First and Second Line Treatment for Uncomplicated Urinary Tract Infection
For uncomplicated UTI in adult women, use nitrofurantoin 100 mg twice daily for 5 days, fosfomycin trometamol 3 g single dose, or pivmecillinam 400 mg three times daily for 3-5 days as first-line therapy; reserve trimethoprim-sulfamethoxazole and fluoroquinolones as second-line alternatives only when first-line agents cannot be used. 1, 2
First-Line Treatment Options for Women
The following agents minimize antimicrobial resistance and "collateral damage" to normal flora 1, 2:
- Fosfomycin trometamol: 3 g single dose (1 day treatment) 1
- Nitrofurantoin: 100 mg twice daily for 5 days (available as monohydrate, macrocrystals, or prolonged-release formulations) 1, 2
- Pivmecillinam: 400 mg three times daily for 3-5 days 1
Key consideration: These agents are preferred because they produce minimal collateral damage to normal vaginal and fecal flora compared to fluoroquinolones and cephalosporins, which promote multi-drug resistant organisms 1, 2
Second-Line (Alternative) Treatment Options for Women
Use these only when first-line agents are contraindicated due to allergy, intolerance, or documented resistance 1:
- Trimethoprim-sulfamethoxazole (TMP-SMX): 160/800 mg twice daily for 3 days—only if local E. coli resistance rates are below 20% 1, 3
- Trimethoprim alone: 200 mg twice daily for 5 days (avoid in first trimester of pregnancy) 1
- Cephalosporins (e.g., cefadroxil 500 mg twice daily for 3 days): Use only if local E. coli resistance is <20% 1
- Fluoroquinolones (ciprofloxacin, levofloxacin): Reserve as last-resort alternatives due to serious FDA warnings regarding tendon, muscle, joint, nerve, and CNS toxicity 2, 4
Treatment for Men
Men require longer treatment duration and mandatory urine culture before initiating therapy 1:
- Trimethoprim-sulfamethoxazole: 160/800 mg twice daily for 7 days 1, 3
- Nitrofurantoin: 100 mg twice daily for 7 days 5
- Trimethoprim: 200 mg twice daily for 7 days 5
Critical caveat: Always consider prostatitis in men with UTI symptoms, as this requires 4-6 weeks of fluoroquinolone therapy rather than short-course treatment 5
When to Obtain Urine Culture
Do NOT routinely obtain urine culture for straightforward uncomplicated cystitis in women 1. However, obtain culture in these specific situations 1:
- Suspected acute pyelonephritis (fever, flank pain, systemic symptoms)
- Symptoms not resolving or recurring within 2-4 weeks after treatment
- Atypical presentation
- Pregnancy
- Men with any UTI symptoms
- Recurrent UTIs (≥3 UTIs per year or 2 in 6 months)
- History of resistant organisms
Critical Contraindications and Warnings
Nitrofurantoin should NOT be used for 2:
- Pyelonephritis (does not achieve adequate tissue concentrations)
- Creatinine clearance <60 mL/min
- Infants under 4 months of age
Fluoroquinolones should be avoided as first-line therapy because 2, 4:
- FDA black box warnings for serious adverse effects (tendon rupture, peripheral neuropathy, CNS effects)
- Significant collateral damage promoting multi-drug resistant organisms
- Should be preserved for pyelonephritis and complicated infections
Symptomatic Treatment Alternative
For women with mild to moderate symptoms, symptomatic therapy with ibuprofen may be considered as an alternative to immediate antibiotics, though this requires shared decision-making with the patient 1, 5. This approach has low risk of complications but may prolong symptom duration 5.
Treatment Duration Principles
- Women with uncomplicated cystitis: 3-5 days maximum (depending on agent) 1
- Men with uncomplicated cystitis: 7 days 1, 5
- Never exceed 7 days for acute cystitis episodes to minimize adverse effects and resistance 1, 2
Asymptomatic Bacteriuria
Do NOT treat asymptomatic bacteriuria except in pregnancy or before urological procedures breaching the mucosa 1. Treatment does not improve outcomes and promotes antimicrobial resistance 2.