Recent Healthcare Exposure Research Articles

Non-HACEK gram-negative bacilli infective endocarditis: data from a retrospective German cohort study

Abstract Purpose Infective endocarditis caused by non-HACEK gram-negative bacilli (GNB-IE) is rare but associated with significant morbidity and case fatality. Evidence on optimal treatment and management is limited. We aimed to describe the characteristics and management of GNB-IE patients, investigating factors associated with disease acquisition and unfavorable outcomes. Methods We conducted a retrospective descriptive single-center study (tertiary care and referral hospital) between 2015 and 2021, including adult patients with definite GNB-IE. We reviewed demographic, clinical and microbiological data, focusing on predisposing factors, clinical outcomes and 1-year mortality. Results Of 1093 patients with probable or definite IE, 19 patients (median age 69 years) had definite GNB-IE, with an increasing incidence throughout the study period. Median age-adjusted Charlson Comorbidity Index score was 4 points. Prosthetic valve IE (PVIE) was present in 7/19 (37%) patients. Nosocomial acquisition occurred in 8/19 (42%) patients. Escherichia coli and Klebsiella pneumoniae were the most common pathogens. Beta-lactam (BL) based combination therapy was applied in 12/19 (63%) patients (58% BL + fluoroquinolone, 42% BL + aminoglycoside). Cardiac surgery was required in 8/19 (42%) patients (PVIE 71%, native valve IE 25%), primarily for embolism prevention and heart failure. Complications occurred in 14/19 (74%) patients. The in-hospital mortality rate was 21% (4/19); the one-year mortality rate was 44% (7/16). One-year mortality did not significantly differ between patients who underwent cardiac surgery and patients managed with anti-infective treatment alone (p = 0.633). Conclusions GNB-IE affects elderly patients with high comorbidity levels and recent health-care exposure. GNB-IE was associated with high complication rates and high mortality.

Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa community acquired pneumonia: Prevalence and locally derived risk factors in a single hospital system.

Current American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) community-acquired pneumonia (CAP) guidelines expand the CAP definition to include infections occurring in patients with recent health care exposure. The guidelines now recommend that hospital systems determine their own local prevalence and predictors of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) among patients satisfying this new broader CAP definition. We sought to carry out these recommendations in our system, focusing on the emergency department, where CAP diagnosis and initial empiric antibiotic selection usually ooccur. We performed a retrospective cohort study of patients admitted with CAP through any of 3 EDs in our hospital system in Northern California between November 2019 and October 2021. Inclusion criteria included an ED admission diagnosis of pneumonia or sepsis, fever or hypothermia, leukocytosis or leukopenia, and consistent chest imaging result. SARS-CoV-2-positive cases were excluded. We abstracted variables historically associated with P. aeruginosa and MRSA. Outcome measures were prevalence of P. aeruginosa and MRSA in the overall clinically defined cohort and among microbiologically confirmed cases and predictors of P. aeruginosa or MRSA isolation, as determined by univariate logistic regression, bootstrapped least absolute shrinkage and selection operator, and random forest analyses. Additionally, we describe the iterative process used and challenges encountered in carrying out the new ATS/IDSA guideline recommendations. There were 1133 unique patients who satisfied our definition of clinically defined CAP, of whom 109 (9.6%) had a bacterial pathogen isolated. There were 24 P. aeruginosa isolates and 11 MRSA isolates in 33 patients. Thus, the prevalence P. aeruginosa and MRSA was 2.9% in the overall CAP cohort, but 30.3% in the microbiologically confirmed cohort. The most important predictors of either P. aeruginosa or MRSA isolation were tracheostomy (odds ratio [OR] 22.08; 95% confidence interval [CI] 10.39-46.96) and gastrostomy tube (OR 14.7; 95% CI 7.14-30.26). Challenges included determining the suspected infection type in patients admitted simply for "sepsis"; interpreting dictated radiology reports; determining functional status, presence of indwelling lines and tubes, and long-term care facility residence from the electronic health record; and correctly attributing culture results to pneumonia. Prevalence of MRSA and P. aeruginosa was low among patients admitted in our medical system with CAP - now broadly defined - but high among those with a microbiologically confirmed bacterial etiology. Our locally derived predictors of MRSA and P. aeruginosa can be used to aid our emergency physicians in empiric antibiotic selection for CAP. Findings from this project might inform efforts at other institutions.

Real-time whole-genome sequencing surveillance for outbreak detection and intervention

