Community Onset Research Articles

Unsuspected Clonal Spread of Methicillin-Resistant Staphylococcus aureus Causing Bloodstream Infections in Hospitalized Adults Detected Using Whole Genome Sequencing.

Though detection of transmission clusters of methicillin-resistant Staphylococcus aureus (MRSA) infections is a priority for infection control personnel in hospitals, the transmission dynamics of MRSA among hospitalized patients with bloodstream infections (BSIs) has not been thoroughly studied. Whole genome sequencing (WGS) of MRSA isolates for surveillance is valuable for detecting outbreaks in hospitals, but the bioinformatic approaches used are diverse and difficult to compare. We combined short-read WGS with genotypic, phenotypic, and epidemiological characteristics of 106 MRSA BSI isolates collected for routine microbiological diagnosis from inpatients in 2 hospitals over 12 months. Clinical data and hospitalization history were abstracted from electronic medical records. We compared 3 genome sequence alignment strategies to assess similarity in cluster ascertainment. We conducted logistic regression to measure the probability of predicting prior hospital overlap between clustered patient isolates by the genetic distance of their isolates. While the 3 alignment approaches detected similar results, they showed some variation. A gene family-based alignment pipeline was most consistent across MRSA clonal complexes. We identified 9 unique clusters of closely related BSI isolates. Most BSIs were healthcare associated and community onset. Our logistic model showed that with 13 single-nucleotide polymorphisms, the likelihood that any 2 patients in a cluster had overlapped in a hospital was 50%. Multiple clusters of closely related MRSA isolates can be identified using WGS among strains cultured from BSI in 2 hospitals. Genomic clustering of these infections suggests that transmission resulted from a mix of community spread and healthcare exposures long before BSI diagnosis.

Morganella morganii, an Emerging Cause of Bloodstream Infections.

ABSTRACTAlthough recent reports of extensively antibiotic-resistant strains have highlighted the importance of Morganella morganii as an emerging pathogen, the epidemiology of serious infections due to this organism is not well defined. The objective of this study was to determine the incidence, determinants, and outcomes of Morganella morganii bloodstream infections (BSIs). Retrospective, population-based surveillance for Morganella morganii BSIs was conducted in Queensland, Australia, in 2000 to 2019; 709 cases were identified, for an annual incidence of 9.2 cases per million population. Most cases were of community onset, with 280 (39.5%) community-associated cases and 226 (31.9%) health care-associated cases. Morganella morganii BSIs were rare in children and young adults, and the incidence increased markedly with advancing age. The most common foci of infection were skin and soft tissue (131 cases [18.5%]), genitourinary (97 cases [13.7%]), and intraabdominal (90 cases [12.7%]). Most patients (580 cases [81.8%]) had at least one comorbid medical illness, with diabetes mellitus (250 cases [35.3%]), renal disease (208 cases [29.3%]), and congestive heart failure (167 cases [23.6%]) being most prevalent. Resistance to one or more of quinolones, co-trimoxazole, aminoglycosides, or carbapenems was observed in 67 cases (9.5%), and this did not change significantly over the study. The 30-day all-cause case fatality rate was 21.2%, and increasing age, nonfocal infection, heart failure, dementia, and cancer were independently associated with increased risk of death. Morganella morganii BSIs are increasing in our population, and elderly male subjects and individuals with comorbidities are at highest risk. Although antibiotic resistance is not a major contributor to the current burden in Queensland, ongoing surveillance is warranted.IMPORTANCE Recent reports of extensively antibiotic-resistant strains have highlighted the importance of Morganella morganii as an emerging pathogen. Despite its present and evolving importance as an agent of human disease, there is a limited body of literature detailing the epidemiology of serious infections due to Morganella morganii. Therefore, the objectives of this study were to examine the incidence and determinants of Morganella morganii BSIs and to examine risk factors for death in a large Australian population in 2000 to 2019.

Introducing the Escalation Antibiogram: A Simple Tool to Inform Changes in Empiric Antimicrobials in the Nonresponding Patient.

Hospital antibiograms guide initial empiric antibiotic treatment selections, but do not directly inform escalation of treatment among nonresponding patients. Using gram-negative bacteremia as an exemplar condition, we sought to introduce the concept of an escalation antibiogram. Among episodes of gram-negative bacteremia between 2017 and 2020 from 6 hospitals in the Greater Toronto Area, we generated escalation antibiograms for each of 12 commonly used agents. Among organisms resistant to that antibiotic, we calculated the likelihood of susceptibility to each of the other 11 agents. In subgroup analyses, we examined escalation antibiograms across study years, individual hospitals, community versus hospital onset, and pathogen type. Among 6577 gram-negative bacteremia episodes, the likelihood of coverage was ampicillin 31.8%, cefazolin 62.7%, ceftriaxone 67.1%, piperacillin-tazobactam 72.5%, ceftazidime 74.1%, trimethoprim-sulfamethoxazole 74.4%, ciprofloxacin 77.1%, tobramycin 88.3%, gentamicin 88.8%, ertapenem 91.0%, amikacin 97.5%, and meropenem 98.2%. The escalation antibiograms revealed marked shifts in likelihood of coverage by the remaining 11 agents. For example, among ceftriaxone-resistant isolates, piperacillin-tazobactam susceptibility (21.2%) was significantly lower than trimethoprim-sulfamethoxazole (54.2%, P < .0001), ciprofloxacin (63.0%, P < .0001), ertapenem (73.4%, P < .0001), tobramycin (80.1%, P < .0001), gentamicin (82.8%, P < .0001), meropenem (94.3%, P < .0001), and amikacin (97.1%, P < .0001). Trimethoprim-sulfamethoxazole was the second-ranked agent in the meropenem escalation antibiogram (49.6%) and first in the amikacin escalation antibiogram (86.0%). Escalation antibiograms were consistent across 4 study years and 6 hospitals. Escalation antibiograms can be generated to inform empiric treatment changes in nonresponding patients. These tools can yield important insights such as avoiding the common maneuver of escalating from ceftriaxone to piperacillin-tazobactam in suspected gram-negative bacteremia.

