bluuebunny/crossref_metadata_2025 huggingface dataset:
125. Effect of Body Temperature Before Hospital Discharge on the Readmission Rate
Authors: Geneva Ivayla I , Lupone Christina , Wegman Adam D , Paolino Kristopher M
Published: January 2021

Background

One of the goals of the Affordable Care Act is to decrease readmission rates, which lead to wasting of resources and are associated with worse patient outcomes. While widely adhered to, there is no published research to support the practice of delaying discharge if the patient exhibits fever or hypothermia in the previous 24 hours. Our study quantifies the effect of abnormal body temperature before discharge on the readmission rate.

Methods

Retrospective analysis of the minimal (Tmin) and maximal (Tmax) body temperatures during the last 24 hrs before discharge of all patients over 1 year period from our tertiary medical center were analyzed with T-test, ANOVA, uni-and multivariate logistic regression. Fever was defined as Tmax > 100.2F(2SDs from mean Tmax), hypothermia as Tmin < 96.7F(2SDs from mean Tmin).

Results

Descriptive analysis of the data from 19,038 inpatients are featured in Table 1 and Figure 1. The overall readmission rate was 10.2% (highest for General Medicine and Pediatrics); 4.7% of patients had an abnormal temperature 24 hrs before discharge; body temperature declined with age. ANOVA showed that 1st, the average number of days to readmission was not different between those with fever, hypothermia, and normothermia (mean+/-SD: 10.6+/-8.6; 12.1+/-8.6; 12.5+/-8.1, respectively); 2nd that the rate of readmission was not different between these groups, although there was trend for higher readmission among normothermic patients (2.9%; 0.3%; 7%, respectively). Table 2 features regression analyses that model readmission. Univariate analysis revealed that higher Tmax and age are associated with lower readmission probability. Both uni- and multivariate analysis showed that the presence of fever is associated with lower readmission probability and that compared with General Medicine, the other major primary services have lower readmission probability, when correcting for all the other listed variables.

Figure 1

Conclusion

Our data clearly showed that abnormal body temperature measured within 24 hrs before discharge is not useful for predicting the chance for readmission. Therefore, delaying patients’ discharge based on Tmax or Tmin alone, taken outside the specific clinical context, may lead to wasting of hospital resources.

Disclosures

All Authors: No reported disclosures
130. increase in Multidrug Resistance (2011–2018) and the Emergence of Extensive Drug Resistance (2020) in shigella Sonnei in the United States
Authors: Logan Naeemah Z , Karp Beth E , Tagg Kaitlin A , Burns-Lynch Claire , Chen Jessica , Garcia-Williams Amanda , Marsh Zachary A , O’Laughlin Kevin , Plumb Ian D , Schroeder Morgan N , Webb Hattie E , Zenas Hannah , Draper Jenny , Ginn Andrew , Martinez Elena , Partridge Sally R , Sim Eby , Sintchenko Vitali , Iredell Jonathan , Watkins Louise Francois
Published: January 2021

Background

Multidrug-resistant (MDR) Shigella sonnei infections are a serious public health threat, and outbreaks are common among men who have sex with men (MSM). In February 2020, Australia’s Department of Health notified CDC of extensively drug-resistant (XDR) S. sonnei in 2 Australian residents linked to a cruise that departed from Florida. We describe an international outbreak of XDR S. sonnei and report on trends in MDR among S. sonnei in the United States.

Methods

Health departments (HDs) submit every 20th Shigella isolate to CDC’s National Antimicrobial Resistance Monitoring System (NARMS) laboratory for susceptibility testing. We defined MDR as decreased susceptibility to azithromycin (MIC ≥32 µg/mL) with resistance to ampicillin, ciprofloxacin, and cotrimoxazole, and XDR as MDR with additional resistance to ceftriaxone. We used PulseNet, the national subtyping network for enteric disease surveillance, to identify US isolates related to the Australian XDR isolates by short-read whole genome sequencing. We screened these isolates for resistance determinants (ResFinder v3.0) and plasmid replicons (PlasmidFinder) and obtained patient histories from HDs. We used long-read sequencing to generate closed plasmid sequences for 2 XDR isolates.

