Antipseudomonal vs narrow-spectrum agents for the treatment of community-onset intra-abdominal infections

Background Antipseudomonal antibiotics are often used to treat community-acquired intra-abdominal infections (CA-IAI) despite common causative pathogens being susceptible to more narrow-spectrum agents. The purpose of this study was to compare treatment-associated complications in adult patients treated for CA-IAI with antipseudomonal versus narrow-spectrum regimens. Methods This retrospective cohort study included patients >18 years admitted for CA-IAI treated with antibiotics. The primary objective of this study was to compare 90-day treatment-associated complications between patients treated empirically with antipseudomonal versus narrow-spectrum regimens. Secondary objectives were to compare infection and treatment characteristics along with patient outcomes. Sub-group analyses were planned to compare outcomes of patients with low-risk and high-risk CA-IAI and patients requiring surgical intervention versus medically managed. Results A total of 350 patients were included: Antipseudomonal, n=204; Narrow-spectrum, n=146. There were no differences in 90-day treatment-associated complications between groups (Antipseudomonal 15.1% vs Narrow-spectrum 11.3%, p=0.296). Additionally, no differences were observed in hospital LOS, 90-day readmission, C. difficile, or mortality. In multivariate logistic regression, treatment with a narrow-spectrum regimen (OR 0.75 [95% C.I 0.39-1.45] was not independently associated with the primary outcome. No differences were observed in 90-day treatment-associated complications for patients with low-risk (Antipseudomonal 15% vs Narrow-spectrum 9.6%, p=0.154) or high-risk CA-IAI (Antipseudomonal 15.8% vs Narrow-spectrum 22.2%, p=0.588), or those who were surgically (Antipseudomonal 8.5% vs Narrow-spectrum 9.2%, p=0.877) or medically managed (Antipseudomonal 23.1 vs Narrow-spectrum 14.5, p=0.178). Conclusion Treatment-associated complications were similar among patients treated with antipseudomonal and narrow-spectrum antibiotics. Antipseudomonal therapy is likely unnecessary for most patients with CA-IAI.

Impact of restriction of over-the-counter sales of antimicrobials on antimicrobial resistance in Escherichia coli from community-onset urinary tract infections in inner São Paulo State, Brazil

Background Antimicrobial resistance in community-associated infections is an increasing worldwide concern. In low-to-middle income countries, over-the-counter (OTC) sales of antimicrobials without medical prescription have been blamed for increasing consumption and resistance. We studied the impact of restriction of OTC sales of antimicrobials in Brazil (instituted in October 2010) on resistance trends of Escherichia coli from community-onset urinary tract infections. Methods We analyzed monthly resistance trend of Escherichia coli from community-onset urinary tract infections from 2005 through 2018. The data were submitted to interrupted time series analysis in both linear and Poisson regression models. Results We found impact on cefazolin (p<0.001) and amikacin (p<0.001) resistance as immediate impact of the intervention, and no beneficial impact on resistance to ciprofloxacin, ceftriaxone or sulfamethoxazole-trimethoprim. Conclusion At the present study, we found that OTC sales restriction did not generally impact on antimicrobial resistance.

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

Background CDI 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). Methods Incident 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. Results 60,492 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. Conclusion CDI 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)

