What is the appropriate empiric antimicrobial therapy, dosage, duration, and follow‑up for a child with a presumed urinary tract infection (UTI) caused by Escherichia coli (E. coli)?

Pediatric UTI with E. coli: Empiric Treatment Protocol

For most children with E. coli UTI, start oral amoxicillin-clavulanate (40-45 mg/kg/day divided twice daily) or a third-generation cephalosporin (cefixime 8 mg/kg once daily or ceftriaxone 50 mg/kg IV/IM once daily if parenteral therapy needed) for 7-14 days, with 10 days being the most common duration. 1

Immediate Diagnostic Requirements

Before starting any antibiotics:

• Obtain urine by catheterization or suprapubic aspiration in non-toilet-trained children—bag specimens have false-positive rates of 12-83% and should never be used for culture 1, 2
• Midstream clean-catch is acceptable for toilet-trained children 1
• Both urinalysis AND culture are mandatory—urinalysis alone is insufficient, as 10-50% of culture-proven UTIs may have false-negative urinalysis 1
• Diagnosis requires BOTH pyuria (≥5 WBC/HPF or positive leukocyte esterase) AND ≥50,000 CFU/mL of a single uropathogen 1

Empiric Antibiotic Selection Algorithm

For Well-Appearing Children (Oral Therapy)

First-line options (choose based on local resistance patterns):

• Amoxicillin-clavulanate: 40-45 mg/kg/day divided every 12 hours 1, 3, 4
• Cefixime: 8 mg/kg once daily 1
• Cephalexin: 50-100 mg/kg/day divided every 6 hours 1

Second-line option:

• Trimethoprim-sulfamethoxazole: 40 mg/kg sulfamethoxazole + 8 mg/kg trimethoprim per 24 hours divided every 12 hours—ONLY if local E. coli resistance is <10% for pyelonephritis or <20% for cystitis 1, 5, 4

Critical caveat: Recent data from Slovakia show third-generation cephalosporins achieved 95.7% clinical response versus only 55.9% for second-generation cephalosporins, making third-generation agents strongly preferred 4

For Toxic-Appearing Children or Unable to Retain Oral Intake (Parenteral Therapy)

• Ceftriaxone: 50-75 mg/kg IV/IM once daily (maximum 2 g) 1, 3
• Transition to oral therapy once clinically improved to complete 7-14 day course 1

Age-Specific Exceptions

• Neonates <28 days: Require hospitalization and ampicillin PLUS gentamicin or cefotaxime for 14 days total—never use oral antibiotics alone 1, 2
• Infants 28 days-3 months: Third-generation cephalosporin; consider hospitalization if toxic-appearing 1

Treatment Duration by Clinical Presentation

Clinical Scenario	Duration	Evidence
Febrile UTI/pyelonephritis	7-14 days (10 days most common)	[1]
Non-febrile cystitis	7-10 days	[1]
Neonates <28 days	14 days	[1,2]

Courses shorter than 7 days are inferior for febrile UTIs and must be avoided. 1

Critical Antibiotics to AVOID

• Nitrofurantoin: Do NOT use for febrile UTI—it does not achieve adequate serum/parenchymal concentrations to treat pyelonephritis 1
• Amoxicillin monotherapy: WHO removed this from empiric recommendations in 2021 due to 75% global E. coli resistance 1
• Fluoroquinolones: Avoid in children due to musculoskeletal safety concerns; reserve only for severe infections where benefits outweigh risks 1

Follow-Up Strategy

Short-Term (1-2 Days)

• Clinical reassessment within 1-2 days to confirm fever resolution and clinical improvement 1, 2
• Defervescence expected within 24-48 hours of appropriate therapy 1, 2
• If fever persists >48 hours: Evaluate for antibiotic resistance, anatomic abnormality, or abscess formation 1

Imaging Recommendations

Renal and bladder ultrasound (RBUS):

• Perform in ALL febrile children <2 years with first UTI to detect anatomic abnormalities 1, 2
• NOT routinely required for children >2 years with first uncomplicated UTI 1

Voiding cystourethrography (VCUG):

• NOT routine after first UTI 1
• Perform VCUG only if:
  • RBUS shows hydronephrosis, scarring, or findings suggesting high-grade VUR/obstruction 1
  • Second febrile UTI occurs (risk of grade IV-V VUR rises to ~18%) 1
  • Fever persists >48 hours despite appropriate therapy 1

Long-Term Follow-Up

• No routine scheduled visits after successful treatment of uncomplicated first UTI 1
• Instruct parents to seek evaluation within 48 hours for any future febrile illness to detect recurrent UTI early 1
• No routine "proof-of-cure" urine culture is needed when child becomes afebrile and symptom-free 1

Antibiotic Adjustment Based on Culture

• Adjust therapy based on culture and sensitivity results when available 1, 2
• Consider local resistance patterns when selecting empiric therapy 1, 4
• E. coli accounts for 80-90% of pediatric UTIs 3
• Recent Brazilian data show E. coli susceptibility: nitrofurantoin 94%, nalidixic acid 95%, cephalexin 81%, trimethoprim-sulfamethoxazole 40% 6

Common Pitfalls to Avoid

• Do NOT delay treatment while awaiting culture—early treatment (≤48 hours) reduces renal scarring risk by >50% 1, 2
• Do NOT use bag-collected urine for culture—false-positive rates approach 85% 1
• Do NOT prescribe <7 days for febrile UTI 1
• Do NOT use nitrofurantoin for febrile UTI in children 1
• Do NOT omit urine culture before starting antibiotics—this is the only opportunity for definitive diagnosis 1
• Do NOT order VCUG routinely after first UTI 1

Prophylaxis Considerations

• NOT routinely recommended after first UTI 1
• Consider only for high-risk patients: recurrent febrile UTI or high-grade VUR 1
• RIVUR trial showed prophylaxis reduced recurrent UTI by ~50% but did NOT reduce renal scarring 1

Long-Term Outcomes

• Renal scarring occurs in ~15% of children after first febrile UTI 1
• Can lead to hypertension (5%) and chronic kidney disease (3.5% of pediatric ESRD) 1
• Early treatment within 48 hours may decrease scarring risk 1, 2