Results

NARMS tested 2,781 S. sonnei surveillance isolates during 2011–2018; 80 (2.9%) were MDR, including 1 (0.04%) that was XDR. MDR isolates were from men (87%), women (9%), and children (4%). MDR increased from 0% in 2011 to 15.3% in 2018 (Figure). In 2020, we identified XDR isolates from 3 US residents on the same cruise as the Australians. The US residents were 41–42 year-old men; 2 with available information were MSM. The US and Australian isolates were highly related (0–1 alleles). Short-read sequence data from all 3 US isolates mapped to the blaCTX-M-27 harboring IncFII plasmids from the 2 Australian isolates with >99% nucleotide identity. blaCTX-M-27 genes confer ceftriaxone resistance.

Increase in Percentage of Shigella sonnei Isolates with Multidrug Resistance* in the United States, 2011–2018†

Conclusion

MDR S. sonnei is increasing and is most often identified among men. XDR S. sonnei infections are emerging and are resistant to all recommended antibiotics, making them difficult to treat without IV antibiotics. This outbreak illustrates the alarming capacity for XDR S. sonnei to disseminate globally among at-risk populations, such as MSM.

Disclosures

All Authors: No reported disclosures
132. Emergence and Spread of Multidrug-resistant salmonella Serotype Infantis Infections in the United States, 2003–2018
Authors: Medalla Felicita , Payne Daniel C , Sundararaman Preethi , Birhane Meseret , Classon Andrew , Caidi Hayat , Folster Jason , Friedman Cindy R , Watkins Louise Francois
Published: January 2021

Background

Infantis re-emerged as a leading Salmonella serotype when a multidrug-resistant (MDR) strain with a rare extended spectrum β-lactamase (ESBL) blaCTX-M-65 gene emerged among returned travelers from Peru in 2012 and then spread domestically. This strain has been isolated from chickens at slaughter and retail, and humans in outbreaks traced to chicken. We reviewed national surveillance data to determine incidence trends and antibiotic resistance among Infantis infections.

Methods

We reviewed data from 2003–2018 from the Foodborne Diseases Active Surveillance Network to determine the incidence and epidemiology of infections in 10 sites under surveillance; PulseNet to determine pulsed-field gel electrophoresis (PFGE) patterns; and National Antimicrobial Resistance Monitoring System (NARMS) to determine antimicrobial susceptibility testing (AST) results and resistance genes of isolates identified by whole genome sequencing (WGS). We defined MDR Infantis as having ceftriaxone resistance by AST and either the blaCTX-M-65 gene or one of 18 PFGE patterns linked to that gene by WGS.

Results

The 2,154 patients with Infantis infection had a median age of 36 years and 57% were female; 86% had isolates from stool, 9% from urine, and 3% from blood. Only 10% reported foreign travel and 27% were hospitalized. The incidence of infections began increasing in 2010 and by 2017–2018 was 2-fold higher than the average during 2003–2009. During 2003–2018, 856 (88%) of 970 NARMS isolates had PFGE or WGS data; 48 isolates were MDR Infantis, and in addition to ceftriaxone and ampicillin resistance (by definition), all 48 were resistant to 3 or more antibiotic classes, 94% had decreased susceptibility to ciprofloxacin, and 67% were resistant to cotrimoxazole. During 2012–2016, 2% of isolates were MDR Infantis; this increased to 17% during 2017–2018 (Figure).

Conclusion

During the past decade, the incidence of Infantis infections markedly increased. This was likely driven by the emergence of an ESBL-producing strain that was initially associated with travel, and is now mostly domestically acquired and associated with consuming chicken. MDR Infantis now accounts for 1 in 5 Infantis infections. Public health strategies to reduce Salmonella contamination of chicken could help prevent these infections.

Disclosures

All Authors: No reported disclosures
133. validation of a Global Respiratory Severity Score in Infants with Primary RSV Infection
Authors: Qiu Xing , Wang Lu , Walsh Edward E , Caserta Mary T
Published: January 2021

Background

We recently developed a global respiratory severity score (GRSS) as a research tool from (n=139) infants with primary respiratory syncytial virus (RSV) infection enrolled prospectively in the Assessing Predictors of Infant RSV Effects and Severity (AsPIRES) study. The objective of the present study was to validate our original findings that the GRSS correlates well with clinical outcomes including hospitalization and length of stay (LOS) utilizing an independent cohort.

