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BACKGROUND. The clinical outcomes associated with, and risk factors for, carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) in solid organ transplant (SOT) recipients remain ill-defined. METHODS. A multicenter retrospective cohort study was performed, including SOT recipients with an Enterobacterales BSI between 2005 and 2018. Exposed subjects were those with a CRE BSI. Unexposed subjects were those with a non-CRE BSI. A multivariable survival analysis was performed to determine the association between CRE BSI and risk of all-cause mortality within 60 d. Multivariable logistic regression analysis was performed to determine independent risk factors for CRE BSI. RESULTS. Of 897 cases of Enterobacterales BSI in SOT recipients, 70 (8%) were due to CRE. On multivariable analysis, CRE BSI was associated with a significantly increased hazard of all-cause mortality (adjusted hazard ratio, 2.85; 95% confidence interval [CI], 1.68-4.84; P < 0.001). Independent risk factors for CRE BSI included prior CRE colonization or infection (adjusted odds ratio [aOR] 9.86; 95% CI, 4.88-19.93; P < 0.001), liver transplantation (aOR, 2.64; 95% CI, 1.23-5.65; P = 0.012), lung transplantation (aOR, 3.76; 95% CI, 1.40-10.09; P = 0.009), and exposure to a third-generation cephalosporin (aOR, 2.21; 95% CI, 1.17-4.17; P = 0.015) or carbapenem (aOR, 2.80; 95% CI, 1.54-5.10; P = 0.001) in the prior 6 months. CONCLUSIONS. CRE BSI is associated with significantly worse outcomes than more antibiotic-susceptible Enterobacterales BSI in SOT recipients.

Background Gram negative rod (GNR) bloodstream infections in patients requiring ICU level of care are associated with high risk of mortality. Very limited data is available on specific risk factors that are associated with this high mortality. The purpose of this study was to identify characteristics associated with mortality in ICU patients who were diagnosed with GNR bacteremia. Methods This was an IRB approved retrospective chart review that was conducted during November 2019 to November 2021 at a three hospital health system in NJ. Patients were included if they required ICU level of care, age ≥ 18 years old and had documented gram negative bacteremia. Patients were excluded if they had metastatic cancer, left against medical advice, or the blood culture was determined to be a contaminant. The primary endpoint of the study was to evaluate the association of characteristics and risk factors with all-cause inpatient mortality (ACIM) in patients with GNR bacteremia requiring ICU level of care. Secondary endpoints included impact of time to appropriate therapy and time to microbiologic cure on ACIM. Results There was a total of 79 patients who met inclusion criteria. The median age of patients was 69 years, 44% of the patients were female, and 81% of patients were in septic shock upon presentation to the ICU. The most common source of GNR bacteremia was urinary tract, followed by lower respiratory tract. The most common causative organism of bacteremia was E.coli, causing 25% of the cases. When evaluating primary endpoint, higher CCI (OR = 1.79, 95% CI [1.09-2.94]), and Pitt Bacteremia (OR = 2.1, 95% CI [1.32-3.35]) scores were independently associated with an increased risk of mortality in patients with gram-negative bacteremia in the ICU setting. Microbiologic cure was associated with a lower risk of mortality (OR=0.02, 95% CI [0.002-0.2]). Longer time to appropriate therapy and microbiologic cure were not associated with increased ACIM. Results Enterobacterales Breakdown Conclusion Patients admitted with GNR bacteremia requiring ICU level of care with higher CCI and Pitt Bacteremia scores have higher likelihood of suffering from ACIM. Microbiologic cure was independently associated with lower risk of ACIM. In a subset of patients, longer time to appropriate therapy and microbiologic cure was not associated with increased ACIM. Disclosures All Authors: No reported disclosures.

Background Approximately 40% of all Enterobacterales (EB) bloodstream infections (BSIs) among solid organ transplant recipients (SOTRs) are due to extended-spectrum β-lactamase (ESBL)–producing organisms, but risk factors for such infections remain ill defined in this population. We sought to determine the risk factors for ESBL-EB BSIs among SOTRs. Methods A multicenter case-control study was performed. All SOTRs with an EB BSI at the Hospital of the University of Pennsylvania and University of Maryland Medical Center between 1 January 2007 and 30 June 2018 and at The Johns Hopkins Hospital between 1 January 2005 and 31 December 2015 were included. Cases were those with an ESBL-EB BSI. Controls were those with a non–ESBL-EB BSI. Multivariable logistic regression was performed to determine risk factors for ESBL-EB BSI. Results There were 988 episodes of EB BSI, of which 395 (40%) were due to an ESBL-EB. On multivariable analysis, the independent risk factors for ESBL-EB BSI included: ESBL-EB on prior culture (aOR, 12.75; 95% CI, 3.23–50.33; P Conclusions We identified several novel risk factors that are uniquely important to the SOTR population, including exposure to trimethoprim-sulfamethoxazole and corticosteroid-containing immunosuppressive regimens. Further studies exploring these associations and testing interventions aimed at these modifiable risk factors among SOTRs are needed.

