In a 6‑year‑old girl with a urinary tract infection treated with oral cephalexin and a culture showing ampicillin‑resistant organism, should cephalexin be continued or switched to another antibiotic?

Cephalexin Should Be Continued for This 6-Year-Old with Ampicillin-Resistant UTI

Cephalexin remains appropriate empiric therapy for this child despite ampicillin resistance, because first-generation cephalosporins like cephalexin retain excellent activity against most ampicillin-resistant E. coli strains and achieve high urinary concentrations that overcome resistance mechanisms. 1, 2

Why Ampicillin Resistance Does Not Predict Cephalexin Resistance

• Ampicillin resistance in E. coli is typically mediated by TEM-1 β-lactamase, which does not hydrolyze first-generation cephalosporins effectively. 2
• Cephalexin achieves urinary concentrations 100-1000 times higher than serum levels, providing a pharmacokinetic advantage that overcomes minimal inhibitory concentration (MIC) elevations caused by ampicillin resistance mechanisms. 3, 2
• Modern CLSI and USCAST cefazolin-cephalexin surrogate testing has reclassified many isolates previously reported as "resistant" to cephalexin as actually susceptible when proper pharmacokinetic/pharmacodynamic (PK/PD) principles are applied. 2

Evidence Supporting Cephalexin for Ampicillin-Resistant UTI

• Community surveillance data from Israel (2015-2017) showed cephalexin resistance rates of only 9.9% in pediatric outpatient UTIs, despite ampicillin resistance exceeding 75% globally. 4
• First-generation cephalosporins are recommended as preferred empiric antibiotics for febrile UTI in outpatient children, with resistance rates remaining low compared to amoxicillin-clavulanate (20.7% resistance). 4
• The American Academy of Pediatrics guidelines list cephalexin as a first-line oral option for pediatric UTI treatment (7-14 days for febrile UTI, 7-10 days for cystitis). 1

When to Switch Therapy

You should switch antibiotics only if:

• The culture shows cephalexin resistance on formal susceptibility testing (not just ampicillin resistance). 1
• The child remains febrile or clinically worsens after 48 hours of appropriate cephalexin therapy, suggesting either resistant organism or anatomic complication. 1
• The culture grows a non-E. coli organism with documented cephalexin resistance (e.g., Enterococcus, Pseudomonas). 1

Practical Management Algorithm

1. Continue cephalexin at 50-100 mg/kg/day divided into 4 doses for 7-10 days total (since this is a 6-year-old with likely uncomplicated cystitis based on the clinical scenario). 1
2. Reassess clinically within 24-48 hours to confirm symptom improvement and fever resolution. 1
3. Adjust therapy only when culture and sensitivity results return showing cephalexin resistance, not based on ampicillin resistance alone. 1
4. If fever persists beyond 48 hours on cephalexin, obtain renal ultrasound to evaluate for anatomic abnormalities or abscess and consider switching to a broader agent based on susceptibility results. 1

Common Pitfalls to Avoid

• Do not reflexively switch antibiotics based solely on ampicillin resistance without waiting for cephalexin susceptibility results, as ampicillin resistance does not reliably predict cephalexin failure. 2
• Do not use amoxicillin or ampicillin for empiric UTI treatment given global resistance rates of 75% (median) in E. coli urinary isolates. 1
• Do not use nitrofurantoin if this child has fever or suspected pyelonephritis, as it does not achieve adequate serum/parenchymal concentrations to treat upper tract infection. 1
• Do not treat for less than 7 days if this is a febrile UTI, as shorter courses are inferior. 1

Alternative Agents if Cephalexin Fails

• Amoxicillin-clavulanate (40-45 mg/kg/day divided twice daily) if cephalexin-resistant but amoxicillin-clavulanate susceptible. 1
• Trimethoprim-sulfamethoxazole only if local resistance rates are <10-20% and organism is susceptible. 5, 1
• Ceftriaxone (50 mg/kg IV/IM once daily) if oral therapy fails or child appears toxic. 1