Methods

Clinical and demographic data on infants with primary RSV infection were abstracted from the electronic medical record. The GRSS was calculated by applying the original training data formula to the new data set. We compared the mean GRSS between the hospitalized and non-hospitalized group with Welch two sample t-test, and correlated it with hospitalization and LOS using Pearson’s correlation test.

Results

A total of 184 (98 hospitalized and 86 non-hospitalized) subjects were enrolled. The hospitalized and non-hospitalized infants were different in general appearance, the percentage with rales, retractions, lethargy, respiratory rate and oxygen saturation. The hospitalized group had a significantly (t=9.334, p< 0.0001) higher GRSS (4.20±2.10) than the non-hospitalized group (1.76±1.41). Using GRSS ≤3.5 as the classification criterion, we correctly predicted the hospitalization status of 131 (71.2%) subjects. The area under the ROC curve of the GRSS as a classifier of hospitalization is AUC=0.8265 (p< 0.0001). Pearson correlation between the GRSS and LOS is (p< 0.0001).

Area under the ROC curve of the GRSS

Boxplot demonstrating the difference in GRSS between hospitalized and non hospitalized infants

Conclusion

Infants hospitalized with RSV have a significantly higher GRSS than non-hospitalized subjects, and the GRSS is strongly associated with LOS. GRSS can also serve as an acceptable predictor of hospitalization. We are currently re-training the GRSS model with both datasets and believe it will lead to an improved predictive power of hospitalization.

Disclosures

All Authors: No reported disclosures
134. idweek Clinician Educator Mentoring Program for Junior Faculty
Authors: Luther Vera , Armstrong Wendy , Bonura Erin , Melia Michael , Riedel David J , Schwartz Brian
Published: January 2021

Background

Effective career mentorship enhances well-being, productivity, and advancement in academic medicine. The pathway to success for clinician educators (CE) is often ill-defined. Career development resources and support for this pathway vary across institutions. To address this need, we created a mentoring program pairing junior faculty pursuing careers as CEs with more experienced CEs from other institutions during IDWeek 2018 and 2019.

Methods

Prior to IDWeek 2018 and 2019, a survey was sent through the IDSA listserv to identify members pursuing CE careers interested in extra-institutional career mentorship. These faculty were paired with mentors who were established career CEs identified via the IDSA Medical Education Workgroup. Mentees completed a brief individual development plan (IDP) and identified 3 discussion topics. Mentors received the mentee’s IDP and CV prior to IDWeek and were given brief guidance on successful mentoring. One hour advising sessions were held during IDWeek and ended with the creation of a mentee action plan and a scheduled follow-up call. Post-participation surveys were sent to mentees and mentors.

Results

31 different mentees and 15 mentors participated in the program over two years. 26 (84%) mentees completed the post-session survey. 25 (96%) mentees and 14 (93%) mentors reported being very satisfied with their meetings at IDWeek. All mentees created an action plan with their mentor. 16 (62%) strongly agreed and 10 (38%) somewhat agreed that they planned to make changes based on the meeting. 21 (81%) mentees strongly agreed they received advice they were unable to get at their own institution. After the session, 18 (69%) strongly agreed they felt connected to a supportive CE community at IDSA; none strongly agreed in the pre-survey. All mentors and mentees agreed that this program was a resource that IDSA should consider expanding. Qualitative response themes from mentees emphasized the usefulness of an external perspective.

Conclusion

A mentoring program for junior faculty during IDWeek was feasible and effective for CEs. Through these interactions, mentees planned changes to enhance their careers and felt newly supported by the IDSA community. This model could be used for other ID career paths at future meetings.

Disclosures

All Authors: No reported disclosures
136. In Their Own words: a Qualitative Analysis of Factors Contributing to Gender Bias in Academic Advancement in Infectious Disease
Authors: Stead Wendy , Manne-Goehler Jennifer , Marcelin Jasmine R , Del Rio Carlos , Krakower Douglas
Published: January 2021

Background

Large and persistent inequities in academic advancement exist between men and women faculty in academic Infectious Diseases (ID). To identify and characterize beliefs about why these inequities persist in ID, we asked ID faculty members to share their thoughts and experiences with the advancement process.