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

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

749. A Nurse-Driven Protocol for Early Detection of Clostridiodes difficile Infections

Background Clostridiodes difficile infections (CDI) are a significant cause of hospital acquired infections, resulting in significant morbidity and mortality. Early detection of CDI has been shown to reduce the spread of CDI within the hospital. As nurses are frequently at the patient’s bedside, we proposed to empower the nursing staff to assess, collect stool samples, and order C. difficile testing. Methods Rates of CDI were measured by our Infection Control Department. Hospital-onset CDI (HO-CDI) was defined as a positive C. difficile PCR assay after 3 days of admission, defined as a stay of at least 3 midnights. Community-onset CDI (CO-CDI) was defined as any case that was diagnosed in the Emergency Department or inpatient ward &lt; 3 days of hospitalization based on stool testing as above. Nursing was instructed and empowered to assess, collect stool specimens, and place an order for C. difficile testing, based on the criteria of ≥3 loose or watery stools over 24 hours. Nursing was also educated to not order a test if patients had received stool softeners, enemas, or laxatives within 24 hours. The protocol was initiated in February 2019. Results Rates of HO-CDI increased during the intervention period, rising from 2.6 cases/10000 patient days and peaking at 17.7 cases/10000 patient days (average 6.7 vs. 12.1 monthly cases per 10,000 patient days. Rates of CO-CDI did not significantly change (12.4 vs. 11.5 monthly cases per 10000 patient days). Due to concerns of inappropriate testing, which included testing after laxatives, enemas, or sending specimens despite &lt; 3 stools over 24 hours, the protocol was discontinued in June 2019. Although the HO-CDI rate remained elevated over the next month, the rate subsequently decreased over the next several months (12.1 vs. 8.0 cases per 10000 patient days). Overall testing also increased over the study period (148.3 vs. 169.9 cases/per 10000 patient days).Figure 1 - Clostridiodes difficile rates Figure 2 - CDI testing rates Conclusion A nursing driven protocol resulted in increased HO-CDI and overall CDI rates suggesting that the intervention may have been a factor in increasing the frequency of HO-CDI diagnoses, although the possibility of misdiagnosis of colonization for true CDI cannot be excluded. Further education of nursing staff may be a potential intervention in improving appropriate CDI testing. Disclosures All Authors: No reported disclosures

695. Antipseudomonal Versus Narrow-spectrum Agents for the Treatment of Community-onset Intra-abdominal Infections

Background Antipseudomonal antibiotic regiments are often used to treat community-acquired intra-abdominal infections (CA-IAI) despite common causative pathogens being susceptible to more narrow-spectrum agents. The purpose of this study was to compare post-infection complications in adult patients treated for CA-IAI with antipseudomonal or narrow-spectrum regimens Methods This retrospective cohort study included patients ≥18 years admitted for CA-IAI treated with antibiotics between January 1, 2013, and December 31, 2019. Patients who had bacteremia or peritonitis were excluded. The primary objective of this study was to compare post-infection complications within 90 days between patients treated empirically with antipseudomonal versus narrow-spectrum regimens. Post-infection complication was defined as post-operative infection, recurrence of diverticulitis, or mortality. Secondary objectives were to compare infection and treatment characteristics along with patient outcomes. Sub-group analyses were planned to compare outcomes of patients with low-risk and high-risk CA-IAI and patients who required surgical intervention versus who were medically managed Results A total of 350 patients were included: Antipseudomonal, n=204; Narrow-spectrum, n=146. There were no differences in 90-day post-infection complications between groups (Antipseudomonal 15.1% vs Narrow-spectrum 11.3%, p=0.296). Additionally, no differences were observed in hospital LOS, 90-day readmission, C. difficile, or mortality. Patients treated with Antipseudomonal regimens received longer durations of therapy (median 11 days [IQR 8-14] vs 9 days [IQR 5-12], p&lt; 0.001). No differences were observed in 90-day post-infection complications for patient with low-risk (Antipseudomonal 15% vs Narrow-spectrum 9.6%, p=0.154) or high-risk CA-IAI (Antipseudomonal 15.8% vs Narrow-spectrum 22.2%, p=0.588), or those who were surgically (Antipseudomonal 8.5% vs Narrow-spectrum 9.2%, p=0.877) or medically managed (Antipseudomonal 17.5% vs Narrow-spectrum 13.1%, p=0.463). Conclusion Post-infection complication rates were similar among patients treated with antipseudomonal and narrow-spectrum antibiotics. Antipseudomonal therapy is likely unnecessary for most patients with CA-IAI Disclosures Lisa E. Dumkow, PharmD, BCIDP, Nothing to disclose

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

Background Staphylococcus 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. Methods This 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. Results Three 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 Conclusion Trends 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

