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.

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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.

Objective: Cohorting patients who are colonized or infected with multidrug-resistant organisms (MDROs) protects uncolonized patients from acquiring MDROs in healthcare settings. The potential for cross transmission within the cohort and the possibility of colonized patients acquiring secondary isolates with additional antibiotic resistance traits is often neglected. We searched for evidence of cross transmission of KPC+ Klebsiella pneumoniae (KPC-Kp) colonization among cohorted patients in a long-term acute-care hospital (LTACH), and we evaluated the impact of secondary acquisitions on resistance potential. Design: Genomic epidemiological investigation. Setting: A high-prevalence LTACH during a bundled intervention that included cohorting KPC-Kp–positive patients. Methods: Whole-genome sequencing (WGS) and location data were analyzed to identify potential cases of cross transmission between cohorted patients. Results: Secondary KPC-Kp isolates from 19 of 28 admission-positive patients were more closely related to another patient’s isolate than to their own admission isolate. Of these 19 cases, 14 showed strong genomic evidence for cross transmission (<10 single nucleotide variants or SNVs), and most of these patients occupied shared cohort floors (12 patients) or rooms (4 patients) at the same time. Of the 14 patients with strong genomic evidence of acquisition, 12 acquired antibiotic resistance genes not found in their primary isolates. Conclusions: Acquisition of secondary KPC-Kp isolates carrying distinct antibiotic resistance genes was detected in nearly half of cohorted patients. These results highlight the importance of healthcare provider adherence to infection prevention protocols within cohort locations, and they indicate the need for future studies to assess whether multiple-strain acquisition increases risk of adverse patient outcomes.

Objective: Cohorting patients who are colonized or infected with multidrug-resistant organisms (MDROs) has been demonstrated to protect uncolonized patients from acquiring MDROs in healthcare settings. A neglected aspect of cohorting is the potential for cross-transmission within the cohort and the possibility of colonized patients acquiring secondary isolates with additional antibiotic resistance traits. We searched for evidence of cross-transmission of KPC+ Klebsiella pneumoniae (KPC-Kp) colonization among cohorted patients in a long-term acute care hospital (LTACH), and evaluated the impact of secondary acquisitions on resistance potential. Design: Genomic epidemiological investigation Setting: A high-prevalence LTACH during a bundled intervention that included cohorting KPC-Kp-positive patients. Methods: Whole-genome sequencing (WGS) and location data were analyzed to identify potential cases of cross-transmission between cohorted patients. Results: Secondary KPC-Kp isolates from 19 of 28 admission-positive patients were more closely related to another patient’s isolate than to their own admission isolate. In 14 of these 19 cases there was strong genomic evidence for cross-transmission (<10 SNVs) and the majority of these patients occupied shared cohort floors (12 cases) or rooms (5 cases) at the same time. Of the 14 patients with strong genomic evidence of acquisition, 12 acquired antibiotic resistance genes not found in their primary isolates. Conclusions: Acquisition of secondary KPC-Kp isolates carrying distinct antibiotic resistance genes was detected in nearly half of cohorted patients. These results highlight the importance of healthcare provider adherence to infection prevention protocols within cohort locations, and motivate future studies to assess whether multiple-strain acquisition increases risk of adverse patient outcomes.

BackgroundClinical culture results are sometimes used to estimate the burden of multidrug-resistant organisms (MDROs) in hospitals. The association between positive clinical culture results and prevalence of MDROs in the gut is incompletely understood.MethodsRectal swab or stool samples were collected daily from adult medical intensive care unit (MICU) patients and cultured for target MDROs using selective media between January 2017 and January 2018 at Rush University Medical Center, a 676-bed tertiary-care center in Chicago. Resistance mechanisms were confirmed by phenotypic methods and/or polymerase chain reaction. Clinical culture results during MICU stay were extracted from the hospital information system. Target MDROs included vancomycin-resistant Enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB). Patients with either a study or clinical culture positive for a target MDRO were analyzed.ResultsWe collected 5,086 study samples from 1,661 unique admissions (1,419 patients) and included here data from 413 unique admissions (397 patients) with completed microbiologic analysis. Median (IQR) patient age was 65 (51–75) years and length of MICU stay was 3 (3–4) days. A total of 156 (37.8%) patients had a target MDRO detected from a study sample at any point; 57 (36.5%) patients had >1 MDRO detected. Overall prevalence of these MDROs was found to be 22.5% VRE, 6.5% CRE, 19.8% ESBL, 4.4% CRPA, and 0.7% CRAB. New MDRO acquisition was observed in 58 (14.6%) patients (figure). Once a target MDRO was detected in a study sample, 82.2% of subsequent study samples were positive for that MDRO. Only 13 (5.8%) patients had a positive clinical culture for any target MDRO during their MICU stay (table).ConclusionClinical cultures capture only the tip of the resistance iceberg and alone are insufficient to guide MDRO-targeted prevention strategies. Universal infection prevention measures are an alternative that may be preferred in settings where overall prevalence of MDROs is moderate or high and patients may be colonized with >1 MDRO. Disclosures All authors: No reported disclosures.