What antibiotics are recommended for empyema necessitans caused by Carbapenem-Resistant Acinetobacter baumannii (CRAB) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)?

Antibiotic Treatment for Empyema Necessitans Caused by CRAB and CRPA

For empyema necessitans caused by both CRAB and CRPA, use combination therapy with polymyxin B (or colistin) plus a second in vitro active agent selected from aminoglycosides, fosfomycin, or high-dose tigecycline, guided by antimicrobial susceptibility testing, along with aggressive surgical drainage. 1, 2, 3

Treatment Strategy for Dual CRAB/CRPA Infection

Immediate Actions

• Obtain antimicrobial susceptibility testing urgently to identify which agents remain active against both organisms 2
• Consult infectious disease specialists immediately given the complexity of dual carbapenem-resistant pathogens 2
• Ensure aggressive source control with surgical drainage or decortication, as antibiotics alone are rarely successful in empyema 4, 5

Antibiotic Selection Framework

For CRAB Component:

• First-line if sulbactam-susceptible: Ampicillin-sulbactam for the CRAB component 1
• If sulbactam-resistant: Use polymyxin B or high-dose tigecycline if active in vitro 1, 3
• Avoid cefiderocol for CRAB treatment (conditional recommendation against use) 1
• Do NOT use polymyxin-meropenem or polymyxin-rifampin combinations for CRAB (strong recommendation against) 1, 3

For CRPA Component:

• Preferred agent if susceptible: Ceftolozane-tazobactam is the first choice for severe difficult-to-treat CRPA 1, 2
• If ceftolozane-tazobactam unavailable or resistant: Consider imipenem-relebactam, cefiderocol, or ceftazidime-avibactam based on susceptibility 1, 2
• For polymyxin-based therapy: Combine polymyxin with a second in vitro active agent (aminoglycoside, fosfomycin, or carbapenem if MIC ≤8 mg/L) 1, 2, 3

Recommended Combination Approach

Given dual infection, the practical regimen should cover both organisms:

1. If CRAB is sulbactam-susceptible and CRPA is ceftolozane-tazobactam-susceptible: Use ampicillin-sulbactam PLUS ceftolozane-tazobactam 1, 2

2. If both organisms are resistant to preferred agents: Use polymyxin B (with loading dose for critically ill patients) PLUS two additional agents active against at least one organism each (e.g., aminoglycoside + high-dose tigecycline or fosfomycin) 1, 2, 3

3. Avoid tigecycline for bloodstream component of infection due to inadequate serum concentrations 2

Critical Management Principles

• Use therapeutic drug monitoring when available, particularly for polymyxins and aminoglycosides 2, 3
• Employ high-dose extended-infusion dosing for carbapenems if used (when MIC ≤8 mg/L) 3
• Prioritize surgical intervention early - empyema necessitans requires drainage, debridement, or decortication; delayed surgery worsens outcomes 4, 5, 6
• Plan for prolonged antibiotic therapy following surgical source control 7, 5

Common Pitfalls to Avoid

• Never use polymyxin monotherapy for severe CRPA infections - associated with higher treatment failure 2
• Do not delay surgical intervention waiting for antibiotics alone to work in empyema necessitans 4, 5
• Avoid carbapenem-polymyxin combinations for CRPA unless meropenem MIC is ≤8 mg/L with high-dose extended infusion 1
• Do not rely solely on culture results - they often underrepresent the full disease process in empyema 4

Nuances in Evidence

The ESCMID guidelines acknowledge very low certainty of evidence for combination therapy recommendations in CRPA, but suggest it over monotherapy for severe infections 1, 2. For CRAB, evidence quality is similarly limited, with no clear preferred agent when sulbactam resistance exists 1. The combination of both organisms in empyema necessitans represents an extreme clinical scenario requiring aggressive multimodal therapy despite limited direct evidence for this specific dual-pathogen presentation 6.