Characteristics of Focus Group Participants

Summary of Main Emergent Themes from Focus Group Analysis

Methods

We conducted four 60-minute focus groups with ID faculty members during IDWeek 2019. We enrolled women that were diverse geographically and in academic rank (i.e., Instructor/Assistant, Associate, Full Professor). We assigned women to focus groups by rank to minimize social desirability bias across rank. Our fourth focus group included only men who were Full Professors, to capture additional perspectives about barriers to advancement and solutions. (Table 1) We analyzed focus group discussion transcripts using content analysis.

Results

We identified nine main themes regarding inequities in academic advancement of women in ID. (Table 2) In all 4 focus groups, gender bias as a barrier to academic advancement was a major theme. Women Full Professors emphasized explicit gender bias such as sexual harassment and “predatory mentoring,” whereas women Instructors/Assistant Professors more frequently cited barriers related to implicit bias, such as obscure maternity leave policies and divisional meetings scheduled during childcare hours. Women Associate Professors cited implicit and explicit gender bias, while men Full Professors focused primarily on implicit bias. Women Instructors/Assistant Professors experienced the greatest difficulty in balancing demands of family with career, though this was a prominent theme in all groups. The perception that women less often utilize negotiation to advance themselves was a dominant theme for women Associate Professors, though all groups raised examples of this theme.

Conclusion

Gender bias, both implicit and explicit, is an important and ongoing barrier to equitable academic advancement of women in ID. Difficulty balancing demands of family with career and gender differences in professional negotiation are also perceived barriers that can be targeted by innovative programs and interventions to address gender disparities in academic advancement.

Disclosures

All Authors: No reported disclosures
141. Rapid Reduction in Concomitant Vancomycin and Piperacillin-tazobactam Use: A Model for Future Antimicrobial Stewardship Interventions
Authors: Kimball Joanna , Deri Connor , Nesbitt Nesbitt J , Nelson George , Staub Milner
Published: January 2021

Background

Concomitant vancomycin and piperacillin-tazobactam use (CVPTU) for >2 days is associated with increased nephrotoxicity. At Vanderbilt University Medical Center, a sustained decline in CVPTU was achieved. A retrospective review of CVPTU and antimicrobial stewardship (AS) interventions was performed to develop a model for future AS quality improvement (QI) initiatives.

Methods

Data for adults receiving CVPTU January 2015 - August 2019 were extracted. No patients were excluded. Change in monthly incidence of CVPTU >2 days in relation to AS interventions was the primary outcome. CVPTU was analyzed with statistical process control (SPC) charts (QI Macros 2019). AS interventions were amassed from AS emails, meeting minutes, presentations and patient-specific interventions. We created a new intervention evaluation tool using the Hierarchy of Effectiveness (1-Education, 2-Policy, 3-Reminders, 4-Simplification, 5-Automation, 6-Forced Function) and a self-designed scale of impact (1-divisional subgroup, 2-division, 3-department, 4-center-wide). Scores were summed for each 6-month period and rated as low, moderate or high intervention strength. Periods were mapped against their corresponding CVPTU rate (Figure 1).

Results

CVPTU Data: During periods 1–5 (January 2015 - February 2018), an average 4% of admitted patients received >2 days CVPTU, decreasing to < 1% from period 5 (March 2018) onward (Figure 1). From period 1–5, an average 52.8% of patients with CVPTU received >2 days and dropped to 41.3% from period 5 onward (Figure 2).

Intervention Data: There was 1 low, 3 moderate and 4 high intensity periods. Intensity decreased as initiatives transitioned from behavior change to sustained behavior (Figure 1). The main interventions were education and patient-specific feedback. Division-specific antibiotic algorithms and computerized order sets re-enforced behavior. Infectious diseases consults and team pharmacists embedded the concept in daily practice.

Figure 1: Proportion of All Admissions with Concomitant Vancomycin and Piperacillin-Tazobactam Use (CVPTU) for >2 Days Mapped Against Simultaneous Quality Improvement Interventions.

