How is Multi-Drug Resistant Organism (MDRO) classified and managed?

Classification and Management of Multi-Drug Resistant Organisms (MDROs)

Multi-Drug Resistant Organisms (MDROs) are classified based on their resistance patterns to antimicrobial agents, with standardized definitions that help guide appropriate management and infection control measures. 1

Classification of MDROs

MDROs are classified into three main categories based on their resistance patterns:

1. Multi-Drug Resistant (MDR)

   • Definition: Non-susceptibility to at least one agent in three or more antimicrobial categories 2
   • Example: MRSA (Methicillin-resistant Staphylococcus aureus)

2. Extensively Drug-Resistant (XDR)

   • Definition: Non-susceptibility to carbapenem and at least one agent in all but 2 antimicrobial categories 1
   • Example: XDR-AB (Extensively drug-resistant Acinetobacter baumannii)

3. Pan-Drug Resistant (PDR)

   • Definition: Non-susceptibility to all agents in all antimicrobial categories 1
   • Example: PDR-AB (Pan-drug resistant Acinetobacter baumannii)

Common MDRO Types

• Carbapenem-resistant Enterobacterales (CRE): Resistant to doripenem, imipenem, or meropenem 1
• Carbapenem-resistant Pseudomonas aeruginosa (CRPA): Non-susceptible to any carbapenem 1
• Difficult-to-treat resistance P. aeruginosa (DTR-PA): Non-susceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, meropenem, imipenem-cilastatin, ciprofloxacin, and levofloxacin 1
• Vancomycin-resistant enterococci (VRE): Ampicillin and vancomycin-resistant enterococci with high-level resistance to aminoglycosides 1

Management of MDROs

General Management Principles

1. Infectious Disease Consultation

   • Highly recommended for all MDRO infections (Strong recommendation, low quality of evidence) 1

2. Antimicrobial Susceptibility Testing

   • Essential for guiding antimicrobial selection 1
   • Rapid diagnostic tests (RDTs) should be used to improve time to appropriate therapy, especially for bloodstream infections (BSIs) 1

3. Optimized Antibiotic Administration

   • Prolonged infusion of β-lactams for pathogens with high MIC (Strong recommendation) 1
   • For critically ill patients, consider altered pharmacokinetics and administer higher loading doses of hydrophilic antimicrobials 1

Infection Control Measures

1. Contact Isolation Precautions

   • Always recommended for patients known or highly suspected for MDROs 1
   • Isolation or cohorting of colonized/infected patients is essential to prevent transmission 1

2. Active Surveillance

   • Surveillance cultures (particularly rectal) for CRE are effective when part of a comprehensive infection control program 1

Specific Treatment Recommendations

For CRAB (Carbapenem-Resistant Acinetobacter baumannii)

1. Pneumonia:

   • Colistin, with or without carbapenems, plus adjunctive inhaled colistin therapy 1
   • Tigecycline monotherapy is NOT recommended (Strong recommendation) 1

2. Bloodstream Infection:

   • Colistin-carbapenem based combination therapy (Weak recommendation) 1

For CRE (Carbapenem-Resistant Enterobacterales)

1. Bloodstream Infection:

   • Polymyxin-based combination therapy 1
   • Ceftazidime-avibactam 2.5g IV q8h infused over 3h 1

2. Complicated UTI:

   • Ceftazidime-avibactam 2.5g IV q8h 1
   • Meropenem-vaborbactam 4g IV q8h or imipenem-cilastatin-relebactam 1.25g IV q6h 1
   • Plazomicin 15 mg/kg IV q12h as an alternative 1
   • Single-dose aminoglycoside for simple cystitis 1

Duration of Therapy

• For uncomplicated infections with adequate source control (e.g., appendicitis, cholecystitis): No post-operative antibiotics needed 1
• For complicated infections with adequate source control: Short course (3-5 days) 1
• Patients with ongoing signs of infection beyond 5-7 days warrant diagnostic investigation 1

Common Pitfalls and Caveats

1. Inappropriate Empiric Therapy

   • Delays in appropriate antimicrobial therapy significantly increase mortality in MDRO infections
   • Use local antibiogram data and patient risk factors to guide empiric choices

2. Overuse of Broad-Spectrum Antibiotics

   • Prolonged and inappropriate use of antibiotics drives resistance 1
   • Implement antimicrobial stewardship programs to optimize antibiotic use

3. Inadequate Source Control

   • Even appropriate antibiotics may fail without adequate source control
   • Surgical consultation should be considered for collections requiring drainage

4. Failure to Recognize Healthcare-Associated Risk

   • Consider healthcare-associated risk factors: recent hospitalization within 90 days, living in long-term care facilities, recent invasive procedures 1

5. Reliance on Monotherapy for Severe MDRO Infections

   • Combination therapy is often recommended for severe MDRO infections, especially for bloodstream infections 1

By understanding the classification of MDROs and implementing appropriate management strategies, clinicians can improve outcomes for patients with these challenging infections while helping to limit further spread of resistance.