What is MDR (Multi-Drug Resistant) E. coli?

MDR E. coli: Definition, Clinical Significance, and Management

MDR (Multi-Drug Resistant) E. coli is defined as E. coli that demonstrates non-susceptibility to at least one agent in three or more antimicrobial categories, posing significant challenges for treatment and increased risks of morbidity and mortality. 1

Definition and Classification

MDR E. coli is part of a standardized international classification system for antimicrobial resistance:

• MDR (Multidrug-resistant): Non-susceptibility to at least one agent in three or more antimicrobial categories 2, 1
• XDR (Extensively drug-resistant): Non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (remaining susceptible to only one or two categories) 1
• PDR (Pandrug-resistant): Non-susceptibility to all agents in all antimicrobial categories 1, 2

This classification was established through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) to standardize terminology for acquired resistance profiles 1.

Clinical Significance

MDR E. coli infections are associated with:

• Longer hospitalization (median 10 days vs. 4 days for non-MDR infections) 3
• Delays in effective antibiotic therapy (median 19.2 hours vs. 0.6 hours) 3
• Higher likelihood of complex infections (35% vs. 17%) 3
• Lower rates of effective empiric antibiotic coverage (47% vs. 74%) 3
• Increased morbidity and mortality due to limited treatment options 2

Risk Factors

Key risk factors for MDR E. coli infections include:

• Genitourinary tract anomalies (OR 2.42,95% CI 1.03-5.68) 3
• Presence of invasive devices (OR 3.48,95% CI 1.37-8.83) 3
• Recent antibiotic use (OR 2.62,95% CI 1.06-6.47) 3
• Healthcare-associated exposures, though community-acquired infections are also common 3

Common Infection Sites

MDR E. coli commonly causes:

• Urinary tract infections (most common) 3, 4
• Bloodstream infections 5
• Surgical site infections 4
• Reproductive tract infections 4
• Wound infections 4

Treatment Approaches

First-line Options for MDR E. coli Infections:

1. For carbapenem-resistant E. coli:

   • Ceftolozane-tazobactam (if susceptible): 1.5g IV q8h with appropriate renal adjustments 6
   • Ceftazidime-avibactam or imipenem-cilastatin-relebactam (preferred over colistin due to better safety profiles) 6

2. For extensively resistant strains:

   • Colistin: Loading dose of 5 mg/kg colistin base activity (CBA) IV, followed by maintenance dose of 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours 6
   • Combination therapy may be necessary (e.g., colistin + carbapenem when MIC ≤32 mg/L) 6

3. Treatment duration:

   • Complicated UTIs: 5-10 days
   • Pneumonia: At least 7 days
   • Bloodstream infections: 10-14 days 6

Special Considerations:

• Monitoring: Close renal function monitoring is essential when using colistin due to nephrotoxicity risk (8-30% of patients) 6
• Infectious Disease Consultation: Strongly recommended for management of MDR E. coli infections 6
• Alternative approaches: For uncomplicated UTIs, phytotherapeutic alternatives like isothiocyanates from nasturtium and horseradish have shown promise in vitro against MDR E. coli 7

Prevention and Control Measures

Guidelines recommend a targeted approach to MDR-GNB control including:

• Hand hygiene with alcohol-based products 2
• Contact precautions (gloves, gowns, clear signage) 2
• Single-room isolation when possible 2
• Patient flagging in medical records 2
• Antimicrobial stewardship to reduce selective pressure 2

Epidemiological Surveillance

Surveillance of MDR E. coli is critical for:

1. Monitoring resistance trends to guide empiric therapy
2. Identifying high-risk populations for targeted interventions
3. Evaluating the effectiveness of control measures 2

MDR E. coli represents a growing challenge in both healthcare and community settings, requiring vigilant surveillance, appropriate infection control measures, and judicious use of remaining effective antimicrobials to preserve treatment options.