Figure 2: Proportion of Patients with Concomitant Vancomycin and Piperacillin-Tazobactam Use (CVPTU) for >2 Days.

Conclusion

Persistent, repetitive center-wide intervention is key to driving and sustaining change. More analysis of specific intervention types and impact of external factors would enhance understanding and future use of this AS change implementation model.

Disclosures

All Authors: No reported disclosures
143. Modification of Linezolid Restriction Criteria Reduces ICU Gram-positive Antibiotic Consumption
Authors: Boulos John M , DeSear Kathryn , Shoulders Bethany , Venugopalan Veena , Voils Stacy A , Vu Catherine , Logan Megan , Santevecchi Barbara A
Published: January 2021

Background

Antibiotic time out (ATO) policies have been proposed by the Centers for Disease Control and Prevention to limit unnecessary use of antibiotics. Critically ill patients are often treated empirically with MRSA-active agents for a prolonged duration. The objective of this study was to assess the impact of an ATO policy by targeting empiric gram-positive coverage.

Methods

Before this intervention, linezolid required pre-approval by the antimicrobial stewardship program or infectious diseases (ID) consult service before dispensing, and no automatic ATO policy was in place for any agent. In 2018, restriction of linezolid was modified to allow 72 hours of empiric use in the intensive care unit (ICU). This retrospective, single-center, pre- post-intervention study looked at eight ICUs at our institution from two equal periods. Adults (age ≥ 18 years) were included who received an IV gram-positive antibiotic (IVGP-AB), specifically linezolid or vancomycin, used for empiric therapy and were admitted to the ICU. The primary outcome was antimicrobial consumption of IVGP-AB defined as days of therapy (DOT) per patient. Secondary outcomes included in-hospital length of stay (LOS), ICU LOS, in-hospital mortality, 30-day readmission, and incidence of acute kidney injury (AKI).

Figure 1. Flowchart of patient inclusion into the study

Results

2718 patients met criteria for inclusion in the study. 1091 patients were included in the pre-intervention group and 1627 patients were included in the post-intervention group. Baseline characteristics between the two groups were similar, with ID consults being higher in the pre-intervention group. Total mean DOT of IVGP-AB in pre- and- post-intervention groups was 4.97 days vs. 4.36 days, p< 0.01. Secondary outcomes of in-hospital LOS, ICU LOS, and in-hospital mortality did not vary significantly between groups. Thirty-day readmission was lower in the post-intervention group (12.9% vs. 3.9%, p< 0.01). AKI did not differ significantly between groups, however the need for renal replacement therapy was higher in the pre-intervention group (1.2% vs. 0.2%, p< 0.01).

Conclusion

This study assessed the impact of an ATO policy allowing 72 hours of empiric linezolid in the ICU. We found a statistically significant reduction in days of therapy of IVGP-AB without increases in LOS, mortality, readmission, and AKI.

Disclosures

All Authors: No reported disclosures
145. the Efficacy and Safety of Low Dose Trimethoprim-sulfamethoxazole for the Treatment of Pneumocystis Pneumonia: A Systematic Review and Meta-analysis
Authors: Tritle Brandon , Hejazi Andre A , Timbrook Tristan
Published: January 2021

Background

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection causing significant morbidity and mortality in immunocompromised patients. The conventional treatment of PJP is sulfamethoxazole-trimethoprim (SMX-TMP) dosed at 15–20 mg/kg/day of the trimethoprim component. This high-dose regimen is associated with severe adverse reactions that result in patient harm or treatment discontinuation. Studies have suggested similar mortality and an improved adverse effect profile using lower dose (< 15 mg/kg/day) SMX-TMP. Our objective of this meta-analysis was to evaluate the safety and efficacy of lower dose SMX-TMP for PJP pneumonia.

Methods

We conducted a systematic review and meta-analysis according to PRISMA guidelines. Pubmed and Embase databases were searched from inception to January 15, 2020, for studies in English evaluating low-dose SMX-TMP (< 15 mg/kg/day) compared with conventional dosing for the treatment of PJP. Additionally, conference proceedings were reviewed to address potential publication bias. Outcomes evaluated in our meta-analysis include survival and adverse reactions. We performed a sensitivity analysis using E-values to determine the robustness of our results.