BackgroundRespiratory infections have long been associated with higher maternal and perinatal morbidity. Early data did not report an increased risk of SARS-CoV-2 infection or disease severity in pregnancy. However, surveillance data from the Center for Disease Control and Prevention (CDC) indicates a higher risk of severe disease and death in pregnant women with symptomatic SARS-CoV-2 infection, although this data is subject to ascertainment bias.ObjectiveTo explore the association between COVID-19 disease severity and pregnancy in our university-based hospital system using measures such as COVID-19 ordinal scale severity score, hospitalization, intensive care unit admission, oxygen supplementation, invasive mechanical ventilation, and death.Study designWe conducted a retrospective, multicenter case-control study to understand the association between COVID-19 disease severity and pregnancy. We reviewed consecutive charts of adult females, ages 18-45, with laboratory-confirmed SARS-CoV-2 infection in six months between March 1, 2020, and August 31, 2020. Cases were patients diagnosed with COVID-19 during pregnancy, whereas controls were not pregnant at the time of COVID-19 diagnosis. Primary endpoints were the COVID-19 severity score at presentation (within four hours) and the nadir of the clinical course. The secondary endpoints were the proportion of patients requiring hospitalization, intensive care unit admission, oxygen supplementation, invasive mechanical ventilation, and death.ResultsA higher proportion of pregnant women had moderate to severe COVID-19 disease at the nadir of the clinical course than nonpregnant women (25% vs. 16.1%, p=0.04, respectively). While there was a higher rate of hospitalization (25.6% vs. 17.2%), ICU admission (8.9% vs. 4.4%), need for vasoactive substances (5.0% vs. 2.8%), and invasive mechanical ventilation (5.6% vs. 2.8%) in the pregnant group, this difference was not significant after the propensity score matching was applied.We found a high rate of pregnancy complications in our population (40.7%). The most worrisome is the rate of hypertensive disorders of pregnancy (20.1%).ConclusionsIn our propensity score-matched study, COVID-19 in pregnancy is associated with an increased risk of disease severity and an increased risk of pregnancy complications.

Background Multidrug-resistant Gram-negative bacterial infections are increasingly common among solid organ transplant (SOT) recipients, leading to challenges in the selection of empiric antimicrobial therapy. We sought to develop a clinical tool to predict which SOT recipients are at high risk for extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (EB) bloodstream infection (BSI). Methods A multicenter case-control study was performed. The source population included SOT recipients with an EB BSI between 2005 and 2018. Cases were those with ESBL-EB BSI; controls were those with non-ESBL EB BSI. The population was subdivided into derivation and validation cohorts based on study site. The predictive tool was developed in the derivation cohort through iterative multivariable logistic regression analyses that maximized the area under the receiver-operating curve (AUC). External validity was assessed using the validation cohort. Results A total of 897 SOT recipients with an EB BSI were included, of which 539 were assigned to the derivation cohort (135, 25% ESBL-EB) and 358 to the validation cohort (221, 62% ESBL-EB). Using multivariable analyses, the most parsimonious model that was predictive of ESBL-EB BSI consisted of 10 variables, which fell into four clinical categories: prior colonization or infection with EB organisms, recent antimicrobial exposures, severity of preceding illness, and immunosuppressive regimen. This model achieved an AUC of 0.81 in the derivation cohort and 0.68 in the validation cohort. Conclusions Though further refinements are needed in additional populations, this tool shows promise for guiding empiric therapy for SOT recipients with EB BSI.

