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Background Foodborne illnesses cost ∼$90 billion in the United States annually. Antibiotic-resistant infections may be more difficult to treat and can be associated with severe outcomes, leading to higher costs and longer length of stay (LOS). We described LOS and costs for hospital admissions for Salmonella and Shigella infections by resistance status. Methods We reviewed all inpatient admissions from ∼300 hospitals in the Premier Healthcare database during 2012–2019 and included records with culture-confirmed nontyphoidal Salmonella (NTS), typhoidal Salmonella (serotypes Typhi and Paratyphi A, B, and C), or Shigella. We classified infections as resistant if laboratory testing found resistance to ≥1 drug in the clinically important antibiotic categories (fluoroquinolones, macrolides, penicillins, folate pathway antagonists, or third-generation cephalosporins) or susceptible otherwise. We used the Wilcoxon rank sum test to assess difference in median LOS and cost of patient hospitalization for resistant vs. susceptible infections by pathogen type. Results Of 4,168 persons hospitalized, about half (n=2,129, 51%) were female; median age was 52 [IQR: 26‒68] years; 29% (n=1,217) of infections were resistant. For NTS infections, median LOS was 4 [IQR: 3‒7] days for resistant and 4 [IQR: 3‒6] (p=0.04) for susceptible; for typhoidal Salmonella, 6 [IQR: 5‒8] for resistant and 5 [IQR: 3‒8] for susceptible (p=0.15); and for Shigella, 3 [IQR: 2‒4] for both (p=0.09). Median costs were highest for typhoidal Salmonella ($12,577 resistant vs. $9,238 susceptible; p=0.21), followed by NTS ($7,179 vs $6,421, p=0.01) and Shigella ($4,975 vs $5,335; p=0.26). Conclusion Hospitalization costs were higher for patients with some resistant infections. Longer LOS may contribute to higher costs; however, it is not clear whether other pathogen or patient factors (e.g., comorbidities) also contributed. Additional data and adjusted analyses may provide insight into reasons for the cost difference. If resistant infections are shown to be the cause, our findings support that public health interventions to limit the spread of resistant infections could reduce costs. Disclosures All Authors: No reported disclosures.

Background Previous estimates of methicillin-resistant and -sensitive Staphylococcus aureus (MRSA, MSSA) bacteremia rates in hospitalized patients showed decreases in hospital-onset (HO) MRSA, no changes in community-onset (CO) MRSA and HO MSSA, and slight increases in CO MSSA rates from 2012–2017; more recent trends have not been well characterized. Methods We calculated monthly S. aureus bacteremia rates using microbiology data from hospitals reporting antibiotic susceptibility results in the Premier Healthcare Database from January 2017- June 2021. S. aureus blood isolates resistant to methicillin, oxacillin, or cefoxitin were categorized as MRSA. Positive blood cultures collected on or before hospital day 3 were categorized as CO; those collected on day 4 or later were categorized as HO. Annual rate differences were assessed using generalized estimating equation models with a negative binomial distribution adjusting for hospital bed size, teaching status, urban/rural designation, discharge month, census division, distributions of patient age, sex and race and hospital-level clustering. Results Among 11 million discharges from 356 hospitals, we identified 5,627 HO S. aureus bacteremia events: 2,558 (45%) MRSA and 3,069 (55%) MSSA. In 2017, we observed HO MRSA bacteremia rates of 0.41 and HO MSSA rates of 0.49 per 10,000 patient-days. Compared with 2017, adjusted rates of HO MRSA and MSSA bacteremia were significantly higher in 2019, 2020, and 2021 (Figure 1). Of 42,587 CO S. aureus bacteremia events, 19,107 (45%) were MRSA and 23,480 (55%) MSSA. CO MRSA bacteremia rates were lowest in 2017 (1.52 per 1,000 discharges), and adjusted rates were significantly higher in all later years (Figure 2); we observed significant regional variability in annual differences (p=0.018). The observed CO MSSA bacteremia rate was 2.03 per 1,000 discharges in 2017, and adjusted rates were significantly higher in 2020 and 2021. Figure 1.Hospital-Onset MRSA and MSSA Bacteremia Incidence Rate Ratios* with 95% confidence intervals, 2017 – 2021**.*Reference year =2017.**2021 includes data during January – June.***Statistically significant at p Conclusion In contrast with previous trends, recent S. aureus bacteremia rates in this cohort have increased in comparison to 2017. Potential explanations warranting exploration include differences in regional trends and pandemic-associated changes in inpatient risk, severity of illness, length of stay, and hospital utilization Disclosures All Authors: No reported disclosures.

Background Inpatient and outpatient fluoroquinolone (FQ) use has decreased substantially in the last decade; however, the impact of this trend on FQ resistance is less clear. During this period, extended-spectrum β-lactamase (ESBL) Escherichia coli infections have increased. We examined hospital-onset (HO) E. coli clinical culture trends and resistance patterns among hospitalized adult patients in the United States. Methods We measured the incidence of positive clinical cultures from inpatient encounters in a cohort of hospitals submitting data to the Premier Healthcare Database from 2012-2020. We included E. coli cultures with susceptibility testing to FQs or extended-spectrum cephalosporins (ESC). ESC resistance was defined as non-susceptibility to cefotaxime, ceftriaxone, ceftazidime, or cefepime and FQ resistance as resistance to ciprofloxacin, levofloxacin, or moxifloxacin. Co-resistance was defined as both ESC and FQ resistance in the same E. coli isolate. Isolates were classified as FQ resistant only (and not ESC), ESC resistant only (and not FQ), co-resistant, or neither FQ nor ESC resistant. Results The overall proportion of HO E. coli with any FQ resistance decreased 12.3% (from 36.7% in 2012 to 32.2% in 2020). The proportion of HO E. coli with only FQ resistance decreased by 39.8% (from 27.9% in 2012 to 16.8% in 2020); the proportion with only ESC resistance increased by 112.5% (from 2.4% to 5.1%), and co-resistance increased by 75.0% (from 8.8% to 15.4%) (Figure). Figure.Proportion of hospital-onset E. coli infections with selected antibiotic resistance patterns, 2012-2020 Conclusion These results suggest that declining FQ use has been accompanied by declining FQ resistance in E. coli. Increases in FQ and ESC co-resistance may be due to factors including increases in the use of non-FQ antibiotics such as cephalosporins and increased transmission of E. coli strains such as ST131 in which co-resistance is prevalent. Antibiotic stewardship across multiple antibiotic classes combined with infection control measures are likely necessary to reduce multidrug resistant E. coli infections. Disclosures All Authors: No reported disclosures.