Genomic Epidemiology Suggests Community Origins of Healthcare-Associated USA300 Methicillin-Resistant Staphylococcus aureus.

Hospital-onset (HO) methicillin-resistant Staphylococcus aureus (MRSA) infections have declined over the past decade due to infection control strategies; community-onset (CO) and healthcare-associated community-onset (HACO) MRSA, particularly USA300, has declined less. We examined the role of community strains to explain the difference. We performed whole-genome sequencing (WGS) on MRSA clinical isolates from Cook County Health patients during 2011-2014. We defined infections as CO, HO, or HACO epidemiologically. We integrated genomic, community exposure, and statewide hospital discharge data to infer MRSA origin. Among 1020 individuals with available WGS, most were USA300 wound infections (580 CO, 143 HO, 297 HACO). USA300 HO, CO, and HACO infections were intermixed on the USA300 phylogeny, consistent with common strains circulating across community and healthcare settings. Community exposures (eg, substance abuse, incarceration, homelessness) were associated with HACO and HO infections, and genetically linked individuals from both groups had little overlap in healthcare facilities, supporting community origins. Most repeat infections-over months to years-occurred in individuals persistently carrying their own strains. These individuals were more likely to have genetic linkages, suggesting a role of persistent colonization in transmission. Efforts to reduce presumed nosocomial USA300 spread may require understanding and controlling community sources and transmission networks, particularly for repeat infections.

Impact of COVID-19 pandemic on hospital onset bloodstream infections (HOBSI) at a large health system

BackgroundThe COVID-19 pandemic has had a considerable impact leading to increases in health care-associated infections, particularly bloodstream infections (BSI). MethodsWe evaluated the impact of COVID-19 in 69 US hospitals on BSIs before and during the pandemic. Events associated with 5 pathogens (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida sp.) were stratified by community onset (CO) if ≤ 3 days from admission or hospital onset (HO) if > 3 days after admission. We compared pre-pandemic CO and HO rates with pandemic periods and the rates of BSI for those with and without COVID-19. ResultsCOVID-19 patients were less likely to be admitted with COBSI compared to others (10.85 vs 22.35 per 10,000 patient days; P < .0001). There was a significant increase between pre-pandemic and pandemic HOBSI rates (2.78 vs 3.56 per 10,000 patient days; P < .0001). Also, COVID-19 infected patients were 3.5 times more likely to develop HOBSI compared to those without COVID-19 infection (9.64 vs 2.74 per 10,000 patient-days; P < .0001). ConclusionsThe COVID-19 pandemic period was associated with substantial increases in HOBSI and largely attributed to COVID-19 infected patients. Future research should evaluate whether such measures would be beneficial to incorporate in evaluating infection prevention trends.

A nationwide population-based study of Escherichia coli bloodstream infections: incidence, antimicrobial resistance and mortality

ObjectivesEscherichia coli is the leading cause of bloodstream infection (BSI). The incidence of E. coli BSI caused by antibiotic-resistant strains is increasing. We aimed to describe the nationwide incidence and resistance profile of E. coli BSI in Israel and its impact on mortality, to compare E. coli BSI mortality with all-cause mortality, and community-onset with hospital-onset E. coli BSIs. MethodsWe used mandatory BSI surveillance reports submitted by all Israeli hospitals to the Ministry of Health and the national death registry. All E. coli BSIs from 1 January 2018 to 31 December 31 2019 in patients aged 18 and over were included. ResultsA total of 11 113 E. coli BSIs occurred in 10 218 patients; 85% (9012/10 583) were community onset. Median age was 76 (IQR 65–85), and 57% (6304/11 113) of cases occurred in women. The annual incidence was 92.5 per 100 000 population. Antibiotic resistance was frequent and significantly more common in hospital-onset than in community-onset BSI; 65% (1021/1571) vs. 45% (4049/9012) were multidrug-resistant (MDR) (p < 0.001). The case fatality rate (CFR) was higher following hospital-onset BSI than community-onset: 23% (276/1214) vs. 12% (926/7620) at 14 days, 31% (378/1214) vs. 16% (1244/7620) at 30 days, and 55% (418/766) vs. 34% (1645/4903) at 1 year (p < 0.001 for all comparisons). The 1-year CFR was 47% (1258/2707) for MDR vs. 28% (928/3281) for non-MDR (p < 0.001). The annual mortality rate was 31.0 per 100 000 population, comprising 4.2% (31.0/734.8) of all causes of deaths. DiscussionE. coli BSI carries a high burden, with a large proportion of MDR isolates, which are associated with increased incidence and CFR.

