cases:

• Intubation/Mechanical Ventilation/ICU Use: Loading dose of 25–30 mg/kg is often used, followed by maintenance dosing based on renal function and therapeutic drug monitoring (TDM).
• Surgical Procedures (Prophylaxis): 15 mg/kg IV within 120 minutes before surgery.

Dosage Adjustments:

Dose adjustments are based on renal function, age, body weight (actual, ideal for obese patients), and TDM results (trough levels).

Side Effects

Common Side Effects:

• Infusion-related reactions (“red man syndrome”): flushing, rash, pruritus, urticaria, tachycardia, hypotension.
• Nephrotoxicity.
• Ototoxicity.
• Phlebitis.
• Pain at injection site.

Rare but Serious Side Effects:

• Anaphylaxis.
• Neutropenia.
• Stevens-Johnson syndrome.
• Toxic epidermal necrolysis.
• Interstitial nephritis.

Adverse Drug Reactions (ADR):

• Severe hypotension (including shock and cardiac arrest)
• Ototoxicity can present as tinnitus or hearing loss

Contraindications:

• Hypersensitivity to vancomycin.
• Caution in patients with pre-existing renal disease or hearing impairment.

Drug Interactions:

• Nephrotoxic Drugs: Aminoglycosides, amphotericin B, cyclosporine, NSAIDs.
• Ototoxic Drugs: Aminoglycosides, cisplatin, loop diuretics.
• Neuromuscular blocking agents: Increased risk of neuromuscular blockade.

Pregnancy and Breastfeeding:

Vancomycin crosses the placenta. It is classified as Pregnancy Category C. Use only if the potential benefit justifies the potential risk to the fetus. Vancomycin is excreted in breast milk. Caution is advised during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial cell wall synthesis.
• Side Effects: Red man syndrome, nephrotoxicity, ototoxicity.
• Contraindications: Hypersensitivity.
• Drug Interactions: Nephrotoxic and ototoxic drugs, neuromuscular blocking agents.
• Pregnancy & Breastfeeding: Category C; use with caution.
• Dosage: Adults: 15–20 mg/kg IV every 8-12 hours; Children: Variable; Special adjustments for renal impairment.
• Monitoring Parameters: Serum creatinine, vancomycin trough levels, hearing tests.

Precautions:

• General Precautions: Renal function monitoring, slow IV infusion.
• Specific Populations: Dose adjustment for elderly and renally impaired patients.

FAQs

Q1: What is the recommended dosage for Vancomycin?

A: Adults: 15-20 mg/kg (actual body weight) IV every 8–12 hours; Children: Variable, with dosage calculated by weight and age. Dose adjustments are required for renal impairment and other special populations.

Q2: What are the common side effects of Vancomycin?

A: The common side effects include infusion-related reactions (“red man syndrome”), nephrotoxicity (kidney damage), and ototoxicity (hearing loss).

Q3: What is “red man syndrome,” and how is it managed?

A: “Red man syndrome” is a collection of symptoms, including flushing, rash, pruritus, urticaria, tachycardia, and hypotension, related to rapid vancomycin infusion. It’s managed by slowing the infusion rate and pre-treating with antihistamines.

Q4: How is vancomycin dosed in patients with renal impairment?

A: Dosage adjustments are crucial in patients with renal impairment. The dose and/or dosing interval should be reduced based on creatinine clearance (CrCl).

Q5: What are the key drug interactions with Vancomycin?

A: Vancomycin can interact with other nephrotoxic or ototoxic drugs, such as aminoglycosides, increasing the risk of kidney damage and hearing loss.

Q6: Can Vancomycin be used during pregnancy and breastfeeding?

A: Vancomycin is a Pregnancy Category C drug, meaning it should be used with caution during pregnancy. It is present in breastmilk, so advise caution during breastfeeding.

Q7: What is the mechanism of action of Vancomycin?

A: Vancomycin inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of peptidoglycan precursors, ultimately leading to bacterial cell death.

Q8: What are the indications for using Vancomycin?

A: Vancomycin is typically used for serious infections caused by Gram-positive bacteria, including MRSA, such as endocarditis, septicemia, skin infections, bone infections, and lower respiratory tract infections, amongst others.

Q9: How should vancomycin be administered?

A: Vancomycin is generally given intravenously (IV) for systemic infections, and the infusion should be over at least 60 minutes for doses of 1gm. It can be given orally for CDAD.

Q10: Why is therapeutic drug monitoring (TDM) necessary for vancomycin?

A: TDM, especially trough level monitoring, guides dosage adjustments to ensure therapeutic levels are achieved while minimizing the risk of toxicity. This is especially important for those with renal impairment and critically ill patients.