Results

After excluding studies that did not meet our inclusion criteria, four studies were analyzed for adverse reaction rates and three for mortality rates. Overall, there was no significant difference in mortality between low-dose and conventional-dose SMX-TMP groups (relative risk [RR]: 0.55, 95% confidence interval [CI], 0.18 -1.70). There was a significant decrease in the rate of adverse reactions for the low-dose group compared with the conventional-dose group (RR: 0.70, 95% CI, 0.53 - 0.91). Sensitivity analyses using E-Values reflect a confounder with RR 2.2 or greater could explain away the estimate on adverse events leading to no difference while mortality would require RR 5.6 to reflect worse outcomes with low dose.

Mortality Forest Plot

Adverse Effects Forest Plot

Conclusion

This meta-analysis shows a significant decrease in adverse reactions and similar mortality rates with lower-dose SMX-TMP compared with conventional dosing. A low-dose SMX-TMP regimen in the treatment of PJP should be considered a viable option with the potential to decrease treatment discontinuation and reduce harm.

Disclosures

All Authors: No reported disclosures
146. antifungal Susceptibility Patterns of candida Parapsilosis Bloodstream Isolates in the US, 2008–2018
Authors: Tesini Brenda L , Lyman Meghan , Jackson Brendan R , Gellert Anita , Schaffner William , Farley Monica M , Shrum Sarah , Phipps Erin C , Zhang Alexia Y , Pattee Brittany , Fischer Jill , Johnston Helen , Barter Devra , Harrison Lee , Marceaux Kaytlynn , Nadle Joelle
Published: January 2021

Background

Multidrug resistant Candida is an increasing concern. C. parapsilosis in particular has decreased in vitro susceptibility to echinocandins. As a result, fluconazole had been favored for C. parapsilosis treatment. However, there is growing concern about increasing azole resistance among Candida species. We report on antifungal susceptibility patterns of C. parapsilosis in the US from 2008 through 2018.

Methods

Active, population-based surveillance for candidemia through the Centers for Disease Control and Prevention’s (CDC) Emerging Infections Program was conducted between 2008–2018, eventually encompassing 9 states (GA, MD,OR, TN, NY, CA, CO, MN, NM). Each incident isolate was sent to the CDC for species confirmation and antifungal susceptibility testing (AFST). Frequency of resistance was calculated and stratified by year and state using SAS 9.4

Results

Of the 8,704 incident candidemia isolates identified, 1,471 (15%) were C. parapsilosis; the third most common species after C. albicans and C. glabrata. AFST results were available for 1,340 C. parapsilosis isolates. No resistance was detected to caspofungin (MIC50 0.25) or micafungin (MIC50 1.00) with only one (< 1%) isolate resistant to anidulafungin (MIC50 1.00). In contrast, 84 (6.3%) isolates were resistant to fluconazole and another 44 (3.3%) isolates had dose-dependent susceptibility to fluconazole (MIC50 1.00). Fluconazole resistance increased sharply from an average of 4% during 2008–2014 to a peak of 14% in 2016 with a subsequent decline to 6% in 2018 (see figure). Regional variation is also observed with fluconazole resistance ranging from 0% (CO, MN, NM) to 42% (NY) of isolates by site.

Conclusion

The recent marked increase in fluconazole resistance among C. parapsilosis highlights this pathogen as an emerging drug resistant pathogen of concern and the need for ongoing antifungal resistance surveillance among Candida species. Our data support the empiric use of echinocandins for C. parapsilosis bloodstream infections and underscore the need to obtain AFST prior to fluconazole treatment. Furthermore, regional variation in fluconazole resistance emphasizes the importance of understanding local Candida susceptibility patterns.

