What is the appropriate management approach for a patient suspected or confirmed to have a Multi-Drug Resistant Organism (MDRO) infection?

Management of Multi-Drug Resistant Organism (MDRO) Infections

Immediately place all patients with known or highly suspected MDRO infections on contact isolation precautions with single-room placement, and consult infectious disease specialists for all MDRO infections due to limited treatment options and need for pharmacokinetic optimization. 1

Immediate Infection Control Measures

Contact isolation precautions are mandatory and must include: 1

• Single-room placement or cohorting with other MDRO-positive patients if single rooms unavailable 2
• Gown and glove use by all healthcare workers before entering the room 2
• Removal of personal protective equipment before leaving the room with immediate hand hygiene using alcohol-based products 2
• Dedicated patient equipment (stethoscopes, blood pressure cuffs) to prevent cross-contamination 2
• Clear signage indicating isolation status 1
• Enhanced environmental cleaning with performance monitoring 2

These precautions should continue throughout the entire hospitalization unless at least three consecutive negative cultures from multiple body sites (including wounds) are obtained at least one week apart. 2

Key MDRO Pathogens and Their Clinical Impact

The major MDROs requiring specific management include: 1

• Methicillin-resistant Staphylococcus aureus (MRSA) - requires contact precautions with wound coverage 2
• Vancomycin-resistant Enterococcus (VRE) - associated with prolonged hospital stays and prior broad-spectrum antibiotic exposure 3
• Extended-spectrum β-lactamase (ESBL) producers - most common among Enterobacterales 4
• Carbapenem-resistant Enterobacterales (CRE) - mortality 6.2 times higher than susceptible strains 3
• Carbapenem-resistant Pseudomonas aeruginosa (CRPA) - 1.5-fold increased mortality 3
• Carbapenem-resistant Acinetobacter baumannii (CRAB) - extremely limited treatment options 3

Risk Stratification for MDRO Infections

Patients with the following risk factors require empirical broad-spectrum therapy covering MDROs: 3, 4

• Prior MDRO infection or colonization 3
• Antibiotic use within past 90 days (especially carbapenems, broad-spectrum cephalosporins, or fluoroquinolones) 3, 4
• Hospitalization for >2 days in past 90 days 3, 4
• Infection occurring ≥5 days after hospital admission 3
• Hemodialysis or chronic renal failure 3, 4
• Nursing home residency 4
• Immunosuppression or poor functional status 3
• Ureteral stent or nephrostomy 4

Antimicrobial Management Principles

General Approach

Obtain cultures before initiating antibiotics, then start empirical broad-spectrum therapy immediately based on risk stratification—do not delay antibiotics in critically ill patients. 3, 5

Infectious disease consultation is strongly recommended for all MDRO infections. 1, 5 This is critical because inappropriate initial antibiotic therapy is strongly associated with increased hospital mortality in critically ill patients with MDR Gram-negative infections. 3

Use prolonged infusions (3-4 hours) of β-lactams for pathogens with high minimum inhibitory concentrations to optimize time above MIC. 1, 3, 5

Reassess therapy at 48-72 hours for de-escalation opportunities based on cultures and clinical response. 3, 5

Specific Pathogen-Directed Therapy

For Carbapenem-Resistant Acinetobacter baumannii (CRAB):

• Pneumonia: Colistin 5 mg CBA/kg IV loading dose, then 2.5 mg CBA × (1.5 × CrCl + 30) IV q12h +/- carbapenem (imipenem 500 mg IV q6h or meropenem 2 g IV q8h) PLUS adjunctive inhaled colistin 1.25-15 MIU/day in 2-3 divided doses 1
• Bloodstream infections: Colistin-carbapenem combination therapy (same dosing) 1
• Never use tigecycline monotherapy for CRAB pneumonia—it is associated with poor outcomes and increased mortality 1, 3, 5

For Carbapenem-Resistant Enterobacterales (CRE):

• First-line: Ceftazidime-avibactam 2.5 g IV q8h infused over 3 hours 1, 5
• Alternatives: Meropenem-vaborbactam 4 g IV q8h or imipenem-cilastatin-relebactam 1.25 g IV q6h 1, 5
• Bloodstream infections: Polymyxin-based combination therapy if above agents unavailable, though nephrotoxicity is a concern 1, 3
• Complicated UTI: Single-dose aminoglycoside for simple cystitis only; plazomicin 15 mg/kg IV q12h for complicated UTI 1

For Carbapenem-Resistant Pseudomonas aeruginosa (CRPA):

• Ceftolozane-tazobactam or ceftazidime-avibactam based on susceptibility 5

For Vancomycin-Resistant Enterococcus (VRE):

• Linezolid 600 mg IV q12h or daptomycin 6 mg/kg IV q24h 5

For MRSA:

• Vancomycin 25-30 mg/kg loading dose, then 15-20 mg/kg q8h (target trough 15-20 mcg/mL for serious infections) 5
• Daptomycin 6-8 mg/kg IV q24h for soft tissue/bone infections 5

Treatment Duration and Source Control

Duration depends on infection site and source control adequacy: 1, 5

• Uncomplicated intra-abdominal infections with complete source control: No post-operative antibiotics needed 1
• Complicated intra-abdominal infections with complete source control: 3-5 days post-operative therapy 1
• Soft tissue infections with adequate source control: 7-14 days 5
• Bloodstream infections: 10-14 days 1
• Pneumonia: At least 7 days 1

Adequate source control (debridement, drainage) is essential—antibiotics alone are insufficient. 5

Surveillance and Prevention Strategies

Active surveillance cultures for CRE using rectal swabs are highly effective when part of comprehensive infection control programs. 1 This allows early detection and prevents transmission through colonization pressure reduction. 1

The three core strategies to address MDROs are: 1

1. Developing new antimicrobial agents
2. Increasing antimicrobial stewardship efforts
3. Interrupting MDRO cross-transmission

Hand hygiene via healthcare personnel is responsible for 20-40% of nosocomial MDRO infections, making compliance monitoring critical. 1

Critical Pitfalls to Avoid

• Never delay empirical antibiotics in critically ill patients—up to half of ICU patients receiving empirical antibiotics have no definitively confirmed infection, yet withholding therapy risks death in truly infected patients 3
• Never use tigecycline monotherapy for serious infections due to poor tissue penetration and increased mortality 3, 5
• Never use aminoglycosides as monotherapy beyond simple cystitis due to inadequate tissue penetration 3, 5
• Never fail to reassess therapy at 48-72 hours for de-escalation opportunities 3, 5
• Never administer standard β-lactam infusions for high-MIC pathogens—always use prolonged infusions (3-4 hours) 3, 5
• Never discontinue contact precautions prematurely—maintain throughout hospitalization unless three consecutive negative cultures obtained 2

Special Considerations

Isolation measures may cause clinical complications due to reduced healthcare worker contact and psychological adverse effects, but transmission prevention takes priority. 3 Focus initial control efforts on high-risk areas like intensive care units where transmission rates are highest. 2

Flag medical records of MDRO-positive patients for prompt identification upon readmission. 2 Colonization with MDROs typically persists for months following discharge, making patients at high risk for continued colonization. 1