What is the recommended treatment for a healthy non‑pregnant adult woman with uncomplicated cystitis?

Recommended Treatment for Uncomplicated Cystitis in Healthy Non-Pregnant Adult Women

For a healthy non-pregnant adult woman with uncomplicated cystitis, prescribe nitrofurantoin 100 mg orally twice daily for 5 days as the preferred first-line agent, achieving approximately 93% clinical cure with minimal resistance and excellent preservation of intestinal flora. 1

First-Line Treatment Options

Nitrofurantoin (Preferred)

• Nitrofurantoin 100 mg orally twice daily for 5 days provides 93% clinical cure and 88% microbiological eradication, with worldwide resistance rates below 1%. 1
• This agent causes minimal disruption to intestinal microbiota compared to fluoroquinolones and cephalosporins, thereby lowering the risk of Clostridioides difficile infection. 1
• Nitrofurantoin retains excellent activity against ESBL-producing E. coli, making it particularly valuable in the era of increasing antimicrobial resistance. 1, 2
• Contraindication: Do not use when estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m² because therapeutic urinary concentrations cannot be achieved. 1

Fosfomycin (Convenient Alternative)

• Fosfomycin trometamol 3 g as a single oral dose yields approximately 91% clinical cure with therapeutic urinary concentrations maintained for 24–48 hours. 1
• The single-dose regimen improves adherence and has minimal propensity for collateral damage to intestinal flora. 1
• Initial-infection resistance rates are only 2.6%, rising to 5.7% at 9 months. 1
• Critical limitation: Fosfomycin should not be used for suspected pyelonephritis or upper urinary tract infections due to insufficient tissue penetration. 1, 2
• Mix the sachet with water before ingesting; do not take in dry form. 3

Trimethoprim-Sulfamethoxazole (Conditional Use)

• TMP-SMX 160/800 mg orally twice daily for 3 days provides 93% clinical cure and 94% microbiological eradication when the pathogen is susceptible. 1
• Use only when BOTH conditions are met: (1) local E. coli resistance is <20%, AND (2) the patient has not received TMP-SMX in the preceding 3 months. 1, 2
• Many regions now report TMP-SMX resistance exceeding 20%, with some areas reaching 78.3% in persistent infections, making verification of local antibiogram data mandatory before selection. 1

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

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 pathogens or documented failure of first-line therapy. 1
• The FDA advisory (July 2016) recommends against fluoroquinolone use for uncomplicated UTIs because serious adverse effects (tendon rupture, peripheral neuropathy, CNS toxicity) outweigh benefits. 1
• Global fluoroquinolone resistance is rising, with some regions reporting ciprofloxacin resistance >83.8% in persistent E. coli infections. 1

Beta-Lactams

• Amoxicillin-clavulanate, cefdinir, or cefpodoxime for 3–7 days achieve only 89% clinical cure and 82% microbiological eradication, significantly inferior to first-line agents. 1
• Beta-lactams are linked to more rapid UTI recurrence due to disturbance of protective peri-urethral and vaginal microbiota. 1
• Never use amoxicillin or ampicillin alone because global E. coli resistance exceeds 55–67%. 1

Clinical Decision Algorithm

Step 1: Confirm Uncomplicated Cystitis

• Verify the patient has dysuria, frequency, and urgency WITHOUT fever, flank pain, pregnancy, catheter use, immunosuppression, or recent instrumentation. 1, 2
• E. coli accounts for 70–85% of uncomplicated cystitis cases. 2

Step 2: Select First-Line Antibiotic

• Default choice: Nitrofurantoin 100 mg twice daily for 5 days (unless eGFR <30 mL/min/1.73 m²). 1
• Single-dose alternative: Fosfomycin 3 g once (if patient prefers convenience and has no upper-tract symptoms). 1
• TMP-SMX option: Only if local resistance is <20% AND no recent TMP-SMX use. 1

Step 3: Manage Treatment Failure

• If symptoms persist after 2–3 days or recur within 2 weeks, obtain urine culture and susceptibility testing immediately. 1
• Switch to a different antibiotic class for a 7-day course (not the original short regimen). 1
• Reserve fluoroquinolones only for culture-proven resistance. 1

When to Obtain Urine Culture

Routine urine culture is NOT required for otherwise healthy women with typical lower-tract symptoms. 1, 2

Obtain culture and susceptibility testing when:

• Persistent symptoms after completing the prescribed regimen 1
• Recurrence of symptoms within 2–4 weeks 1
• Fever >38°C, flank pain, or costovertebral angle tenderness suggesting pyelonephritis 1
• Atypical presentation or presence of vaginal discharge 1, 4
• History of recurrent infections or prior isolation of resistant organisms 1

Adjunctive Symptomatic Management

• Ibuprofen may be offered for mild-to-moderate symptoms as an alternative to antibiotics after shared decision-making, provided the patient agrees to seek care if symptoms do not improve within 48–72 hours. 2, 4
• NSAIDs can be added to antibiotic regimens for additional relief during the first 24–48 hours. 4
• Pain typically resolves within 48–72 hours after appropriate antimicrobial therapy. 4

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 because of serious adverse effects and rising resistance. 1
• Do not prescribe TMP-SMX without confirming that local resistance is <20%; failure rates increase sharply above this threshold. 1
• Do not use nitrofurantoin when eGFR <30 mL/min/1.73 m² or for suspected pyelonephritis. 1
• Do not use oral fosfomycin for suspected upper-tract infection or pyelonephritis. 1
• Routine post-treatment urinalysis or urine cultures are unnecessary for asymptomatic patients who have completed therapy successfully. 1

Special Considerations

• In elderly women, atypical presentations are common; maintain a lower threshold for in-person assessment and culture to avoid misdiagnosis. 2, 4
• Treatment courses longer than 3–5 days do not improve outcomes and increase adverse effects; short courses are sufficient for uncomplicated cystitis. 4
• The presence of microscopic or macroscopic hematuria does not alter the selected antibiotic or duration of therapy for uncomplicated acute cystitis. 1