Background: Detecting healthcare-associated transmission and outbreaks often relies on reactive whole-genome sequencing (WGS), which occurs after the suspected transmission has occurred. Additionally, reactive WGS frequently misidentifies transmission and misses transmission when it has occurred. We initiated weekly real-time WGS to detect bacterial transmission and direct infection prevention interventions. We describe our experience after 1 year of real-time WGS surveillance at the University of Pittsburgh Medical Center–Presbyterian Hospital, a large, tertiary-care facility. Methods: Weekly WGS surveillance was performed from November 1, 2021, to October 31, 2022. Cultured isolates of select bacterial pathogens from patients who were hospitalized for ≥3 days or had a recent healthcare exposure in the prior 30 days were collected and sequenced. Isolates that were ≤15 single-nucleotide polymorphisms (SNPs) were considered genetically related clusters except for Clostridioides difficile (≤2 SNPs). Genetically related clusters were investigated for epidemiological links and interventions to interrupt transmission were implemented at the discretion of the infection prevention team. We analyzed subsequent infections that occurred within an outbreak after an intervention was in place. Results: In total, 1,909 isolates were sequenced. Of 1,633 unique patient isolates clustered by sequence type, 74 clusters were identified comprising 210 (12.9%) patient isolates (Table 1). The median time from culture date to sequencing was 14 days (IQR, 5.25). The median cluster size was 2 (IQR, 1) (Table 2). Overall, 118 patient isolates (56.2%) had an epidemiological link to a prior isolate, indicating potential transmission. Of 74 clusters, 66 (89.2%) received infection prevention interventions after notification based upon epidemiological data. The infection prevention team performed 69 total interventions, which included unit education (n = 28), hand hygiene observations (n = 16), enhanced cleaning (n = 16), environmental cultures or removal of endoscope (n = 7), and enhanced microbiology surveillance (n = 2). The 59 subsequent infections after infection prevention notification included 17 (28.8%) with no clear epidemiological link, and 41 (69.5%) with an epidemiological link either to a new transmission route (n = 37) or the same route prior to infection prevention intervention (n = 4). Only 1 (1.7%) subsequent infection within a cluster occurred after an infection prevention intervention from the same potential route, which was a suspected unit-based transmission of vancomycin-resistant Enterococcus faecium. Conclusions: Real-time WGS was effective at detecting genetically related clusters, finding potential sources, and halting further transmission after interventions by the infection prevention team. Quick turnaround times from patient culture to sequencing and analysis were vital for successful WGS surveillance. Real-time WGS surveillance has the potential to substantially shift the infection prevention paradigm for outbreak detection.Disclosure: None

Colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in hospitalized patients in Botswana

Background: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in hospitalized patients in low- and middle-income countries (LMICs) is poorly described. Although risk factors for ESCrE clinical infection have been studied, little is known of the epidemiology of ESCrE colonization. Identifying risk factors for ESCrE colonization, which can predispose to infection, is therefore critical to inform antibiotic resistance reduction strategies. Methods: This study was conducted in 3 hospitals located in 3 districts in Botswana. In each hospital, we conducted ongoing surveillance in sequential units hospitalwide. All participants had rectal swabs collected which were inoculated onto chromogenic media followed by confirmatory testing using MALDI-TOF MS and VITEK-2. Data were collected via interview and review of the inpatient medical record on demographics, comorbidities, antibiotic use, healthcare exposures, invasive procedures, travel, animal contact, and food consumption. Participants with ESCrE colonization (cases) were compared to noncolonized participants (controls) using bivariable and multivariable analyses to identify risk factors for ESCrE colonization. Results: Enrollment occurred from January 15, 2020, to September 4, 2020, and 469 participants were enrolled. The median age was 42 years (IQR, 31–58) and 320 (68.2%) were female. The median time from hospital admission to date of sampling was 5 days (IQR, 3–12). There were 179 cases and 290 controls (ie, 38.2% of participants were ESCrE colonized). Independent risk factors for ESCrE colonization were a greater number of days on antibiotic, recent healthcare exposure, and tending swine prior to hospitalization. (Table). Conclusions: ESCrE colonization among hospitalized patients was common and was associated with several exposures. Our results suggest prior healthcare exposure may be important in driving ESCrE. The strong link to recent antibiotic use highlights the potential role of antibiotic stewardship interventions for prevention. The association with tending swine suggests that animal husbandry practices may play a role in community exposures, resulting in colonization detected at the time of hospital admission. These findings will help to inform future studies assessing strategies to curb further emergence of hospital ESCrE in LMICs.Disclosures: None

Infective Endocarditis due to Non-HACEK Gram-Negative Bacilli: Clinical Characteristics and Risk Factors from a Prospective Multicenter Brazilian Cohort.

Background: Non-HACEK Gram-negative bacilli (NGNB) infective endocarditis (IE) has a growing frequency. We aimed to describe cases of NGNB IE and find associated risk factors. Methods: We conducted a prospective observational study of consecutive patients with definitive IE according to the modified Duke criteria in four institutions in Brazil. Results: Of 1154 adult patients enrolled, 38 (3.29%) had IE due to NGNB. Median age was 57 years, males predominated, accounting for 25/38 (65.8%). Most common etiologies were Pseudomonas aeruginosa and Klebsiella spp. (8 episodes, 21% each). Worsening heart failure occurred in 18/38 (47.4%). Higher prevalence of embolic events was found (55,3%), mostly to the central nervous system 7/38 (18.4%). Vegetations were most commonly on aortic valves 17/38 (44.7%). Recent healthcare exposure was found in 52.6% and a central venous catheter (CVC) in 13/38 (34.2%). Overall mortality was 19/38 (50%). Indwelling CVC (OR 5.93; 95% CI, 1.29 to 27.3; p = 0.017), hemodialysis (OR 16.2; 95% CI, 1.78 to 147; p = 0.008) and chronic kidney disease (OR 4.8; 95% IC, 1.2 to 19.1, p = 0.049) were identified as risk factors for mortality. Conclusions: The rate of IE due to NGNB was similar to that in previous studies. Enterobacterales and P. aeruginosa were the most common etiologies. NGNB IE was associated with central venous catheters, prosthetic valves, intracardiac devices and hemodialysis and had a high mortality rate.

