I am still symptomatic after completing a standard course of macrobid (nitrofurantoin) for an Escherichia coli urinary tract infection; what should I do?

Management of Persistent Symptoms After Nitrofurantoin Treatment for E. coli UTI

You need to obtain a urine culture with antimicrobial susceptibility testing immediately and assume the E. coli is resistant to nitrofurantoin, then retreat with a different antibiotic for 7 days. 1

Immediate Next Steps

Obtain Urine Culture and Susceptibility Testing

• A urine culture with antimicrobial susceptibility testing is mandatory when symptoms do not resolve by the end of treatment 1
• The European Association of Urology guidelines explicitly state this should be performed for women whose symptoms do not resolve or recur within 2-4 weeks after completion of treatment 1
• Do not wait—obtain the culture now while symptoms are present 1

Assume Resistance and Retreat

• You must assume the infecting E. coli is NOT susceptible to nitrofurantoin 1
• Retreatment should use a 7-day regimen with a different antimicrobial agent (not the standard 3-5 day course) 1
• This longer duration is specifically recommended for treatment failures 1

Appropriate Alternative Antibiotic Choices

First-Line Alternatives (in order of preference):

• Fosfomycin trometamol 3g single dose - though you may need to consider a repeat dose given the treatment failure context 1, 2
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days - only if local E. coli resistance rates are <20% 1
• Pivmecillinam 400 mg three times daily for 7 days (if available in your region) 1

Second-Line Alternatives:

• Cephalosporins (e.g., cefadroxil 500 mg twice daily for 7 days) - if local E. coli resistance is <20% 1
• Fluoroquinolones should be reserved as last-resort alternatives due to serious FDA warnings about tendon, muscle, joint, nerve, and CNS adverse effects 2, 3

Critical Considerations Before Prescribing

Rule Out Complicated UTI

You must determine if this represents a complicated infection requiring different management: 1

• Check for fever, flank pain, or systemic symptoms - these suggest pyelonephritis, which nitrofurantoin cannot treat due to inadequate tissue penetration 2, 4
• Assess for rapid recurrence - if symptoms returned within 2 weeks of initial treatment, this may indicate bacterial persistence from an anatomic abnormality 1
• Consider imaging if: 1
  • Symptoms recurred rapidly (within 2 weeks)
  • Patient has risk factors for complicated UTI (diabetes, immunosuppression, anatomic abnormalities)
  • This represents repeated treatment failure

Common Pitfalls to Avoid

• Do NOT retreat with another 5-day course of nitrofurantoin - the guidelines are clear that you should assume resistance 1
• Do NOT use the same antibiotic class - switch to a mechanistically different agent 1
• Do NOT use a 3-5 day course - treatment failures require 7 days 1
• Do NOT prescribe empirically without culture - susceptibility testing is essential for treatment failures 1

Why Nitrofurantoin May Have Failed

Resistance Patterns

• While nitrofurantoin maintains excellent activity against E. coli overall (95.6% susceptibility in community settings), individual isolates can be resistant 5, 6
• The 2.3% resistance rate means approximately 1 in 43 E. coli UTIs will be nitrofurantoin-resistant 5

Inadequate Tissue Penetration

• Nitrofurantoin achieves therapeutic concentrations only in urine and bladder tissue, not in renal parenchyma or prostate 2, 4
• If the patient has unrecognized upper tract involvement or (in males) prostatic involvement, nitrofurantoin will fail 2, 4, 7

Bacterial Persistence

• Persistent symptoms may indicate an underlying anatomic abnormality (bladder diverticulum, calculi, foreign body) harboring bacteria 1

Follow-Up Strategy

After Starting New Antibiotic:

• Reassess symptoms at 48-72 hours - if no improvement, adjust therapy based on culture results 4
• Complete the full 7-day course even if symptoms resolve quickly 4
• Do NOT obtain a post-treatment urine culture if symptoms resolve - this is not indicated for asymptomatic patients 1

If This Becomes Recurrent (≥3 UTIs in 12 months):

• Consider prophylactic strategies after acute treatment 1
• Implement behavioral modifications: adequate hydration, post-coital voiding, avoid spermicide-containing contraceptives 1
• For postmenopausal women, consider topical vaginal estrogen 1