429. Infection Prevention During Use of a Warm Zone Model in Cohort Patient Care Locations during the COVID-19 Pandemic

BackgroundThe COVID-19 pandemic required hospitals to care for influxes of patients in cohort locations during critical shortages of personal protective equipment (PPE). Safety zones can be used to protect healthcare workers caring for patients with infectious pathogens. During the COVID-19 pandemic, our hospital developed a Warm Zone model (WZM) to streamline the care of patients with COVID. We established specific areas in our COVID cohort units where staff were permitted to bridge between rooms without doffing gowns, but still doffing gloves and performing hand hygiene between patients. We recognized that a WZM could inadvertently increase risk of nosocomial transmission of pathogens if gowns acted as fomites. For this reason, patients with known infectious pathogens were excluded from the WZM. To measure for unintended harmful consequences of the WZM, our Infection Prevention (IP) department performed surveillance for hospital onset (HO) Clostridioides difficile (CDI), Carbapenem-resistant enterobacteriaceae (CRE) and Methicillin-resistant Staphyloccocus aureus (MRSA) bloodstream infections on units that implemented the WZM.MethodsTwo intensive care units and 3 wards where COVID positive patients were cohorted were included in surveillance. The timeframe for this analysis was 7/1/2020 - 3/31/2021. An electronic surveillance system was used to measure HO infections. The National Healthcare Surveillance Network (NHSN) LabID definitions were used when determining HO CDI and MRSA bloodstream infections (BSI).ResultsDuring the study period, there were no HO CRE, 1 HO CDI, and 2 HO MRSA BSI in cohort units. There was no evidence to suggest that the HO CDI or HO MRSA BSI were associated with use of a WZM. During this time period, there were 14 cases of community onset (CO) CDI, 2 cases of CO MRSA BSI, and one CO CRE.ConclusionDuring use of a WZM in COVID cohort units, IP did not identify significant increase in HO CDI, CRE, or MRSA BSI compared to non-cohort units. We were limited in our ability to measure acquisition of pathogens because active surveillance screening for colonization was not performed. However, we were able to safely employ a WZM to streamline patient care in COVID cohort areas without evidence of causing nosocomial infections via patient-to-patient transmission.Disclosures All Authors: No reported disclosures

796. Burden of Healthcare-associated (HA) Respiratory Syncytial Virus (RSV) in Hospitalized Adults

BackgroundLittle is known about the burden of HA-RSV in hospitalized adults. We assessed risk factors and clinical outcomes in hospitalized adults diagnosed with HA-RSV.MethodsA retrospective case-control study was performed from 2017-2020 in two academic hospital systems. HA-RSV cases were >18 years of age, hospitalized >4 days, and developed new or worsening respiratory signs and symptoms that prompted clinicians to test for respiratory pathogens; cases were RSV-positive by PCR assays. Two community-onset (CO) RSV-positive controls (admitted with >2 acute respiratory symptoms), were matched to each HA-RSV case by age, sex, and RSV season. We compared risk factors and outcomes in cases vs. controls. We assessed escalation of respiratory support in HA-RSV cases, defined as new or increased respiratory support from Day -2 to Day +4 of their RSV-positive test. Exact conditional logistic regression compared outcomes of HA-RSV vs. CO-RSV subjects, adjusting for demographic and clinical characteristics.Results84 cases and 160 controls (both median 64 years) were included; 87% had ≥1 comorbidity. HA-RSV cases were hospitalized for a median of 10 (IQR: 5-17) days prior to their RSV-positive test. CO-RSV controls were more likely to have pulmonary comorbidities than HA-RSV cases (46% vs. 31%, p=0.02). 38% of HA-RSV vs. 15% of CO-RSV subjects were hospitalized ≥15 days after their RSV-positive test (p=0.047). 14% of HA-RSV and 6% of CO-RSV subjects died (p=0.25). Among patients who survived, HA-RSV cases were more likely discharged to a skilled nursing or rehabilitation facility than CO-RSV controls (46% vs. 17%, p=0.04). Of the 44 HA-RSV cases assessed thus far, 25% required escalation of respiratory support; none required initiation of mechanical ventilation.ConclusionHA-RSV was associated with increased morbidity and increased health care resource use during and after hospitalization. RSV vaccines could prevent CO- and HA-RSV infections in adults.Disclosures Edward E. Walsh, MD, GSK (Advisor or Review Panel member)Janssen (Grant/Research Support)Merck (Grant/Research Support)Merck (Grant/Research Support) William G. Greendyke, MD, Merck (Grant/Research Support) Angela Branche, MD, Merck Dohme and Sharpe (Grant/Research Support) Ann Falsey, MD, BioFire Diagnostics (Grant/Research Support)Janssen (Grant/Research Support)Merck (Grant/Research Support)Novavax (Other Financial or Material Support, DSMB member)Pfizer (Grant/Research Support) Matthew R. Phillips, MPH, Merck & Co., Inc. (Employee, Shareholder) Yoonyoung Choi, PhD, MS, RPh, Merck (Employee) Lyn Finelli, DrPH, MS, Merck (Employee) Lisa Saiman, MD, MPH, Merck (Grant/Research Support, Research Grant or Support)Merk Co., Inc (Grant/Research Support, Advisor or Review Panel member)

2. Space Time Trends of Community Onset Staphylococcus aureus Infections in Children Living in Southeastern United States: 2002-2016