2317. Persistent Bacterial Carriage and Hospital Transmission Detected by Whole Genome Sequence Surveillance.

Healthcare-associated infections can be acquired via transmission of pathogens within the healthcare setting. Often, patients are assumed to have short duration (< 90 days) of transmissibility with bacterial pathogens after developing a clinical infection. This assumption may wrongly exclude patients as sources of transmission when they have persistent bacterial carriage. We studied patients with persistent carriage and associated transmission using whole genome sequencing surveillance. Patient culture positive isolates for select bacterial pathogens between 11/2016 and 11/2019 were collected if the patient was housed in the hospital for ≥3 days or had a recent healthcare exposure in the prior 30 days. Isolates were considered genetically related with ≤15 SNPs for all organisms except C. difficile (≤2 SNPs). Patients with serial isolates separated by >100 days were examined for other patients with related isolates and epidemiological commonalities between the first and last culture dates. There were 779 related isolates from 369 unique patients (range 2-11 isolates/patient). The mean time from first to last culture date was 81.9 days (median 33 days, range 1-899 days) (Figure 1). 77 patients had isolates that were related to another patient of which 18 (23%) patients had >100 days between their first and last isolate (median 216, range 103-899). Of these, 9 (50%) patients had epidemiological links with another patient between their first and last isolate culture dates. The median time from exposure to positive culture date of the exposed patient was 14 days (mean 34, range 2-115). An example of potential transmission is shown in Figure 2.Days between the first and last related isolates within the same patientExample of patient with persistent carriage of K. pneumoniae and evidence of transmission to another patient. Some patients had persistent carriage with the same strain for over two years and appear to be a potential source of ongoing transmission to other patients. WGS surveillance, in addition to detecting outbreaks, can identify patients with persistent colonization as potential a transmission source. Healthcare outbreak investigations should include patients with persistent carriage as potential sources based upon temporal restrictions. Graham Snyder, MD, SM, Infectious Diseases Connect: Advisor/Consultant Daria Van Tyne, PhD, Century Therapeutics, Inc: Advisor/Consultant.

Research and implementation of a whole-genome sequencing surveillance system for outbreak detection

Background: Traditional infection prevention (IP) methods for outbreak detection often rely on geotemporal clustering confined to single locations. We recently developed the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), which combines whole-genome sequencing (WGS) surveillance and machine learning of the electronic health record (EHR). Our retrospective research findings show potential transmissions averted and cost savings using EDS-HAT in real time. Here, we describe the process and initial findings from EDS-HAT real-time implementation. Methods: Real-time whole-genome sequencing surveillance began on November 1, 2021. Patient cultures positive for select bacterial pathogens who were hospitalized for ≥3 days or had a recent healthcare exposure in the prior 30-days were collected. Isolates were deemed genetically related if ≤15 single-nucleotide polymorphisms (SNPs) were identified for all organisms except Clostridioides difficile (≤2 SNPs). Clusters were manually investigated by both research and IP teams, and interventions were performed by the IP team. Data on collection, analysis, notification, and intervention dates were gathered. Results: As of January 11, 2022, 413 isolates had undergone whole-genome sequencing. Among them, 18 unique patient isolates were genetically related to ≥1 other isolate, comprising 7 clusters (range, 2–6 patients). Notable findings include a Pseudomonas aeruginosa cluster possibly related to a shared bronchoscope, a pseudo-outbreak of Serratia marcescens related to autopsy blood culture practice, and a cluster of vancomycin-resistant Enterococcus faecium on a shared transplant unit. Only 1 cluster of 2 isolates of Klebsiella pneumoniae had no known possible transmission routes. The median turnaround time from patient’s culture date to IP notification was 19 days (range, 13–28), with noted delays over the winter holiday. Concusions: Real-time WGS can identify small clusters including potentially interruptible transmission routes. Rapid turnaround time, coordination between clinical and genomic laboratories, and a robust IP team are key factors in implementing a WGS surveillance program. Real-time WGS surveillance has the potential to reduce costs for hospitals, improve patient safety, and save lives.Funding: NoneDisclosures: None

263. An Evaluation of Quality Indicators for the Management of Staphylococcus aureus Bacteremia: A Nested Case-Control Study

BackgroundCommunity-acquired Staphylococcus aureus bacteremia (CA SAB) is a common infection with high mortality. Ten Oever et al. recently used expert consensus methods to develop a set of 25 quality indicators for SAB care in five domains (i.e., follow up blood cultures, echocardiography, non-antibiotic interventions including source control, antibiotic treatment, and other management aspects). Associations between these quality indicators and patient outcomes have not been evaluated. We assessed associations between proposed quality indicators and all-cause 30-day mortality among patients with CA SAB.MethodsWe conducted a nested case-control study within a described national multicenter cohort of patients with SAB in the Veterans Health Administration (VHA). The cohort included 2,093 patients who were: 1) admitted to acute care hospitals between 1/2012 and 12/2014 for CA SAB (the first positive blood culture before or within 48 hours of admission with no recent healthcare exposure); 2) survived at least 96 hours after the SAB onset. We identified paired cases (who died within 30 days) and controls (who survived an equal time), matched 1:1 for age (+/- 5 years), gender, admission year and month, and methicillin susceptibility of isolates. We reviewed charts to extract information for quality indicators. We estimated associations between quality indicators and mortality using logistic regression, adjusting for patient demographics and comorbidity.Results164 patients (82 cases and 82 controls) were included. The median patient age was 68.5 (IQR: 62–80) years, and 74 (45.1%) had methicillin-resistant isolates. All patients received at least one domain of quality indicator (median: 3 [IQR: 2–4]). When analyzed individually, only two domains (follow-up blood cultures: OR 0.27 [95% CI: 0.11–0.68]; source control: OR: 0.13 [0.05–0.31]) were associated with mortality. There was a dose-response relationship in which more domains received was associated with decreased mortality (Figure).Association Between the Number of Satisfied Quality Indicator Domains and All-Cause 30-day Mortality ConclusionAmong patients with CA-SAB, the number of satisfied quality indicator domains was associated with 30-day mortality with a dose-response relationship. This finding supports the relevance of these quality indicators for SAB management.Disclosures All Authors: No reported disclosures

