Importance Universal decolonization and enhanced cleaning are strategies to prevent multidrug-resistant organism (MDRO) transmission. Whether their associations with MDRO burden are overlapping, additive, or synergistic remains unknown. Objective To evaluate independent and combined associations of decolonization and enhanced cleaning with MDRO carriage and environmental contamination. Design, Setting, and Participants This quality improvement study was conducted in 2 Southern California nursing homes from March 2019 to April 2021. This 4-phase study implemented (1) universal decolonization only, (2) routine care (control), (3) enhanced cleaning only, and (4) universal decolonization plus enhanced cleaning sequentially and compared them to determine their associations with MDRO body-site carriage and environmental contamination. Analyses were performed from 2024 to 2025. Interventions Universal decolonization involved chlorhexidine bathing and nasal iodophor for all residents. Enhanced daily cleaning included staff education and ultraviolet-marker feedback. Main Outcomes and Measures The main outcomes were serial point-prevalence assessments (n = 6 per phase) of MDRO carriage (nares, skin), as well as MDRO contamination of high-touch objects in bedrooms and common areas. Differences in the odds of any MDRO and MDRO-specific carriage and contamination during each intervention phase compared with the control were assessed using generalized linear mixed models. Results Point-prevalence sampling generated 5856 swabs to evaluate MDRO carriage (n = 3840 swabs) and environmental contamination (n = 2016 swabs). For MDRO carriage, prevalence during the control phase was 50.0% (n = 240 of 480 objects). Decolonization alone was associated with markedly lower carriage compared with either the control (adjusted odds ratio AOR, 0.41 95% CI, 0.27-0.61) or enhanced cleaning (AOR, 0.36 95% CI, 0.24-0.55). Enhanced cleaning alone did not reduce carriage (AOR, 1.14 95% CI, 0.77-1.69) and provided no additional benefit when combined with decolonization compared with decolonization alone (AOR, 1.37 95% CI, 0.88-2.14). For environmental contamination, 62.5% of bedroom objects (n = 225 of 360) and 72.9% of common area objects (n = 105 of 144) were contaminated during the control phase. In bedrooms, decolonization alone was associated with markedly lower contamination compared with either the control (AOR, 0.16 95% CI, 0.08-0.32) or enhanced cleaning (AOR, 0.26 95% CI, 0.12-0.54). Enhanced cleaning alone did not reduce bedroom contamination (AOR, 0.63 95% CI, 0.32-1.24) and provided no additional benefit when combined with decolonization compared with decolonization alone (AOR, 1.35 95% CI, 0.66-2.75). In contrast, MDRO contamination in common areas was significantly reduced by both decolonization (AOR, 0.19 95% CI, 0.08-0.45) and enhanced cleaning (AOR, 0.15 95% CI, 0.07-0.35) compared with the control. The combined intervention was associated with markedly lower common area contamination than either enhanced cleaning (AOR, 0.39 95% CI, 0.16-0.91) or decolonization alone (AOR, 0.30 95% CI, 0.11-0.82). Conclusions and Relevance In this quality improvement study, only decolonization was associated with reduced MDRO carriage and bedroom contamination, and only common area contamination appeared to be further reduced by adding once-daily enhanced cleaning.
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