Disclosures

Lee Harrison, MD, GSK (Consultant)Merck (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)
149. Efficacy of Cochleated Amphotericin B (CAMB) in Mouse and Human Mucocutaneous Candidiasis
Authors: Desai Jigar V , Urban Amanda , Swaim Doris Z , Ferre Elise , Colton Benjamin , Lu Ruying , Matkovits Theresa , Mannino Raphael J , Tramont Edmund , Lionakis Michail , Freeman Alexandra
Published: January 2021

Background

Candida albicans causes debilitating mucosal infections in patients with inherited susceptibility to chronic mucocutaneous candidiasis (CMC), often requiring long-term azole-based treatment. Due to increasing azole resistance, alternative treatments are desirable. Acquired resistance to amphotericin B (AMB) is rare but AMB use is limited by parenteral administration and nephrotoxicity. Cochleated AMB (CAMB) is a new oral formulation of AMB and thus an attractive option for oropharyngeal candidiasis (OPC), esophageal candidiasis (EC) and vulvovaginal candidiasis (VVC). We assessed the efficacy of CAMB in mouse models of OPC and VVC and in 4 patients with azole resistant CMC manifesting as OPC, EC or VVC.

Methods

Act1 -/- mice were infected with C. albicans in models of OPC and VVC and were treated once daily via oral gavage with CAMB or vehicle or intraperitoneal AMB-deoxycholate (AMBd) from day 1 through 4 post-infection (pi). At day 5 pi, the tongue or vaginal tissue was harvested to quantify fungal burden. Patients with azole resistant CMC enrolled in a phase 2A CAMB dose escalation study. The primary endpoint was clinical improvement at 2 weeks based on an efficacy scale, followed by optional extension for long-term suppression of CMC to assess safety and efficacy.

Results

CAMB-treated mice had significantly reduced tongue and vaginal tissue fungal burden compared to vehicle-treated mice, while they exhibited comparable fungal control relative to AMBd-treated mice. Among 4 CAMB-treated patients, 3 reached clinical efficacy by 2 weeks at a dose of 400 mg twice daily and one reached clinical efficacy at 200 mg twice daily. Three of 4 patients continued on the extension phase past 48 months with sustained clinical improvement of OPC and EC; patient #3 had relapse of esophageal symptoms at week 24 and was withdrawn from further study. Clinical response was not seen for onychomycosis or VVC. CAMB was safe and well-tolerated without renal toxicity.

Conclusion

Oral administration of CAMB in IL-17-signaling deficient mice resulted in reduced tongue and vaginal tissue fungal burden during mucosal C. albicans infections. A proof-of-concept clinical trial in humans with inherited CMC showed efficacy in OPC and EC with good tolerability and safety.

Disclosures

Benjamin Colton, PharmD, Merck (Shareholder)Pfizer (Shareholder) Ruying Lu, n/a, Matinas BioPharma Inc. (Employee)Matinas BioPharma Inc. (Employee, Shareholder) Theresa Matkovits, PhD, Matinas BioPharma (Employee, Shareholder) Raphael J. Mannino, n/a, Matinas BioPharma Inc. (Employee, Shareholder) Michail Lionakis, MD, ScD, Matinas BioPharma (Research Grant or Support)
150. the RAPID trial: randomized Controlled Trial assessing point-of-care influenza and Other Respiratory Virus diagnostics in the Pediatric ED Setting
Authors: Rao Suchitra , Lamb Molly , Moss Angela , Mistry Rakesh , Dominguez Samuel
Published: January 2021

Background

Respiratory illnesses represent one of the commonest reasons for pediatric visits to the ED, and over 50% of these children are prescribed antibiotics despite a viral etiology in most cases. Our objectives were to determine whether rapid respiratory pathogen (RRP) testing decreases antibiotic and health care utilization among children evaluated in the ED with a respiratory illness.

Methods

We conducted a randomized controlled trial among children 1 mo-18 yrs of age attending an ED with influenza like illness (ILI). All children received a nasopharyngeal swab for RRP testing, and were randomized to the intervention group (result given to providers and parents) or control group (result not given, routine clinical care). Families were interviewed on enrollment, 1 and 10 days later. The primary outcome was antibiotic use. Secondary outcomes included antiviral use, hospitalization and recurrent medical visits. Intention to treat (ITT) (assigned group) and pragmatic (provider knows test results) analyses were conducted using SAS v 9.4. Pragmatic analyses were adjusted using multivariable Poisson regression.

