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An isolation-targeted screening is non-inferior to universal screening-isolation.This strategy provides similar rates of acquired MDRO colonization or infection.It could be appropriate in some ICU and allow consumption of fewer resources.A hospital stay of more than 5 days is associated with MDRO carriage on admission.The choice of risk factors may influence the suitability of such a strategy.Although additional contact precautions (ACPs) are routinely used to reduce cross-transmission of multidrug-resistant organisms (MDROs), the relevance of isolation precautions remains debated. We hypothesized that the collection of recognized risk factors for MDRO carriage on intensive care unit (ICU) admission might be helpful to target ACPs without increasing MDRO acquisition during ICU stays, compared with universal ACPs.This is a sequential single-center observational study performed in consecutive patients admitted to a French medical and surgical ICU. During the first 6-month period, screening for MDRO carriage and ACPs were performed in all patients. During the second 6-month period, screening was maintained, but ACP use was guided by the presence of at least 1 defined risk factor for MDRO.During both periods, 33 (10%) and 30 (10%) among 327 and 297 admissions were, respectively, associated with a positive admission MDRO carriage. During both periods, a second screening was performed in 147 (45%) and 127 (43%) patients. Altogether, the rate of acquired MDRO (positive screening or clinical specimen) was similar during both periods (10% [n = 15] and 11.8% [n = 15], respectively; P = .66).The results of our study contribute to support the safety of an isolation-targeted screening policy on ICU admission compared with universal screening and isolation regarding the rate of ICU-acquired MDRO colonization or infection.