Background Pseudomonas aeruginosa is an opportunistic pathogen commonly found in the environment, including water and plumbing, which may serve as a reservoir of spread. We examined P. aeruginosa and carbapenem resistant P. aeruginosa (CRPA) rates and trends in recent years. Methods We assessed rates of P. aeruginosa using microbiology data from over 265 hospitals in the Premier Healthcare Database from January 2017 – December 2020. We identified a cohort of inpatients with any clinical culture yielding an isolate of P. aeruginosa with accompanying susceptibility testing results. Any isolate with at least 1 resistant result to imipenem, meropenem, or doripenem was considered CRPA. Cases were defined as community-onset (CO) when the culture was obtained immediately preceding admission or within the first 3 days of hospitalization, and hospital-onset (HO) when the culture was obtained on day 4 or later. Using monthly hospital level data we modeled cases per discharge, controlling for hospital characteristics, month of discharge, proportion of patients in specific age groups, and proportion of male patients. We developed weights using a raking procedure to match the American Hospital Association distribution for acute care hospitals to produce national estimates. Weighted multivariable logistic regression models were used to estimate national trends in rates per 10,000 discharges. Results Weighted rates of overall, HO, and CO P. aeruginosa and CRPA are shown in Figure 1. From 2019 – 2020, P. aeruginosa adjusted rates increased 7% (p=0.037) (Figure 2). HO P. aeruginosa rates declined 15% from 2017 – 2018 (p=0.014), however HO rates increased 29% in 2020 compared with 2019 (p< .0001). HO CRPA rates did not change during 2018 – 2019 compared with 2017, however HO rates increased 44% in 2020 compared with 2019 (p=0.001). Figure 1.Weighted Rates per 10,000 discharges, 2017 – 2020Figure 2.Pseudomonas aeruginosa and Carbapenem Resistant Pseudomonas aeruginosa Non-Linear Trend Comparisons, 2017 – 2020*Indicates statistical significance at p Conclusion We observed an increase in the overall rate of P. aeruginosa in 2020 compared with 2019, driven by an increase in HO P. aeruginosa rates. HO CRPA rates also increased. Further evaluation of drivers of increasing HO P. aeruginosa infections is warranted, including exploration of the hypothesis that pandemic-associated changes in water use and management, such as intermittent closure and reopening of hospital units, may have increased exposure to water harboring P. aeruginosa. Disclosures All Authors: No reported disclosures.

Background Several studies demonstrated an increase in hospital-onset (HO) infections during the COVID-19 pandemic. We examined trends in the rates of multidrug-resistant (MDR) infections among acute care hospitals in the United States (U.S.) for bacteria commonly associated with healthcare: methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum cephalosporin resistance in Enterobacteriaceae suggestive of extended-spectrum beta-lactamase production (ESBL), vancomycin resistant Enterococcus (VRE), MDR Pseudomonas aeruginosa, carbapenem resistant Enterobacteriaceae (CRE), and carbapenem-resistant Acinetobacter species (CRAB). Methods We measured incidence of clinical cultures yielding the bacterial species of interest among hospitalized patients in a dynamic cohort of hospitals submitting data to the Premier Healthcare Database Special COVID-19 Release during 2019-June 2021. Community-onset (CO) cultures were obtained ≤ day 3 of hospitalization; HO were obtained ≥ day 4. We determined monthly hospital-specific rates for each species. We used generalized estimating equations (GEE) multivariable negative binomial regression models adjusting for hospital characteristics to examine trends. Results From 2019-June 2021, the overall number of hospitals contributing data was 318. Rates for each pathogen are shown in Figures 1 and 2. All pathogens’ HO rates were significantly higher in 2021 compared with 2019. The rates of ESBL, VRE, and CRE were also significantly higher in 2021 when compared to 2020 (Table 1a). For CO rates, we found that MRSA rates decreased significantly during the study period, while ESBL, VRE, and CRE increased with varying degree of significance (Table 1b). Rates of CO MDR Pseudomonas and CO CRAB did not significantly change. Conclusion Our study confirmed that the rates of several MDR infections increased during the COVID-19 pandemic through June 2021, especially HO infections. CO MRSA was the only pathogen with consistent and significant decline. As infections caused by MDR pathogens represent a serious threat to patient safety, further study of factors contributing to the emerging trends may inform prevention strategies during a pandemic. Disclosures All Authors: No reported disclosures.

Background Reports suggest the COVID-19 pandemic in 2020 was associated with increases in hospital-onset AR infections, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp., carbapenem-resistant Enterobacterales (E. coli, Klebsiella spp., and Enterobacter spp.) (CRE) and Acinetobacter spp. (CRAsp), extended-spectrum cephalosporin resistance suggestive of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), and multidrug-resistant Pseudomonas aeruginosa (MDR-PA). To evaluate whether trends were similar for susceptible and resistant strains, we estimated the proportions of these resistant phenotypes in U.S. hospitals. Figure 1.Proportion of hospital-onset pathogens expressing resistant phenotypes, 2018 – 2020 Methods We analyzed 2018–2020 hospital microbiology data in the Premier Healthcare and BD Insights Research Databases. Hospital-onset (HO) infections were those with positive cultures collected after hospital day 3. We used a raking procedure to produce weights to match national hospital characteristics, specifically: U.S. census division, bed size, teaching status, age, gender and urban/rural designation. We used a weighted means survey procedure for annual national estimates and generated annual comparisons with multivariable logistic regression adjusted by hospital characteristics. Results In 589 hospitals, the percentages of HO ESBL-E and CRAsp increased from 2019 to 2020 (Table). Among enterococci, the percentage with vancomycin resistance decreased. The percentages of MRSA, CRE, and MDR-PA did not change. Conclusion Our findings suggest pandemic-related factors, such as changes in antibiotic use or infection control, may have differentially affected susceptible and resistant phenotypes of hospital pathogens. Increases in the percentages of HO CRAsp and ESBL-E suggest these resistant phenotypes may have had a selective advantage over susceptible strains during the pandemic. In contrast, no changes in the percentages of HO MRSA or MDR-PA were observed, suggesting that infection rates increased similarly for resistant and susceptible strains. These findings underscore the importance of strategies to prevent hospital-associated infections and AR that are resilient to pandemic-related stresses on the healthcare system. Disclosures All Authors: No reported disclosures.