Effectiveness of Ultraviolet-C Room Disinfection on Preventing Healthcare-Associated Clostridioides difficile Infection

Background: Enhanced terminal room cleaning with ultraviolet C (UVC) disinfection has become more commonly used as a strategy to reduce the transmission of important nosocomial pathogens, including Clostridioides difficile, but the real-world effectiveness remains unclear. Objectives: We aimed to assess the association of UVC disinfection during terminal cleaning with the incidence of healthcare-associated C. difficile infection and positive test results for C. difficile within the nationwide Veterans Health Administration (VHA) System. Methods: Using a nationwide survey of VHA system acute-care hospitals, information on UV-C system utilization and date of implementation was obtained. Hospital-level incidence rates of clinically confirmed hospital-onset C. difficile infection (HO-CDI) and positive test results with recent healthcare exposures (both hospital-onset [HO-LabID] and community-onset healthcare-associated [CO-HA-LabID]) at acute-care units between January 2010 and December 2018 were obtained through routine surveillance with bed days of care (BDOC) as the denominator. We analyzed the association of UVC disinfection with incidence rates of HO-CDI, HO-Lab-ID, and CO-HA-LabID using a nonrandomized, stepped-wedge design, using negative binomial regression model with hospital-specific random intercept, the presence or absence of UVC disinfection use for each month, with baseline trend and seasonality as explanatory variables. Results: Among 143 VHA acute-care hospitals, 129 hospitals (90.2%) responded to the survey and were included in the analysis. UVC use was reported from 42 hospitals with various implementation start dates (range, June 2010 through June 2017). We identified 23,021 positive C. difficile test results (HO-Lab ID: 5,014) with 16,213 HO-CDI and 24,083,252 BDOC from the 129 hospitals during the study period. There were declining baseline trends nationwide (mean, −0.6% per month) for HO-CDI. The use of UV-C had no statistically significant association with incidence rates of HO-CDI (incidence rate ratio [IRR], 1.032; 95% CI, 0.963–1.106; P = .65) or incidence rates of healthcare-associated positive C. difficile test results (HO-Lab). Conclusions: In this large quasi-experimental analysis within the VHA System, the enhanced terminal room cleaning with UVC disinfection was not associated with the change in incidence rates of clinically confirmed hospital-onset CDI or positive test results with recent healthcare exposure. Further research is needed to understand reasons for lack of effectiveness, such as understanding barriers to utilization.Funding: NoneDisclosures: None

S1159 Hepatic Steatosis Is Associated With Elevated Alanine Aminotransferase (ALT) but Not Elevated Bilirubin or Hepatic Decompensation in Patients With Coronavirus Disease (COVID)-19

INTRODUCTION: COVID-19 is a global pandemic. However, the effects of underlying liver disease on COVID-19 in the United States is not well described. We investigated whether COVID-19 was associated with elevations in liver enzymes or hepatic decompensation in patients with underlying hepatic steatosis. METHODS: We retrospectively reviewed the charts of consecutive adults with RT-PCR positive for COVID-19 treated at Michigan Medicine between March 1 and April 30, 2020, who had ultrasound, computed tomography, or magnetic resonance imaging >30 days before COVID-19 diagnosis. Hepatic steatosis was defined based on imaging. Outcomes were: (1) peak ALT or bilirubin following COVID-19 diagnosis, (2) ALT >2 or 5 times upper limit of normal (ULN), defined as the higher of baseline ALT or 19 U/L in women and 30 U/L in men, (3) jaundice defined as bilirubin >2 or 4 mg/dl, and (4) new/worsening ascites or encephalopathy. We conducted regressions with the above outcomes as dependent variables and hepatic steatosis as the primary predictor, adjusting for age, sex, race, recent healthcare exposure, body mass index, hypertension, dyslipidemia, and diabetes. These regression models were logistic for outcomes of abnormal ALT or bilirubin, and linear for maximal ALT or bilirubin. RESULTS: Of patients with prior imaging, 80/159 (50.3%) had steatosis. Overall, 89% of patients were hospitalized, 51% were admitted to intensive care, and 16% died. 14% had chronic liver disease other than NAFLD, 5% had cirrhosis, and 2.7% had prior liver decompensation with ascites, variceal bleeding, or hepatic encephalopathy. Patients with steatosis were older, had higher body mass index, and were more often Black than those without steatosis (Table 1). Baseline ALT and total bilirubin were higher in the steatosis group (Table 1). Hepatic steatosis was associated with increased incidence of ALT >2x ULN (OR 2.93 [1.23–6.97]) or >5x ULN (OR 6.21 [1.45–26.62]), and with peak ALT (beta 39.7 [7.85–71.49]) (Table 2). Hepatic steatosis was not associated with increased bilirubin (Table 2). Rates of new/worsening ascites and encephalopathy were very low: 1.3% and 2.5%, respectively, with no difference based on NAFLD status (P > 0.4 for both). CONCLUSION: Hepatic steatosis is associated with acute hepatocellular injury with COVID-19 infection. Steatosis was not associated with jaundice. Rates of new/worsening ascites or hepatic encephalopathy were very low and unrelated to steatosis status.Table 1Table 2

