Guidelines for Polymyxin-Based Combination Therapy in CRPA Infections in the ICU
Preferred Treatment Hierarchy
- The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommends using combination therapy with two in vitro active drugs rather than polymyxin monotherapy for severe CRPA infections in the ICU, with a conditional recommendation and very low certainty of evidence 1, 2, 3
- Ceftolozane-tazobactam is the preferred agent for severe difficult-to-treat CRPA infections if the organism is susceptible in vitro, according to the Clinical Microbiology and Infection guidelines 1, 4
- Newer beta-lactam/beta-lactamase inhibitors (imipenem-relebactam, cefiderocol, ceftazidime-avibactam) should be considered based on susceptibility testing, though evidence remains limited 1, 4
Polymyxin-Based Therapy
- The Clinical Microbiology and Infection guidelines recommend using polymyxin B (or colistin) combined with a second in vitro active agent from: aminoglycosides, fosfomycin, or carbapenems (if MIC ≤8 mg/L) for severe CRPA infections in the ICU 1, 2, 3
- No specific combination has proven superiority; selection must be guided by antimicrobial susceptibility testing, as stated by the Clinical Microbiology and Infection guidelines 1, 4
Critical Management Principles
- The Clinical Microbiology and Infection guidelines recommend obtaining antimicrobial susceptibility testing immediately to guide combination selection for severe CRPA infections in the ICU 1, 4
- Consult infectious disease specialists early in management, and ensure optimal source control (drainage of abscesses, removal of infected devices), as recommended by the Praxis Medical Insights guidelines 4, 6
- Utilize therapeutic drug monitoring when available, as stated by the Praxis Medical Insights guidelines 6
Common Pitfalls and Caveats
- The Praxis Medical Insights guidelines recommend avoiding polymyxin monotherapy for severe CRPA infections in the ICU—it is associated with higher treatment failure rates 4
- The Praxis Medical Insights guidelines recommend avoiding tigecycline for CRPA bacteremia—serum concentrations are inadequate for bloodstream infections 4
- The Clinical Microbiology and Infection guidelines recommend avoiding polymyxin-rifampin combinations—there is no evidence supporting this regimen for CRPA 1