Treating Difficult-to-Treat Resistant Pseudomonas aeruginosa

In "Treating Difficult-to-Treat Resistant Pseudomonas aeruginosa," the panel explains why Pseudomonas requires a different playbook than the Enterobacterales. Difficult-to-treat resistant Pseudomonas aeruginosa demands a different mindset than carbapenemase-producing Enterobacterales, because its resistance arises from several overlapping mechanisms rather than a single enzyme.

Dr. Shields defines difficult-to-treat resistance (DTR) as nonsusceptibility to all traditional beta-lactams and fluoroquinolones, and outlines the three preferred agents in the guidance, namely ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam where available. He explains that comparative studies have not shown a mortality difference between the first two agents but suggest fewer recurrent infections with ceftolozane-tazobactam in pneumonia. Dr. Shields attributes this to better lung penetration and to the fact that ceftolozane does not depend on an inhibitor for antipseudomonal activity, which is why the guidance favors it for DTR pneumonia.

Dr. Shields positions cefiderocol as an alternative, with a specific niche in rare carbapenemase-producing Pseudomonas, particularly isolates carrying Verona integron-encoded metallo-beta-lactamase (VIM). He encourages carbapenemase testing when isolates resist the newer agents or when patients have relevant travel histories. Dr. Pogue cautions that aztreonam-avibactam offers no advantage against metallo-beta-lactamase-producing Pseudomonas, because efflux and other non-enzymatic mechanisms are common.

Dr. Tamma emphasizes testing all preferred agents, since activity cannot be predicted reliably. Dr. Shields adds that cross-resistance between ceftolozane-tazobactam and ceftazidime-avibactam is common, so prior exposure to one does not guarantee activity of the other, and that the withdrawal of imipenem-relebactam narrows the options. Dr. Haidar reflects that empiric selection for DTR Pseudomonas still requires clinical intuition and unit-level epidemiology. Clinicians should test every relevant agent against each isolate, consider carbapenemase testing when results are unexpected, and favor ceftolozane-tazobactam for DTR Pseudomonas pneumonia.

Dr. Haidar turns to one of the most feared pathogens in critical care in "Sulbactam-Durlobactam for Carbapenem-Resistant Acinetobacter."