Treatment of Urinary Tract Infections
Uncomplicated Cystitis in Women
For uncomplicated cystitis in otherwise healthy, non-pregnant women, nitrofurantoin (100 mg twice daily for 5 days) is the preferred first-line treatment, with trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) and fosfomycin (3 g single dose) as alternatives. 1, 2
First-Line Antibiotic Options
Nitrofurantoin: 100 mg twice daily for 5 days is the drug of choice because it spares more systemically active agents, has low resistance rates, and resistance decays quickly even when present 1, 2
Fosfomycin trometamol: 3 g single oral dose provides convenient single-dose therapy with minimal resistance 1, 2, 3
Trimethoprim-sulfamethoxazole (TMP-SMX): 160/800 mg twice daily for 3 days, but only use if local resistance rates are <20% 1, 2, 3
Pivmecillinam: 3 days where available 1
Second-Line Options
Amoxicillin-clavulanate can be used as an alternative, particularly in young children, though it was removed from WHO first-line recommendations in 2021 due to high resistance rates (median 75% of E. coli resistant to amoxicillin alone) 1
Fluoroquinolones should NOT be used as first-line therapy due to increasing resistance, serious adverse effects (tendon, muscle, joint, nerve, and CNS toxicity), and the FDA's 2016 warning that the risks outweigh benefits for uncomplicated UTI 1, 2
Treatment Duration
- Nitrofurantoin: 5 days 1, 2
- TMP-SMX: 3 days 1, 2
- Fosfomycin: Single dose 1, 2
- Fluoroquinolones (if used): 3 days 1
- Pivmecillinam: 3 days 1
Acute Pyelonephritis
For acute pyelonephritis requiring oral therapy, TMP-SMX or first-generation cephalosporins are reasonable first-line agents if local resistance rates permit; for patients requiring intravenous therapy, ceftriaxone is the recommended empirical choice. 1, 2
Treatment Options
Oral therapy: TMP-SMX or first-generation cephalosporins, depending on local resistance patterns 1
Intravenous therapy: Ceftriaxone is preferred due to low resistance rates and clinical effectiveness, unless risk factors for multidrug resistance exist 1
Ciprofloxacin can be used as first-line for mild-to-moderate pyelonephritis only if local/national antimicrobial resistance data support its use (resistance should be <10%) 1
Severe cases: Amikacin (preferred over gentamicin), ceftriaxone, or cefotaxime 1
Treatment Duration
- Beta-lactams: 7 days 1
- Fluoroquinolones: 5-7 days 1
- TMP-SMX: Insufficient evidence for clear duration recommendation 1
Do NOT use nitrofurantoin for pyelonephritis as it does not achieve adequate tissue concentrations 2
Uncomplicated UTI in Men
Men with uncomplicated UTI should receive trimethoprim, TMP-SMX, or nitrofurantoin for 7 days (longer than women), and always obtain urine culture to guide therapy. 2, 3
- Treatment duration is 7 days for men (versus 3-5 days for women with cystitis) 2
- Consider urethritis and prostatitis as alternative diagnoses 3
- Urine culture with susceptibility testing should always be obtained 3
Critical Diagnostic and Treatment Principles
When to Obtain Urine Culture
Obtain urine culture before treatment in: 2
- Suspected pyelonephritis
- Symptoms persisting >4 weeks after treatment
- Atypical symptoms
- Recurrent UTIs
- Pregnant women
- All men with UTI symptoms 3
What NOT to Do
Do NOT treat asymptomatic bacteriuria except in pregnant women and patients scheduled for urologic procedures 2
Do NOT classify recurrent UTI patients as "complicated" as this leads to unnecessary broad-spectrum antibiotics; reserve "complicated" for structural/functional urinary tract abnormalities, immunosuppression, or pregnancy 1
Do NOT use single-dose antibiotics (except fosfomycin) due to higher bacteriological persistence rates 2
Do NOT obtain routine post-treatment urine cultures in asymptomatic patients 2
Do NOT use fluoroquinolones as first-line therapy due to serious adverse effects and the need for antimicrobial stewardship 1, 2
Empiric Treatment Selection Framework
When selecting empiric therapy, consider: 1
- Local resistance patterns (antibiograms)
- Prior culture results if available
- Patient allergies and prior adverse effects
- Risk factors for antimicrobial resistance
- Clinical severity
- Cost considerations
Special Considerations for Resistance
Nitrofurantoin resistance decays rapidly: only 20.2% at 3 months and 5.7% at 9 months, with initial prevalence of only 2.6% 1
Fluoroquinolones and cephalosporins cause more collateral damage to fecal microbiota and increase C. difficile risk compared to other antibiotic classes 1
Beta-lactam antibiotics promote more rapid UTI recurrence due to disruption of protective periurethral and vaginal microbiota 1
Recurrent UTI Prevention
For patients with recurrent UTI (>2 culture-positive UTIs in 6 months or >3 in one year): 1
Postmenopausal Women
- Vaginal estrogen with or without lactobacillus-containing probiotics 1
Premenopausal Women with Post-Coital Infections
- Low-dose post-coital antibiotics within 2 hours of sexual activity for 6-12 months 1
- Preferred agents: nitrofurantoin 50 mg, TMP-SMX 40/200 mg, or trimethoprim 100 mg 1