S1111 Non-Alcoholic Fatty Liver Disease Is Associated With Increased Disease Severity in Patients With COVID-19

INTRODUCTION: Coronavirus disease (COVID)-19 is a global pandemic that carries significant morbidity and mortality. However, the effect of COVID-19 on liver disease, and vice versa, is not well-characterized in the United States. Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition associated with metabolic disease including diabetes and obesity. We examined the association between NAFLD and COVID19 disease severity in a large cohort of patients. METHODS: We retrospectively reviewed a cohort of 396 consecutive adult patients with RT-PCR positive for COVID-19 between March 1 and April 30, 2020 at Michigan Medicine. NAFLD was defined as either prior imaging evidence of steatosis or hepatic steatosis index >36 for Asians or >39 for non-Asians, with no history of alcohol abuse. The primary outcome was disease severity based on admission to intensive care, intubation, death, or the World Health Organization (WHO) ordinal scale. We used multivariable logistic regression to assess the predictors of intensive care, intubation, or death and linear regression for disease severity on WHO ordinal scale. NAFLD was the primary predictor and models were adjusted for age, sex, race, recent healthcare exposure, hypertension, and dyslipidemia. RESULTS: The median age was 60.5 years, 52% were male, 46% were Black, 41% were White and 54% had NAFLD. Of 396 patients, 86% were hospitalized, 45% required intensive care, 30% required intubation, and 14% died. 213 (54%) patients had NAFLD. Patients with NAFLD were older (65 vs. 57 years; P < 0.001), had higher body mass index (34.5 vs. 26.4; P < 0.001), and higher prevalence of diabetes (45% vs. 34%; P = 0.039) than those without NAFLD (Table 1). NAFLD was independently associated with increased odds of requiring admission to the intensive care unit (odds ratio [OR] 1.66 [1.06-2.62], P = 0.027) and intubation (OR 2.46 [1.50-4.04], P < 0.001), as well as higher WHO ordinal scale (beta 0.43 [0.03-0.84], P = 0.036). There was no significant association between NAFLD and death (OR 0.84 [0.46-1.67], P = 0.62) (Table 2.) CONCLUSION: Our study shows that patients with NAFLD were more likely to develop severe disease with COVID-19.Table 1Table 2

Assessment of Health Care Exposures and Outcomes in Adult Patients With Sepsis and Septic Shock

Current information on the characteristics of patients who develop sepsis may help in identifying opportunities to improve outcomes. Most recent studies of sepsis epidemiology have focused on changes in incidence or have used administrative data sets that provided limited patient-level data. To describe sepsis epidemiology in adults. This retrospective cohort study reviewed the medical records, death certificates, and hospital discharge data of adult patients with sepsis or septic shock who were discharged from the hospital between October 1, 2014, and September 30, 2015. The convenience sample was obtained from hospitals in the Centers for Disease Control and Prevention Emerging Infections Program in 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee). Patients 18 years and older with discharge diagnosis codes for severe sepsis or septic shock were randomly selected. Data were analyzed between May 1, 2018, and January 31, 2019. The population's demographic characteristics, health care exposures, and sepsis-associated infections and pathogens were described, and risk factors for death within 30 days after sepsis diagnosis were assessed. Among 1078 adult patients with sepsis (569 men [52.8%]; median age, 64 years [interquartile range, 53-75 years]), 973 patients (90.3%) were classified as having community-onset sepsis (ie, sepsis diagnosed within 3 days of hospital admission). In total, 654 patients (60.7%) had health care exposures before their hospital admission for sepsis; 260 patients (24.1%) had outpatient encounters in the 7 days before admission, and 447 patients (41.5%) received medical treatment, including antimicrobial drugs, chemotherapy, wound care, dialysis, or surgery, in the 30 days before admission. A pathogen associated with sepsis was found in 613 patients (56.9%); the most common pathogens identified were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Clostridioides difficile. After controlling for other factors, an association was found between underlying comorbidities, such as cirrhosis (odds ratio, 3.59; 95% CI, 2.03-6.32), immunosuppression (odds ratio, 2.52; 95% CI, 1.81-3.52), vascular disease (odds ratio, 1.54; 95% CI, 1.10-2.15), and 30-day mortality. Most adults experienced sepsis onset outside of the hospital and had recent encounters with the health care system. A sepsis-associated pathogen was identified in more than half of patients. Future efforts to improve sepsis outcomes may benefit from examination of health maintenance practices and recent health care exposures as potential opportunities among high-risk patients.