BACKGROUND AND OBJECTIVES Limited postauthorization safety data for the Pfizer-BioNTech coronavirus disease 2019 vaccination among children ages 5 to 11 years are available, particularly for the adverse event myocarditis, which has been detected in adolescents and young adults. We describe adverse events observed during the first 4 months of the United States coronavirus disease 2019 vaccination program in this age group. METHODS We analyzed data from 3 United States safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health effects; the Vaccine Adverse Events Reporting System (VAERS), the national spontaneous reporting system comanaged by the Centers for Disease Control and Prevention and Food and Drug Administration; and the Vaccine Safety Datalink, an active surveillance system that monitors electronic health records for prespecified events, including myocarditis. RESULTS Among 48 795 children ages 5 to 11 years enrolled in v-safe, most reported reactions were mild-to-moderate, most frequently reported the day after vaccination, and were more common after dose 2. VAERS received 7578 adverse event reports; 97% were nonserious. On review of 194 serious VAERS reports, 15 myocarditis cases were verified; 8 occurred in boys after dose 2 (reporting rate 2.2 per million doses). In the Vaccine Safety Datalink, no safety signals were detected in weekly sequential monitoring after administration of 726 820 doses. CONCLUSIONS Safety findings for Pfizer-BioNTech vaccine from 3 United States monitoring systems in children ages 5 to 11 years show that most reported adverse events were mild and no safety signals were observed in active surveillance. VAERS reporting rates of myocarditis after dose 2 in this age group were substantially lower than those observed among adolescents ages 12 to 15 years.

Background Multidrug-resistant (MDR) bacteria that are commonly associated with health care cause a substantial health burden. Updated national estimates for this group of pathogens are ne...

Background Although studies have shown blood culture rates have remained stable in recent years, understanding the variability in positivity over time and among hospitals may inform diagnostic and antimicrobial stewardship efforts. Methods We included all discharges from hospitals participating in the Premier Healthcare Database and Cerner Health Facts from 2012-2017 in months where a hospital reported at least one blood culture with antimicrobial susceptibility results. A blood culture episode was defined as one or more cultures drawn within 1 hour. Episodes on or before day 3 were defined as admission episodes (AE), and those drawn on day 4 or later were defined as post-admission episodes (PAE). Culture episodes yielding any organism were categorized as pathogen+ (i.e., at least 1 non-commensal organism identified) or commensal (i.e., only commensal organisms identified). Positive or commensal episode rates were calculated as the percentage of pathogen+ or commensal episodes among all blood culture episodes for AE and PAE. Logistic regression with generalized estimating equation models accounting for hospital-level clustering were used to measure time trends and facility level associations. Results Among 19.6 million discharges in 493 hospitals, 7.5 million blood culture episodes were identified; 336,102 (4.5%) were pathogen+, and 110,236 (1.5%) were commensals. The rate of pathogen+ AEs increased from 4.2% to 4.7% over the study period (p< .0001) and there was no significant temporal trend in the rate of pathogen+ PAEs (p=.7956) (Figure 1). AE commensals decreased significantly in 2016-2017 compared to previous years (1.6% in 2012 to 1.3% in 2017; p=.0092), and PAE commensals decreased significantly over the study period from 2.0% to 1.2% (p< .0001) (Figure 1). We observed substantial inter-hospital variability for each outcome (Figure 2). In addition, differences among hospital characteristics and seasonality were noted for AE and PAE pathogen+ rates and AE commensal rates (Figure 3), but not urbanicity or teaching hospital status. Monthly Positivity Rate of Blood Culture Episodes, Premier Healthcare Database and Cerner Health Facts, 2012-2017 Adjusted Odds Ratios and 95% Confidence Intervals of Blood Culture Episode Positive (Non-Commensal) and Commensal Rates and Associated Characteristics Conclusion While an increase AE pathogen+ rates and decrease in commensal rates could indicate improved culture ordering and collection practices, significant seasonal, regional, and facility-level variability calls for further investigation. Disclosures John A. Jernigan, MD, MS, Nothing to disclose

Background Treating patients with infections due to multidrug-resistant pathogens often requires substantial healthcare resources. The purpose of this study was to report estimates of the healthcare costs associated with infections due to multidrug-resistant bacteria in the United States (US). Methods We performed retrospective cohort studies of patients admitted for inpatient stays in the Department of Veterans Affairs healthcare system between January 2007 and October 2015. We performed multivariable generalized linear models to estimate the attributable cost by comparing outcomes in patients with and without positive cultures for multidrug-resistant bacteria. Finally, we multiplied these pathogen-specific, per-infection attributable cost estimates by national counts of infections due to each pathogen from patients hospitalized in a cohort of 722 US hospitals from 2017 to generate estimates of the population-level healthcare costs in the US attributable to these infections. Results Our analysis cohort consisted of 16 676 patients with community-onset infections and 172 712 matched controls and 8246 patients with hospital-onset infections and 66 939 matched controls. The highest cost was seen in hospital-onset invasive infections, with attributable costs (95% confidence intervals) ranging from $30 998 ($25 272–$36 724) for methicillin-resistant Staphylococcus aureus to $74 306 ($20 377–$128 235) for carbapenem-resistant (CR) Acinetobacter. The highest attributable costs for community-onset invasive infections were seen in CR Acinetobacter ($62 396; $20 370–$104 422). Treatment of these infections cost an estimated $4.6 billion ($4.1 billion–$5.1 billion) in 2017 in the US for community- and hospital-onset infections combined. Conclusions We found that antimicrobial-resistant infections led to substantial healthcare costs.

