Treatment of Multi-Drug Resistant Pseudomonas Infections

First-Line Treatment Options

The International Journal of Antimicrobial Agents recommends novel β-lactam agents such as ceftolozane/tazobactam and ceftazidime/avibactam as first-line treatment options for multi-drug resistant Pseudomonas aeruginosa infections, with imipenem/cilastatin/relebactam and colistin-based therapy as alternatives 1, 2
Ceftolozane/tazobactam 1.5-3g IV q8h (use 3g dose for pneumonia) is recommended for difficult-to-treat resistant Pseudomonas aeruginosa 3, 4
Ceftazidime/avibactam 2.5g IV q8h is recommended for difficult-to-treat resistant Pseudomonas aeruginosa 3, 4
Imipenem/cilastatin/relebactam 1.25g IV q6h is recommended for difficult-to-treat resistant Pseudomonas aeruginosa 3, 4

Monotherapy with a highly active agent is generally preferred for severe infections with difficult-to-treat resistant Pseudomonas aeruginosa if susceptibility is confirmed 1, 2
Combination therapy should not be routine but may be considered on a case-by-case basis, especially upon consultation with infectious disease specialists 1, 2
Combination regimens including fosfomycin as a companion agent could be considered for difficult cases 1, 2
For polymyxin-based therapy (colistin), combination with another active agent is suggested for severe infections 5, 6

5-10 days is recommended for complicated urinary tract infections and intra-abdominal infections 3, 4
10-14 days is recommended for hospital-acquired pneumonia, ventilator-associated pneumonia, and bloodstream infections 3, 4
Treatment duration should be individualized based on infection site, source control, underlying comorbidities, and initial response to therapy 3

For CRAB pneumonia, colistin (5 mg CBA/kg IV loading dose, then 2.5 mg CBA per [1.5 CrCl + 30] IV q12h) with or without carbapenems, plus adjunctive inhaled colistin is recommended 6
For DTR-PA pneumonia, ceftolozane/tazobactam 3g (2g ceftolozane/1g tazobactam) IV q8h is recommended 4
For DTR-PA bloodstream infections, novel β-lactams (ceftolozane/tazobactam or ceftazidime/avibactam) are preferred 1, 2
For CRAB bloodstream infections, colistin-carbapenem combination therapy is recommended 6

Cefiderocol shows promising activity against MDR/XDR P. aeruginosa in early studies 1, 2

Aminoglycoside monotherapy should only be used for urinary tract infections 3, 4
Tigecycline monotherapy is not recommended for the treatment of Pseudomonas pneumonia 6
Infectious disease consultation is highly recommended for management of MDR Pseudomonas infections 6
Prolonged infusion of β-lactams is recommended for pathogens with high minimum inhibitory concentrations (MICs) 6

Prior antimicrobial therapy, especially within the previous 90 days, is a risk factor for MDR Pseudomonas infections 7
Hospital stay of more than 5 days is a risk factor for MDR Pseudomonas infections 7
Renal replacement therapy is a risk factor for MDR Pseudomonas infections 7
Septic shock or ARDS is a risk factor for MDR Pseudomonas infections 7