BackgroundStaphylococcus aureus (S. aureus) remains a serious cause of infections in the United States and worldwide. Methicillin susceptible S. aureus (MSSA) is the cause of half of all health care–associated staphylococcal infections, and Methicillin Resistant S. aureus (MRSA) is the leading cause of community onset skin and soft tissue infections in the US. This study looks at a 15-year trend of community onset (CO)-MRSA and MSSA infections and determines ‘best’ to ‘worst’ infection trends. We identified distinct groups of CO-MRSA and MSSA infection rate trajectories by grouping census tracts of the 20 county Atlanta Metropolitan Statistical Area (MSA) between 2002 to 2016 with similar temporal trajectories. MethodsThis is a retrospective study from 2002-2016, using electronic health records of children living in Atlanta, Georgia with S. aureus infections and relevant US census data (at the census tract level). A group based trajectory model was applied to generate community onset S. aureus trajectory infection groups (low, high, very high) by census tract and were mapped using ArcGIS. ResultsThree CO-MSSA infection groups (low, high, very high) and two CO-MRSA infection groups (low, high) were detected among 909 census tracts in the 20 counties. We found ~74% of all the census tracts with S.aureus occurrence during this time period belonged to low infection rate groups for both MRSA and MSSA, with a higher proportion occurring in the less densely populated counties. Census tracts in DeKalb County, one of Atlanta’s most densely populated areas, had the highest proportion of the worst infection trend patterns (CO-MRSA high or very high, CO-MSSA high or very high). Trends of Community-Onset MRSA and MSSA Infection Rates Based on Group-based Trajectory Models Spatial patterns for CO-MRSA and CO-MSSA Trajectory Trends in the Atlanta Metropolitan Area Between 2002 to 2016 ConclusionTrends of S. aureus infection patterns, stratified by antibiotic resistance over geographic areas and time, identify communities with higher risks for MRSA infection compared to MSSA infection. Further investigation of the determinants of the trajectory groupings and the geographic outliers identified by this study may be a way to target prevention strategies aimed to prevent S. aureus infections. Disclosures All Authors: No reported disclosures

752. Costs Attributable to Clostridioides difficile Infection in the Presence of Differential Mortality

BackgroundCDI imposes a major burden on the U.S. healthcare system. Obtaining accurate estimates of economic costs is critical to determining the cost-effectiveness of preventive measures. This task is complicated by differences in epidemiology, mortality, and baseline health status of infected and uninfected individuals, and by the statistical properties of costs data (e.g., right-skewed, excess of zeros costs).MethodsIncident CDI cases were identified from Medicare 5% fee-for-service data between 2011 and 2017 and classified into standard surveillance definitions: hospital-onset (HO); other healthcare facility-onset (OHFO); community-onset, healthcare-associated (CO-HCFA); or community-associated (CA). Cases were frequency matched 1:4 to uninfected controls based on age, sex, and year of CDI. Controls were assigned to surveillance definitions based on location at index dates. Medicare allowed costs were summed in 30-day intervals up to 3 years following index. One- and 3-year cumulative costs attributable to CDI were computed using a 3-part estimator consisting of a parametric survival model and a pair of 2-part models predicting costs separately in intervals where death did and did not occur, adjusting for underlying acute and chronic conditions.Results60,492 CDI cases (Figure 1) were matched to 241,968 controls. Three-year mortality was higher among CDI cases compared to matched controls for HO (45% vs 26%) and OHFO (42% vs 36%), whereas mortality was slightly lower for CDI cases compared to controls for those with community onset (CO-HCFA: 28% vs 32%; CA: 10% vs 11%). One- and 3-year attributable costs due to CDI are shown in Figure 2. Adjusted 1-year attributable costs amounted to &26,954 (95% CI: &26,154–&27,939) for HO; &10,539 (&9,564–&11,518) for OHFO; &6,525 (&5,012–&8,171) for CO-HCFA; and &3,171 (&1,841–&4,200) for CA. Adjusted 3-year attributable costs were &44,736 (&43,063–&46,483) for HO; &13,994 (&12,529–&15,975) for OHFO; &7,349 (&4,738–&10,246) for CO-HCFA; and &2,377 (&166–&4,722) for CA.Figure 1. Proportion of Cases by CDI Surveillance Definitions Abbreviations: HO: hospital-onset; OHFO: other healthcare facility-onset; CO-HCFA: community-onset, healthcare-associated; CA: community-associated.Figure 2. Estimates of Costs Attributable to CDI by CDI Surveillance Definitions at One and Three Years after Onset Top panels: One-year cost estimates. Bottom panels: Three-year cost estimates. Abbreviations: HO: hospital-onset; OHFO: other healthcare facility-onset; CO-HCFA:community-onset, healthcare-associated; CA:community-associated.ConclusionCDI was associated with increased healthcare costs across surveillance definitions in Medicare fee-for-service patients after adjusting for survival and underlying conditions.Disclosures Dustin Stwalley, MA, AbbVie Inc (Shareholder)Bristol-Myers Squibb (Shareholder) Margaret A. Olsen, PhD, MPH, Pfizer (Consultant, Research Grant or Support) Holly Yu, MSPH, Pfizer (Employee) Erik R. Dubberke, MD, MSPH, Ferring (Grant/Research Support)Merck (Consultant)Pfizer (Consultant, Grant/Research Support)Seres (Consultant)Summit (Consultant)

1145. The Role of the Plasmid-Mediated Fluoroquinolone-Resistance (PMFQR) Genes As Resistance Mechanisms in Pediatric Infections due to Enterobacterales (Ent)

