What is the next step in treating a Urinary Tract Infection (UTI) that has failed treatment with Amoxicillin?

Treatment of Amoxicillin-Resistant UTI

Switch to amoxicillin-clavulanate (20-40 mg/kg/day in 3 doses for adults, or 2875 mg twice daily for severe cases) as the first-line alternative, or use a cephalosporin, nitrofurantoin, or trimethoprim-sulfamethoxazole based on local resistance patterns. 1, 2

Immediate Next Steps

Obtain Urine Culture Before Changing Antibiotics

• Mandatory urine culture and susceptibility testing must be performed before switching antibiotics to guide tailored therapy and identify the specific resistance pattern 3
• The most common cause of amoxicillin failure is resistance by the uropathogen, particularly E. coli (74.5% of UTIs) and Klebsiella species (8.7%) 2, 4

First-Line Alternative Antibiotics

For uncomplicated cystitis in non-pregnant women:

• Amoxicillin-clavulanate is the most effective oral alternative, showing superior susceptibility among Enterobacteriaceae compared to other commonly used oral antibiotics 2
• Nitrofurantoin 5-day course is highly effective for uncomplicated lower UTI 5
• Fosfomycin 3g single dose is an excellent alternative 5
• Cephalosporins (cephalexin 50-100 mg/kg/day in 4 doses, cefixime 8 mg/kg/day, or cefpodoxime 10 mg/kg/day in 2 doses) 1

Avoid these empiric choices:

• Trimethoprim-sulfamethoxazole should not be used empirically due to high resistance rates in many communities 5, 2
• Ciprofloxacin and fluoroquinolones should be avoided if local resistance exceeds 10% or if the patient used fluoroquinolones in the last 6 months 3
• Ampicillin has inadequate coverage for empirical treatment 2

Treatment Duration and Monitoring

Standard Duration

• 7-14 days total for complicated UTI or pyelonephritis 3
• 3-5 days for uncomplicated cystitis in younger women after catheter removal or with prompt symptom resolution 1, 5
• For febrile UTI in children 2-24 months: 7-14 days total 1

Clinical Response Assessment

• Expect clinical improvement within 24-48 hours 1
• If fever persists beyond 72 hours, consider imaging (ultrasound or CT) to rule out obstruction, abscess, or other complications 1
• Treatment failure at 28 days occurs in 12-16% of patients regardless of initial antibiotic choice 6

Special Considerations

ESBL-Producing Organisms

If culture reveals ESBL-producing E. coli or Klebsiella:

• High-dose amoxicillin-clavulanate (2875 mg amoxicillin + 125 mg clavulanic acid twice daily) can break ESBL resistance in select outpatient cases 7
• Oral alternatives include nitrofurantoin, fosfomycin, or pivmecillinam 5
• Parenteral options include carbapenems, ceftazidime-avibactam, or piperacillin-tazobactam (for ESBL E. coli only) 5

Catheter-Associated UTI

• Remove or replace the catheter if it has been in place >2 weeks to hasten symptom resolution 1
• Requires aggressive IV antimicrobial therapy per complicated UTI protocols 3

Pregnancy and Children

• Pregnant women require ultrasound or MRI (not CT) for upper tract evaluation 1
• Children who appear toxic or cannot retain oral intake need parenteral therapy initially (ceftriaxone 75 mg/kg every 24h or cefotaxime 150 mg/kg/day divided every 6-8h) 1

Common Pitfalls to Avoid

• Never treat based on symptoms alone without culture confirmation when amoxicillin has failed 3
• Do not use nitrofurantoin for febrile UTI or pyelonephritis as it does not achieve adequate tissue concentrations 1
• Avoid continuing the same antibiotic class (e.g., switching from amoxicillin to ampicillin) as cross-resistance is likely 4
• Do not delay culture to start symptomatic treatment - obtain culture first, then start both antibiotics and phenazopyridine if needed 3
• Amoxicillin monotherapy has significantly higher failure rates (14% requiring second course within 28 days) compared to amoxicillin-clavulanate 6