What is the appropriate management for a 41‑year‑old woman with dysuria and malodorous urine suggestive of acute uncomplicated cystitis but a negative urine culture?

Management of Suspected Cystitis with Negative Urine Culture

In a 41-year-old woman with dysuria and malodorous urine but a negative urine culture, empiric antibiotic therapy is appropriate when clinical symptoms strongly suggest acute uncomplicated cystitis, as culture is not required for diagnosis in typical presentations. 1, 2

Clinical Diagnosis Without Culture

• Dysuria and frequency in the absence of vaginal discharge or irritation are highly predictive of acute cystitis, achieving sufficient diagnostic accuracy to proceed with treatment without culture confirmation. 3
• Urine culture is not recommended for routine uncomplicated cystitis in otherwise healthy women presenting with typical lower-tract symptoms (dysuria, frequency, urgency). 1, 2
• A negative culture does not exclude cystitis when symptoms are classic, as the diagnosis is primarily clinical rather than microbiologic. 2, 3

First-Line Empiric Antibiotic Options

Nitrofurantoin (Preferred)

• Nitrofurantoin 100 mg orally twice daily for 5 days achieves approximately 93% clinical cure and 88% microbiological eradication, with worldwide resistance rates below 1%. 1
• This agent preserves intestinal flora better than fluoroquinolones or broad-spectrum agents, reducing the risk of Clostridioides difficile infection. 1
• Avoid when estimated glomerular filtration rate 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 provides approximately 91% clinical cure and maintains therapeutic urinary concentrations for 24–48 hours. 1, 4
• The FDA label specifically indicates fosfomycin for uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of E. coli and Enterococcus faecalis. 4
• Not recommended for pyelonephritis or upper-tract infections due to insufficient tissue penetration. 1, 4

Trimethoprim-Sulfamethoxazole (Conditional)

• TMP-SMX 160/800 mg orally twice daily for 3 days achieves 93% clinical cure and 94% microbiological eradication when the pathogen is susceptible. 1
• Use only when local E. coli resistance is <20% and the patient has not received TMP-SMX in the preceding 3 months. 1, 2, 5
• Many regions now report resistance exceeding 20%, necessitating verification of local antibiogram data before selection. 1

When to Obtain Urine Culture

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

• Persistent symptoms after completing the prescribed antibiotic course 1, 2
• Recurrence of symptoms within 2–4 weeks after treatment 1, 2, 3
• Fever >38°C, flank pain, or costovertebral angle tenderness suggesting pyelonephritis 1
• Atypical presentation or presence of vaginal discharge 1, 2
• History of recurrent infections or prior isolation of resistant organisms 1

Management of Treatment Failure

• If symptoms do not resolve by the end of therapy or recur within 2 weeks, obtain a urine culture and susceptibility test immediately and switch to a different antibiotic class for a 7-day course (not the original short regimen). 1, 2
• Consider imaging (ultrasound or CT) if fever persists beyond 72 hours to exclude obstruction or abscess. 1

Reserve Agents (Use Only When First-Line Fails)

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 agents. 1, 6
• Empiric fluoroquinolone use is inappropriate for uncomplicated cystitis because serious adverse effects (tendon rupture, peripheral neuropathy, CNS toxicity) outweigh benefits. 1, 6
• Global fluoroquinolone resistance exceeds 10% in several regions, and their use promotes resistance among gram-negative bacilli. 1

Beta-Lactams

• Amoxicillin-clavulanate, cefdinir, or cefpodoxime given for 3–7 days achieve only 89% clinical cure and 82% microbiological eradication, significantly inferior to first-line agents. 7, 1
• Amoxicillin or ampicillin alone should never be used because worldwide E. coli resistance exceeds 55–67%. 1

Critical Pitfalls to Avoid

• Do not withhold treatment pending culture results when clinical presentation is typical for uncomplicated cystitis; the diagnosis is clinical, not microbiologic. 2, 3
• Do not treat asymptomatic bacteriuria in non-pregnant, non-catheterized women, as this promotes resistance without clinical benefit. 1, 8
• Do not use oral fosfomycin for suspected pyelonephritis or upper-tract involvement. 1, 4
• Do not prescribe empiric fluoroquinolones as first-line therapy despite their high efficacy, because of serious adverse-effect profiles and the need to preserve these agents for complicated infections. 1, 6