Time-Dependent Association Between Invasive Procedures, Carbapenem Exposure, and Multidrug-Resistant Bloodstream...

Critically ill patients frequently undergo invasive procedures and receive broadspectrum antibiotics, both of which are associated with an increased risk of multidrugresistant organism (MDRO) bloodstream infections (BSI). However, the temporal relationship between these exposures during the early postprocedural period remains incompletely understood. We conducted a retrospective cohort study of 380 adult intensive care unit (ICU) admissions at The First Affiliated Hospital of Jinan University, Guangzhou, China, between 2020 and 2023. Propensity score matching (1:1, n = 248) was performed to balance age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, baseline serum albumin level, and major comorbidities. Timedependent Cox proportional hazards models were used to evaluate the associations of invasive procedures (central venous catheterization or mechanical ventilation), carbapenem exposure, and their overlap with the development of MDRO BSI. Exploratory mediation analyses were conducted to assess the potential contributions of hypoalbuminemia and elevated C-reactive protein (CRP). Early postprocedural time windows were specifically examined. Overlapping exposure to invasive procedures and carbapenems was associated with a significantly higher risk of MDRO BSI compared with either exposure alone (adjusted hazard ratio [HR]: 4.0, 95% confidence interval [CI]: 2.2-7.3). The association was strongest within the first 12 hours after invasive procedures (HR: 5.1, 95% CI: 2.8-9.3) and remained elevated through 48 hours (HR: 3.3, 95% CI: 1.8-6.0). Exploratory mediation analyses suggested that hypoalbuminemia (serum albumin <30 g/L) and elevated CRP (≥50 mg/L) accounted for approximately 32% and 21% of the observed association, respectively. Patients with overlapping exposures also demonstrated lower 28-day infection-free survival than those in other exposure groups. In critically ill patients, carbapenem exposure occurring shortly after invasive procedures was temporally associated with an increased risk of MDRO BSI, particularly during the first 48 hours following the procedure. Host nutritional and inflammatory status may partially contribute to this association. These findings highlight the importance of considering exposure timing and patient vulnerability when evaluating early broad-spectrum antibiotic use in ICU settings.