What is the treatment for multidrug-resistant organism (MDRO) infections after below-knee amputation (BKA)?

Treatment of MDRO Infections Post Below-Knee Amputation

Obtain infectious disease consultation immediately and initiate broad-spectrum empirical antibiotics targeting the most likely MDRO pathogens based on local resistance patterns and patient risk factors, then narrow therapy based on culture results and susceptibility testing. 1

Initial Management Approach

Immediate Actions

• Consult infectious disease specialists as this is a strong recommendation for all MDRO infections due to limited treatment options, need for pharmacokinetic/pharmacodynamic optimization, and complex disease evaluation 1, 2

• Obtain cultures before initiating antibiotics from wound/tissue specimens to guide definitive therapy 1

• Perform antimicrobial susceptibility testing or genotypic characterization to guide antibiotic selection 1

Empirical Antibiotic Selection

The choice of empirical therapy depends critically on whether this is a healthcare-associated infection (which it likely is post-operatively) and local MDRO prevalence 1, 2:

For Healthcare-Associated MDRO Infections (Post-Surgical Setting)

Recommended empirical regimens for critically ill patients:

• Meropenem 1 g IV q8h (covers CRE, CRPA, and most Gram-negatives) 1
  • Alternative: Doripenem 500 mg IV q8h or Imipenem/Cilastatin 1 g IV q8h 1

PLUS

• Vancomycin 25-30 mg/kg loading dose, then 15-20 mg/kg q8h (covers MRSA and ampicillin-susceptible enterococci) 1
  • Alternative: Teicoplanin 12 mg/kg q12h × 3 doses, then 12 mg/kg q24h 1

Consider adding for VRE risk (if patient has prior enterococcal colonization, immunocompromised, prolonged ICU stay, or recent vancomycin exposure):

• Linezolid 600 mg IV q12h or Daptomycin 6 mg/kg IV q24h 1

Carbapenem-Sparing Alternative

If carbapenem stewardship is a priority:

• Ceftolozane/Tazobactam 1.5 g IV q8h + Metronidazole 500 mg IV q6h 1
  • OR Ceftazidime/Avibactam 2.5 g IV q8h + Metronidazole 500 mg IV q6h 1
• PLUS Vancomycin (as above) 1

Targeted Therapy Based on Culture Results

For Carbapenem-Resistant Enterobacterales (CRE)

• Ceftazidime-avibactam 2.5 g IV q8h infused over 3 hours (first-line for CRE bloodstream/tissue infections) 1
• Alternative: Meropenem-vaborbactam 4 g IV q8h or Imipenem-cilastatin-relebactam 1.25 g IV q6h 1
• Polymyxin-based combination therapy if above agents unavailable or resistant 1

For Carbapenem-Resistant Acinetobacter baumannii (CRAB)

• Colistin-carbapenem combination therapy (colistin dosing based on colistin base activity) 1
• Combination therapy is preferred over monotherapy for bloodstream/tissue infections 1

For Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)

• Ceftolozane/Tazobactam or Ceftazidime/Avibactam based on susceptibility 1, 2
• For NDM-producing Pseudomonas: Ceftazidime/avibactam plus aztreonam as first-line, or Cefiderocol as alternative 2

For MRSA

• Vancomycin (target trough 15-20 mcg/mL for serious infections) or Daptomycin 6-8 mg/kg IV q24h for soft tissue/bone infections 1

For VRE

• Linezolid 600 mg IV q12h or Daptomycin 6 mg/kg IV q24h (higher doses may be needed for complicated infections) 1

Critical Pharmacokinetic Considerations

• Use prolonged infusions of beta-lactams (infuse over 3-4 hours) for pathogens with high MICs to optimize time above MIC 1
• This is particularly important in critically ill patients with altered pharmacokinetics 1

Key Risk Factors That Guided This Approach

Post-BKA patients are at high risk for MDROs due to:

• Recent surgery and hospitalization (healthcare-associated infection) 2, 3
• Likely prior antibiotic exposure perioperatively (strongest risk factor for MDROs, OR 5.1) 3
• Possible prior intubation if critically ill (OR 31 for MDROs) 4
• Antibiotic use >5 days before complications significantly increases MDRO risk 2

Common Pitfalls to Avoid

• Do not use tigecycline monotherapy for serious infections—it has poor tissue penetration and is associated with increased mortality 1
• Avoid aminoglycosides as monotherapy for anything beyond simple cystitis due to poor tissue penetration 1
• Do not delay infectious disease consultation—inappropriate initial antibiotic therapy is independently associated with increased mortality (OR 7.1) 4
• Inadequate empirical coverage in MDRO infections leads to 88% inappropriate treatment rates versus 5% in non-MDRO infections 4

Duration and De-escalation

• Narrow antibiotics within 48-72 hours based on culture results and clinical response 5
• Treatment duration depends on infection source control, clinical response, and specific pathogen (typically 7-14 days for soft tissue infections with adequate source control) 1
• Ensure adequate source control (debridement, drainage) as antibiotics alone are insufficient 1