Antibiotics for Urinary Tract Infections Caused by Enteric Gram-Negative Rods
For uncomplicated UTIs caused by susceptible enteric gram-negative rods (primarily E. coli), nitrofurantoin or fosfomycin are first-line agents, while severe infections or those caused by third-generation cephalosporin-resistant organisms require carbapenems (imipenem or meropenem). 1
Treatment Algorithm Based on Infection Severity and Resistance Pattern
Non-Severe, Uncomplicated UTIs (Susceptible Organisms)
First-line options:
- Nitrofurantoin 100 mg orally every 6 hours for 5-7 days remains highly effective with 91-96% susceptibility rates against E. coli across all regions 1, 2, 3
- Fosfomycin 3 g as a single oral dose demonstrates 95.9-96.1% susceptibility against both non-ESBL and ESBL E. coli 4
Second-line options (when first-line unavailable):
- Fluoroquinolones (ciprofloxacin) only if local resistance rates are <10% and patient lacks risk factors for resistant organisms 1, 2
- Trimethoprim-sulfamethoxazole if susceptibility confirmed (resistance rates 23-36% in North America) 5, 3
- Amoxicillin-clavulanate for susceptible strains 1, 2
Critical caveat: Avoid empiric fluoroquinolones due to rising resistance (25.6% in recent studies) and FDA warnings about unfavorable risk-benefit ratios for uncomplicated UTIs 5
Severe Infections or Bloodstream Infections (Third-Generation Cephalosporin-Resistant Enterobacterales)
For patients with septic shock or severe infection:
- Carbapenem (imipenem or meropenem) is the strongly recommended targeted therapy 1
- Ertapenem may be substituted for bloodstream infections without septic shock 1
For complicated UTIs without septic shock:
- Aminoglycosides (gentamicin) when active in vitro for short durations (3-5 days) 1, 2
- IV fosfomycin as an alternative 1
Carbapenem-Resistant Enterobacterales (CRE)
For severe CRE infections:
- Meropenem-vaborbactam or ceftazidime-avibactam if active in vitro 1
- Cefiderocol for metallo-β-lactamase producers or organisms resistant to all other options 1
For non-severe CRE UTIs:
- Aminoglycosides (including plazomicin) preferred over tigecycline 1
- Fosfomycin demonstrates 36.5-38.1% susceptibility against ESBL K. pneumoniae 4
Combination therapy consideration:
- Aztreonam plus ceftazidime-avibactam for metallo-β-lactamase producers with severe infections 1
- Avoid tigecycline for bloodstream infections (use only high-dose for pneumonia if necessary) 1
Antibiotic Stewardship Principles
Reserve newer agents appropriately:
- New β-lactam/β-lactamase inhibitor combinations (ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam) should be reserved for extensively resistant bacteria, not routine third-generation cephalosporin-resistant organisms 1
De-escalation strategy:
- Once patients stabilize following carbapenem therapy, step down to narrower agents (older β-lactam/β-lactamase inhibitors, quinolones, or trimethoprim-sulfamethoxazole) based on susceptibility patterns 1
Avoid these agents:
- Do not use tigecycline for third-generation cephalosporin-resistant Enterobacterales 1
- Do not use cephamycins (cefoxitin) or cefepime for these infections 1
- Discourage extended cephalosporin use due to selective pressure for ESBL emergence 1
Common Pitfalls to Avoid
Resistance pattern awareness:
- Amoxicillin resistance in E. coli reaches 61.7% in recent studies; avoid empiric use without susceptibility data 5
- Ciprofloxacin resistance varies dramatically by region (4% North America vs 55% Latin America for P. aeruginosa) 3
- ESBL rates are 4% for E. coli and 19% for Klebsiella spp., requiring carbapenem consideration 3
Geographic and institutional variation:
- Always consider local antibiograms when selecting empiric therapy 2, 3
- Resistance patterns differ significantly between community-acquired and hospital-acquired infections 1
Inappropriate agent selection: