Antipseudomonal cephalosporins versus piperacillin/tazobactam or carbapenems for the definitive antibiotic treatment of Pseudomonas aeruginosa bacteraemia: new kids on the ICU block?

Background: Pseudomonas aeruginosa bloodstream infections (Pa-BSIs) are still a major cause of mortality in ICUs, posing many treatment uncertainties.

Methods: This multicentre, retrospective study analysed data from 14 Italian hospitals, including all consecutive adults developing Pa-BSI in ICU during 2021-22 and treated with antibiotics for at least 48 h. The primary aim was to identify predictors of 30 day mortality using Cox regression. Results were adjusted with inverse probability of treatment weighting (IPTW) and for immortal time bias.

Results: Overall, 170 patients were included. High-risk BSI (source: lung, intra-abdominal, CNS) occurred in 118 (69%) patients, and 54 (32%) had septic shock. In 37 (22%), 73 (43%), 12 (7%) and 48 (28%) the definitive backbone therapy was piperacillin/tazobactam, carbapenems, colistin or new antipseudomonal cephalosporins (ceftolozane/tazobactam, n = 20; ceftazidime/avibactam, n = 22; cefiderocol, n = 6), respectively. Moreover, 58 (34%) received a second drug as combination therapy. The incidence of 30 day all-cause mortality was 27.6% (47 patients). By Cox regression, Charlson comorbidity index, neutropenia, septic shock and high-risk BSI were independent predictors of 30 day mortality, while previous colonization by P. aeruginosa, use of antipseudomonal cephalosporins as definitive treatment, and combination therapy were shown to be protective. However, after IPTW adjustment, only the protective effect of antipseudomonal cephalosporins was confirmed (adjusted HR = 0.27, 95% CI = 0.10-0.69), but not for combination therapy. Hence, the treatment effect was calculated: antipseudomonal cephalosporins significantly reduced mortality risk [-17% (95% CI = -4% to -30%)], while combination therapy was beneficial only in the case of septic shock [-66% (95% CI = -44% to -88%].

Conclusions: In ICU, antipseudomonal cephalosporins may be the preferred target therapy for the treatment of Pa-BSI; in addition, initial combination therapy may be protective in the case of septic shock.