What is the first-line treatment for pediatric urinary tract infections (UTIs)?

First-Line Treatment for Pediatric Urinary Tract Infections

For most children with UTI, oral antibiotics are equally effective as parenteral therapy and should be the preferred initial route of administration, with treatment duration of 7-14 days. 1

Route of Administration

Oral therapy is the first-line approach for most pediatric UTIs, as initiating treatment orally or parenterally is equally efficacious. 1

• Reserve parenteral antibiotics for children who appear "toxic," are unable to retain oral intake, or when compliance with oral medication is uncertain. 1
• In a study of 309 febrile infants with UTIs, only 1% were too ill to be treated orally. 1
• Children receiving parenteral therapy should transition to oral antibiotics once they show clinical improvement (typically within 24-48 hours) and can retain oral fluids. 1

First-Line Oral Antibiotic Choices

The usual first-line oral agents include: 1

• Cephalosporins (cefixime 8 mg/kg/day in 1 dose, cefpodoxime 10 mg/kg/day in 2 doses, cefuroxime axetil 20-30 mg/kg/day in 2 doses, or cephalexin 50-100 mg/kg/day in 4 doses) 1
• Amoxicillin-clavulanate 20-40 mg/kg/day in 3 doses 1
• Trimethoprim-sulfamethoxazole (TMP-SMX) 6-12 mg/kg trimethoprim and 30-60 mg/kg sulfamethoxazole per day in 2 doses 1, 2, 3

Critical Caveat on Antibiotic Selection

Selection must be based on local antimicrobial resistance patterns, particularly for TMP-SMX and cephalexin, as there is substantial geographic variability. 1 Amoxicillin alone is no longer recommended due to high resistance rates (median 75% of E. coli isolates resistant globally). 1

First-Line Parenteral Antibiotic Choices

For children requiring parenteral therapy: 1

• Ceftriaxone 75 mg/kg every 24 hours (preferred due to low resistance rates and clinical effectiveness) 1
• Cefotaxime 150 mg/kg/day divided every 6-8 hours 1
• Gentamicin 7.5 mg/kg/day divided every 8 hours 1

Treatment Duration

The total course of therapy should be 7-14 days, regardless of whether treatment is initiated orally or parenterally. 1

• Courses of 1-3 days are inferior and should not be used for febrile UTIs. 1
• The minimum duration should be 7 days. 1

Important Contraindications

Nitrofurantoin should NOT be used to treat febrile infants with UTIs, as it does not achieve therapeutic concentrations in the bloodstream and parenchymal concentrations may be insufficient to treat pyelonephritis or urosepsis. 1 While the 2024 JAMA guidelines recommend nitrofurantoin for uncomplicated cystitis in adults 1, the American Academy of Pediatrics explicitly contraindicates it for febrile pediatric UTIs. 1

Age-Specific Considerations

For neonates <28 days: Hospitalization with parenteral amoxicillin plus cefotaxime for 3-4 days, then transition to oral therapy to complete 14 days total. 4

For infants 28 days to 3 months:

• If clinically ill: hospitalize with parenteral third-generation cephalosporin or gentamicin until afebrile for 24 hours, then complete 14 days with oral antibiotics. 4
• If not acutely ill: may manage as outpatient with daily parenteral ceftriaxone or gentamicin until afebrile for 24 hours, then complete 14 days orally. 4

For children >3 months with uncomplicated pyelonephritis: Oral antibiotics for 7-10 days are adequate if the child responds well to treatment. 5, 6