Treatment of Multidrug-Resistant Organisms in the ICU
For patients with multidrug-resistant (MDR) organism infections in the intensive care unit (ICU), infectious disease consultation is strongly recommended along with targeted antimicrobial therapy based on susceptibility testing and site of infection. 1
General Management Principles
- Infectious disease consultation is highly recommended for all MDR organism infections in the ICU to optimize treatment outcomes 1
- Antimicrobial susceptibility testing or genotypic characterization of resistance is essential to guide appropriate antibiotic selection 1
- Prolonged infusion of β-lactams is recommended for pathogens with high minimum inhibitory concentrations (MICs) to optimize pharmacodynamics 1
- All antibiotic treatments should be reassessed at 48-72 hours and de-escalated based on clinical condition and microbiological data 1
Treatment Recommendations by Pathogen Type
Carbapenem-Resistant Acinetobacter baumannii (CRAB)
- For CRAB pneumonia, colistin or polymyxin B with or without carbapenems, plus adjunctive inhaled colistin/polymyxin B therapy is recommended 1, 2
- Tigecycline monotherapy should NOT be used for CRAB pneumonia 1
- For CRAB bloodstream infections, colistin-carbapenem based combination therapy is recommended, especially when carbapenem MIC is ≤32 mg/L 1, 2
Carbapenem-Resistant Enterobacterales (CRE)
- For CRE bloodstream infections, polymyxin-based combination therapy is recommended based on susceptibility testing 1
- Ceftazidime-avibactam 2.5g IV q8h infused over 3 hours is recommended for CRE bloodstream infections 1
- For complicated urinary tract infections (cUTI) caused by CRE:
Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)
- For severe CRPA infections, combination therapy with two in vitro active drugs, including polymyxin B, is suggested 2, 3
- For non-severe CRPA infections, monotherapy with an active agent may be appropriate 2
- Newer agents like ceftolozane-tazobactam should be used over polymyxin B when available and active in vitro due to lower nephrotoxicity 3
Vancomycin-Resistant Enterococci (VRE)
- Linezolid 600 mg IV or PO every 12 hours is recommended for VRE infections 1
- High-dose daptomycin (8-12 mg/kg IV daily) alone or in combination with β-lactams is recommended for VRE bloodstream infections 1
- Tigecycline 100 mg IV loading dose then 50 mg IV q12h is recommended for intra-abdominal infections due to VRE 1
Combination Therapy Considerations
- Empirical combination treatment is suggested for patients with shock, neutropenia, or suspected MDR bacterial infections 1
- Combination therapy may reduce mortality, treatment failure, and pathogen eradication failure compared to monotherapy for certain MDR organisms 2, 3
- For pan-resistant carbapenem-resistant gram-negative bacteria, treatment with the least resistant antibiotic(s) based on MICs relative to breakpoints is considered good clinical practice 3
Antibiotic Administration Strategies
- Administer β-lactams (cefepime, piperacillin-tazobactam, meropenem, doripenem) by prolonged intravenous infusion (3-4 hours) to treat severe infections, especially with high MIC pathogens 1
- Consider continuous infusion for carbapenems, ceftazidime, and piperacillin-tazobactam when there is risk of pharmacodynamic failure 1
- Administer vancomycin by continuous infusion after a loading dose to reach early target plasma concentrations 1
Duration and De-escalation
- Procalcitonin can guide antibiotic discontinuation - consider stopping when levels are below 0.5 ng/mL or decreased by >80% from peak value 1
- For non-immunosuppressed patients with ventilator-associated pneumonia, limit treatment to 8 days when initial therapy is adequate 1
- De-escalate from broad-spectrum to narrow-spectrum antimicrobials when possible to decrease antibiotic selection pressure without negative impact on mortality 4
Common Pitfalls and Caveats
- Previous antibiotic therapy between initial intervention and reoperation is a significant risk factor for emergence of MDR bacteria (OR = 5.1) 5
- Not all regimens proposed by guidelines provide acceptable adequacy rates for empiric therapy - local resistance patterns must be considered 5
- Modifying initially inadequate therapy according to microbiological results often does not improve outcomes, emphasizing the importance of appropriate initial therapy 6
- Rapid diagnostics and efficient laboratory workflows are essential for early diagnosis and appropriate antimicrobial spectrum narrowing 7
By following these evidence-based recommendations and considering local resistance patterns, clinicians can optimize treatment outcomes for patients with MDR organism infections in the ICU while practicing responsible antimicrobial stewardship.