469. Contributions of Infections among Persons Who Inject Drugs to the Changing Incidence of Healthcare-Associated, Community-Onset Methicillin-Resistant Staphylococcus aureus Infections, 2009–2017

BackgroundRecently, overall reductions for invasive MRSA infections (isolation from a normally sterile site) have slowed. Healthcare-associated community-onset (HACO) invasive methicillin-resistant Staphylococcus aureus (MRSA) infections are those with recent healthcare exposures who develop MRSA infection outside acute care hospitals, and account for most invasive MRSA infections. HACO incidence decreased 6.6% per year during 2005–2008; the contribution of persons who inject drugs (PWID) to HACO incidence has not been reported.MethodsWe identified invasive MRSA infections using active, population- and laboratory-based surveillance data during 2009–2017 from 25 counties in 7 sites (CA, CT, GA, MD, MN, NY, TN). Cases were HACO if culture was obtained from an outpatient, or ≤3 days after hospitalization in a patient with ≥1 of the following healthcare exposures (HEs): hospitalization, surgery, dialysis, or residence in a long-term care facility (LTCF) in the past year; or central vascular catheter ≤2 days before culture. We calculated incidence (per census population) overall, for PWID cases and others, and for cases associated with each HE. For each HE, we calculated the proportion of overall incidence increase for PWID and others.ResultsHACO MRSA incidence declined overall from 2009 to 2016 but increased from 2016 to 2017 overall (8%), for both PWID (63%) and others (5%) (figure). For both PWID and non-PWID, incidence from 2016 to 2017 increased by 0.5 cases/100,000 population; 91% of the increase in PWID occurred in cases with a past year hospitalization while 78% of the increase in cases not associated with injection drug use (IDU) occurred in cases with past year LTCF residence. Past year LTCF residence was less common among PWID (16%) then among other cases (38%, P < 0.01).ConclusionAfter years of declines, HACO MRSA incidence increased equally in 2017 for cases associated with IDU and in cases unrelated to IDU. Increases in PWID-associated cases account for half the overall increase, indicating that efforts to reduce HACO MRSA should address PWID risk factors as these infections may be due to self-injection. In addition, increases not related to PWID, if sustained, would be a reversal of historic trends and require further investigation into causes. Disclosures All authors: No reported disclosures.

DUAL MRSA COVERAGE FOR NECROTIZING PNEUMONIA IN A CRITICAL CARE PATIENT

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the common causes of health care-associated pneumonia. Choice of antibacterial therapy can affect outcome. Vancomycin continues to remain the drug of choice for MRSA. Persistent MRSA (pMRSA) pneumonia has been described however the role of dual antimicrobial coverage for MRSA is not well known. Here, we present a case of pMRSA pneumonia that failed initial treatment with vancomycin followed by linezolid but improved with dual treatment consisting of vancomycin and ceftaroline. CASE PRESENTATION: 52-year-old male with PMHx of chronic back pain with recent lumbar spine surgery and history of opioid dependence presented with altered mental status, acute hypoxemic respiratory failure and shock. Initial Labs showed a wbc 9 with 80% left shift. CXR was consistent with pneumonia with a dense right basilar opacity. He was empirically started on vancomycin and zosyn given recent health care exposure. Respiratory culture (RC) grew MRSA and pan sensitive enterobacter; despite appropriate weight based dosing, vancomycin levels remained slightly subtherapeutic so antibiotics were switched to linezolid and ceftriaxone. He improved clinically and was extubated. 3 days after completion of 2 weeks of appropriate antibiotic therapy, he again decompensated requiring intubation and vasopressors. Meropenem and vancomycin were empirically administered. Repeat RC again grew MRSA, vancomycin minimum inhibitory concentration (MIC) DISCUSSION: MRSA is defined as an oxallicin MIC ≥4 mcg/ml. In the United States, about 7% of patients are colonized with MRSA. Vancomycin is the mainstream treatment for MRSA pneumonia. PMRSA pneumonia has not been well described and the role of dual antimicrobial coverage is not well known. In vitro synergy between vancomycin and ceftaroline has been reported in some studies but clinical experience with this therapy is limited. Our patient failed vancomycin followed by linezolid therapy. He improved rapidly with combination therapy. CONCLUSIONS: Further study is needed for the role of dual antimicrobial coverage for pMRSA. Reference #1: Gritsenko, Diana, et al. “Combination Therapy With Vancomycin and Ceftaroline for Refractory Methicillin-Resistant Staphylococcus Aureus Bacteremia: A Case Series.” Clinical Therapeutics, vol. 39, no. 1, 2017, pp. 212–218., https://doi.org/10.1016/j.clinthera.2016.12.005. Reference #2: Katie E. Barber, Michael J. Rybak, George Sakoulas; Vancomycin plus ceftaroline shows potent in vitrosynergy and was successfully utilized to clear persistent daptomycin-non-susceptible MRSA bacteraemia, Journal of Antimicrobial Chemotherapy, Volume 70, Issue 1, 1 January 2015, Pages 311–313 Reference #3: Choo, Eun Ju and Henry F Chambers. “Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia” Infection & chemotherapy vol. 48,4 (2016): 267-273. DISCLOSURES: No relevant relationships by Obed Adarkwah, source=Web Response No relevant relationships by Mona Alipour, source=Web Response No relevant relationships by Louis Gerolemou, source=Web Response No relevant relationships by Nabil Mesiha, source=Web Response Speaker/Speaker's Bureau relationship with Allergan Please note: $20001 - $100000 Added 03/18/2019 by Joshua Rosenberg, source=Web Response, value=Honoraria No relevant relationships by jad sargi, source=Web Response

Candida Bloodstream Infections Among Persons Who Inject Drugs - Denver Metropolitan Area, Colorado, 2017-2018.

