Treatment of Urinary Tract Infections
For uncomplicated UTIs in otherwise healthy adult nonpregnant women, use nitrofurantoin for 5 days, fosfomycin 3g single dose, or pivmecillinam for 5 days as first-line therapy. 1, 2
Classification Framework
UTI treatment depends critically on proper classification into two key dimensions 3:
- Complicated vs. Uncomplicated: Complicated UTIs involve anatomic/functional genitourinary abnormalities, urinary catheters, immunosuppression, or resistant organisms 3, 4
- Upper vs. Lower tract: Pyelonephritis (upper) requires more aggressive therapy than cystitis (lower) 3
- Community-acquired vs. Hospital-acquired: Hospital-acquired infections carry higher resistance rates 3
The ORENUC criteria provide systematic risk stratification for complicated UTIs, incorporating factors like catheterization and anatomic abnormalities 3.
Uncomplicated Cystitis (Lower UTI)
First-Line Options
The three preferred antibiotics are nitrofurantoin, fosfomycin, and pivmecillinam because they maintain activity against resistant organisms and have low propensity to select for resistance 2:
- Nitrofurantoin: 5-day course 1, 2
- Fosfomycin tromethamine: 3g single dose 1, 2
- Pivmecillinam: 5-day course 1, 2
Second-Line Options
Use these when first-line agents are contraindicated or unavailable 1:
- Oral cephalosporins (cephalexin, cefixime) 1
- Fluoroquinolones (only if local resistance <20% and no recent exposure) 1
- Amoxicillin-clavulanate 1
Critical Caveat on Traditional Agents
Trimethoprim-sulfamethoxazole and ciprofloxacin should NOT be used empirically in many communities due to high resistance rates in E. coli, particularly if patients had recent antibiotic exposure or risk factors for ESBL-producing organisms 1. The historical 3-day TMP-SMX regimen is no longer universally appropriate 5.
Complicated UTIs
Mild Lower Complicated UTIs
For mild cases without systemic symptoms 4:
- Fluoroquinolones (if susceptibility confirmed) 4
- Trimethoprim-sulfamethoxazole (if susceptibility confirmed) 4
- Nitrofurantoin (limited to lower tract only, after organism identification) 4
Serious Complicated UTIs or Pyelonephritis
For serious complicated UTIs, especially with risk factors for resistant organisms (recent antibiotic use, healthcare exposure, known ESBL carriage), initiate empiric therapy with carbapenems or piperacillin-tazobactam 4:
- Carbapenems (meropenem, imipenem-cilastatin, ertapenem) 4
- Piperacillin-tazobactam 4
- Cefepime (for AmpC-producing organisms) 1
ESBL-Producing Organisms
Oral options for ESBL E. coli 1:
- Nitrofurantoin (lower tract only)
- Fosfomycin
- Pivmecillinam
- Amoxicillin-clavulanate
- Finafloxacin or sitafloxacin
Parenteral options for ESBL organisms 1:
- Carbapenems (including meropenem-vaborbactam, imipenem-cilastatin-relebactam)
- Piperacillin-tazobactam (ESBL E. coli only, not Klebsiella)
- Ceftazidime-avibactam
- Ceftolozane-tazobactam
- Aminoglycosides including plazomicin
- Cefiderocol
Carbapenem-Resistant Enterobacterales (CRE)
Reserve these agents for confirmed CRE infections 1:
- Ceftazidime-avibactam
- Meropenem-vaborbactam
- Imipenem-cilastatin-relebactam
- Cefiderocol
- Aminoglycosides including plazomicin
- Combination therapy: aztreonam plus ceftazidime-avibactam or amoxicillin-clavulanate
Treatment Duration
- Uncomplicated cystitis: 3-5 days suffices 2
- Complicated UTIs: 1-4 weeks depending on clinical severity, anatomic involvement, and response to therapy 4
Key Clinical Pitfalls
Avoid fluoroquinolones as first-line empiric therapy for serious complicated UTIs when resistance risk factors exist 4. The widespread use of fluoroquinolones has driven resistance in E. coli globally 1, 4.
Do not use nitrofurantoin or fosfomycin for pyelonephritis or upper tract infections—these agents achieve inadequate tissue concentrations outside the bladder 4.
Always obtain urine culture before initiating therapy for complicated UTIs, as organism susceptibility is unpredictable 4. De-escalate to narrow-spectrum agents once susceptibilities return 3.
Consider delaying antibiotics in uncomplicated cystitis: The risk of progression to pyelonephritis is only 1-2%, and starting with ibuprofen for pain relief while awaiting culture results is reasonable 2.