What is the treatment for Pseudomonas aeruginosa bacteremia according to Infectious Diseases Society of America (IDSA) guidelines?

Treatment of Difficult-to-Treat Resistant (DTR) Pseudomonas aeruginosa Bacteremia

For DTR Pseudomonas aeruginosa bacteremia, use ceftolozane/tazobactam or ceftazidime/avibactam as first-line monotherapy, with imipenem/cilastatin-relebactam and cefiderocol as alternatives; reserve combination therapy for patients in septic shock or at high risk of death (mortality risk >25%). 1

Understanding DTR Pseudomonas aeruginosa

DTR-PA is defined as isolates non-susceptible to ALL of the following first-line agents: ceftazidime, cefepime, piperacillin/tazobactam, aztreonam, imipenem, meropenem, levofloxacin, and ciprofloxacin. 1 This definition is more clinically relevant than traditional "carbapenem-resistant" classifications, which may include isolates that simply lost OprD porin but remain susceptible to other beta-lactams. 1

First-Line Treatment Algorithm

For Hemodynamically Stable Patients (Not in Septic Shock, Mortality Risk <15%)

• Initiate monotherapy with novel beta-lactam/beta-lactamase inhibitor combinations as first-line treatment once susceptibilities are known. 1
• Preferred agents (in order):
  • Ceftolozane/tazobactam (if susceptible) 1
  • Ceftazidime/avibactam (if susceptible) 1
  • Imipenem/cilastatin-relebactam (alternative option) 1
  • Cefiderocol (alternative option) 1
• If only susceptible to polymyxins: Use intravenous colistin or polymyxin B as monotherapy. 1

For Critically Ill Patients (Septic Shock or Mortality Risk >25%)

• Use combination therapy with TWO active agents to which the isolate is susceptible until clinical improvement occurs. 1
• Combination strategies:
  • Novel beta-lactam (ceftolozane/tazobactam or ceftazidime/avibactam) PLUS an aminoglycoside (if susceptible) 1
  • Novel beta-lactam PLUS a fluoroquinolone (ciprofloxacin or levofloxacin 750mg) if susceptible 1
  • Consider adding fosfomycin as companion agent on case-by-case basis with infectious disease consultation 1
• Critical caveat: Once septic shock resolves and susceptibilities confirm adequate coverage, de-escalate to monotherapy—continued combination therapy is NOT recommended after stabilization. 1

What NOT to Do

• Never use aminoglycoside monotherapy for Pseudomonas bacteremia—this is strongly contraindicated due to poor outcomes. 1
• Avoid moxifloxacin and standard-dose levofloxacin (500mg) as these lack adequate Pseudomonas coverage. 2
• Do not routinely use combination therapy in stable patients—this increases toxicity risk without mortality benefit once susceptibilities are known. 1

Empirical Therapy Considerations

While awaiting blood culture results and susceptibilities:

• For suspected DTR-PA bacteremia in critically ill patients: Initiate empirical combination therapy with an antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, or meropenem) PLUS either ciprofloxacin/levofloxacin 750mg OR an aminoglycoside. 1
• Rationale: Adequate empirical combination therapy until antibiogram receipt significantly improves 30-day survival compared to monotherapy (adjusted HR 3.7 for monotherapy vs combination). 3
• Once susceptibilities return: Immediately tailor therapy based on the algorithm above—adequate definitive monotherapy is equivalent to combination therapy in stable patients. 3

Key Clinical Pitfalls

• Resistance development during therapy: The major concern with DTR-PA is emergence of resistance even to novel agents during treatment. 4, 5 Obtain repeat blood cultures at 48-72 hours to document clearance and monitor for resistance. 1
• Polymyxin-only susceptibility: When isolates are only susceptible to colistin/polymyxin B, monotherapy with IV polymyxins is recommended for bacteremia (unlike pneumonia where adjunctive inhaled therapy may be considered). 1
• High mortality despite treatment: Even with appropriate therapy, mortality in DTR-PA bacteremia remains substantial, particularly in immunocompromised hosts where combination therapy historically shows better outcomes. 6, 7

Treatment Duration and Monitoring

• Minimum 14 days of therapy for Pseudomonas bacteremia, longer if complicated by endocarditis or metastatic foci. 2
• Obtain susceptibility testing for ALL antipseudomonal agents including newer beta-lactam combinations, as resistance patterns vary significantly. 1
• Infectious disease consultation is strongly recommended for all DTR-PA bacteremia cases given complexity of treatment decisions and need for individualized combination therapy considerations. 1