Candidemia, a bloodstream infection caused by Candida species, is typically considered a health care-associated infection, with known risk factors including the presence of a central venous catheter, receipt of total parenteral nutrition or broad-spectrum antibiotics, recent abdominal surgery, admission to an intensive care unit, and prolonged hospitalization (1,2). Injection drug use (IDU) is not a common risk factor for candidemia; however, in the context of the ongoing opioid epidemic and corresponding IDU increases, IDU has been reported as an increasingly common condition associated with candidemia (3) and methicillin-resistant Staphylococcus aureus bacteremia (4). Little is known about the epidemiology of candidemia among persons who inject drugs. The Colorado Department of Public Health and Environment (CDPHE) conducts population-based surveillance for candidemia in the five-county Denver metropolitan area, encompassing 2.7 million persons, through CDC's Emerging Infections Program (EIP). As part of candidemia surveillance, CDPHE collected demographic, clinical, and IDU behavior information for persons with Candida-positive blood cultures during May 2017-August 2018. Among 203 candidemia cases reported, 23 (11%) occurred in 22 patients with a history of IDU in the year preceding their candidemia episode. Ten (43%) of the 23 cases were considered community-onset infections, and four (17%) cases were considered community-onset infections with recent health care exposures. Seven (32%) of the 22 patients had disseminated candidiasis with end-organ dysfunctions; four (18%) died during their hospitalization. In-hospital IDU was reported among six (27%) patients, revealing that IDU can be a risk factor in the hospital setting as well as in the community. In addition to community interventions, opportunities to intervene during health care encounters to decrease IDU and unsafe injection practices might prevent infections, including candidemia, among persons who inject drugs.

Outcomes associated with the use of a revised risk assessment strategy to predict antibiotic resistance in community-onset pneumonia: a stewardship perspective

There is growing evidence that patients with community-onset pneumonia and recent healthcare exposure are not at equally high risk of infection with MDR organisms. An individualized approach is necessary with regard to risk assessment and choice of antibiotics. We reviewed the records of 102 patients admitted for community-onset pneumonia, before and after the implementation of a revised risk assessment programme for MDR organisms using the drug resistance in pneumonia (DRIP) score. The primary aim of the study was to identify the effects of this intervention on antibiotic days of therapy (DOT), and secondary outcomes included all-cause readmissions and time to clinical improvement. Statistical analysis was performed using generalized linear regression and Cox hazards models. Implementation of the programme resulted in a decrease in anti-MRSA (-1.44 DOT, P = 0.007) and anti-pseudomonal (-2.03 DOT, P < 0.001) antibiotic utilization, but was not associated with a significant difference in the odds of readmissions (OR 0.64, 95% CI 0.16-2.57) or in time to clinical improvement (HR 1.19, 95% CI 0.62-2.21). An individualized MDR organism risk assessment strategy using a clinical prediction score for community-onset pneumonia can decrease the utilization of broad-spectrum antibiotics without an increase in adverse outcomes.

Elizabethkingia anophelis: Clinical Experience of an Academic Health System in Southeastern Wisconsin.

In late 2015 and early 2016, 11 patients were identified with cultures positive for Elizabethkingia anophelis in our health system. All patients had positive blood cultures upon admission. Chart review showed that all had major comorbidities and recent health care exposure. The attributable mortality rate was 18.2%.

Genome Analysis of Clostridium difficile PCR Ribotype 014 Lineage in Australian Pigs and Humans Reveals a Diverse Genetic Repertoire and Signatures of Long-Range Interspecies Transmission.

Clostridium difficile PCR ribotype (RT) 014 is well-established in both human and porcine populations in Australia, raising the possibility that C. difficile infection (CDI) may have a zoonotic or foodborne etiology. Here, whole genome sequencing and high-resolution core genome phylogenetics were performed on a contemporaneous collection of 40 Australian RT014 isolates of human and porcine origin. Phylogenies based on MLST (7 loci, STs 2, 13, and 49) and core orthologous genes (1260 loci) showed clustering of human and porcine strains indicative of very recent shared ancestry. Core genome single nucleotide variant (SNV) analysis found 42% of human strains showed a clonal relationship (separated by ≤2 SNVs in their core genome) with one or more porcine strains, consistent with recent inter-host transmission. Clones were spread over a vast geographic area with 50% of the human cases occurring without recent healthcare exposure. These findings suggest a persistent community reservoir with long-range dissemination, potentially due to agricultural recycling of piggery effluent. We also provide the first pan-genome analysis for this lineage, characterizing its resistome, prophage content, and in silico virulence potential. The RT014 is defined by a large “open” pan-genome (7587 genes) comprising a core genome of 2296 genes (30.3% of the total gene repertoire) and an accessory genome of 5291 genes. Antimicrobial resistance genotypes and phenotypes varied across host populations and ST lineages and were characterized by resistance to tetracycline [tetM, tetA(P), tetB(P) and tetW], clindamycin/erythromycin (ermB), and aminoglycosides (aph3-III-Sat4A-ant6-Ia). Resistance was mediated by clinically important mobile genetic elements, most notably Tn6194 (harboring ermB) and a novel variant of Tn5397 (harboring tetM). Numerous clinically important prophages (Siphoviridae and Myoviridae) were identified as well as an uncommon accessory gene regulator locus (agr3). Conservation in the pathogenicity locus and S-layer correlated with ST affiliation, further extending the concept of clonal C. difficile lineages. This study provides novel insights on the genetic variability and strain relatedness of C. difficile RT014, a lineage of emerging One Health importance. Ongoing molecular and genomic surveillance of strains in humans, animals, food, and the environment is imperative to identify opportunities to reduce the overall CDI burden.

