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In adult LTACH patients, carbapenem receipt was associated with increased hazard for high relative abundance of KPC-Kp in the gut microbiota. Increased relative abundance of KPC-Kp was associated with KPC-Kp bacteremia. Whether bacteremia arose directly from bacterial translocation or indirectly from skin contamination followed by bloodstream invasion remains to be determined.

BackgroundvSNF patients are at high risk of colonization and infection with C. auris. CHG bathing has been used as an intervention to reduce nosocomial transmission of multi-drug-resistant organisms, but its effect on C. auris is unclear.MethodsWe studied a 70-bed ventilator ward in a 300-bed vSNF in Chicago, IL with a high prevalence of C. auris and established CHG bathing. Swab samples were collected from patients for culture, microbiome analysis, and CHG skin concentration testing (Table 1).ResultsWe collected 2,467 samples (950 culture, 950 microbiome, 567 CHG) from 57 patients during 2 surveys conducted January–March 2019. Forty-six (81%) patients had C. auris cultured from ≥1 body site. Mean (±SD) age was 59 (±14) years, 40% were women, 70% were African American, mean (±SD) Charlson score was 3 (±2). Patients colonized with C. auris were more likely to be mechanically ventilated (50% vs. 0%, P < 0.001), have a gastrostomy tube (78% vs. 27%, P < 0.001) or have urinary catheter (72% vs. 23%, P = 0.01) than noncolonized patients. Frequency of C. auris isolation varied among 10 body sites tested (P < 0.001); colonization of anterior nares (41%) and hands (40%) was detected most often (Figure 1). By ITS1 analysis, all isolates were members of the C. auris South American clade. Skin microbiome sequencing confirmed culture Results. While Malassezia is the dominant genera observed in healthy volunteers and patients in this vSNF, C. auris was observed to dominate the fungal community of multiple skin sites, including nares, hands, inguinal, toe web (Figure 2). Other Candida spp. were also identified on the skin of patients in the current study, but at lower relative abundance. CHG was detected on skin of 52 (91%) patients (median CHG concentration 19.5 µg/mL; IQR 4.9–78.1 µg/mL). In a mixed-effects model controlling for body site and multiple measurements per patient, odds of C. auris detection by culture were less at CHG concentrations ≥625 µg/mL than at lower concentrations (Figure 3; OR 0.25, 95% CI: 0.10–0.66; P = 0.005).ConclusionFrequent C. auris colonization of vSNF patients’ anterior nares and hands suggests that nasal decolonization and patient hand hygiene are potential options to reduce C. auris transmission. High concentrations of CHG may be needed to suppress C. auris on skin. Disclosures All Authors: No reported Disclosures.

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Background Carbapenem-resistant Enterobacteriaceae have been recognized as an urgent antibiotic resistance threat for more than a decade. Despite this attention, their prevalence has remained steady or increased in some settings, suggesting that transmission pathways remain uncontrolled by current prevention strategies. We hypothesized that these transmission pathways, and hence targets for improved prevention, could be elucidated through comprehensive patient sampling, followed by integration of whole-genome sequencing (WGS) and epidemiological data. Methods Longitudinal KPC+ Klebsiella pneumoniae (KPC-Kp) surveillance cultures were collected from 94% of patients in a long-term acute care hospital (LTACH) during a one-year bundled intervention to reduce KPC-Kp prevalence. WGS of 462 KPC-Kp isolates from 256 patients, and associated surveillance data were integrated using a distance threshold-free approach to identify transmission clusters that grouped patients acquiring KPC-Kp in the LTACH with the admission-positive "index" patients that imported their strain into the facility. Plausible transmission pathways within clusters were identified using patient location data. Findings Transmission clusters (N=49) had between 2-14 patients, capturing KPC-Kp acquisitions from 100 (80%) patients who first acquired KPC-Kp in the LTACH. Within-cluster genetic diversity varied from 0-154 (median 9) single-nucleotide variants (SNVs), with elevated diversity being driven by prolonged asymptomatic colonization and evolution of hypermutator strains. Transmission between patients in clusters could be explained by spatiotemporal overlap in patient rooms (14%), wards (66%), or facility (81%). Sequential exposure to the same patient room was the only epidemiological link for one patient, indicating that residual environmental contamination of rooms after patient discharge contributed little to transmission. Persistent, modifiable routes of transmission were associated with lapses in patient cohorting, transmission between cohort and non-cohort locations and clusters propagating due to false-negative surveillance. Interpretation Integration of comprehensive surveillance and WGS data using a SNV threshold-free approach disclosed specific instances where improved patient and healthcare worker cohorting, reducing exposures to common locations outside of patient rooms, and improved KPC-Kp colonization detection could reduce transmission. Overall, results highlight the potential for WGS to monitor and improve infection prevention and the importance of combining rigorous sampling with appropriate analytical strategies to generate actionable hypotheses.