Background Multidrug-resistant (MDR) Gram-negative (GN) bloodstream infections (BSI) are a major cause of morbidity and mortality among solid organ transplant recipients (SOTR). We determined risk factors associated with subsequent MDR-GN BSI following an initial Enterobacterales (EB) BSI among SOTRs. Methods A retrospective cohort study was performed. All SOTR with an EB BSI at the Hospital of the University of Pennsylvania and University of Maryland Medical Center between 1 Jan 2007 and 30 June 2018 and The Johns Hopkins Hospital between 1 Jan 2005 and 31 Dec 2015 were included. The primary outcome was any MDR-GN BSI within 60 days of the EB BSI, including MDR-EB (defined by ceftriaxone MIC ≥8μg/mL), and MDR-Pseudomonas and Acinetobacter (defined by resistance to three or more antibiotic classes). Unadjusted analyses were performed to identify possible risk factors, using a Fisher’s exact or χ 2 test for categorical and Student’s t-test for continuous variables. Results Of 988 SOTR with an EB BSI, 138 (14%) had a MDR-GN BSI within 60 days. In unadjusted analyses, possible risk factors for a subsequent MDR-GN BSI (Table 1) included: (1) an index BSI due to extended-spectrum beta-lactamase (ESBL)-producing EB (compared to a susceptible index EB BSI); (2) a carbapenem-resistant EB (CRE) index BSI (compared to a susceptible index EB BSI); (3) exposure to piperacillin-tazobactam or carbapenems in the 6 months prior to the index EB BSI; (4) prior liver transplantation; and (5) need for reoperation within four weeks of the original transplantation. There was no significant association between recurrent MDR-GN BSI and immunosuppression at time of infection, induction immunosuppression history, acute rejection history, or primary graft dysfunction. Table 1. Risk factors for subsequent MDR-GN BSI following EB BSI among SOTR. Data are presented as numbers (percentages) except where noted. Abbreviations: BSI, bloodstream infection; CRE, carbapenem-resistant Enterobacterales; EB, Enterobacterales; ESBL, extended-spectrum beta-lactamase; GN, Gram-negative; IQR, interquartile range; MDR, multidrug-resistant Conclusion This study shows that liver transplantation, reoperation following transplantation, an index ESBL-EB or CRE BSI, and recent exposure to broad-spectrum beta-lactam antibiotics are associated with an increased odds of subsequent MDR-GN BSI in SOTR, and underscores the need for future studies aimed at preventing emergence of MDR-GN infections in this vulnerable population. Disclosures Jennifer Han, MD, MSCE, GlaxoSmithKline (Employee, Shareholder) Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB)) Pranita Tamma, MD, MHS, Nothing to disclose Emily Blumberg, MD, Amplyx (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))Hologic (Research Grant or Support)Merck (Grant/Research Support, Other Financial or Material Support, Member of Scientific Advisory Committee)Takeda (Research Grant or Support, Other Financial or Material Support, Member of Scientific Advisory Committee) Judith A. Anesi, MD, MSCE, Nothing to disclose

Antimicrobial stewardship (AS) programs are expanding efforts across the entire healthcare continuum. Antimicrobials are commonly overused in outpatient care locations, which have not received the same intensity of AS intervention as inpatient settings. Guidance for AS programs is needed on how to implement interventions and monitor for improvement. Antimicrobials prescribed in the outpatient setting are inappropriate in 23–76% of cases. Factors associated with inappropriate prescribing include older adult patients, advanced practice practitioner prescribers, and urgent care clinics. Indications such as upper respiratory infections and asymptomatic bacteriuria are common conditions in which antibiotics should not be used yet they are major contributors to inappropriate antibiotic use. Promising interventions include peer comparison and clinical decision support, but gaps remain. There is little evidence for how to limit the use of fluoroquinolones and newly approved antibiotics. Improving antibiotic use is needed in the outpatient setting and poses unique challenges for AS programs. Defining problems unique to designated outpatient centers and implementing proposed interventions targeting these problems is an effective strategy. Collaboration with State Health Departments, health insurers, and healthcare systems will be essential.

Background Outpatient antibiotic stewardship is an emerging area of interest. The COVID-19 pandemic has led to unique restrictions such as social distancing and an increase in telemedicine visits. The effects on outpatient antimicrobial prescription needs further exploration. Methods We investigated the outpatient antimicrobial prescription trend pre (January 5 to March 14 2020) and post (March 15 to May 31 2020) COVID-19 restrictions at the Veteran’s Affairs Maryland Health Care System. We compared prescribing characteristics pre and post restrictions using Chi-squared and Mann Whitney U tests. Segmented regression analysis was used to compare antimicrobial prescriptions per 1000 encounters, with a control group from the same weeks in 2019. Results There were 3,881 total antibiotics prescribed for 382501 encounters during the 16 weeks in 2020. Post-restrictions, there was a significant decrease in encounters and antibiotics per week with mean difference of -15241 and -147, for encounters and antibiotics, respectively. The mean antibiotics per 1000 encounters was slightly higher in the post-restriction group, but without statistical significance by this analysis (10.1 vs 10.4, p-value 0.48). Other notable changes post-prescription described in the Table was a decrease in macrolide and an increase in trimethoprim-sulfamethoxazole; urgent care prescriptions decreased, while primary care prescription increased; and refill prescriptions were less common, while mail prescriptions were more common. On regression analysis, we found a significant level change of +2.7 antibiotics per 1000 encounters (p=0.02) immediately after restrictions were placed, without any significant change in trend (Figure). This translates to an additional 243 antibiotics prescribed during the post-restriction weeks. This was in comparison to data from 2019 which had no significant level or trend change during the same weeks. Table 1. Characteristics of antibiotics prescribed and comparison between pre and post COVID-19 restrictions in 2020, with 2019 control. Figure 1. Segmented Regression of antibiotic prescription per 1000 encounters pre and post COVID-19 restrictions with 2019 as control group. Conclusion We found an immediate increase in antibiotics relative to encounters post COVID-19 restrictions though antibiotics and encounters were all generally decreased with azithromycin showing the most appreciable decrease. Further investigation is needed to understand these findings and the implications on the population. Disclosures All Authors: No reported disclosures

Hand hygiene compliance is subject to the Hawthorne effect, which may be attenuated by covert observers and brief observation periods. This study demonstrated that hand hygiene compliance rates were between 8% and 29% greater when reported by infection prevention programs than when reported by covert observers over brief observation periods.