Treatment of E. coli Urinary Tract Infections
For acute uncomplicated cystitis caused by E. coli in otherwise healthy adult nonpregnant females, use nitrofurantoin 5-day course, fosfomycin 3-g single dose, or pivmecillinam 5-day course as first-line therapy. 1
First-Line Empiric Treatment
The recommended first-line agents are based on their maintained efficacy despite rising resistance patterns:
- Nitrofurantoin (5-day course) remains the most active agent with 94% susceptibility rates and should be considered the preferred option 1, 2
- Fosfomycin tromethamine (3-g single dose) provides excellent coverage and convenience 1
- Pivmecillinam (5-day course) offers reliable activity against E. coli 1
These agents maintain superior activity compared to traditional options, with nitrofurantoin demonstrating the highest susceptibility rates in surveillance studies 2.
Agents to AVOID as First-Line Empiric Therapy
Do not use trimethoprim-sulfamethoxazole (TMP-SMX) or fluoroquinolones empirically unless local resistance rates are documented below 20%. 1
- TMP-SMX resistance ranges from 37-44% in community isolates, rendering it unsuitable for empirical use in most communities 2, 3
- Fluoroquinolone (ciprofloxacin) resistance has increased significantly, with rates reaching 11-27% 3
- Ampicillin shows extremely high resistance (47-64%) and should not be used empirically 2, 3
Risk Factors Requiring Alternative First-Line Therapy
Avoid fluoroquinolones in patients with:
- Prior fluoroquinolone exposure within 90 days (OR 30.35 for resistance) 4
- Recurrent UTI (OR 8.13 for ciprofloxacin resistance) 4
Avoid TMP-SMX in patients with:
- TMP-SMX use within 90 days (OR 8.77 for resistance) 5
- Recurrent UTIs (OR 2.27 for resistance) 5
- Genitourinary abnormalities (OR 2.31 for resistance) 5
Second-Line Treatment Options
When first-line agents are contraindicated or unavailable:
- Oral cephalosporins (cephalexin, cefixime, cefuroxime) maintain reasonable activity 1, 3
- Amoxicillin-clavulanate can be used, though resistance has increased to 18-29% 1, 3
- Fluoroquinolones only if patient lacks risk factors above and local resistance <20% 1, 4
Treatment for ESBL-Producing E. coli
For oral treatment of ESBL-producing E. coli UTIs:
- Nitrofurantoin, fosfomycin, or pivmecillinam remain effective 1
- Amoxicillin-clavulanate can be considered for ESBL E. coli specifically 1
- Finafloxacin and sitafloxacin are newer alternatives 1
For parenteral treatment when required:
- Carbapenems (meropenem/vaborbactam, imipenem/cilastatin-relebactam) 1
- Piperacillin-tazobactam (for ESBL E. coli only, not Klebsiella) 1
- Ceftazidime-avibactam or ceftolozane-tazobactam 1
Critical Pitfalls to Avoid
- Do not rely on institutional antibiograms alone for ED patients—ED populations demonstrate higher resistance rates (25.1% vs 20% for TMP-SMX) compared to overall institutional data 5
- Do not use TMP-SMX or ciprofloxacin in patients recently exposed to these agents—prior exposure is the strongest predictor of resistance 4, 5
- Do not assume cefpodoxime susceptibility—ESBL production (indicated by cefpodoxime resistance) occurs in 5.7% of community and 21.6% of nosocomial isolates 2