What is the recommended vancomycin dosing regimen for patients undergoing peritoneal dialysis?

Vancomycin Dosing for Peritoneal Dialysis

For patients undergoing peritoneal dialysis with peritonitis, administer vancomycin intraperitoneally with a loading dose of 20 mg/kg (or 1000 mg/L dialysate for adults, 500 mg/L for children <35 kg), followed by continuous dosing of 50 mg/L in each dwell, with serum level monitoring on day 5 to prevent toxicity.

Intraperitoneal Administration Route

• Intraperitoneal (IP) administration is the preferred route for treating peritoneal dialysis-associated peritonitis, as approximately 60% of an IP dose is absorbed systemically within 6 hours, achieving serum concentrations around 10 mcg/mL with 30 mg/kg dosing 1.

• The FDA label confirms that IP vancomycin achieves therapeutic systemic absorption, though it notes that safety and efficacy of IP use has not been established in adequate controlled trials 1.

Loading Dose Strategy

Adults

• Administer a loading dose of 20 mg/kg (approximately 1000 mg/L dialysate) intraperitoneally 2.
• This loading dose translates to roughly 30 mg/kg in 2 L dialysate for standard adult dosing 3.

Pediatric Patients (<35 kg)

• Use 500 mg/L dialysate loading dose instead of 1000 mg/L to avoid excessive vancomycin exposure 3.
• The standard 1000 mg/L loading dose produces peak levels >50 mg/L in patients <35 kg and >60 mg/L in patients <15 kg, which remain above 20 mg/L for over 2 days 3.
• This weight-based adjustment is critical because dialysate volume in pediatrics is normalized to body surface area, not weight 3.

Maintenance Dosing

Continuous Dosing (Preferred)

• Add 50 mg/L vancomycin to each dialysate dwell following the loading dose 2.
• Continuous dosing is superior to intermittent dosing because intermittent regimens fail to maintain therapeutic peritoneal dialysate effluent (PDE) concentrations above the MIC of 4 mg/L in 23% of patients 4.

Intermittent Dosing (Alternative)

• If continuous dosing is not feasible, a single 1 g IV dose can maintain therapeutic serum levels (>5 mcg/mL) for more than 16 days in patients on chronic intermittent peritoneal dialysis 5.
• However, intermittent dosing cannot guarantee therapeutic PDE concentrations during active peritonitis, with poor correlation (R² = 0.18) between serum and PDE levels 4.

Therapeutic Drug Monitoring

• Measure serum vancomycin level on day 5 of treatment to ensure levels are therapeutic (15-20 mg/L for serious infections) but not toxic (>20 mg/L) 2.
• Serum concentrations >12-15 mg/L are recommended for peritonitis treatment, achievable in 98% of patients with appropriate dosing 4.
• Adjust subsequent doses based on day 5 serum level to prevent toxicity in patients susceptible to overdose 2.

Pharmacokinetic Considerations

• Vancomycin has a half-life of approximately 18 hours during peritoneal dialysis, with peritoneal clearance of 6.1 ml/min (range 4.2-9.8) and overall clearance of 2.1-2.3 ml/min 5, 6.
• Distribution volume approximates total body water (37-59 L), with serum-to-PDE ratio of 1.27 5.
• Following IP administration of 50 mcg/mL dialysate, serum concentrations of 5.1-21.5 mcg/mL are achieved, with 35% of instilled vancomycin absorbed during 15 hours of dialysis 6.

Critical Pitfalls to Avoid

• Do not use standard 1000 mg/L loading dose in children <35 kg, as this causes excessive exposure and prolonged supratherapeutic levels 3.
• Avoid relying solely on serum levels to predict PDE concentrations, as the correlation is poor during active infection 4.
• Do not use intermittent dosing as first-line, as it fails to maintain adequate PDE levels in nearly one-quarter of patients 4.
• Do not assume vancomycin dosing for hemodialysis applies to peritoneal dialysis, as drug removal mechanisms differ substantially between modalities 7.

Monitoring for Nephrotoxicity

• Monitor serum creatinine for increases ≥0.5 mg/dL or 150% from baseline, which defines vancomycin-induced nephrotoxicity 8.
• Sustained trough concentrations >20 μg/mL significantly increase nephrotoxicity risk 8.
• Consider alternative therapies if vancomycin MIC ≥2 mg/L, as target AUC/MIC ratios are not achievable with conventional dosing 8, 9.