What are the guidelines for managing multidrug-resistant infections in Intensive Care Unit (ICU) settings?

Guidelines for Managing Multidrug-Resistant Infections in ICU Settings

Updated local antibiograms with pathogen-specific susceptibility data should be produced at least annually together with data on antimicrobial use to optimize expert-based recommendations for empirical therapy for multidrug-resistant infections in ICU settings. 1

Diagnostic Approach

Rapid Diagnostics

• Implement molecular rapid diagnostic testing (mRDT) with an antimicrobial stewardship program (ASP) to reduce time to effective therapy and length of stay in patients with bloodstream infections caused by multidrug-resistant bacteria 1
• Rapid molecular tests with prompt communication are particularly valuable for ICU patients, where immediate adjustment of antibiotic treatment is critical 1
• The real-time approach is especially useful for critically ill patients undergoing continuous monitoring 1

Microbiological Surveillance

• Utilize computerized tools that provide time series analyses of antimicrobial resistance surveillance together with antimicrobial consumption data 1
• Preliminary microbiological reports with therapeutic recommendations have shown to improve clinical success rates (82.4%) and antibiotic appropriateness (80% vs. 26%) 1

Treatment Recommendations by Pathogen Type

Extended-Spectrum Beta-Lactamase-Producing Enterobacterales (3GCephRE)

• For patients with severe infections due to 3GCephRE, carbapenems remain the treatment of choice 1
• For non-severe infections and low-risk sources, consider carbapenem-sparing options:
  • For urinary tract infections: Aminoglycosides for short durations when active in vitro 1
  • Consider beta-lactam/beta-lactamase inhibitors (BLBLI) if susceptible 1
• Avoid tigecycline for 3GCephRE infections 1

Carbapenem-Resistant Enterobacterales (CRE)

• For severe infections due to CRE:
  • Meropenem-vaborbactam or ceftazidime-avibactam if active in vitro 1
  • For CRE carrying metallo-β-lactamases and/or resistant to all other antibiotics: Cefiderocol 1
• For non-severe infections due to CRE:
  • Use in vitro active older antibiotics based on source of infection 1
  • For urinary tract infections: Aminoglycosides, including plazomicin, over tigecycline 1
• Avoid tigecycline for bloodstream infections and hospital-acquired/ventilator-associated pneumonia 1

Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)

• For severe infections due to difficult-to-treat CRPA, consider ceftolozane-tazobactam if active in vitro 1

Carbapenem-Resistant Acinetobacter baumannii (CRAB)

• For CRAB susceptible to sulbactam and hospital-acquired/ventilator-associated pneumonia, consider ampicillin-sulbactam 1
• For CRAB resistant to sulbactam, polymyxins or high-dose tigecycline can be used if active in vitro 1

Antimicrobial Stewardship Strategies

Multifaceted Interventions

• Implement multifaceted interventions rather than simple, passive interventions 1
• Key components include:
  1. Locally developed, unit-specific protocols
  2. Computer-assisted order entry
  3. ICU-based pharmacist facilitation 1

Evidence-Based Guidelines

• Develop locally adapted, interdisciplinary evidence-based guidelines that incorporate:
  • Risk stratification (severity and community-acquired vs. hospital-acquired infections)
  • Local resistance data 1
• Pre-existing locally developed antibiotic protocols have been independently associated with improved time to antibiotic treatment and survival 1

Combination Therapy Recommendations

• For patients with CRE infections susceptible to and treated with ceftazidime-avibactam, meropenem-vaborbactam, or cefiderocol, monotherapy is sufficient 1
• For severe infections caused by CRE carrying metallo-β-lactamases, consider aztreonam and ceftazidime-avibactam combination therapy 1
• For severe infections caused by CRE susceptible in vitro only to polymyxins, aminoglycosides, tigecycline, or fosfomycin, consider treatment with more than one drug active in vitro 1

Common Pitfalls and Caveats

Antibiotic Selection Pitfalls

• Avoid using new beta-lactam/beta-lactamase inhibitors for infections caused by 3GCephRE due to antibiotic stewardship considerations - reserve these for extensively resistant bacteria 1
• Avoid tigecycline for bloodstream infections and hospital-acquired/ventilator-associated pneumonia; if necessary in patients with pneumonia, use high-dose tigecycline 1, 2
• Avoid carbapenem-based combination therapy for CRE infections unless the meropenem MIC is ≤8 mg/L, where high-dose extended-infusion meropenem may be used as part of combination therapy 1

Risk Factors for MDR Infections

• Mechanical ventilation and urinary catheterization are significant risk factors for multidrug-resistant bacterial infections in ICU settings 3
• Other risk factors include prolonged hospital stay, presence of invasive devices, colonization with resistant pathogens, and prior use of broad-spectrum antibiotics 4

Implementation Strategies

Computer-Assisted Systems

• Utilize computer-assisted order entry and therapeutic drug monitoring to improve antibiotic prescribing practices 1
• Implement computerized tools that provide time series analyses of antimicrobial resistance surveillance together with antimicrobial consumption data 1

Education and Communication

• Develop educational tools and programs involving multidisciplinary groups 1
• Ensure rapid communication of microbiological results to lead to immediate adjustment of antibiotic treatment 1

By following these guidelines and implementing comprehensive antimicrobial stewardship programs, ICUs can effectively manage multidrug-resistant infections while preserving the efficacy of current and future antimicrobial agents.