What is the appropriate management for an uncomplicated lower urinary tract infection in a non‑pregnant adult woman?

Management of Uncomplicated Lower Urinary Tract Infection in Non-Pregnant Adult Women

For an otherwise healthy non-pregnant adult woman with uncomplicated cystitis, prescribe nitrofurantoin 100 mg orally twice daily for 5 days as the preferred first-line therapy. 1, 2, 3

First-Line Antibiotic Options

• Nitrofurantoin 100 mg orally twice daily for 5 days achieves approximately 93% clinical cure and 88% microbiological eradication, maintains worldwide resistance rates below 1%, and causes minimal disruption to intestinal flora compared with fluoroquinolones or broad-spectrum agents. 1, 2, 3

• Fosfomycin trometamol 3 g as a single oral dose provides approximately 91% clinical cure with therapeutic urinary concentrations maintained for 24–48 hours, offering the convenience of single-dose administration with resistance rates around 2.6% in initial infections. 1, 2, 3, 4

• Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg orally twice daily for 3 days yields 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, 3, 5

Comparative Efficacy Evidence

• A 2018 randomized trial of 513 women demonstrated that 5-day nitrofurantoin resulted in significantly greater clinical resolution (70% vs 58%) and microbiological resolution (74% vs 63%) compared with single-dose fosfomycin at 28 days after therapy completion. 6

• The superior efficacy of nitrofurantoin over fosfomycin in this head-to-head trial, combined with its minimal resistance profile and low collateral damage, supports nitrofurantoin as the preferred first-line agent. 6

When to Avoid First-Line Agents

• Do not use nitrofurantoin when estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m² because therapeutic urinary concentrations cannot be achieved. 2, 3

• Do not use fosfomycin for suspected pyelonephritis or upper urinary tract infections due to insufficient tissue penetration and lack of efficacy data. 1, 2, 3

• Do not use TMP-SMX empirically without confirming that local E. coli resistance is <20%; treatment failure rates increase sharply when this threshold is exceeded. 1, 2, 3

Reserve (Second-Line) Agents

• Fluoroquinolones (ciprofloxacin 250–500 mg twice daily or levofloxacin 250–750 mg once daily for 3 days) should be reserved exclusively for culture-proven resistant organisms or documented failure of first-line therapy because serious adverse effects (tendon rupture, peripheral neuropathy, CNS toxicity) outweigh benefits for uncomplicated UTI. 1, 2, 3, 7

• The FDA issued warnings in 2016 recommending against fluoroquinolone use for uncomplicated UTIs due to the risk of disabling and potentially permanent adverse effects. 2

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

• Amoxicillin or ampicillin alone should never be used because worldwide E. coli resistance exceeds 55–67%. 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 vaginal discharge. 1, 2, 3

• Obtain urine culture and susceptibility testing when any of the following occur:

  • Persistent symptoms after completing the prescribed regimen 2, 3
  • Recurrence of symptoms within 2–4 weeks 2, 3
  • Fever >38°C, flank pain, or costovertebral angle tenderness suggesting pyelonephritis 2, 3
  • Atypical presentation or presence of vaginal discharge 2, 3
  • History of recurrent infections or prior isolation of resistant organisms 2, 3

Management of Treatment Failure

• If symptoms persist after 2–3 days of therapy or recur within 2 weeks, obtain a urine culture and susceptibility testing immediately and switch to a different antibiotic class for a 7-day course (not the original short regimen). 2, 3

• When retreating, assume the original pathogen is resistant to the previously used agent. 2, 3

• Perform renal ultrasound or CT imaging if fever persists beyond 72 hours to exclude obstruction, abscess, or structural abnormality. 2

Critical Pitfalls to Avoid

• Do not treat asymptomatic bacteriuria in non-pregnant, non-catheterized women; treatment provides no clinical benefit and promotes antimicrobial resistance. 1, 2, 3

• Do not use empiric fluoroquinolones as first-line therapy for uncomplicated cystitis due to serious adverse effects, rising global resistance, and the need to preserve their efficacy for complicated infections. 1, 2, 3

• Do not perform routine post-treatment urinalysis or urine cultures in asymptomatic patients who have completed therapy successfully. 2, 3

• Do not prescribe nitrofurantoin for suspected pyelonephritis or when eGFR <30 mL/min/1.73 m². 2, 3