Background/Objective: Multidrug-resistant (MDR) bacteria pose a significant threat to global health, especially in intensive care units (ICUs), where high antibiotic consumption drives antimicrobial resistance. Selective digestive decontamination (SDD) is a strategy designed to prevent nosocomial infections and colonization by MDR pathogens. This study aimed to evaluate the impact of implementing an SDD protocol on antibiotic consumption and colonization by carbapenemase-producing Enterobacterale (CPE) in a specific ICU setting. Methods: This quasi-experimental study was conducted in the ICU of a university hospital from June 2021 to June 2023. Patients were divided into two groups: pre-intervention (before SDD) and post-intervention (after SDD implementation). Data on antibiotic consumption (expressed as defined daily doses (DDDs) per 100 stays), nosocomial infections, colonization rates, and the incidence of MDR bacteria were collected. A statistical analysis was conducted to compare the pre- and post-intervention groups. Results: A total of 3266 patients were included, with 1532 in the pre-intervention group and 1734 in the post-intervention group. The implementation of the SDD protocol resulted in a significant reduction in total antibiotic consumption (p = 0.028), with notable decreases in carbapenem use (p < 0.01) and colonization by CPE (p = 0.0099). The incidence of nosocomial infections also decreased in the post-SDD group, although this reduction was not statistically significant. Conclusions: The implementation of the SDD protocol in this ICU setting significantly reduced antibiotic consumption and colonization by CPE. These findings suggest that SDD may be a valuable tool in managing antimicrobial resistance in critical care settings, without contributing to the development of MDR bacteria.

Background: Cefiderocol, a novel siderophore cephalosporin, has shown promising activity against multidrug-resistant (MDR) Gram-negative pathogens, including metallo-β-lactamase (MBL) producers. However, emerging reports suggest rapid resistance development under selective pressure, particularly in epidemic Pseudomonas aeruginosa lineages. Case presentation: We describe a 50-year-old man with a history of aortic dissection who developed ventilator-associated pneumonia due to P. aeruginosa ST175 carrying an IMP-type carbapenemase. Initial treatment with ceftazidime/avibactam plus aztreonam was followed by cefiderocol monotherapy. Although the patient showed early improvement, clinical relapse occurred within days, with subsequent isolation of cefiderocol-resistant P. aeruginosa. Whole-genome sequencing revealed high-impact mutations in iron acquisition systems (including fptA and pvdE) and multiple resistance determinants (oprD, efflux pump regulators, ampD/ampR), disrupting siderophore-mediated uptake and favoring multidrug resistance. Despite rescue therapy with ceftazidime/avibactam plus aztreonam and adjunctive agents, the patient ultimately died from septic shock and multiorgan failure. Discussion: This case highlights the ability of high-risk P. aeruginosa clones to rapidly adapt to cefiderocol, driven by combined alterations in iron metabolism and classical resistance pathways. The development of resistance within less than one week of exposure underscores the risk of using cefiderocol as monotherapy in infections caused by epidemic MDR clones. Conclusions: Cefiderocol resistance can emerge rapidly in vivo during treatment of infections caused by P. aeruginosa ST175. Continuous surveillance, molecular characterization of resistance mechanisms, and cautious use of cefiderocol—preferably in combination regimens—are warranted to preserve its clinical utility.