What is the recommended treatment for Carbapenem-Resistant Organism (CRO) Pseudomonas bacteremia?

Treatment for Carbapenem-Resistant Organism (CRO) Pseudomonas Bacteremia

For carbapenem-resistant Pseudomonas aeruginosa (CRPA) bacteremia, ceftolozane-tazobactam is recommended as first-line therapy if the organism is susceptible in vitro, with combination therapy using two active agents recommended for severe infections when using older antimicrobials such as polymyxins or aminoglycosides. 1

General Management Principles

• Infectious disease consultation is strongly recommended for management of infections caused by multidrug-resistant organisms (MDRO) 1
• Antimicrobial susceptibility testing is essential to guide appropriate antibiotic selection for CRPA infections 1
• Prolonged infusion of β-lactams is recommended for pathogens with high minimum inhibitory concentrations (MICs) 1

First-Line Treatment Options

• Ceftolozane-tazobactam is suggested as the preferred therapy for difficult-to-treat CRPA infections if active in vitro 1
• Newer agents such as imipenem-relebactam, cefiderocol, and ceftazidime-avibactam may be considered, though evidence for their use specifically in CRPA bacteremia is limited 1
• Ceftazidime-avibactam has shown efficacy in treating Gram-negative bacteremia in clinical trials, with clinical cure rates of 87% across multiple infection types 2

Combination Therapy Considerations

• For severe CRPA infections treated with older agents (polymyxins, aminoglycosides, or fosfomycin), combination therapy with two in vitro active drugs is recommended 1
• No specific combination regimen has demonstrated superiority over others; selection should be based on susceptibility testing 1
• For less severe infections, monotherapy with an agent active in vitro may be appropriate 1

Special Considerations for Polymyxin-Based Therapy

• When polymyxins (colistin) are used for CRPA bacteremia, combination therapy is preferred over monotherapy 1
• Colistin dosing for patients with normal renal function typically includes a loading dose of 300 mg colistimethate sodium (9 MU) followed by maintenance doses of 300-360 mg (9-10.9 MU) divided into two daily doses 1
• Polymyxin-based therapy carries significant risk of nephrotoxicity compared to newer agents 3, 4

Emerging Evidence for Newer Agents

• Ceftazidime-avibactam has demonstrated efficacy in carbapenem-resistant Enterobacterales (CRE) bacteremia with lower 30-day mortality compared to colistin-based regimens (RR = 0.48,95% CI 0.33-0.69) 3
• In patients with KPC-producing Klebsiella pneumoniae bacteremia, ceftazidime-avibactam salvage therapy was associated with significantly lower 30-day mortality compared to other treatments (36.5% vs 55.8%) 5
• Ceftazidime-avibactam is dosed at 2.5g IV q8h (infused over 3 hours) for treatment of resistant gram-negative infections 6

Practical Approach to Management

1. Obtain appropriate cultures and antimicrobial susceptibility testing before initiating therapy 1
2. Consult infectious disease specialists early in the management 1
3. For severe CRPA bacteremia:
   • Use ceftolozane-tazobactam if susceptible 1
   • If ceftolozane-tazobactam is not available or the organism is resistant, consider other newer agents (ceftazidime-avibactam, imipenem-relebactam, cefiderocol) based on susceptibility 1
   • If only older agents are active, use combination therapy with two active drugs 1
4. For non-severe CRPA bacteremia:
   • Consider monotherapy with the most appropriate in vitro active agent 1
   • Select therapy based on patient-specific factors, source of infection, and antibiotic stewardship principles 1, 7

Common Pitfalls and Caveats

• Tigecycline should not be used for bloodstream infections due to inadequate serum concentrations 1
• Monotherapy with polymyxins or aminoglycosides for severe CRPA bacteremia is associated with higher treatment failure rates 1
• Dose adjustment is required for many antimicrobials in patients with renal impairment, including those on continuous renal replacement therapy 8
• Development of resistance during therapy is a concern, particularly with ceftazidime-avibactam monotherapy in KPC-producing organisms 3, 5