What is the recommended treatment for uncomplicated cystitis in an otherwise healthy adult woman?

Treatment of Uncomplicated Cystitis in Adult Women

Nitrofurantoin 100 mg orally twice daily for 5 days is the preferred first-line treatment for uncomplicated cystitis in otherwise healthy adult women. 1, 2

First-Line Treatment Options

Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is the recommended initial therapy, achieving 88–93% clinical cure and 81–92% microbiological eradication rates with minimal resistance (<1% worldwide) and low collateral damage to intestinal flora. 1, 2

Fosfomycin trometamol 3 g as a single oral dose provides approximately 91% clinical cure with the convenience of single-dose administration, maintaining therapeutic urinary concentrations for 24–48 hours and demonstrating only 2.6% resistance in initial E. coli infections. 1, 3

Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg twice daily for 3 days achieves 93% clinical cure and 94% microbiological eradication only when local E. coli resistance is <20% and the patient has not received TMP-SMX in the preceding 3 months. 1, 2, 4

Critical Decision Algorithm

Step 1: Verify local E. coli TMP-SMX resistance rates. If <20% and no recent TMP-SMX exposure → prescribe TMP-SMX 160/800 mg twice daily for 3 days. 1, 4

Step 2: If TMP-SMX is unsuitable (resistance ≥20%, recent use, or unavailable data) → prescribe nitrofurantoin 100 mg twice daily for 5 days or fosfomycin 3 g single dose. 1, 2

Step 3: If symptoms persist after 2–3 days or recur within 2 weeks → obtain urine culture with susceptibility testing and switch to a different antibiotic class for a 7-day course. 1, 2

Contraindications to First-Line Agents

Nitrofurantoin must be avoided when estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m² because therapeutic urinary concentrations cannot be achieved. 1, 2

Fosfomycin should not be used for suspected pyelonephritis or upper urinary tract infections due to insufficient tissue penetration and lack of efficacy data. 1, 2

TMP-SMX is contraindicated in the last trimester of pregnancy, when local resistance exceeds 20%, or when the patient has used TMP-SMX within the prior 3 months. 1, 4

Reserve (Second-Line) Agents

Fluoroquinolones (ciprofloxacin 250 mg twice daily or levofloxacin 250 mg once daily for 3 days) achieve 93–97% bacteriologic eradication but should be reserved exclusively for culture-proven resistant pathogens or documented failure of first-line therapy because serious adverse effects (tendon rupture, peripheral neuropathy, CNS toxicity) outweigh benefits in uncomplicated cystitis. 1, 2, 4

Beta-lactam agents (amoxicillin-clavulanate, cefdinir, cefpodoxime for 3–7 days) achieve only 89% clinical cure and 82% microbiological eradication, significantly inferior to first-line agents, and should be used only when all recommended options are contraindicated. 1, 2

Amoxicillin or ampicillin alone should never be used empirically because worldwide E. coli resistance exceeds 55–67%, resulting in unacceptably high treatment failure rates. 1, 2

Diagnostic Recommendations

Routine urine culture is not required for otherwise healthy women presenting with typical lower urinary tract symptoms (dysuria, frequency, urgency) without fever, flank pain, or vaginal discharge. 1, 2, 5

Obtain urine culture and susceptibility testing when:

• Symptoms persist after completing the prescribed regimen 1, 2
• Symptoms recur within 2–4 weeks 1, 2
• Fever >38°C, flank pain, or costovertebral angle tenderness suggesting pyelonephritis 1, 2
• Atypical presentation or presence of vaginal discharge 1, 2
• Pregnancy with urinary symptoms 1, 2

Critical Pitfalls to Avoid

Do not treat asymptomatic bacteriuria in non-pregnant, non-catheterized women; this promotes resistance without clinical benefit. 1, 2

Do not use empiric fluoroquinolones as first-line therapy for uncomplicated cystitis despite high efficacy; reserve them for serious infections to prevent resistance development and avoid serious adverse effects. 1, 2

Do not prescribe TMP-SMX without confirming local resistance is <20%; treatment failure rates increase sharply above this threshold, with cure rates dropping from 84–100% (susceptible organisms) to 41–54% (resistant organisms). 1, 4

Do not shorten nitrofurantoin therapy below 5 days; the full 5-day course is required for optimal efficacy. 1, 2

Do not use fosfomycin when pyelonephritis is suspected (fever, flank pain); switch to fluoroquinolone or parenteral cephalosporin. 1, 2

Management of Treatment Failure

If symptoms do not resolve by the end of therapy or recur within 2 weeks, immediately obtain urine culture and susceptibility testing and switch to a different antibiotic class for a full 7-day course (not the original short regimen), assuming the original pathogen is resistant. 1, 2

If fever persists beyond 72 hours, perform renal ultrasound or CT imaging to exclude obstruction, abscess, or calculi requiring non-antibiotic intervention. 1