Crohnʼs Disease, Antibiotic Use, and Recent Health Care Exposures Are Associated with Clostridium difficile Isolation in IBD

Introduction:Clostridium difficile is the most commonly isolated stool pathogen in inflammatory bowel disease (IBD). Although previous studies have identified risk factors for the isolation of C. difficile in the setting of clinically active IBD, no studies have assessed the risk factors for the isolation of C. difficile in both symptomatic and asymptomatic IBD outpatients. Methods: We recruited consecutive IBD patients presenting to our outpatient clinic between April 1 and August 1, 2015. Demographics, healthcare exposures, need for medical and surgical therapies and disease activity were recorded from prospectively completed surveys. Asymptomatic disease was defined by a Harvey Bradshaw Index 4 or Simple Colitis Activity Index 2. Self-reported dietary intake was performed. A rectal swab was performed from which toxigenic culture, PCR toxin analysis and PCR-ribotyping was performed. The primary outcome of interest was isolation of C. difficile. Data were analyzed with Student's t-tests for continuous variables and chi-squared analysis for dichotomous variable. Results: One hundred thirty-five patients were included in this study (67% Crohn's disease) of which 82 (61%) were clinically asymptomatic. C. difficile was isolated from 10 patients (7.4%) of which 6 patients were asymptomatic. Among the C. difficile strains isolated, 7 were toxin-producing strains and 3 were non-toxigenic. Hypervirulent ribotypes (027/078) were not isolated in this population. Factors associated with the isolation of C. difficile among all IBD patients are listed in Table 1. Significant factors include Crohn's disease diagnosis, recent antibiotic use and healthcare exposures. Among asymptomatic IBD patients, Crohn's disease diagnosis and history of IBD hospitalization were associated with the isolation of C. difficile (Table 2). Daily self-reported intake of fruit was associated with a decreased risk of C. difficile isolation in both the entire cohort and asymptomatic IBD populations (P = 0.05 and 0.02, respectively). Probiotic use was associated with an increased risk of C. difficile isolation in the asymptomatic population (P = 0.004).Table 1: Factors associated with the isolation of C. difficile among all IBD patientsTable 2: Factors associated with the isolation of C. difficile among asymptomatic IBD patientsConclusion: This is the largest study to assess risk factors for the isolation of C. difficile among both symptomatic and asymptomatic outpatients with IBD. Crohn's disease diagnosis, antibiotic use and healthcare exposures were associated with an increased risk for isolation of C. difficile, while intake of fruits was associated with a reduced risk.

Epidemiology and economics of adult patients hospitalized with urinary tract infections

Background: Urinary tract infections (UTI) are among the most common bacterial diseases worldwide, with significant clinical and economic burden. Surveillance of pathogen epidemiology and risk factors for resistant pathogens in the hospital setting may improve the management of UTI. Objective: To evaluate microbiology and antimicrobial susceptibility of UTI pathogens, with associated costs, in hospitalized patients. Methods: Patients diagnosed with UTI between July and September 2013 were retrospectively screened for clinical symptoms and treatment within 24 hours of admission, then categorized into groups: community acquired (Group 1); recent healthcare exposure (Group 2); or a history of identification of an extended-spectrum beta lactamase (ESBL)-producing organism (Group 3). Clinical, epidemiological, and financial data were compared between groups. Results: From 308 included patients, a total of 216 pathogens were identified. Escherichia coli was most commonly identified pathogen, but frequencies differed between groups (p = 0.002), as did those of ESBL-producing pathogens (p < 0.001) and Pseudomonas aeruginosa (p = 0.005). Appropriate empirical therapy also differed between groups (p = 0.003). Length of stay was longer for healthcare associated UTI with inappropriate empirical therapy (5.2 versus 6.3 days, p = 0.016). Increased cost was associated with factors other than antimicrobial costs. Intensive care unit (ICU) stay (p < 0.001), care facility at discharge (p = 0.001), Foley catheter (FC) present on admission (p = 0.002), and Charlson comorbidity index (CCI) (p = 0.017) predicted increased cost overall, while ICU stay (p < 0.001), time to appropriate therapy (p < 0.001), and CCI (p = 0.015) predicted higher cost in patients with pathogens identified. Conclusions: Changes in antimicrobial susceptibility are evident with exposure to healthcare, the presence of a FC, and a history of resistant pathogens. Risk-based empirical prescribing and rapid de-escalation may improve care and reduce costs.