What are the recommended antibiotics for treating urinary tract infections (UTIs) caused by Extended-Spectrum Beta-Lactamase (ESBL)-producing bacteria in the pediatric population?

Treatment of ESBL-Producing UTIs in Pediatric Patients

For pediatric urinary tract infections caused by ESBL-producing bacteria, carbapenems (meropenem, imipenem, or ertapenem) remain the gold-standard definitive therapy, but amikacin should be strongly considered as first-line empiric treatment to preserve carbapenem activity and facilitate outpatient management. 1

Empiric Treatment Strategy

First-Line Empiric Options

Amikacin is the preferred initial empiric agent for febrile UTI when ESBL is suspected or confirmed, particularly for patients presenting to emergency departments or requiring hospitalization 1, 2. This aminoglycoside remains active against the majority of ESBL-producing strains and serves as a critical carbapenem-sparing strategy 3, 1.

Dosing for amikacin:

• 15-22.5 mg/kg/day divided every 8-24 hours (based on once-daily dosing protocols) 3
• Requires monitoring of serum concentrations and renal function 3
• Limit duration to ≤7 days to minimize nephrotoxicity risk 3

Alternative Empiric Options for Lower-Risk Patients

For non-severe cases in low-risk patients (age >3 months, preserved general condition, fever duration <4 days, no comorbidities, no prior UTI/uropathy, no recent antibiotic exposure), oral cefixime may be considered while awaiting culture results 2. However, this approach carries risk given that 7-10% of pediatric E. coli strains in France produce ESBLs 2.

Definitive Therapy Based on Susceptibility

Carbapenem Therapy (Gold Standard)

When ESBL is confirmed, carbapenems are the most reliable definitive treatment 3:

• Meropenem: 60 mg/kg/day divided every 8 hours 3
• Imipenem-cilastatin: 60-100 mg/kg/day divided every 6 hours 3
• Ertapenem: 15 mg/kg twice daily (not to exceed 1 g/day) for ages 3 months-12 years; 1 g/day for ≥13 years 3

Carbapenem-Sparing Alternatives

For uncomplicated cystitis or pyelonephritis with documented susceptibility, consider these alternatives to preserve carbapenems 3:

• Piperacillin-tazobactam: 200-300 mg/kg/day (piperacillin component) divided every 6-8 hours for stable patients with ESBL E. coli (controversial for ESBL K. pneumoniae) 3
• Cefepime: 100 mg/kg/day divided every 12 hours (may be effective for some ESBL strains with low MICs) 3
• Intravenous fosfomycin: Demonstrated non-inferiority to meropenem for bacteremic UTI caused by cephalosporin-resistant Enterobacterales in adults, though pediatric data are limited 3

Oral Step-Down Therapy

Once clinical improvement occurs and susceptibility results are available, transition to oral therapy guided by testing 2:

• Amoxicillin-clavulanate: 20-40 mg/kg/day (amoxicillin component) divided into 3 doses if susceptible 4
• Cefixime + clavulanate (non-orthodox combination): May be necessary when no single oral agent is active against ESBL strains 1, 2
• Nitrofurantoin: For lower UTI/cystitis only (not for pyelonephritis due to inadequate tissue penetration) 3

Treatment Duration

• Total duration: 7-10 days for febrile UTI/pyelonephritis 4, 2
• Minimum 7 days required; shorter courses (1-3 days) are inferior 4
• 5 days for uncomplicated cystitis 2

Critical Clinical Considerations

Risk Factors for ESBL in Pediatric Patients

Strongly consider ESBL empiric coverage if the patient has 5:

• Cystostomy (OR 3.7) 5
• Underlying comorbidities (OR 2.4) 5
• Prior ICU admission 5
• Recent hospitalization (within 30 days) 5
• Recent cephalosporin exposure (within 30 days) 5

Important caveat: The majority of pediatric ESBL-UTI cases occur in patients WITHOUT identifiable risk factors 5, making empiric coverage decisions challenging.

When to Obtain Cultures

Always obtain urine culture before initiating antibiotics in the following scenarios 3, 2:

• Febrile UTI/pyelonephritis 2
• Patients with risk factors for ESBL 5
• Healthcare-associated infections 3
• Prior antibiotic exposure 3

Urine dipstick positive for leukocytes and/or nitrites should precede culture in most cases (except neonates, neutropenia, sepsis) 1, 2.

Antimicrobial Stewardship Priorities

Avoid routine carbapenem use for empiric therapy to prevent selection of carbapenem-resistant organisms 1, 2. The increase in first-line carbapenem use represents a major environmental hazard and exposes patients to risk of untreatable future infections 2.

Rapidly adapt therapy once susceptibility results are available (typically 24-48 hours) to narrow spectrum and utilize carbapenem-sparing agents when possible 2.

Safety Monitoring

• Aminoglycosides: Monitor serum concentrations and renal function; nephrotoxicity risk increases after 7 days 3
• Intravenous fosfomycin: Monitor for heart failure, particularly in at-risk patients (8.6% incidence in adult trials) 3
• Co-amoxiclav: Higher gastrointestinal adverse event rate compared to amoxicillin alone 4

Special Populations

Neonates (<28 days): Use ampicillin + gentamicin or ampicillin + cefotaxime instead of standard regimens 3, 4. Consider meropenem for confirmed ESBL 3.

Patients with septic shock or severe illness: Initiate parenteral carbapenem therapy immediately; do not delay for carbapenem-sparing alternatives 3, 2.