BackgroundFluoroquinolones (FQs) are not commonly prescribed in children, yet the increasing incidence of multidrug resistant (MDR) Ent infections in this population often reveals FQ resistance. We sought to define the role of FQ resistance in the epidemiology of MDR Ent in children, with an overall goal to devise treatment and prevention strategies.MethodsA case-control study of children (0-18 years) at 3 Chicago hospitals was performed. Cases had infections by FQ susceptible, 3rd generation cephalosporin-resistant (3GCR) and/or carbapenem-resistant (CR) Ent harboring a non or low level expressed PMFQR gene (PMFQS Ent). Controls had FQR infections due to 3GCR and/or CR Ent with expressed PMFQR genes (PMFQR Ent). We sought bla genes by PCR or DNA (BD Max Check-Points assay®) and PMFQR genes by PCR. We performed Rep-PCR, MLST, and E. coli phylogenetic grouping. Demographics; comorbidities; and device, antibiotic, and healthcare exposures were evaluated. Predictors of infection were assessed.ResultsOf 170 G3CR and/or CR Ent isolates, 85 (50%) were FQS; 23 (27%) had PMFQR genes (PMFQS cases). 85 (50%) were FQR; 53 (62%) had PMFQR genes (PMFQR controls). The median age for children with PMFQS Ent and PMFQR Ent were 4.3 and 6.2 years, respectively (p=NS). Of 23 PMFQS Ent, 53% were Klebsiella and of 53 PMFQR Ent, 76% were E. coli. The most common bla and PMFQR genes in PMFQS Ent were blaSHV ESBL (44%); oqxB (57%) and aac-6’1b-cr (52%) and in PMFQR Ent were blaCTX-M-1 group (76%); aac-6’1b-cr (91%) and oqxA (17%).Multivariable regression analysis showed children with PMFQS Ent infections were more likely to have hospital onset infection (OR 5.7, 95% CI 1.6-22) and isolates with multiple bla genes (OR 3.8, 95% CI 1.1-14.5). The presence of invasive devices mediated the effects of healthcare setting in the final model. Differences in demographics, comorbidities, or antibiotic use were not found.ConclusionParadoxically, PMFQS Ent infections were often hospital onset and PMFQR Ent infections were community onset. PMFQS Ent commonly co-harbored multiple bla and PMFQR genes, affecting therapeutic options and suggesting need for contact precautions. Control of PMFQS Ent infections in children will require validating sources and risk factors.Disclosures Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)

9. The Skip Phenomenon in Staphylococcus aureus Bacteremia: Clinical Associations

BackgroundSerial blood cultures are integral in managing Staphylococcus aureus bacteremia (SAB) as clinicians rely on the results to determine infectious complication risks and antibiotic duration. Current IDSA guidelines suggest a single set of negative blood cultures is adequate evidence of SAB clearance. Several studies, however, have identified the skip phenomenon (SP), which is the occurrence of intermittent negative blood cultures, and have recommended obtaining additional blood cultures to document bacterial clearance (Table 1). We therefore examined patients who manifested the SP to determine its clinical significance and to study this, associations were tested for SP in relation to various baseline factors as well as clinical outcomes. MethodsWe performed a retrospective, multicenter study of all patients with a positive blood culture for S. aureus from January 2019 to December 2019 using data collected from electronic health records and the clinical microbiology laboratory. ResultsA total of 602 patients with SAB were identified and 495 patients were included in the investigation (Figure 1). Overall, 25 (5.1%) patients had the SP. Significant differences between those who did and did not manifest the SP included higher rates of injection drug use, automatic implantable cardioverter defibrillator, and community onset of infection in the SP cohort (Table 2). Moreover, the median duration of SAB was longer (3.2 [2.3-5.4] vs 1.90 [1.2-2.9] days, p=0.002), and high-grade SAB, (88.0% vs 58.7%, p=0.004), complicated bacteremia (92.0% vs 67.9%, p=0.011) and IE diagnosis (28.0% vs 11.3%, p=0.013) were all more common in the SP group. In unadjusted outcome analyses, association of SP with hospital length of stay was not significant, although a higher risk of in-hospital mortality among SP patients approached statistical significance (p=0.055). Analysis of 435 hospital survivors revealed no significant differences in rates of 1-year mortality or 90-day relapse between the two groups (Table 3). ConclusionFindings of the current investigation demonstrates an increased risk of SAB complications in patients with the SP and support the notion that serial negative blood cultures are needed to document clearance of SAB. Disclosures Larry M. Baddour, MD, Boston Scientific (Individual(s) Involved: Self): Consultant; Botanix Pharmaceuticals (Individual(s) Involved: Self): Consultant; Roivant Sciences (Individual(s) Involved: Self): Consultant Muhammad R. Sohail, MD, Medtronic (Consultant)Philips (Consultant)

227. Epidemiology of bloodstream infections in Veterans Health Administration, 2010-2020

Abstract Background National trends of bloodstream infections (BSI), their etiologies, and prevalence of resistance are not well described. We reviewed BSI during 2010-2020 in the Veterans Health Administration (VHA), the largest healthcare system in the United States. Methods Demographic, microbiological, and healthcare exposure data were extracted from VHA databases. A case was defined as isolation of a microbe from blood specimens collected from a hospitalized person; common commensals required matching organisms isolated within two consecutive days. The first organism-specific episode within a 14-day period was counted. Staphylococcus, Enterococcus, S. pneumoniae, and gram-negative isolates were assessed for resistance to methicillin, vancomycin, any antimicrobial, and extended-spectrum cephalosporins or carbapenems, respectively. Cases were classified as community acquired (CA-), healthcare-associated community onset (HCO-), and hospital onset (HO-). Trends were estimated by generalized linear mixed models. Results During 2010-2020, incidence of CA-BSI decreased from 42.2 to 27.6 per 100,000 users, HCO-BSI decreased from 63.7 to 40.7 per 100,000 users, and HO-BSI decreased from 28.2 to 16.4 per 100,000 users (Figure 1A). S. aureus and E. coli were the most common in CA-BSI and HCO-BSI; S. aureus and Enterococcus were the most common in HO-BSI; the prevalence of E. coli increased in BSI across classifications (Figure 1B). Incidence of BSI caused by resistant Pseudomonadales and Enterococcus decreased by more than 15% annually; annual incidence of BSI caused by other organisms decreased by less than 10% or remained unchanged with the exception of extended-spectrum cephalosporin resistant E. coli, which increased 6% annually (Figure 2). HO-BSI were more resistant than CA-BSI and HCO-BSI across organisms; resistance among E. coli and S. pneumoniae BSI increased across classifications (Figure 3). Figure 1. Trends of bloodstream infections by organism in Veterans Health Administration, 2010-2020. (A) Incidence per 100,000 users. (B) Percentage of incident BSI by organism. Trends are adjusted for distributions of age, gender, and number of users, in addition to accounting for clustering by county and facility. Community acquired: positive culture collected less than 4 days after hospitalization from a person without previous healthcare exposures. Healthcare-associated community onset: positive culture collected less than 4 days after hospitalization from a person with previous healthcare exposures. Hospital onset: positive culture collected 4 or more days after hospitalization. Figure 2. Percentage change in annual incidence of bloodstream infections by organism in Veterans Health Administration, 2010-2020. Dots represent point estimates and horizontal bars represent 95% confidence intervals. Figure 3. Trends in prevalence of resistance among organisms causing bloodstream infection by epidemiological classification in Veterans Health Administration, 2010-2020 Trends are adjusted for distributions of age, gender, and number of users, in addition to accounting for clustering by county and facility. Community acquired: positive culture collected less than 4 days after hospitalization from a person without previous healthcare exposures. Healthcare-associated community onset: positive culture collected less than 4 days after hospitalization from a person with previous healthcare exposures. Hospital onset: positive culture collected 4 or more days after hospitalization. Conclusion BSI incidence decreased during 2010-2020 across classifications. CO-BSI and HCO-BSI occurred more frequently and were less resistant than HO-BSI. S. pneumoniae and E. coli BSIs became more resistant over time. Increasing incidence of BSI caused by E. coli resistant to extended-spectrum cephalosporins warrants urgent investigation. Disclosures All Authors: No reported disclosures