The Centers for Disease Control and Prevention provides trainings to support implementation of five evidence-based HIV prevention interventions (EBIs) for men who have sex with men (MSM): d-up: Defend Yourself!; Many Men, Many Voices; Mpowerment; Personalized Cognitive Counseling; and Popular Opinion Leader. We evaluated trainees' implementation of these EBIs and, using multivariable logistic regression, examined factors associated with implementation. Approximately 43% of trainees had implemented the EBIs for which they received training. Implementation was associated with working in community-based organizations (vs. health departments or other settings); acquiring training for Mpowerment or Popular Opinion Leader (vs. Personalized Cognitive Counseling); having ≥3 funding sources (vs. one); and having (vs. not having) sufficient time and necessary EBI resources. Findings suggest that implementation may vary by trainee characteristics, especially those related to employment setting, EBI training, funding, and perceived implementation barriers. Efforts that address these factors may help to improve EBI implementation among trainees.

Background Community-onset urinary tract infections (coUTIs) are one of the most common indications for antibiotic prescribing. It is important to understand patient demographic factors associated with microorganisms causing coUTI and their antibiotic resistance profiles, to tailor antibiotic prescribing practices. We analyzed microbiology data to understand factors associated with coUTI in the United States (US). Methods CoUTIs were identified in the Premier Healthcare Database and Cerner Health Facts among patients treated at participating healthcare facilities in the US between 2012-2017. Cases were defined by urine cultures yielding a bacterial organism and were collected in outpatient settings or within three days of hospitalization. Only the first specimen for each encounter was included in the analysis. Data on the organisms isolated, patient’s age, sex, and US census regions of the submitting facilities were described and compared using chi-square tests for associations. Encounters were classified as inpatient (INPT), observation (OBS), emergency department (ED), and outpatient (OTPT) based on the setting in which the culture was submitted. Results Using data from 637 acute care hospitals, urine samples from 3,291,561 encounters were included, with 776,653 (25.7%) INPT, 1,063,219 (34.8%) ED, 107,760 (3.5%) OBS, and 1,092,658 (35.8%) OTPT. The pathogens most frequently associated with coUTIs were Escherichia coli (57.3%), Klebsiella pneumoniae (9.7%), Enterococcus faecalis (5.1%), Proteus mirabilis (4.9%), and Pseudomonas aeruginosa (2.9%). Female sex, age < 65y and OTPT and ED settings were associated with higher relative frequency of E. coli (all p < 0.0001). Male sex, INPT setting and age >65 y were associated with higher relative frequency of P. aeruginosa, P. mirabilis and E. faecalis (all p < 0.0001, Figure). K. pneumoniae was found at higher relative frequency in those >45y, and in INPT and OBS settings (all p < 0.0001). Figure. Distribution of pathogens most frequently associated with community onset urinary tract infections Conclusion Understanding patient factors associated with the microbiology of coUTIs is an important step in developing treatment recommendations and antibiotic stewardship efforts. Further analyses will include assessing the impact of major antibiotic resistance phenotypes, geographic and healthcare settings. Disclosures All Authors: No reported disclosures

Background: Microbiology data are utilized to quantify epidemiology and trends in pathogens, antimicrobial resistance, and bloodstream infections. Understanding variability and trends in rates of hospital-level blood culture utilization may be important for interpreting these findings. Methods: We used clinical microbiology results and discharge data to identify monthly blood culture rates from US hospitals participating in the Premier Healthcare Database during 2012–2017. We included all discharges from months where a hospital reported at least 1 blood culture with microbiology and antimicrobial susceptibility results. Blood cultures drawn on or before day 3 were defined as admission cultures (ACs); blood cultures collected after day 3 were defined as a postadmission cultures (PACs). The AC rate was defined as the proportion of all hospitalizations with an AC. The PAC rate was defined as the number of days with a PAC among all patient days. Generalized estimating equation regression models that accounted for hospital-level clustering with an exchangeable correlation matrix were used to measure associations of monthly rates with hospital bed size, teaching status, urban–rural designation, region, month, and year. The AC rates were modeled using logistic regression, and the PAC rates were modeled using a Poisson distribution. Results: We included 11.7 million hospitalizations from 259 hospitals, accounting for nearly 52 million patient days. The median annual hospital-level AC rate was 27.1%, with interhospital variation ranging from 21.1% (quartile 1) to 35.2% (quartile 3) (Fig. 1). Multivariable models revealed no significant trends over time (P = .74), but statistically significant associations between AC rates with month (P < .001) and region (P = .003), associations with teaching status (P = .063), and urban-rural designation (P = .083) approached statistical significance. There was no association with bed size (P = .38). The median annual hospital-level PAC rate was 11.1 per 1,000 patient days, and interhospital variability ranged from 7.6 (quartile 1) to 15.2 (quartile 3) (Fig. 2). Multivariable models of PAC rates showed no significant trends over time (P = .12). We found associations between PAC rates with month (P = .016), bed size (P = .030), and teaching status (P = .040). PAC rates were not associated with urban–rural designation (P = .52) or region (P = .29). Conclusions: Blood culture utilization rates in this large cohort of hospitals were unchanged between 2012 and 2017, though substantial interhospital variability was detected. Although both AC and PAC rates vary by time of year and potentially by teaching status, AC rates vary by geographic characteristics whereas PAC rates vary by bed size. These factors are important to consider when comparing rates of bloodstream infections by hospital.Funding: NoneDisclosures: None

