Treatment of Urinary Tract Infections
Uncomplicated Cystitis in Women
For uncomplicated cystitis in women, first-line treatment should be 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. 1, 2
First-Line Agents
- Nitrofurantoin is highly effective with minimal resistance patterns globally, dosed as 100 mg twice daily for 5 days 1, 2
- Fosfomycin trometamol offers the convenience of single-dose therapy (3 g once), though it may have slightly inferior efficacy compared to multi-day regimens based on FDA data 1, 2
- Pivmecillinam 400 mg three times daily for 3-5 days is an excellent option where available (limited availability in North America), with minimal resistance and collateral damage 1, 2
Alternative Agents (When First-Line Cannot Be Used)
- Cephalosporins (e.g., cefadroxil 500 mg twice daily for 3 days) can be used only if local E. coli resistance is <20% 1, 2
- Trimethoprim 200 mg twice daily for 5 days is acceptable but avoid in first trimester of pregnancy 1, 2
- Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days is appropriate only if local resistance is <20% or the organism is known to be susceptible; avoid in last trimester of pregnancy 1, 2
Critical Resistance Thresholds
The 20% resistance threshold for trimethoprim-sulfamethoxazole is based on expert consensus from clinical and modeling studies—above this level, empiric use is not recommended 1. Recent data from Germany shows resistance rates for trimethoprim at 21.4% and cotrimoxazole at 19.3% in recurrent UTIs, making these agents less reliable in that setting 3.
Agents to Avoid
- Fluoroquinolones (ciprofloxacin, levofloxacin) are highly effective but should be reserved for more serious infections due to collateral damage and rising resistance rates 1
- Beta-lactams (except pivmecillinam) have inferior efficacy and more adverse effects compared to other UTI antimicrobials 1
- Amoxicillin or ampicillin should never be used empirically due to poor efficacy and very high global resistance rates 1
Diagnostic Considerations
- Diagnosis can be made clinically based on dysuria, frequency, urgency, and absence of vaginal discharge—no urine culture needed for typical presentations 1, 4
- Urine culture is mandatory for: suspected pyelonephritis, symptoms persisting/recurring within 4 weeks, atypical symptoms, pregnant women, or treatment failure 1, 4
- Dipstick testing adds minimal diagnostic value in typical cases but can help when diagnosis is unclear 1
Uncomplicated Cystitis in Men
Men with uncomplicated UTI should receive trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days, with fluoroquinolones as alternatives based on local susceptibility. 1, 2
- Treatment duration is longer in men (7 days vs 3-5 days in women) due to anatomical differences 1, 2, 4
- Always obtain urine culture in men before initiating therapy to guide antibiotic selection 4
- Consider urethritis and prostatitis as alternative diagnoses in men presenting with UTI symptoms 4
Acute Pyelonephritis
For outpatient management of pyelonephritis, use ciprofloxacin 500 mg twice daily for 7 days (or levofloxacin 750 mg daily for 5 days) only if local fluoroquinolone resistance is <10%, with an initial dose of IV ceftriaxone 1 g if resistance exceeds 10%. 1, 5
Outpatient Treatment Algorithm
- If fluoroquinolone resistance <10%: Oral ciprofloxacin 500 mg twice daily for 7 days, with or without initial IV ciprofloxacin 400 mg 1
- If fluoroquinolone resistance >10%: Give initial IV ceftriaxone 1 g or consolidated 24-hour aminoglycoside dose, then transition to oral fluoroquinolone 1
- Alternative oral agents: Levofloxacin 750 mg daily for 5 days (if resistance <10%) 1, 5
When Fluoroquinolones Cannot Be Used
- Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days is appropriate only if the organism is known to be susceptible; give initial IV ceftriaxone 1 g if susceptibility unknown 1
- Oral beta-lactams are less effective than other agents; if used, always give initial IV ceftriaxone 1 g or aminoglycoside, then continue for 10-14 days 1
Hospitalized Patients
- Initiate IV therapy with fluoroquinolone, aminoglycoside (with or without ampicillin), extended-spectrum cephalosporin/penicillin (with or without aminoglycoside), or carbapenem 1
- Tailor therapy based on culture results and local resistance patterns 1
Critical Pitfall
The 10% fluoroquinolone resistance threshold for pyelonephritis is lower than the 20% threshold for cystitis because pyelonephritis carries higher morbidity risk 1. Many regions now exceed this threshold, making empiric fluoroquinolone monotherapy inappropriate without initial parenteral therapy.
Recurrent UTIs
For women with recurrent UTIs (≥3 episodes/year or ≥2 in 6 months), diagnose each episode with urine culture and consider non-antibiotic preventive measures before resorting to antibiotic prophylaxis. 1
Preventive Strategies
- Increase fluid intake in premenopausal women 1
- Vaginal estrogen replacement in postmenopausal women 1, 6
- Cranberry products and methenamine hippurate can prevent recurrences 4
- Antibiotic prophylaxis is effective but carries risks of adverse effects and resistance development 4, 6
Diagnostic Workup
- Urine culture is mandatory for each recurrence 1
- Extensive workup (cystoscopy, abdominal ultrasound) is not needed in women <40 years without risk factors 1
Treatment Considerations
- For recurrent infections, resistance rates are higher—trimethoprim shows 21.4% resistance and cotrimoxazole 19.3% resistance 3
- If symptoms don't resolve or recur within 2 weeks, perform culture and assume the organism is resistant to the initial agent; retreat with a different 7-day regimen 1
Special Populations and Resistant Organisms
Elderly Patients (≥65 Years)
- First-line antibiotics and durations are the same as for younger adults 4
- Always obtain urine culture with susceptibility testing to adjust therapy after empiric treatment 4
- Distinguish true infection from asymptomatic bacteriuria, which does not require treatment 6
Resistant Organisms
- ESBL-producing E. coli: Nitrofurantoin, fosfomycin, pivmecillinam, or amoxicillin-clavulanate for oral therapy; carbapenems, piperacillin-tazobactam, or ceftazidime-avibactam for parenteral therapy 7
- Carbapenem-resistant Enterobacteriaceae: Single-dose aminoglycoside for simple cystitis; ceftazidime-avibactam, meropenem-vaborbactam, or cefiderocol for complicated infections 2, 7
- VRE (vancomycin-resistant Enterococcus): Fosfomycin 3 g single dose, nitrofurantoin 100 mg four times daily, or high-dose ampicillin/amoxicillin 500 mg every 8 hours 2
Pregnancy
- Trimethoprim: avoid in first trimester 1, 2
- Trimethoprim-sulfamethoxazole: avoid in last trimester 1, 2
- Nitrofurantoin and fosfomycin are generally safe options 1, 2
- Pyelonephritis in pregnancy requires hospitalization and IV antibiotics 6
Symptomatic Treatment Without Antibiotics
For women with mild to moderate uncomplicated cystitis symptoms, symptomatic treatment with NSAIDs (e.g., ibuprofen) may be considered as an alternative to immediate antibiotics, given the low risk of complications. 1, 4