What is the first‑line antibiotic for an otherwise healthy menopausal woman with uncomplicated cystitis and estimated glomerular filtration rate ≥60 mL/min?

First-Line Antibiotic for Menopausal Women with Uncomplicated Cystitis

Nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5 days is the recommended first-line treatment for an otherwise healthy menopausal woman with uncomplicated cystitis and eGFR ≥60 mL/min. 1

Rationale for Nitrofurantoin as First-Line

• Nitrofurantoin achieves clinical cure rates of 88-93% and bacteriologic cure rates of 81-92% in uncomplicated cystitis, with minimal resistance patterns and limited collateral damage to normal flora. 1

• The Infectious Diseases Society of America, American College of Obstetricians and Gynecologists, and European Association of Urology all recommend nitrofurantoin as the preferred first-line agent due to its excellent efficacy profile and preservation of more systemically active antibiotics. 1, 2

• A 2018 randomized clinical trial in JAMA demonstrated that 5-day nitrofurantoin resulted in 70% clinical resolution versus 58% for single-dose fosfomycin (difference 12%, P=0.004), with microbiologic resolution of 74% versus 63% respectively. 3

• A 2021 real-world study of over 1 million premenopausal women showed that nitrofurantoin had the lowest risk of treatment failure compared to trimethoprim-sulfamethoxazole and other agents, with a pyelonephritis risk of only 0.3%. 4

Alternative First-Line Options (when nitrofurantoin cannot be used)

• Fosfomycin trometamol 3 g as a single oral dose is an appropriate alternative with clinical cure rates of 90-91%, though microbiologic cure rates are lower at 78-80%. 1, 5

  • Fosfomycin offers the convenience of single-dose therapy and should be considered when adherence to multi-day regimens is uncertain. 1
  • Avoid fosfomycin if early pyelonephritis is suspected (presence of fever, flank pain, or systemic symptoms). 1

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days may be used only if local E. coli resistance is documented to be <20% and the patient has not received this antibiotic in the preceding 3 months. 1, 2, 6

  • When organisms are susceptible, TMP-SMX achieves 90-100% clinical cure rates, but efficacy plummets to 41-54% against resistant strains. 6
  • Recent international travel within 3-6 months is an additional risk factor for resistance and contraindicates empiric use. 6

Second-Line (Reserve) Options

• Fluoroquinolones (ciprofloxacin 250 mg twice daily for 3 days or levofloxacin) achieve bacteriologic eradication rates of 93-97% but should be reserved for situations where first-line agents are unsuitable. 1

  • These agents promote resistance and cause collateral damage to normal flora, making them inappropriate for routine uncomplicated cystitis despite high efficacy. 1, 2

• Oral β-lactams (cefdinir, cefaclor, cefpodoxime-proxetil, cephalexin) for 3-7 days have inferior efficacy and more adverse effects compared to nitrofurantoin or TMP-SMX, and should only be used when recommended agents are unavailable. 1

Critical Renal Function Consideration

• With eGFR ≥60 mL/min, nitrofurantoin is safe and effective. 1

• If eGFR is 30-60 mL/min, nitrofurantoin remains effective in most patients, though some sources recommend caution. 7

• If eGFR <30 mL/min, switch to fosfomycin 3 g single dose as the preferred alternative, as nitrofurantoin efficacy decreases significantly below this threshold. 1, 7

Agents to Avoid

• Never use amoxicillin or ampicillin empirically due to poor efficacy and worldwide resistance rates exceeding 30%. 1, 2

• Do not use TMP-SMX without knowledge of local resistance patterns or if the patient has received it within the past 3 months. 6

Common Pitfalls to Avoid

• Shortening nitrofurantoin therapy to less than 5 days reduces efficacy; always prescribe the full 5-day course. 1

• Using fluoroquinolones as first-line therapy despite their high efficacy promotes unnecessary resistance. 1

• Prescribing TMP-SMX empirically in areas where local E. coli resistance exceeds 20% leads to predictable treatment failures. 6

• Relying on hospital antibiograms for community-acquired cystitis overestimates resistance; outpatient surveillance data are more accurate. 6