Hierarchical multilevel prospective study of multidrug-resistant organisms: Decolonization, mortality, and...

Prior long-term-care (LTC) studies confound anatomic reservoir and pathogen effects when multiple multidrug-resistant organisms (MDROs) circulate. We created a four-tier clearance framework to disentangle site- and species-specific behavior and quantify decolonization, mortality, and asymmetric co-colonization.

Between January 2024 and May 2025, 98 LTC residents colonized with carbapenem-resistant Enterobacterales (CRE), vancomycin-resistant Enterococcus (VRE), or multidrug-resistant Pseudomonas aeruginosa (MRPA) or Acinetobacter baumannii (MRAB) underwent weekly stool, urine, sputum, wound, blood cultures, yielding a total of 2772 specimens. Clearance- operationally defined as three consecutive negatives-was analyzed across four tiers (site-atomic, pathogen-atomic, pathogen-level, patient-level). Conditional-probability tables were constructed to summarize how frequently the four MDROs co-colonized the same patient.

Clearance was slowest in stool and for CRE, independent of patient attributes of age or sex. In this LTCF cohort, mortality depended on sputum carriage and host factors rather than pathogen identity. More than half of residents carried multiple MDROs, and conditional-probability analysis revealed asymmetric co-colonization: non-CRE organisms almost always co-colonized with CRE, whereas the reverse was uncommon.

The hierarchical analysis showed that, contrary to common expectations, decolonization was independent of patient attributes (age and sex) and that, in this LTCF setting, mortality was unrelated to pathogen identity. Asymmetric co-colonization therefore warrants automatic CRE screening following MRAB, MRPA, or VRE isolation, and underscores the need to investigate directional co-colonization patterns among multiple MDRO co-colonizations commonly observed in LTCFs-as exemplified by vanA transfer from VRE to MRSA (methicillin-resistant Staphylococcus aureus) yielding VRSA (vancomycin-resistant Staphylococcus aureus).