Ann Intensive Care. 2025 Dec 1;15(1):190. Revista: 10.1186/s13613-025-01605-1.
BACKGROUND: While antibiotic exposure is a known key risk factor for acquiring Carbapenem-resistant Gram-negative bacteria (CR-GNB) in the ICU, the independent contributions and relative importance of its core dimensions-spectrum, dose, and duration-remain poorly understood. This study aimed to clarify these specific relationships to inform the optimization of antibiotic stewardship strategies.
METHODS: We prospectively enrolled consecutive adult patients admitted to 4 ICUs at a university hospital between March 2024 and January 2025. Patients were screened for CR-GNB upon admission and weekly. Antibiotic exposure was quantified by spectrum (Antibiotic Spectrum Index per antibiotic day [ASI]), dose (Defined Daily Doses [DDDs]), and duration (Length of Therapy [LOT]). The primary outcome was ICU-acquired CR-GNB. We used interval-censored Cox regression to assess associations. Restricted cubic splines were used to explore potential non-linear relationships, and relative importance analysis was performed to compare the impact of the exposure metrics.
RESULTS: Overall, 151 of 422 patients (35.8%) acquired CR-GNB during their ICU stay, with a median follow-up of 12.0 days (interquartile range, 8.0-17.0). ASI per antibiotic day was independently associated with an increased risk of ICU-acquired CR-GNB (adjusted Hazard Ratio [aHR] per 1-unit increase, 1.14; 95% Confidence Interval [CI] 1.09-1.19; P < 0.001), exhibiting a non-linear J-shaped relationship (P for nonlinearity = 0.027). In contrast, after full adjustment, DDDs were not significantly associated with CR-GNB acquisition (aHR per 1-unit increase, 0.89; 95% CI 0.69-1.15; P = 0.374), despite displaying a non-linear inverted U-shaped relationship (P for nonlinearity < 0.001). Similarly, LOT showed no significant independent association in the fully adjusted model (aHR per 1-day increase, 1.03; 95% CI 0.97-1.11; P = 0.214), although a non-linear trend suggested increasing risk with longer durations (P for nonlinearity < 0.001). Relative importance analysis identified ASI per antibiotic day as the most critical factor (P 0.05).
CONCLUSIONS: This study identifies ASI per antibiotic day as the principal independent risk factor for ICU-acquired CR-GNB, significantly outweighing the adjusted impact of DDDs or LOT. Therefore, prioritizing antibiotic spectrum optimization is crucial for stewardship strategies targeting CR-GNB prevention in the ICU.
TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier ChiCTR2400081352. Registered 28 February 2024.
PubMed:41320739 | PMC:PMC12665641 | Revista:10.1186/s13613-025-01605-1