What is the recommended prophylactic antibiotic regimen for infants with vesicoureteric (VUR) reflux?

Prophylactic Antibiotic Regimen for Infants with Vesicoureteral Reflux

Continuous antibiotic prophylaxis (CAP) is recommended for infants with vesicoureteral reflux (VUR), particularly those with high-grade reflux (grades III-V), using trimethoprim-sulfamethoxazole, amoxicillin, or nitrofurantoin at one-quarter to one-half of the regular therapeutic dose. 1

Antibiotic Selection Based on Age

• Under 6 weeks of age: Amoxicillin (preferred)

  • TMP-SMZ must be avoided due to risk of hepatic injury 1
  • Nitrofurantoin should be avoided before 4 months due to risk of hemolytic anemia 1

• 6 weeks to 4 months: Amoxicillin (preferred)

  • TMP-SMZ can be used if no renal insufficiency
  • Continue to avoid nitrofurantoin 1

• Over 4 months:

  • TMP-SMZ (first choice)
  • Amoxicillin (alternative)
  • Nitrofurantoin (alternative) 1

Dosing Guidelines

• Trimethoprim-sulfamethoxazole: 2-3 mg/kg of trimethoprim component once daily
• Amoxicillin: 10-15 mg/kg once daily
• Nitrofurantoin: 1-2 mg/kg once daily 1

Duration of Prophylaxis

The optimal duration of CAP remains controversial, but evidence suggests:

• Continue CAP until spontaneous resolution occurs (typically 12-48 months in approximately half of infants) 1
• Patients who have received CAP for less than 1 year after the last febrile UTI and those with bilateral VUR are at higher risk for recurrences 1
• A practical approach is to continue CAP until bladder and bowel dysfunction (BBD) resolves in older children 1

Risk Stratification for CAP

CAP benefit varies based on risk factors:

• Higher benefit in:

  • High-grade reflux (grades III-V)
  • Bilateral VUR
  • History of febrile UTI
  • Female sex (after infancy)
  • Uncircumcised males
  • Presence of bladder and bowel dysfunction in older children 1

• Lower benefit in:

  • Low-grade reflux (grades I-II)
  • Unilateral VUR
  • No history of UTI 1

Management of Breakthrough UTIs

If a breakthrough UTI occurs while on prophylaxis:

1. Treat the acute infection with appropriate therapeutic antibiotics
2. Consider switching to an alternative antibiotic for prophylaxis
3. Use antibiogram results to guide selection if available
4. Consider surgical intervention if breakthrough infections continue despite CAP 1

Monitoring

• Routine laboratory tests (CBC, electrolytes, creatinine) are not mandatory in otherwise healthy children on CAP 1
• Monitor for signs of UTI, particularly fever in infants who cannot verbalize symptoms 1
• Regular renal ultrasound to assess for upper tract dilation 2

Important Considerations

• The PREDICT trial demonstrated that CAP provided a small but significant benefit in preventing first UTI in infants with grade III-V VUR, with a number needed to treat of 7 children over 2 years 3
• CAP is associated with increased occurrence of non-E. coli organisms and antibiotic resistance 1, 3
• Patient compliance with CAP is often poor, with studies showing only 17% of pediatric VUR patients are fully compliant with therapy 4
• The benefit of CAP must be weighed against the risk of microbial resistance 1

By following these guidelines, clinicians can optimize prophylactic antibiotic therapy for infants with VUR while minimizing risks of breakthrough infections and antibiotic resistance.