What is the first-line antibiotic for an otherwise healthy adult with uncomplicated cystitis?

First-Line Antibiotic for Uncomplicated Cystitis

Nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5 days is the preferred first-line antibiotic for otherwise healthy adults with uncomplicated cystitis.

Primary Recommendation

• Nitrofurantoin 100 mg twice daily for 5 days achieves clinical cure rates of 88–93% and bacterial eradication rates of 81–92%, with worldwide resistance rates below 1% and minimal disruption to intestinal flora 1.
• This regimen is endorsed by the Infectious Diseases Society of America, European Association of Urology, and American Urological Association as the preferred empiric therapy 1.
• Nitrofurantoin preserves more systemically active antibiotics for serious infections and exhibits minimal collateral damage compared to fluoroquinolones or broad-spectrum agents 1.

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

Fosfomycin

• Fosfomycin trometamol 3 g as a single oral dose provides clinical cure rates of 90–91% and maintains therapeutic urinary concentrations for 24–48 hours 1, 2.
• Microbiologic cure rates are slightly lower (78–80%) compared to nitrofurantoin, but the single-dose convenience improves adherence 1.
• Do not use fosfomycin for suspected pyelonephritis (fever, flank pain) due to inadequate tissue penetration 1, 3.

Trimethoprim-Sulfamethoxazole (TMP-SMX)

• TMP-SMX 160/800 mg twice daily for 3 days achieves 93% clinical cure and 94% microbiological eradication when the organism is susceptible 1.
• Use only when BOTH conditions are met:
  • Local E. coli resistance is documented to be <20% 1, 4
  • Patient has not received TMP-SMX in the preceding 3 months 1
• Many regions now exceed the 20% resistance threshold, making TMP-SMX unsuitable as empiric therapy without local susceptibility data 1, 4.

Reserve (Second-Line) Agents – Use Only When First-Line Options Fail

Fluoroquinolones

• Ciprofloxacin 250 mg twice daily for 3 days or levofloxacin 250 mg once daily for 3 days achieve approximately 95% clinical cure rates 1.
• Reserve fluoroquinolones exclusively for culture-proven resistant organisms or documented failure of first-line therapy 1.
• Serious adverse effects (tendon rupture, peripheral neuropathy, CNS toxicity, C. difficile infection) outweigh benefits in uncomplicated cystitis 1, 3.
• Global resistance is rising, with some regions exceeding 10% 1.

Beta-Lactams

• Amoxicillin-clavulanate, cefdinir, cefaclor, or cefpodoxime for 3–7 days achieve only 89% clinical cure and 82% microbiological eradication—significantly inferior to first-line agents 1.
• Use only when nitrofurantoin, fosfomycin, and TMP-SMX are all contraindicated 1.
• Never use amoxicillin or ampicillin alone—worldwide E. coli resistance exceeds 55–67% 1, 3.

Contraindications to First-Line Agents

• Nitrofurantoin: Avoid when eGFR <30 mL/min/1.73 m² because adequate urinary concentrations cannot be achieved 1, 5.
• Fosfomycin: Do not use for pyelonephritis or upper urinary tract infections 1, 3.
• TMP-SMX: Contraindicated in sulfa allergy; avoid when local resistance ≥20% 1, 5.

When to Obtain Urine Culture

• Routine urine culture is NOT required for typical uncomplicated cystitis in otherwise healthy women 1.
• Obtain culture and susceptibility testing when:
  • Symptoms persist after completing therapy 1
  • Symptoms recur within 2–4 weeks 1
  • Fever >38°C, flank pain, or costovertebral angle tenderness (suggests pyelonephritis) 1
  • Atypical presentation or vaginal discharge present 1
  • Pregnancy 1
  • History of recurrent infections or prior resistant organisms 1

Management of Treatment Failure

• If symptoms persist at the end of therapy or recur within 2 weeks, obtain urine culture immediately and switch to a different antibiotic class for a 7-day course (not the original short regimen) 1.
• Assume the original pathogen is resistant to the previously used agent 1.
• If fever persists beyond 72 hours, perform renal ultrasound or CT to exclude obstruction or abscess 1.

Critical Pitfalls to Avoid

• Do not treat asymptomatic bacteriuria in non-pregnant, non-catheterized patients—this promotes resistance without clinical benefit 1, 3.
• Do not use empiric fluoroquinolones as first-line therapy despite high efficacy—reserve them for serious infections 1, 4.
• Do not prescribe TMP-SMX without confirming local resistance is <20%—failure rates rise sharply above this threshold 1, 4.
• Do not use nitrofurantoin for suspected pyelonephritis or when eGFR <30 mL/min/1.73 m² 1, 5.
• Do not use oral fosfomycin for upper tract infections 1, 3.