Background In 2019, CDC updated national estimates of antibiotic resistance. In this abstract we provide national estimates of and trends in proportion of bacterial pathogens expressing resistant phenotypes (%R), specifically: MRSA, VRE, CRE, ESBL, CRAsp, and MDR Pseudomonas, see Figure. Methods We measured incidence of clinical cultures yielding the bacterial species of interest among hospitalized adults in hospitals submitting data to the Premier Healthcare Database, Cerner Health Facts and BD Insights Research Database from 2012- 2017. Community-onset (CO) cultures were obtained ≤ day 3 of hospitalization; hospital-onset (HO) were obtained ≥ day 4. We determined hospital-specific %R for each species. We generated national estimates using a raking procedure to generate weighted adjustments to match the distribution for all U.S. acute care hospitals based on U.S. census division, bed size, teaching status, and urban/rural designation. We applied a weighted means survey procedure to calculate national estimates for each year. We used weighted multivariable logistic regression adjusting for hospital characteristics to examine trends. Results From 2012-2017, the overall number of hospitals contributing data was 890 (over 20% of U.S. hospital hospitalizations annually). National estimates and trends of %R are shown in the Figure. Between 2012-2017, significant annual decreases in %R were observed for MRSA, VRE, CRAsp, and MDR Pseudomonas. CRE %R did not change. Overall ESBL %R increased by 44% (CO=49% increase, HO=27% increase). Conclusion Reductions in %R were observed among MRSA, VRE, CRAsp, and MDR Pseudomonas, suggesting that prevention efforts focused in health care settings are having a disproportionate effect on resistant strains. However, %R remains unacceptably high for all pathogens we studied, and %R among ESBL-producing Enterobacteriaceae has increased, most prominently among CO infections. Continued focus on currently recommended intervention strategies as well as new ones for community onset infections is needed. Disclosures All Authors: No reported disclosures

Background Escherichia coli is a common cause of community-onset (CO) infections, including urinary tract and abdominal infections, and CO sepsis. Fluoroquinolones (FQ) are used in the empiric treatment of E. coli infections, but FQ-resistance may limit their effectiveness. We examined trends and regional differences in FQ-resistant E. coli clinical cultures among hospitalized adult patients in the U.S. Methods We measured the incidence of E. coli clinical cultures among hospitalized adults in a cohort of hospitals in the Premier Healthcare Database and Cerner Health Facts from 2012 through 2017. FQ resistance was defined as resistance to ciprofloxacin, levofloxacin, or moxifloxacin. Only cultures collected prior to day 4 of hospitalization, defined as CO, were considered. We extrapolated national estimates using a raking procedure to generate weighted adjustments matching the American Hospital Association distribution for U.S. acute care hospitals. Weights were based on U.S. census division, bed size category, teaching status, and urban/rural designation. We used a weighted means survey procedure to calculate national estimates and weighted multivariable logistic regression to examine trends and regional differences. Results In 2017, we estimated 949,393 CO E. coli infections with FQ susceptibility testing; 312,304 (33%) were due to E. coli resistant to FQ. Of FQ-resistant E. coli isolates, 76% were isolated from urine. We did not observe a significant trend in FQ-resistant E. coli from 2012 to 2017 (p = 0.85). Percent FQ-resistant varied significantly by region (p < 0.0001) with an estimated range of 19% (Mountain) to 42% (Southeast Central) in 2017. We also found variability by hospital (2017 Q1: 26% and Q3: 39%). FQ-resistance rates were higher in urine (36%: 95% CI 34-38%) than blood isolates (27%: 95% CI 26-29%) and higher for males (40%: 95% CI 38-42%) than females (33%: 95% CI 31-35%). Conclusion FQ-resistance is common in CO E. coli infections with significant variability by region and hospital. Empiric FQ treatment for infectious syndromes commonly caused by E. coli may need to be reconsidered. Clinicians should consult with local antibiograms and antibiotic stewardship programs to determine the most appropriate empiric treatment of E. coli infections in hospitalized adults. Disclosures All Authors: No reported disclosures

Background Decreasing inappropriate urine cultures in hospitalized patients has been a target of diagnostic stewardship to improve infection surveillance and antimicrobial use. The impact of such efforts has been largely unstudied. This study assessed temporal trends in urine culture rates in a cohort of acute care hospitals (ACHs) between 2012 and 2017. Hospital Level Variation in Admission Urine Culture Rates Hospital Level Variation in Post-admission Urine Culture Rates Methods We used microbiology data from ACHs participating in the Premier Healthcare Database and Cerner Health Facts to measure monthly urine culture rates. All cultures from the urinary tract collected on or before day 3 were defined as admission cultures (AC) and those collected on day 4 or later as post-admission cultures (PAC). Temporal trends in AC and PAC rates were estimated using general estimating equation models adjusting for hospital-level clustering, hospital size, teaching status, urban/rural designation, discharge month, and region. Results During the study period, ACHs had 20.8 million discharges and performed 4,946,717 urine cultures, of which 21% were PAC. In 2012 and 2017, the unadjusted AC rates were 18.7 and 18.4 per 100 discharges; the unadjusted PAC rates were 11.5 and 8.5 per 1,000 patient days (PD) respectively. The median annual hospital-level AC rate was 17.2 with inter-hospital variation ranging from 12.7 (quartile 1) to 24.1 (quartile 3) per 100 discharges, Figure 1. Similarly, the PAC rates varied among the ACHs with a median of 7.1 and inter-hospital variation ranging from 4.6 (quartile 1) to 10.5 (quartile 3) per 1,000 PDs, Figure 2. In multivariable analysis, no temporal trends in AC rates were detected (rate ratio (RR) 1.01; 95% confidence interval (CI): 0.99–1.02). However, PAC rates decreased 6.3% annually (RR 0.937; 95% CI: 0.93–0.95). Factors significantly associated (p< 0.02) with PAC rates were discharge month, teaching status, bed size, and region. For AC, significant associations (p< 0.0001) were discharge month and region. Conclusion Between 2012 and 2017, the rate of AC remained unchanged, but PAC rates decreased significantly. Factors driving this trend are unknown, but potential explanations include changes in culturing practices and/or decreases in hospital-onset urinary tract infections. Understanding factors related to the decrease and the impact on patient outcomes warrants further study. Disclosures All Authors: No reported disclosures

