What is the recommended treatment for an adult with uncomplicated cystitis, normal renal function (eGFR ≥ 60 mL/min), and who is not pregnant?

Treatment of Uncomplicated Urinary Tract Infection (UTI)

For an adult with uncomplicated cystitis, normal renal function (eGFR ≥ 60 mL/min), and who is not pregnant, prescribe nitrofurantoin 100 mg orally twice daily for 5 days as first-line therapy. 1, 2

First-Line Treatment Options

Nitrofurantoin (Preferred)

• Nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5 days achieves 88-93% clinical cure and 81-92% microbiological eradication rates. 1, 2
• Worldwide resistance rates remain below 1%, making it highly reliable for empiric therapy. 1
• Causes minimal disruption to intestinal flora compared to fluoroquinolones and cephalosporins, thereby reducing the risk of Clostridioides difficile infection. 1, 2
• Contraindication: Do not use when eGFR < 30 mL/min/1.73 m² because therapeutic urinary concentrations cannot be achieved. 1, 2

Trimethoprim-Sulfamethoxazole (TMP-SMX)

• TMP-SMX 160/800 mg (one double-strength tablet) orally twice daily for 3 days provides 90-100% clinical cure and 91-100% microbiological eradication when the organism is susceptible. 1, 3
• Critical prescribing criteria: Use only when both of the following conditions are met:
  • Local E. coli resistance is documented to be < 20%. 1, 2, 3
  • The patient has not received TMP-SMX in the preceding 3 months. 1, 3
• When resistance exceeds 20%, clinical cure rates plummet to 41-54%, making treatment failure the expected outcome. 1, 3

Fosfomycin

• Fosfomycin trometamol 3 g as a single oral dose achieves approximately 91% clinical cure with 78-83% microbiological eradication. 1, 4
• Provides therapeutic urinary concentrations for 24-48 hours with a single dose, improving adherence. 1
• Resistance rates are low (2.6% in initial infections). 1
• Contraindication: Do not use for suspected pyelonephritis or upper urinary tract infections due to insufficient tissue penetration. 1, 2

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

Fluoroquinolones

• Ciprofloxacin 250 mg orally twice daily for 3 days or levofloxacin 250 mg orally once daily for 3 days achieve 93-97% bacteriologic eradication. 1, 3
• Reserve exclusively for culture-proven resistant pathogens or documented failure of first-line agents. 1, 2
• The FDA (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 > 10% resistance. 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, 2
• Use only when first-line agents are contraindicated or unavailable. 1, 2
• Never use amoxicillin or ampicillin alone because worldwide E. coli resistance exceeds 55-67%. 1, 2

Clinical Decision Algorithm

Step 1: Assess Local TMP-SMX Resistance

• If local E. coli resistance is < 20% AND the patient has not used TMP-SMX in the past 3 months → prescribe TMP-SMX 160/800 mg twice daily for 3 days. 1, 3
• If resistance is ≥ 20% or data are unavailable → proceed to Step 2. 1, 3

Step 2: Choose Between Nitrofurantoin or Fosfomycin

• Prescribe nitrofurantoin 100 mg twice daily for 5 days (preferred for higher efficacy). 1, 2
• Alternatively, prescribe fosfomycin 3 g single dose (preferred for convenience or adherence concerns). 1, 4

Step 3: If Symptoms Persist or Recur

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

When to Obtain Urine Culture

Routine urine culture is NOT required for straightforward uncomplicated cystitis in otherwise healthy women. 1, 2

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

• Persistent symptoms after completing the prescribed regimen. 1, 2
• Recurrence of symptoms 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
• History of recurrent infections or prior isolation of resistant organisms. 1

Critical Pitfalls to Avoid

• Do not treat asymptomatic bacteriuria in non-pregnant, non-catheterized patients, as this promotes resistance without clinical benefit. 1, 2
• Do not prescribe TMP-SMX without confirming local resistance is < 20%; failure rates increase sharply above this threshold. 1, 3
• Do not use empiric fluoroquinolones as first-line therapy for uncomplicated cystitis despite high efficacy, to preserve their utility for serious infections. 1, 2
• Do not use nitrofurantoin for suspected pyelonephritis or when eGFR < 30 mL/min/1.73 m². 1, 2
• Do not use oral fosfomycin for suspected upper-tract infection or pyelonephritis. 1, 2
• Do not prescribe amoxicillin or ampicillin alone due to worldwide resistance exceeding 55-67%. 1, 2

Special Considerations

Men with Uncomplicated Cystitis

• Require a 7-day course of the selected antibiotic (not the 3-day regimen effective in women). 2, 3
• TMP-SMX 160/800 mg twice daily for 7 days is appropriate when susceptibility is confirmed. 3

Renal Impairment (eGFR 30-60 mL/min)

• Nitrofurantoin can be used at standard dosing when eGFR is 30-60 mL/min, though efficacy may be reduced below 30 mL/min. 5
• Fosfomycin and TMP-SMX remain acceptable options when eGFR ≥ 30 mL/min. 1