1298. Validation of Local Pseudomonas aeruginosa Risk Factors in Patients with Community-Onset Bacterial Pneumonia

Background Clinical guidelines for community-acquired pneumonia (CAP) encourage validation of local risk factors for multidrug-resistant organisms. This study aimed to validate previously derived, local risk factors for Pseudomonas aeruginosa in patients with community-onset bacterial pneumonia at Prisma Health-Midlands’ hospitals. Methods In this retrospective, observational cohort study, adult patients hospitalized with pneumonia MS-DRG codes from January 1, 2017 to March 31, 2020 were randomly screened. Enrolled subjects were admitted to 1 of 3 Prisma Health-Midlands’ hospitals with: diagnosis of pneumonia; receipt of inpatient antibiotics within 48 hours of symptom onset; receipt of over 48 hours of antibiotic therapy; and a causative bacterial pathogen identified via respiratory or blood culture, urinary antigen, or respiratory multiplex PCR panel. Performance of the locally derived score was compared to the Drug Resistance in Pneumonia (DRIP) Score, IDSA 2019 CAP guideline risk factors, and healthcare-associated pneumonia (HCAP) risk factors. Endpoints included sensitivity, specificity, positive and negative predictive value, overall accuracy, and over- and undertreatment rates. Overall accuracy was defined as a case in which the gram-negative antibiotic coverage recommended by the scoring schema would have been appropriate for the identified organism, i.e. neither overtreatment (overly broad-spectrum) nor undertreatment (inadequate spectrum). Results Of 713 patients screened, 36 patients met criteria and were enrolled. The most common bacterial pathogens identified were Pseudomonas aeruginosa (n = 10, 27.8%) and Streptococcus pneumoniae (n = 10, 27.8%). Performance characteristics for each scoring schema are summarized in Table 1. Table 1. Performance characteristics of risk scores predicting for Pseudomonas aeruginosa community-onset bacterial pneumonia. MDRO=multidrug-resistant organism; DRIP=Drug Resistance in Pneumonia Score; IDSA=Infectious Diseases Society of America 2019 Community-Acquired Pneumonia Guideline risk factors ; HCAP=healthcare-associated pneumonia risk factors Conclusion Compared to DRIP or IDSA 2019 CAP risk scores, the local risk score performed well at ruling out resistant gram-negatives given its higher specificity and lower overtreatment rate; yet, it did not perform as well at ruling in resistant gram-negatives given a lower sensitivity and undertreatment rate. All scores performed better than HCAP risk factors. Data from this study will be utilized to further refine the local risk score algorithm. Disclosures P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member) Hana Winders, PharmD, BCIDP, biomerieux (Grant/Research Support) Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder)

Molecular Epidemiology of Community-Onset Clostridioides Difficile Infections At A Tertiary Hospital In Mainland China: A Ten-Year (2010-2019) Retrospective Study

Background: Clostridioides difficile infection (CDI) is an increasingly common disease in healthcare facilities and community settings. However, there are limited reports of community-onset CDI (CO-CDI) in China. We retrospectively analyzed the molecular epidemiology of CO-CDI at a tertiary hospital over a period of 10 years. A total of 1307 stool samples from 1213 outpatients were tested by culturing. The presence of toxin genes (tcdA, tcdB, cdtA, and cdtB) were confirmed by PCR. Toxigenic strains were typed using multilocus sequence typing (MLST). Susceptibility to 9 antimicrobials was evaluated using the E-test.Results: Eighty-nine of 1213 outpatients (7.3%) had CO-CDI, 4 of these patients (4.5%) had one or more recurrence, and there were 95 strains of toxigenic C. difficile. Among these strains, 82 (86.3%) had the tcdA and tcdB genes (A+B+) and 5 of these 82 strains were positive for the binary toxin genes (cdtA and cdtB); the other 13 strains (13.7%) had the tcdB gene only (A−B+). There were 15 different STs, and the most prevalent were ST-54 (23.2%), ST-35 (16.8%), and ST-2 (13.7%). All strains were susceptible to metronidazole and vancomycin, and had low resistance to moxifloxacin and tetracycline, but had high resistance to ciprofloxacin, clindamycin, and erythromycin. Twenty-three isolates (24.2%) were multidrug-resistant.Conclusions: Outpatients with CDI were common during this period in our hospital. The C. difficile isolates had high genetic diversity. All isolates were susceptible to metronidazole and vancomycin, and nearly one quarter of all isolates had multidrug resistance.