Background: Studies on the effectiveness of hospital-based interventions often measure hospital-onset infections as the outcome of interest. However, hospital-associated infections may manifest after patient discharge (classified as hospital-associated community-onset, HACO), and the epidemiology may vary by antibiotic resistance (AR) profile. We examined the epidemiology and trends of HACO infections of AR and non–antibiotic-resistant (non-AR) bacteria. Methods: We included clinical community-onset (CO) cultures (obtained sooner than or on day 3 of hospitalization) yielding the bacterial species of interest among hospitalized patients in 260 hospitals in the Premier Healthcare Database from 2012 to 2017. HACO infections were defined as CO cultures in a patient who had a previous hospitalization in the same hospital within 30 days. We examined methicillin resistance among Staphylococcus aureus (MRSA), vancomycin resistance among Enterococcus spp (VRE), carbapenem resistance among Enterobacteriaceae (E. coli, Klebsiella spp, and Enterobacter spp) (CRE), extended-spectrum cephalosporin resistance suggestive of extended-spectrum β-lactamase (ESBL) production in Enterobacteriaceae, carbapenem resistance among Acinetobacter spp (CRAsp), and carbapenem resistance among Pseudomonas aeruginosa (CRPA). We described the proportion of CO infections that were HACO, the proportion of HACO infections from sterile sites, overall HACO rates, and annual trends for sensitive and resistant phenotypes. Generalized estimating equation regression models that accounted for hospital-level clustering were used to estimate annual trends controlling for hospital characteristics and month of discharge. Results: The rate of HACO infections by pathogen ranged from 0.78 to 38.76 per 10,000 hospitalizations; 7%–34% were sterile site infections (Table 1). For each bacterial pathogen, a significantly higher proportion of AR CO infections had a previous hospitalization compared to non-AR CO infections (all χ2, P < .05). The annual trends for AR and non-AR HACO infections between 2012 and 2017 were significantly decreasing for most pathogens, except ESBL HACO infections. Conclusions: Even when using a definition limited to readmission to the same hospital, HACO infections occur commonly with differing rates by pathogen and antibiotic resistance profile. Although these rates are decreasing for most of the pathogens studied, improving surveillance and identifying prevention strategies for these infections are necessary to further reduce the burden of hospital-associated infections.Funding: NoneDisclosures: None

Background Difficult-to-treat resistance (DTR) is a metric for clinically relevant “pan-resistance” to available high-efficacy, low-toxicity antibiotic treatment options at any given time. Previous DTR prevalence estimates in Gram-negative (GN) bloodstream isolates from 2009 to 2014 have ranged between 1 and 1.5%. We sought to estimate the national burden of DTR GN isolates and more recent trends by region, site, and species. Methods Clinical cultures with GN isolates were identified from inpatient encounters in hospitals reporting at least one culture with susceptibility testing for a given month to Premier Healthcare Database or Cerner Health Facts Database from 2012 to 2017. DTR was defined as intermediate susceptibility or resistance to all tested carbapenems, other β-lactams, and fluoroquinolones, but not including agents introduced 2014 onwards. For each year, a raking procedure generated weights to extrapolate the sample estimate to match American Hospital Association distributions based on US census division, hospital bed capacity, teaching status, and urban designation. A weighted means survey procedure was used to extrapolate the sample estimate to obtain national DTR burden. Trends in DTR incidence were examined by using weighted multivariable logistic regression. Results Extrapolating from a 373-hospital sample, the estimated 2017 US inpatient burden of DTR isolates was 3,315 (1.3%) among sterile-site and 31,509 (1.7%) among all cultures, ranging from 0.5% to 3.3% in Mountain and New England regions respectively. P. aeruginosa was the most common species overall (37%), while A. baumannii was most common among sterile sites (31%). Between 2012 and 2017, there was no annual percent change in DTR incidence for sterile sites [OR 0.99 (0.93, 1.06)] but for all cultures it decreased 4.1% annually [OR 0.95 (0.91, 0.99)], including 9% annually for A. baumannii [OR 0.905 (0.860, 0.953)] and K. pneumonia [OR 0.903 (0.824, 0.991)], respectively. Conclusion The US inpatient burden of GN isolates displaying DTR is relatively low, varies by region, and has remained stable or declined slightly in recent years. Periodic inclusion of emerging antibiotics in the DTR classification will allow for a dynamic index between resistance and available agents. Disclosures All Authors: No reported Disclosures.

Background Extended spectrum β-lactamase-producing Enterobacteriaceae (ESBLs) have been identified as a serious antibiotic-resistant threat. Studies have shown that ESBL infection rates were increasing through 2014. Our objective was to examine more recent ESBL trends and to evaluate differences across regions in the United States. Methods We measured the incidence of positive clinical cultures from inpatient encounters in a cohort of hospitals submitting data to the Premier Healthcare Database and Cerner Health Facts from 2012 through 2017. We included Escherichia coli and Klebsiella spp. cultures and defined ESBL as non-susceptibility to cefotaxime, ceftriaxone, ceftazidime, or cefepime. Cultures collected on days 1, 2, or 3 of hospitalization were considered community-onset (CO); cultures from day 4 or later were considered hospital onset (HO). We developed weights using a raking procedure to match the American Hospital Association distribution for acute care hospitals based on US census division, bed size category, teaching status, and urban/rural designation. We used weighted multivariable logistic regression adjusting for hospital characteristics to examine trends and regional differences in ESBL rates. Results In 2017, the estimated rate of ESBLs was 40.3 per 10,000 discharges for CO and 6.4 per 10,000 discharges for HO; 86% of all ESBLs were CO. The percent that were ESBLs among all included cultures increased for CO (8.2% in 2012 to 11.6% in 2017) and HO (13.1 to 16.8%) cultures. From 2012 – 2017, adjusted ESBL rates increased for CO (7.9% annually, P < 0.0001), while HO rates did not change significantly over time (P = 0.39, Figure 1). We found significant regional differences in the rates of ESBL (P < 0.0001) across US census divisions in 2017 (Figure 2). Estimated rates for 2017 varied 5-fold from 15.3 ESBLs per 10,000 discharges in the Northwest Central to 82.4 ESBLs in the Mid-Atlantic. Conclusion We estimated a 40% increase in the rate of CO-ESBLs among hospitalized patients from 2012 to 2017, but no increase in HO rates. ESBL rates varied greatly by region of the country and are estimated as much as 5× higher in some areas. A better understanding of factors contributing to community transmission and regional variation is necessary in order to inform ESBL prevention efforts. Disclosures All authors: No reported disclosures.

