What are the recommended antibiotic regimens, including drug choice, dose, route, and duration, for an otherwise healthy child with urinary tract infection: (1) infants younger than 2 months, (2) children 2 months or older with uncomplicated cystitis, and (3) children 2 months or older with febrile urinary tract infection or suspected pyelonephritis?

Pediatric UTI Treatment: Evidence-Based Antibiotic Regimens

Infants Younger Than 2 Months

Neonates and young infants (<2 months) with UTI require hospitalization and parenteral therapy with ampicillin plus an aminoglycoside (or third-generation cephalosporin) for a total of 14 days. 1, 2, 3

Specific Regimen:

• Ampicillin 50 mg/kg IV every 12 hours (age <7 days) or every 8 hours (age 7-28 days) PLUS 3
• Gentamicin 5 mg/kg IV every 24 hours OR 3
• Cefotaxime 50 mg/kg IV every 12 hours (age <7 days) or every 8 hours (age 7-28 days) 3

Critical Management Points:

• After 3-4 days of parenteral therapy with good clinical response, transition to oral antibiotics to complete the full 14-day course 3
• These infants have approximately 5% risk of bacteremia, necessitating broader coverage than older children 1
• Do not use ceftriaxone in neonates due to bilirubin displacement risk 3

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Children 2 Months or Older with Uncomplicated Cystitis

For non-febrile cystitis in children ≥2 months, treat with oral antibiotics for 7-10 days using amoxicillin-clavulanate, cephalexin, or nitrofurantoin as first-line agents. 1, 2, 4

First-Line Oral Options:

• Amoxicillin-clavulanate 40-45 mg/kg/day divided twice daily 1
• Cephalexin 50-100 mg/kg/day divided into 4 doses 1, 2
• Nitrofurantoin 5-7 mg/kg/day divided twice daily (preferred for uncomplicated cystitis; spares broader-spectrum agents) 1, 5

Alternative Agent (Resistance-Dependent):

• Trimethoprim-sulfamethoxazole 6-12 mg/kg/day (TMP component) divided twice daily—only if local E. coli resistance is <20% 1, 5

Duration Evidence:

• Shorter courses (3-5 days) appear comparable to longer courses (7-14 days) for cystitis, though 7-10 days remains most commonly recommended 1
• Children with moderate-to-severe symptoms should receive the full 7-10 day course 1

Critical Pitfall:

• Never use nitrofurantoin for febrile UTI/pyelonephritis—it does not achieve adequate serum or parenchymal concentrations to treat upper tract infection 1, 2

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Children 2 Months or Older with Febrile UTI or Suspected Pyelonephritis

Most children with febrile UTI can be treated with oral antibiotics for 7-14 days (10 days most common); reserve parenteral therapy only for toxic-appearing children, those unable to retain oral intake, or infants <3 months. 1, 2, 6

First-Line Oral Regimens:

• Amoxicillin-clavulanate 40-45 mg/kg/day divided twice daily 1, 2
• Cefixime 8 mg/kg once daily 1, 2, 6
• Cephalexin 50-100 mg/kg/day divided into 4 doses 1, 2

Parenteral Options (When Indicated):

• Ceftriaxone 50 mg/kg IV/IM once daily (maximum 2 g) 1, 2
• Gentamicin 5 mg/kg IV once daily 1, 3

Treatment Duration:

• 7-14 days total (regardless of initial route; 10 days is most commonly recommended) 1, 2, 4
• Courses shorter than 7 days are inferior and should never be used for febrile UTI 1, 2

Transition Strategy:

• For children initially requiring parenteral therapy, switch to oral antibiotics once afebrile for 24 hours and clinically improved to complete the 7-14 day course 2, 3
• The landmark 1999 multicenter trial demonstrated that oral cefixime for 14 days was equally effective as initial IV cefotaxime followed by oral therapy, with identical rates of renal scarring (9.8% vs 7.2%) and defervescence times (25 vs 24 hours) 6

Antibiotic Selection Based on Local Resistance:

• Trimethoprim-sulfamethoxazole should only be used if local E. coli resistance is <10% for pyelonephritis 1, 2, 5
• The WHO removed amoxicillin from empiric recommendations in 2021 after global surveillance showed 75% median E. coli resistance (range 45-100%) 1
• Always consider local antimicrobial resistance patterns when selecting empiric therapy 1, 2

Critical Timing:

• Early treatment within 48 hours of fever onset reduces renal scarring risk by >50% 1, 2
• Clinical reassessment within 24-48 hours is mandatory to confirm defervescence and treatment response 1

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Imaging Recommendations

For Febrile UTI in Children <2 Years:

• Obtain renal and bladder ultrasound (RBUS) for all children <2 years with first febrile UTI to detect anatomic abnormalities 1, 2, 4
• VCUG is NOT routinely recommended after first UTI; perform only if RBUS shows hydronephrosis/scarring or after a second febrile UTI 1, 2, 4

For Non-Febrile Cystitis or Children >2 Years:

• No routine imaging required after first uncomplicated cystitis 1
• Consider RBUS if fever persists >48 hours on appropriate therapy, recurrent UTIs, or non-E. coli organisms 1

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Common Pitfalls to Avoid

• Never delay antibiotic treatment when febrile UTI is suspected—early treatment prevents renal scarring 1, 2
• Never use nitrofurantoin for febrile UTI/pyelonephritis—inadequate tissue penetration 1, 2
• Never treat febrile UTI for <7 days—shorter courses are inferior 1, 2
• Never fail to obtain urine culture before starting antibiotics—this is the only opportunity for definitive diagnosis and antibiotic adjustment 1
• Never use bag specimens for culture—70% specificity results in 85% false-positive rate; use catheterization or suprapubic aspiration 1, 2
• Never use trimethoprim-sulfamethoxazole empirically if local resistance exceeds 10% for pyelonephritis or 20% for cystitis 1, 5

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Antibiotic Prophylaxis

Routine antimicrobial prophylaxis is NOT recommended after first UTI in children, even with vesicoureteral reflux (VUR) grades I-IV. 1, 2, 4

• The RIVUR trial showed prophylaxis reduced recurrent UTI by 50% but did not reduce renal scarring 1
• Consider prophylaxis only for high-risk patients: recurrent febrile UTIs (≥2 episodes), high-grade VUR (grades IV-V), or bowel/bladder dysfunction 1, 2