Generic Name

Vancomycin

Mechanism

• Inhibits bacterial cell‑wall synthesis by binding the D‑alanine‑D‑alanine (D‑Ala‑D‑Ala) terminus of the peptidoglycan precursor.
• This prevents cross‑linking of cell‑wall strands, resulting in bacteriostatic activity at lower concentrations and bactericidal activity at higher concentrations.
• Bacterial resistance mainly arises through alteration of the peptidoglycan terminus to D‑alanine‑D‑glycine (VISA/VRSA).

Pharmacokinetics

• Absorption: Limited oral absorption; the drug is used orally only for *Clostridioides difficile* colitis.
• Distribution: Large volume of distribution (~0.5 L/kg) with marked inter‑individual variability.
• Protein binding: ~30–50 % (variable).
• Metabolism: Minimal hepatic metabolism.
• Excretion: Primarily renal (≈70 % unchanged in urine).
• Half‑life: 4–8 h in patients with normal renal function; prolonged in renal impairment.
• Tissue penetration: Variable; good for skin/soft tissue, moderate for lungs, poor for CNS (unless meningitis and the BBB is inflamed).

Indications

• Severe MRSA infections: bacteremia, endovascular, osteomyelitis, prosthetic‑device infections, pneumonia, and sepsis.
• Enterococcus faecium (VRE) infections (usually in combination).
• *Clostridioides difficile* colitis (oral).
• Empiric therapy for suspected gram‑positive infections pending culture results.

Contraindications

• Hypersensitivity to vancomycin or any excipients.
• Renal dysfunction: dose adjustment required; avoid if eGFR < 10 mL/min/1.73 m² (consider alternatives).
• Pregnancy/Breastfeeding: Category B – use only if benefit outweighs risk.
• Drug interactions:
• Nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin) – avoid concurrent use or monitor closely.
• Calcium channel blockers – potential for additive hypotension.

> Warning: Red Man Syndrome (infusion‑rate related anaphylactoid reaction).

Dosing

• IV infusion (preferred).
• *Adult severe infection:* 15–20 mg /kg IV every 6–8 h.
• *Steady‑state trough target:* 15–20 µg/mL (sepsis, MRSA).
• *Osteomyelitis, prosthetic‑device infections:* 2000 mg IV every 12 h (after initial 6000 mg loading dose).
• Oral (for C. difficile): 500–1250 mg PO every 6–12 h; duration 10–14 days.
• Infusion time: Minimum 1 h; slower infusion reduces Red Man Syndrome.
• Loading dose: 25–30 mg /kg IV (if total daily dose > 2000 mg).
• Adjust for renal impairment using eGFR tables.

Adverse Effects

• Common:
• Nausea/vomiting
• Diarrhea
• Vascular irritation (rash, erythema at infusion site)
• Serious:
• Red Man Syndrome – flushing, pruritus, hypotension.
• Nephrotoxicity – acute tubular necrosis; dose‑dependent.
• Ototoxicity – hearing loss, vertigo (especially with aminoglycosides).
• Guillain-Barré syndrome (rare).
• Anemia (pancytopenia) – possible immune‑mediated.
• Neurotoxicity – peripheral neuropathy in prolonged use.

Monitoring

• Trough serum levels (before next dose) – target 15–20 µg/mL for severe infections, 10–15 µg/mL for bacteremia, 5–10 µg/mL for uncomplicated infections.
• Renal function: Creatinine, BUN, eGFR – at least twice weekly during therapy.
• Audiometry in patients ≥ 1 month of therapy, especially with aminoglycosides.
• Complete blood count for early detection of hematologic toxicity.
• Inflammation markers (CRP, procalcitonin) to gauge response.
• Infusion rate documentation – enforce 1 h minimum.

Clinical Pearls

1. TDM is non‑negotiable. Without trough monitoring, you risk under‑dosing (MRSA relapse) or overdosing (nephrotoxicity).

2. Infusion engineering matters. A 1‑hour infusion will cut Red Man Syndrome rates by >50 %. Use bolus only for loading dose.

3. Renal adjustment formulas:
• *Standard:* Dose interval = (40 mL/min × 1.5) × 1.5 ÷ 50 % clearance quanta.
• *Rapid calculators* (e.g., vancomycin calculator tools) simplify this.

4. Avoid concomitant nephrotoxins unless absolutely necessary; if unavoidable, double‑check troughs and renal indices.

5. Weight‑based dosing in obesity uses *adjusted body weight* (ABW) to keep Vd within normal limits.

6. Oral vancomycin is NOT for systemic infections. It’s a stool‑directed therapy only for C. difficile.

7. Red Man Syndrome: prophylactic dexamethasone is optional; the gold‑standard is slow infusion rather than steroids.

8. Monitor serum zinc & magnesium in long‑term therapy; low levels augment neurotoxicity.

> Quick Tip: Keep a “Vancomycin Box” on your chart – columns for dose, interval, last trough, eGFR, and infusion time – to instantly rise or adjust therapy.

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• Vancomycin remains a vital but demanding weapon in the antimicrobial arsenal; mastery of its pharmacokinetic nuances and vigilant monitoring ensures therapeutic success while minimizing harm.