Objective: The purpose of this study was to evaluate the use of empirical vancomycin for patients with neutropenic fever (NF) with regard to adherence to treatment guidelines. Methods: Adult patients with a diagnosis of neutropenia, who met the definition of NF as per treatment guidelines, were identified. Use of vancomycin was evaluated as part of empirical therapy and again after 72 h. Outcomes were assessed using descriptive statistics, the Chi-square or Fisher’s exact test, and univariate exact logistic regression analyses. Results: Sixty-four patients were included. Overall, inappropriate empirical vancomycin use was observed in more than 30% of patients. Of 35 patients with indications for empirical vancomycin, only 68% received it. At 72 h, appropriate vancomycin continuation, de-escalation, or discontinuation occurred in 21 of 33 patients. On univariate regression, hematological malignancy was associated with appropriate empirical vancomycin prescribing, whether initiating or withholding (odds ratio 4.0, 95% confidence interval 1.31–12.1). No variable was independently associated with inappropriate continuation at 72 h. Conclusions: There is poor guideline adherence to vancomycin prescribing as empirical therapy and at 72-h reassessment in patients with NF. Further efforts are needed to foster a more rational use of vancomycin in patients with NF. Keywords: Antibiotics, Neutropenia, Neutropenic fever, Vancomycin

The incidence of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection has been increasing with over 10 million people affected globally. The role biomarkers play as predictors of cardiovascular disease (CVD) risk among coinfected individuals is not well defined. We aimed to systematically review current evidence describing CVD biomarkers among individuals with HIV/HCV coinfection. We searched EMBASE, CINAHL, Google Scholar, PubMed, and Web of Science from inception to June 2017. MeSH terms and keywords were used to identify studies with information on HIV/HCV coinfection and CVD biomarkers (structural, functional, and serological) such as carotid intima-media thickness (CIMT), endothelial markers, C-reactive protein (CRP), homocysteine, and lipids. Among 332 articles screened, 28 were included (39,498 participants). Study designs varied: 18 cross-sectional, 9 cohort, and 1 clinical trial. Compared with healthy controls and people with HIV or HCV monoinfection, individuals with HIV/HCV coinfection had statistically significant lower levels of lipids and CRP and higher levels of endothelial markers (sICAM-1 and sVCAM-1), CIMT, homocysteine, and IL-6. One study found the odds of carotid plaque in coinfected individuals was 1.64 (0.91-2.94) compared with healthy controls, and another study showed the prevalence of vascular plaques (carotid and femoral) in coinfected individuals was higher compared with HIV monoinfected individuals (44% vs 14%, P = 0.04). Biomarkers of CVD have different patterns of association with HIV/HCV coinfection compared with monoinfection and healthy controls. Prospective studies are needed to confirm the predictive value of these biomarkers for clinical CVD risk among coinfected individuals.

Introduction: With improved antiretroviral therapy, the life expectancy of people living with human immunodeficiency virus (HIV) has increased. However, these individuals are now more susceptible to developing cardiovascular diseases (CVD). Prior studies examining the association between HIV and hepatitis C virus (HCV) co-infection and the risk of CVD, compared to HIV mono-infection, have differed in their conclusions. We conducted a systematic review and meta-analysis to clarify and quantify the association between HIV/HCV co-infection and CVD risk. We hypothesized that CVD risk will be synergistically increased by the persistent inflammatory responses of both viruses. Methods: We searched EMBASE, CINAHL, Google Scholar, PubMed, and Web of science from inception to October 2016 to identify studies on HIV/HCV co-infection and CVD, defined as coronary artery disease, congestive heart failure and stroke. The search was supplemented with a review of the reference list of articles. We used a random-effects model to abstract and pool data on the hazard ratios (HRs) for CVD. Hazard ratios were adjusted for traditional CVD risk factors. Results: Among the 280 articles reviewed, 4 cohort studies met the inclusion criteria with a total of 33,723 participants. Of these, 8,109 (24%) were HIV/HCV coinfected, 18,958 (56%) were HIV monoinfected while 6,656 (20%) comprised HCV monoinfected, HIV uninfected, and HIV/HBV coinfected participants. Pooled adjusted HRs for the association between HIV/HCV co-infection and CVD was 1.24 (95% CI 1.07-1.40) compared to HIV mono-infection. Test for homogeneity was not statistically significant [I 2 = 0.0%, P=0.397] (Figure). Conclusion: We found a consistent positive association showing that individuals with HIV/HCV coinfection had an increased CVD risk compared to those with HIV monoinfection. However, more research is needed to further examine this association, determine potential underlying mechanisms and evaluate whether treatment for HIV and HCV infections can reduce CVD outcomes.

Background Carbapenem-nonsusceptible Acinetobacter spp. (CNAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are recognized causes of severe and difficult to treat healthcare-associated infections. This study estimated and compared the incidence of CNAB and CRPA among patients admitted to US acute care hospitals in 2012–2017. Methods We measured the incidence of positive clinical cultures from inpatient encounters in a cohort of over 300 hospitals submitting data to the Premier Healthcare Database and Cerner Health Facts in 2012–2017. We included clinical cultures from any body site yielding Acinetobacter spp./P. aeruginosa non-susceptible/resistant to imipenem, meropenem, or doripenem. Cultures collected on days 1–3 of hospitalization were considered community-onset (CO) and cultures from later were hospital-onset (HO). Duplicate isolates identified within 14 days of an incident culture and surveillance cultures were excluded. For each year, a raking procedure generated weights to extrapolate the sample estimate to match the American Hospital Association distributions based on US census division, hospital bed capacity, teaching status, and urban designation. We compared estimated rates in 2017 vs. 2012 using weighted multivariable logistic regression adjusting for hospital characteristics and hospital-level clustering. Results In 2017, the estimated rates of HO and CO CNAB rates were 0.77 and 1.39/10,000 discharges, and HO and CO CRPA rates were 3.14 and 6.57, respectively. Compared with 2017, rates of HO CNAB decreased 49% (Odds Ratio (OR) 0.51; 95% CI: 0.34–0.75) and rates of CO CNAB decreased 29% (OR 0.71; 95% CI: 0.54–0.92). For CRPA, the incidence of HO decreased (OR 0.66; CI: 0.49–0.88) with no change in CO rates (OR 0.93; CI: 0.79–1.11). Assessment of cultures from sterile sites alone showed similar results, but they did not reach statistical significance, Figure 1. Conclusion We estimate significant national decreases in the rates of HO and CO CNAB, and HO CRPA. Risk factors and effective interventions to reduce CO CRPA might differ from CNAB and HO CRPA. Additional prevention strategies are needed to address CO CRPA. Disclosures All authors: No reported disclosures.