Epidemiology and Clinical Characteristics of Staphylococcal Bacteremia in Bahrain

Background and Objectives: Staphylococcus aureus bacteremia (SAB) is a significant health problem with high morbidity &amp; mortality. The aim of this study was to evaluate the epidemiology of SAB in Bahrain along with withs clinical characteristics and outcomes. Methods: This study was conducted at Salmaniya medical complex (SMC) microbiology laboratory including all patients with SAB for one year period (2019). Demographic, lab data &amp; outcomes were obtained from the electronic record system of patients. Results: A total of 164 episodes of SAB were identified during the study period. About 137 were encountered among inpatients, while 27 cases among outpatients attending hemodialysis unit. Bahraini nationality &amp; male gender were predominant (141, 85.98% &amp; 108, 65.85% respectively). Nosocomial SAB accounts for only 29.37%, while the majority of SAB cases were of community-onset (116, 70.37%), but among such community-onset cases; 83 (50.61% of total) were of health care-associated category (56 had prior hospitalization and 27 were on regular dialysis). Among all patients with SAB, diabetes was the commonest risk factor encountered, followed by dialysis dependence and sickle cell diseases (SCD). Mortality rate was 25.6% (42 patients). Among the 122 survivors of the initial SAB episode, recurrence of bacteremia was documented among 26 cases (21.3%). Conclusion: SAB was a significant health problem among the Bahraini. Diabetes Mellitus, SCD and dialysis dependence were found to be important risk factors. Recurrence of bacteremia was a common complication among the patient’s dependant on hemodialysis Keywords: Staphylococcus aureus, Bacteremia, Nosocomial, Community onset, Hemodialysis

Risk Factors for Extended-Spectrum-β-Lactamase-Producing Escherichia coli in Community-Onset Bloodstream Infection: Impact on Long-Term Care Hospitals in Korea.

BackgroundThe prevalence of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) in the community has increased worldwide due to multifactorial reasons. ESBL-EC bloodstream infection (BSI) complicates the decision for proper antimicrobial administration. In this multicenter study, we investigated the prevalence, risk factors, and molecular background of community-onset (CO) ESBL-EC BSI.MethodsWe included data for all episodes of ESBL-EC BSI of community origin from May 2016 to April 2017 obtained from the Korean national antimicrobial resistance surveillance system, which comprises six sentinel hospitals. Data, including previous history of admission and use of antimicrobials and medical devices before BSI, were collected, along with microbiological analysis results.ResultsAmong 1,189 patients with CO BSI caused by E. coli, 316 (27%) were identified as ESBL producers. History of admission, especially to a long-term care hospital (LTCH), and previous use of β-lactams/β-lactamase inhibitors, carbapenem, lincosamide, aminoglycoside, and extended-spectrum cephalosporin were independent risk factors for CO ESBL-EC BSI; admission to an LTCH showed the highest odds ratio (3.8, 95% confidence interval 2.3-6.1). The most common genotype was CTX-M-15 (N=131, 41%), followed by CTX-M-14 (N=86, 27%). ST131 was the most common sequence type among ESBL-EC groups (57%).ConclusionsIn Korea, 27% of CO E. coli BSI were caused by ESBL producers. From perspectives of empirical treatment and infection control, history of admission to an LTCH and antimicrobial use should be noted.

Risk factors and outcomes associated with community-onset and hospital-acquired coinfection in patients hospitalized for coronavirus disease 2019 (COVID-19): A multihospital cohort study.

