What is the recommended intra-peritoneal (IP) antibiotic regimen, including dosing, for pediatric patients with peritonitis associated with peritoneal dialysis (PD)?

Intraperitoneal Antibiotic Dosing for Pediatric PD-Associated Peritonitis

For pediatric peritoneal dialysis-associated peritonitis, initiate empiric therapy with intraperitoneal cefazolin (or vancomycin if methicillin-resistant organisms are suspected) plus ceftazidime, with specific weight-based dosing adjusted for the patient's residual renal function and dialysis modality.

Initial Empiric Antibiotic Regimen

First-Line Combination Therapy

• Combine a first-generation cephalosporin (cefazolin) with a third-generation cephalosporin (ceftazidime) for uncomplicated peritonitis 1
• Reserve glycopeptide (vancomycin) plus third-generation cephalosporin combinations for high-risk patients: those younger than 2 years, with severe clinical presentation, or recent methicillin-resistant organism infection 1
• Intraperitoneal administration is superior to intravenous administration for treating PD-associated peritonitis 2

Specific Intraperitoneal Dosing Regimens

Cefazolin:

• Loading dose: 500 mg/L of dialysate 3
• Maintenance dose: 125 mg/L of dialysate in each exchange 3
• For pediatric patients, calculate total daily dose at 25-50 mg/kg/day for mild-moderate infections, up to 100 mg/kg/day for severe infections 3

Ceftazidime:

• Loading dose: 500 mg/L of dialysate 4
• Maintenance dose: 125 mg/L of dialysate in each exchange 4
• For pediatric patients 1 month to 12 years: 30-50 mg/kg IV every 8 hours (maximum 6 grams/day) can guide IP dosing calculations 4
• For neonates (0-4 weeks): 30 mg/kg IV every 12 hours 4

Vancomycin (when indicated):

• Loading dose: 500 mg/L of dialysate (NOT 1000 mg/L) 5
• The traditional 1000 mg/L loading dose causes dangerously elevated vancomycin levels (>50 mg/L) in children weighing <35 kg and >60 mg/L in children <15 kg 5
• Maintenance dose: Target serum trough levels <2 mcg/mL to minimize ototoxicity and nephrotoxicity 6
• Weight-based dosing: 0.6 mg/kg body weight per exchange 6
• Monitor serum vancomycin concentrations and renal function throughout therapy 6

Gentamicin (alternative aminoglycoside):

• Dose: 0.6 mg/kg body weight per exchange 6
• Alternative weight-based dosing: 3-7.5 mg/kg/day 6
• Target trough levels <2 mcg/mL 6
• Avoid aminoglycosides when possible in patients with residual renal function, as they may accelerate loss of kidney function 7

Administration Schedule

• Continuous dosing: Add antibiotics to each dialysate exchange 2
• Intermittent dosing: Antibiotics can be given once daily in the long-dwell exchange 2
• Both continuous and intermittent schedules have similar treatment failure and relapse rates 2
• For automated PD (APD), incorporate antibiotics into the dialysis fluid at appropriate concentrations 4

Dosing Adjustments for Residual Renal Function

• Patients with significant residual renal function (creatinine clearance >50 mL/min) may require dose adjustments 7, 6
• For anuric patients or those without residual function, standard IP dosing applies 6
• Monitor serum antibiotic concentrations, particularly for vancomycin and aminoglycosides, to guide dose adjustments 6

Treatment Duration and Response Assessment

• Continue antibiotics for 2 days after signs and symptoms resolve, but complicated infections may require longer therapy 4
• Standard treatment duration is typically 14-21 days depending on organism and clinical response 2
• Assess treatment response at 48-72 hours; if no improvement, consider catheter removal 2

Critical Pitfalls to Avoid

• Do NOT use the adult vancomycin loading dose of 1000 mg/L in pediatric patients - this causes toxic levels in children <35 kg 5
• Do NOT rely on antibiotics alone for relapsing or persistent peritonitis - simultaneous catheter removal and replacement is superior to urokinase for treatment failure 2
• Do NOT use aminoglycosides as first-line in patients with preserved residual renal function - they accelerate kidney function decline 7
• Do NOT administer ceftazidime or cefazolin in the same solution as aminoglycosides - potential drug interaction requires separate administration 4
• Do NOT continue antibiotics beyond clinical resolution - prolonged therapy increases risk of resistance and complications 7

Special Considerations for Automated PD

• Peritonitis rates are significantly lower with automated PD compared to continuous ambulatory PD 8
• Antibiotic concentrations of 250 mg per 2 L of dialysis fluid can be incorporated directly into APD solutions 4
• Ensure adequate dwell times to allow antibiotic absorption from the peritoneal cavity 9