Management of Uncomplicated Urinary Tract Infections in Adults
First-Line Antibiotic Treatment for Women with Uncomplicated Cystitis
For women with uncomplicated cystitis, fosfomycin trometamol 3g single dose, nitrofurantoin 100mg twice daily for 5 days, or pivmecillinam 400mg three times daily for 3-5 days are the recommended first-line antibiotics. 1
Recommended First-Line Regimens
- Fosfomycin trometamol: 3g single dose (1 day treatment) - recommended only for women with uncomplicated cystitis 1
- Nitrofurantoin: 100mg twice daily for 5 days (available as monohydrate, macrocrystals, or prolonged-release formulations) 1
- Pivmecillinam: 400mg three times daily for 3-5 days 1
These agents are prioritized because they demonstrate minimal "collateral damage" in terms of selecting for multidrug-resistant organisms, unlike fluoroquinolones and third-generation cephalosporins 1, 2. The European Association of Urology 2024 guidelines explicitly position these as first-line options based on their efficacy, favorable resistance patterns, and reduced ecological impact 1.
Alternative Second-Line Options
When first-line agents cannot be used due to allergy, intolerance, or local resistance patterns:
- Trimethoprim-sulfamethoxazole: 160/800mg twice daily for 3 days - only if local E. coli resistance is <20% 1, 2
- Trimethoprim alone: 200mg twice daily for 5 days (avoid in first trimester of pregnancy) 1
- Oral cephalosporins (e.g., cefadroxil 500mg twice daily for 3 days): only if local E. coli resistance <20% 1
Critical caveat: Fluoroquinolones should be reserved for complicated infections or pyelonephritis, not uncomplicated cystitis, due to FDA warnings about serious adverse effects and their importance in treating life-threatening infections 1, 2.
Non-Antibiotic Management Option
For women with mild to moderate symptoms, symptomatic therapy with ibuprofen may be considered as an alternative to immediate antimicrobial treatment after shared decision-making with the patient 1. This approach is supported by evidence showing that uncomplicated UTIs have a low risk (1-2%) of progressing to pyelonephritis 3.
First-Line Treatment for Men with Uncomplicated UTI
Men with UTI require longer treatment duration (7-14 days) because male UTIs are considered complicated infections due to anatomical factors and the need to exclude prostatitis. 4
Recommended Regimens for Men
- Trimethoprim-sulfamethoxazole: 160/800mg twice daily for 7-14 days (14 days when prostatitis cannot be excluded) 4
- Fluoroquinolones (ciprofloxacin 500mg twice daily or levofloxacin 750mg daily): only when local resistance <10% and no recent fluoroquinolone exposure 4
- Oral cephalosporins: cefpodoxime 200mg twice daily for 10 days or ceftibuten 400mg daily for 10 days 4
Always obtain urine culture before initiating antibiotics in men to guide potential therapy adjustments based on susceptibility results 4. The standard duration is 14 days when prostatitis cannot be excluded, which applies to most male UTI presentations 4. A shorter 7-day course may be considered only if the patient becomes afebrile within 48 hours with clear clinical improvement, though recent evidence suggests 7-day therapy may be inferior to 14-day therapy for clinical cure (86% vs 98%) 4.
Management of Complicated UTIs
For complicated UTIs requiring parenteral therapy, use a combination of amoxicillin plus aminoglycoside, second-generation cephalosporin plus aminoglycoside, or intravenous third-generation cephalosporin as empirical treatment. 1
Initial Empiric Parenteral Options
- Ceftriaxone: 2g IV once daily 5
- Cefepime: 1-2g IV every 12 hours (use higher dose for severe infections) 5
- Piperacillin-tazobactam: 3.375-4.5g IV every 6-8 hours 5
- Carbapenems (meropenem 1g three times daily, imipenem/cilastatin 0.5g three times daily): reserved for multidrug-resistant organisms 5
Fluoroquinolones should only be used empirically when local resistance is <10%, the patient has not used them in the past 6 months, and there is no recent fluoroquinolone exposure. 1
Oral Step-Down Therapy
Once clinically stable (afebrile for 48 hours, hemodynamically stable) and culture results available:
- Ciprofloxacin: 500-750mg twice daily for 7 days (if susceptible and local resistance <10%) 5
- Levofloxacin: 750mg once daily for 5 days 5
- Trimethoprim-sulfamethoxazole: 160/800mg twice daily for 14 days (if susceptible) 5
- Oral cephalosporins: cefpodoxime 200mg twice daily for 10 days or ceftibuten 400mg once daily for 10 days 5
Treatment Duration
Treat for 7-14 days total, with 7 days appropriate if prompt clinical response and 14 days if delayed response or if prostatitis cannot be excluded in males 1, 5. When the patient is hemodynamically stable and has been afebrile for at least 48 hours, a shorter treatment duration (7 days) may be considered 1.
Management of Multidrug-Resistant Organisms
For Carbapenem-Resistant Enterobacteriaceae (CRE)
- Ceftazidime-avibactam: 2.5g IV every 8 hours 1, 5
- Meropenem-vaborbactam: 2g IV three times daily 5
- Cefiderocol: 2g IV three times daily 5
- Plazomicin: 15mg/kg IV every 12 hours (weak recommendation for cUTI due to CRE) 1
For ESBL-Producing Organisms
Parenteral options include carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, aminoglycosides including plazomicin, and cefiderocol 6. Oral options for ESBL-E. coli include nitrofurantoin, fosfomycin, and pivmecillinam 6.
For VRE Uncomplicated UTI
- Fosfomycin: 3g PO single dose 1
- Nitrofurantoin: 100mg PO every 6 hours 1
- High-dose ampicillin: 18-30g IV daily in divided doses or amoxicillin 500mg IV/PO every 8 hours 1
Critical Pitfalls to Avoid
- Never use nitrofurantoin or fosfomycin for complicated UTIs or pyelonephritis - these agents have limited tissue penetration and are only appropriate for uncomplicated lower UTIs 5
- Avoid aminoglycosides until creatinine clearance is calculated - these are nephrotoxic and require precise weight-based dosing adjusted for renal function 5
- Do not treat asymptomatic bacteriuria except in pregnant women or prior to mucocutaneous traumatizing interventions of the urinary tract 1, 2
- Avoid fluoroquinolones empirically if local resistance exceeds 10% or if the patient has recent fluoroquinolone exposure 1, 5
- Do not use moxifloxacin for UTI treatment due to uncertainty regarding effective urinary concentrations 5
- Replace indwelling catheters that have been in place for ≥2 weeks at the onset of catheter-associated UTI to hasten symptom resolution and reduce recurrence risk 5
When to Obtain Urine Culture
- Always obtain culture in men before initiating antibiotics 4
- Obtain culture in women with recurrent infection, treatment failure, history of resistant isolates, atypical presentation, suspected pyelonephritis, symptoms not resolving within 4 weeks, or pregnancy 1, 7
- Do not perform routine post-treatment cultures in asymptomatic patients 1