We sought to determine the incidence of community-onset and hospital-acquired coinfection in patients hospitalized with coronavirus disease 2019 (COVID-19) and to evaluate associated predictors and outcomes. In this multicenter retrospective cohort study of patients hospitalized for COVID-19 from March 2020 to August 2020 across 38 Michigan hospitals, we assessed prevalence, predictors, and outcomes of community-onset and hospital-acquired coinfections. In-hospital and 60-day mortality, readmission, discharge to long-term care facility (LTCF), and mechanical ventilation duration were assessed for patients with versus without coinfection. Of 2,205 patients with COVID-19, 141 (6.4%) had a coinfection: 3.0% community onset and 3.4% hospital acquired. Of patients without coinfection, 64.9% received antibiotics. Community-onset coinfection predictors included admission from an LTCF (OR, 3.98; 95% CI, 2.34-6.76; P < .001) and admission to intensive care (OR, 4.34; 95% CI, 2.87-6.55; P < .001). Hospital-acquired coinfection predictors included fever (OR, 2.46; 95% CI, 1.15-5.27; P = .02) and advanced respiratory support (OR, 40.72; 95% CI, 13.49-122.93; P < .001). Patients with (vs without) community-onset coinfection had longer mechanical ventilation (OR, 3.31; 95% CI, 1.67-6.56; P = .001) and higher in-hospital mortality (OR, 1.90; 95% CI, 1.06-3.40; P = .03) and 60-day mortality (OR, 1.86; 95% CI, 1.05-3.29; P = .03). Patients with (vs without) hospital-acquired coinfection had higher discharge to LTCF (OR, 8.48; 95% CI, 3.30-21.76; P < .001), in-hospital mortality (OR, 4.17; 95% CI, 2.37-7.33; P ≤ .001), and 60-day mortality (OR, 3.66; 95% CI, 2.11-6.33; P ≤ .001). Despite community-onset and hospital-acquired coinfection being uncommon, most patients hospitalized with COVID-19 received antibiotics. Admission from LTCF and to ICU were associated with increased risk of community-onset coinfection. Future studies should prospectively validate predictors of COVID-19 coinfection to facilitate the reduction of antibiotic use.

Successful Control of Human Parainfluenza Type 3 Outbreak in a Level IV Neonatal Intensive Care Unit

Human parainfluenza (HPIV) is a common cause for upper respiratory tract illnesses (URTI) and lower respiratory tract illnesses (LRTI) in infants and young children. Here, we describe successful control of an HPIV type 3 (HPIV3) outbreak in a neonatal intensive care unit (NICU). NICU babies with new-onset clinical signs or symptoms of RTI and positive HPIV-3 nasopharyngeal specimen by respiratory pathogen panel (RPP) test on hospital day 14 or later were diagnosed with hospital-onset (HO) HPIV-3 infection. After 3 NICU babies were diagnosed with HO HPIV-3, an outbreak investigation was initiated on May 3, 2019, and continued for 2 incubation periods since the last identified case. Enhanced infection prevention measures were immediately implemented. All positive cases were placed in a cohort in a single pod of the NICU and were placed on contact precautions with droplet isolation precautions. Dedicated staffing and equipment were assigned. Environmental cleaning and disinfection with hospital-approved disinfectant wipes was performed daily. Visitors were restricted in the NICU. All employees entering the NICU underwent daily symptom screening for respiratory tract illness. All NICU babies were screened daily for respiratory tract illness with prompt isolation and RPP testing on positive screen. To determine the source of the HPIV3 outbreak, all HPIV3-positive specimens from the NICU and available temporally associated community-onset (CO) controls collected from non-NICU units were sent to the Centers for Disease Control and Prevention (CDC) for whole-genome sequencing (WGS) analysis. The first and last cases of HPIV-3 were diagnosed on May 1 and May 5, 2019, respectively. In total, 7 HO HPIV3 cases were reported: 1 in newborn nursery (NBN) and 6 in NICU. The case from the NBN was determined to be unrelated to the outbreak and the source was linked to a sick visitor. Of the 6 NICU babies, 5 had an LRTI and 1 had a URTI. Average time from admission to diagnosis was 71 days (range, 24–112). None had severe illnesses requiring intubation, and all had full recovery. No CO HPIV3 cases were reported from the NICU during the investigation. A maximum likelihood phylogenetic tree of HPIV3 WGS (Figure 1) showed that sequences from the 6 HO cases clustered together separately from the 3 CO controls, suggesting a single source of transmission, and 3 CO cases were not related to the HO cases or source of the outbreak. Early diagnosis and isolation of respiratory tract viral infections is important to prevent an outbreak. Successful control of outbreak in NICU requires prompt implementation of infection prevention measures with focus on symptom screening, cohorting, and disinfection practices.Funding: NoDisclosures: None

A Cluster of Aspergillosis Associated with SARS-CoV-2

Background: Coronavirus disease 2019 (COVID-19) has demonstrated a variety of presentations and clinical complications, among them coinfection of pneumonia with the mold Aspergillus spp. Patients at risk for invasive disease include transplant recipients and those with prolonged neutropenia, immune disorders, cystic fibrosis, and steroid use. There have been recent descriptions of coronavirus disease–associated pulmonary aspergillosis (CAPA). An outbreak investigation into a cluster of Aspergillus fumigatus infections in a health system intensive care unit uncovered a community-onset (CO) increase in CAPA. Methods: A multidisciplinary outbreak investigation was conducted evaluating sources of contamination, completion of construction projects, and changes in clinical processes. Retrospective chart review was done for the prior 18 months and incidence density rates for Aspergillus infections from June 2019 through December 2020 were calculated per 10,000 patient days, stratified by unit, specimen source, and coinfection with COVID-19. Data were linked with all positive and negative COVID-19 tests performed by the health system’s regional laboratory from March to December 2020. Healthcare-onset (HO) classification was based on infections identified ≥7 days after admission. Statistical analysis was calculated with significance at p &lt; 0.05. Results: Over the last 18 months, 82 patients were identified positive with Aspergillus cultures; of which 10 (12%) met CAPA definitions. Aspergillus fumigatus was the most common species and accounted for 62% of samples, followed by Aspergillus niger (17%). Median rates of HO Aspergillosis were 0.45 cases per 10,000 patient days, whereas the median total rates of infection were 1.97 cases per 10,000 patient days. Rates of CAPA coincided with COVID-19 hospitalization rates. In the spring and fall, surges of COVID-19, the rate ratio of CAPA to COVID hospitalized infections per 10,000 patient days, ranged from 0.006 to 0.015. Once CAPA infections were adjusted for, rates of CO Aspergillus remained high, whereas HO cases suggested baseline acquisition. Conclusion: This study outlines rates of CO aspergillosis as well as CAPA rates coinciding with the healthcare system’s spring and fall surges of COVID-19 hospitalizations. Despite the determination that this was not a hospital-acquired cluster, the investigation revealed some areas for opportunity in construction processes along with maintaining coverage of all patient supplies to reduce the risk of contamination.Funding: NoDisclosures: None