The emergence of improved antiretroviral therapy has increased the life expectancy of human immunodeficiency virus (HIV)-infected individuals, though there is an increased susceptibility to developing cardiovascular diseases (CVD). The risk for CVD is purported to be even higher among people with HIV and hepatitis C virus (HCV) co-infection because of the increased inflammatory response, which may synergistically impact CV risk; however, studies comparing CV outcomes between HIV alone and HIV/HCV individuals have been discordant. Accordingly, we conducted a meta-analysis to clarify and quantify the association between HIV/HCV co-infection and the risk for CVD. We searched EMBASE, CINAHL, Google Scholar, PubMed, and Web of Science from inception to December 2016 to identify studies that provided information on HIV/HCV co-infection and CVD, defined as coronary artery disease, congestive heart failure and stroke. We used a random-effects model to abstract and pool data on the hazard ratios (HRs) for CVD. Hazard ratios were adjusted for traditional CVD risk factors including age, sex, smoking, hypertension, diabetes, and LDL cholesterol. Among the 283 articles reviewed, 4 cohort studies met inclusion criteria with a total of 33,723 participants. The pooled adjusted HRs for the association between HIV/HCV co-infection and CVD was 1.24 (95% CI 1.07-1.40) compared to HIV mono-infection. The test for heterogeneity was not statistically significant (I2= 0.0%, P=0.397). In conclusion, individuals with HIV/HCV coinfection had an increased risk compared to those with HIV monoinfection. More research is needed to further examine the nature of this association, and response to traditional risk reductive therapies. This article is protected by copyright. All rights reserved.

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Bacillus subtilis consists of a large collection of strains from which several cryptic species have been delineated, and most of these along with strains within the species are important biocontrol agents. Bacillus mojavensis , a species recently distinguished from this broad B. subtilis group of bacteria, was determined to be endophytic and to have biocontrol potential due to its inhibition of the maize mycotoxic fungus Fusarium verticillioides . Recently, we reported that a patented strain B. mojavensis produced the biosurfactant Leu 7 -surfactin that was inhibitory to fungi. In this study, the first objective was to validate the identity of strains, and analyze genotypically a collection of B. mojavensis strains, which involved analysis of repetitive-PCR amplified Bacillus DNA sequences with a PCR genotyping bar system. In an effort to understand further surfactin production, a second objective was to screen this collection of B. mojavensis strains for surfactin analogs. The results indicated that all strains are valid B. mojavensis , and that there was genotypic diversity among strains from the great deserts. Further, the study established that most strains can produce a mixture of surfactins that was comprised of acyl chain lengths ranging from C-11 to C-17. These experiments indentified high producers of C-15 surfactin, the most biologically active isoform. However, the in vitro inhibition observed did not necessarily relate to total surfactin concentrations, suggesting a complex mechanism for inhibition and/or the presence of other unknown factors.

Gram-positive endophytic bacteria are difficult to transform. To study the interactions between Bacillus mojavensis and maize, a method was developed to transform the microbe by electroporation with three integration plasmids expressing green, cyan and yellow fluorescent proteins (GFP variants). GFP Transformations were verified by antibiotic selection, microscopy and amylase deficiency, based on incorporation of the plasmids through recombination with the amylase gene. Phenotypic expressions of endophytism and fungal antagonisms of the transformants were the same as wild type stains. This represents the first successful transformation of this endophytic species with GFP markers.

In an alternate reading frame overlapping the viral envelope gene, HIV-1 has been shown to encoded a truncated glutathione peroxidase (GPx) module. Essential active site residues of the catalytic core regions of mammalian GPx sequences are conserved in the putative viral GPx (vGPx, encoded by the env-fs gene). Cells transfected with an HIV-1 env-fs construct show up to a 100% increase in GPx enzyme activity, and are protected against the loss of mitochondrial transmembrane potential and subsequent cell death induced by exogenous oxidants or mitochondrial reactive oxygen species. An intact vGPx gene was observed to be more common in HIV-1-infected long-term non-progressors, as compared to HIV-1 isolates from patients developing AIDS. An antioxidant/antiapoptotic protective role of the vGPx is also consistent with the observation that -1 frameshifting induced by the HIV-1 env-fs sequence AAAAAGA (which contains a potential "hungry" arginine codon, AGA) increases during arginine deficiency, which has been associated with increased oxidative stress. Under arginine-limited conditions, nitric oxide synthase generates superoxide, which rapidly combines with NO to form peroxynitrite, which can cause activated T-cells to undergo apoptosis. Thus, biosynthesis of the HIV-1 GPx as an adaptive response to low arginine conditions might delay oxidant-induced apoptotic cell death, providing an enhanced opportunity for viral replication.

Ribosomal frameshifting is used by various organisms to maximize protein coding potential of genomic sequences. It is commonly exploited by RNA viruses to overcome the constraint of their limited genome size. Frameshifting requires specific RNA structural features, such as a suitable heptanucleotide “slippery” sequence and an RNA pseudoknot. Previous genomic analysis of HIV-1 indicated the potential for several hidden genes encoded through frameshifting; one of these, overlapping the envelope gene, has an RNA pseudoknot just downstream from a slippery sequence, AAAAAGA that features an adenine quadruplet prior to a potential hungry arginine codon (AGA). This env-frameshift (env-fs) gene has been shown to encode a truncated glutathione peroxidase homologue, with both antioxidant and anti-apoptotic activities in transfected cells. Using a dual reporter cell-based frameshift assay, we demonstrate that the env-fs frameshift sequence is active in vitro. Furthermore, in arginine deficient media, env-fs frameshifting increased over 100% (p < 0.005), consistent with the hypothesized hungry codon mechanism. As a response to arginine deficiency, increased expression of the antioxidant viral GPx gene (env-fs) by upregulation of frameshifting could be protective to HIV-infected cells, as a countermeasure to the increased oxidative stress induced by arginine deficiency (because NO is a known scavenger of hydroxyl radical).