Effectiveness of conventional antimicrobial agents against carbapenem resistant non-carbapenem β-lactams susceptible Pseudomonas aeruginosa infection in critically ill patients: a multicentre retrospective study

BACKGROUND: Carbapenem resistant non-carbapenem β-lactam susceptible (CRBS) Pseudomonas aeruginosa (PA) is a unique phenotype of carbapenem-resistant Pseudomonas aeruginosa (CRPA). While guidelines suggest using conventional β-lactams, clinical evidence supporting their effectiveness in critically ill patients remains limited. This study evaluated the associations of conventional antimicrobial agents with clinical outcomes in CRBS PA infections in the intensive care unit (ICU). METHODS: This multicentre retrospective cohort study included 178 patients with CRPA-associated pneumonia or bloodstream infections, comprising 119 patients with CRBS PA and 59 patients with carbapenem-resistant non-carbapenem β-lactam resistant (CRBR) PA. Patient outcomes were compared between phenotypes. The primary endpoint was to evaluate the associations between specific antimicrobial agents and clinical outcomes in CRBS PA infections, using multivariable stepwise logistic regression analyses for in-hospital mortality, day-28 mortality, day-28 clinical failure, and day-28 microbiological eradication. RESULTS: The CRBS PA group demonstrated significantly lower clinical failure rates compared to the CRBR PA group (45.4% vs. 62.7%, p = 0.034), suggesting potential clinical relevance of this phenotype. In the multivariable analysis of CRBS PA infections, treatment with piperacillin-tazobactam (OR: 0.52, p = 0.03) and ceftazidime (OR: 0.27, p = 0.01) was independently associated with lower in-hospital mortality. Levofloxacin was also associated with lower in-hospital mortality (OR: 0.40, p = 0.01), lower day-28 clinical failure, and higher day-28 microbiological eradication rates (OR: 4.87, p = 0.02), although this finding should be interpreted separately from the β-lactam-based CRBS phenotype. CONCLUSIONS: This study suggests that piperacillin-tazobactam, ceftazidime, and levofloxacin may be reasonable definitive treatment options for critically ill patients with CRBS PA infections. These findings support the consideration of carbapenem-sparing approaches in this specific CRPA phenotype, in line with current therapeutic guidance.