Hospital Onset Vancomycin-Resistant Enterococci Infections in a Northern California Tertiary-Care Center From 2019 to 2020

Background: Understanding the epidemiology and risk factors for nosocomial infections with vancomycin-resistant enterococci (VRE) is necessary for the prevention and control of VRE infections in the hospital setting. We sought to determine the incidence of nosocomial infections of VRE and to ascertain predictors associated with nosocomial infection. Methods: In this retrospective cohort study, data were collected from patients with VRE infection from January 2019 to December 2020 at a tertiary-care center in northern California. VRE infections were designated as hospital onset (HO) if the specimen was collected &gt;3 days after hospital admission or community onset (CO) if the specimen was collected ≤3 days after admission. Associations between HO infections with time, unit, and specimen were identified. Results: Over the 2-year period, 214 unique VRE infections were identified in hospitalized patients; 115 infections were CO and 99 were HO. HO-VRE were associated most frequently with stay in medical/telemetry units (68%), followed by oncology–transplant units (15%) and ICUs (12%). There were ~4.7 and ~3.6 HO-VRE infections per month in 2019 and 2020, respectively. No differences were identified between HO-VRE infections in 2 medical units regarding glycopeptide and cephalosporin use in those units. The sources of VRE infections were urinary 45%, bloodstream 15%, stool 10%, and other 30%. Of the 45 infections in urine, 51% were identified from catheters (Foley and straight) and 27% were identified from clean-catch urine. Interestingly, 71% of patients with VRE identified from urine did not report urinary tract infection (UTI) symptoms at the time of collection. Urine was most often collected for urinalysis and culture from patients with nonspecific symptoms such as fever, leukocytosis, hypotension, tachycardia, or altered mental status. All urine collected from patients who reported UTI symptoms grew &gt;100,000 CFU/mL in culture, while only 75% of cultures from patients without symptoms grew &gt;100,000 CFU/mL. The most common antibiogram was resistance to ampicillin, cefazolin, levofloxacin, minocycline, penicillin, tetracycline, and/or vancomycin (42% of cases) and susceptibility to both daptomycin and linezolid (60% of cases). Conclusions: HO-VRE infections were frequently identified with urinary sources and were often associated with catheter use. However, the frequent lack of concurrent UTI symptoms suggests VRE colonization rather than infection in many cases. Understanding the epidemiology and risk factors for HO-VRE infections is essential for developing infection prevention protocols to reduce the incidence of those infections.Funding: NoDisclosures: None

Surveillance of Candidemia in Connecticut: An Epidemiological Comparison Between Two Periods

Background: Candidemia is the fourth most common bloodstream infection in hospitalized patients in the United States, with an attributable mortality rate between 30% and 50%. Understanding the epidemiology of candidemia is critical due to its prevalence and association with extended hospital stays, high treatment cost, and significant morbidity and mortality. In 2019 the Connecticut Department of Public Health deemed candidemia a mandatory reportable condition and began state-wide surveillance in conjunction with the CDC’s Emerging Infections Program (EIP). Previously, the EIP had conducted population-based statewide surveillance of candidemia in Connecticut from 1998 to 2000, allowing an opportunity to assess how the epidemiology of candidemia has evolved. The goal of this study is to compare state-wide Connecticut EIP candidemia data from 2 periods (1998–2000 and 2019) to identify trends in infections and incidence, providing insight for potential improvements to current prevention measures and treatments. Methods: The sample population included all Connecticut residents aged ≥20 who tested positive for a candidemia infection during 1998–2000 and 2019. Patients who had positive blood cultures for Candida spp but were &lt; 20 years old or were not Connecticut residents were excluded. Connecticut EIP candidemia case report forms from each time period were compared and matching fields were chosen as variables for univariate analysis to search for statistically significant differences. Selected variables include: Candida species present in blood culture, patient demographics, previous exposures to healthcare settings, length of stay, presence of central venous catheter (CVC), and location of the patient at diagnosis (community vs. hospital onset). De-identified patient-level information was provided by the EIP. Results: In total, 381 candidemia episodes from 1998–2000 were compared to 247 episodes in 2019. The proportion of C. albicans species in 1998–2000 was 49.9% and declined to 40.5% of cases in 2019 (P = .02). Outcomes improved as well, with 65.2% of patients in 2019 having survived compared to 51.4% in 1998–2000 (P = .001). Other findings indicate that patients with candidemia in 2019 were less likely to have a central venous catheter, less likely to have undergone a recent surgery, and were more likely to have community-onset infection (all p &lt; 0.05). Conclusions: The epidemiology of candidemia has changed over the past 20 years, with significant improvements in patient survival and a shift toward community-onset infections and non-Albicans spp. These findings have important implications in designing prevention strategies and optimizing candidemia management, particularly in the community setting where increased intravenous drug use and the availability of home healthcare may be important factors.Funding: NoDisclosures: None