Results

Among 920 visits (890 children) with ILI, 795 (85%) were RRP positive. Sociodemographic characteristics between groups were similar; 37% of children in the intervention group were discharged before results were available and 12% of children in the control group underwent clinical testing. The median age was 2.1 yrs (IQR 0.88–5.6); 35% had high-risk comorbidities. In the ITT intervention group, children were more likely to receive antibiotics (RR 1.3, 95% CI 1.0–1.7) (Table 1). In adjusted pragmatic analyses, children with known results were more likely to receive antivirals (RR 2.6 95% CI 1.5–4.3) and be hospitalized (RR 2.0, 95% CI 1.5–2.7); antibiotic use was not significant (Table 2). Children testing negative for a virus were more likely to receive antibiotics than those with a virus (35% vs 23%, p = 0.01).

Table 1. Clinical Outcomes by Study Arm, Intention to Treat Analyses

Table 2. Clinical Outcomes by Study Arm, Pragmatic Analyses

Conclusion

Knowledge of testing led to a paradoxical increase in antibiotic prescribing, as well as an increase in appropriate antiviral prescribing, ED length of stay and hospitalization. Further studies are needed to assess whether RRP testing with faster turn around times or coupled with stewardship interventions may impact outcomes.

Disclosures

Suchitra Rao, MD, BioFire (Grant/Research Support) Molly Lamb, PhD, BioFire (Grant/Research Support) Rakesh Mistry, MD, MSCE, BioFire (Grant/Research Support) Samuel Dominguez, MD, PhD, BioFire (Consultant, Research Grant or Support)
154. comparative Genomics Reveals Extra-hospital Transmission Networks of Carbapenem-resistant acinetobacter Baumannii sustained over Multiple Years in a US Midwest City
Authors: Calix Juan J , de Almeida Maria Claudia Stockler , Potter Robert , Wallace Meghan , Burnham Carey-Ann , Dantas Gautam
Published: January 2021

Background

The transmission dynamics of Acinetobacter baumannii (Ab) outside the setting of hospital outbreaks is underinvestigated. The BJC Healthcare System in St. Louis, MO has not experienced an Ab hospital outbreak since 2012. Despite this, nearly 60% of all BJC Ab isolates are carbapenem-resistant Ab (CrAb).

Methods

We acquired whole genome sequences (WGSs) of 110 Ab isolates identified in five BJC hospitals from July 2017 to May 2019. We performed multilocus sequence typing, core genome alignment and pairwise average nucleotide identity analysis to compare WGSs from BJC isolates and GenBank-available WGSs of Ab isolates from other US hospitals. Further epidemiologic characterization was performed using BJC electronic medical records and detailed chart review.

Results

Though the majority of CrAb isolates in other US studies belonged to globally-prevalent sequence type 2 (ST2 [Pasteur scheme]), 62% and 26% of BJC CrAb index isolates belonged to the unrelated ST499 and ST406, respectively. BJC ST499 and ST406 isolates were phylogenetically distinct compared to corresponding isolates from other US hospitals. Under the assumption that Ab transmission occurs primarily through nosocomial spread, we expected BJC isolates from the same hospital and timespan to share the highest degree of homogeneity. However, geotemporal proximity between ST499 or ST406 BJC isolates was a poor predictor of their genetic relatedness, according to multiple comparative methods. Review of patient metadata did not identify epidemiological links between BJC isolates within phylogenetic subgroups.

Conclusion

We combined comparative genomics and detailed clinical chart review to characterize the transmission dynamics of two emerging US CrAb sequence types, ST499 and ST406. Though these highly homogeneous Ab isolates were identified over two years in multiple BJC hospitals, we found no evidence of robust intra-hospital transmission networks. Instead, it appears that these CrAb isolates independently emerged from yet-to-be-identified regional, extra-hospital Ab populations. To neutralize the threat of drug-resistant infections in the US, it is essential to identify, characterize and disrupt emergent CrAb transmission networks that exist outside of hospital environments.

Disclosures

All Authors: No reported disclosures
155. Public Health Action-based System for Tracking and Responding to U.S. candida Drug Resistance: AR Lab Network, 2016–2019
Authors: Forsberg Kaitlin , Lyman Meghan , Chaturvedi Sudha , Schneider Emily C , Fischer Jill , Baynham Dorothy F , Dunbar Denise F , Plehn Michele , Podzorski Diane , Gumbis Stephanie , Sievert Dawn , Jackson Brendan R , Lockhart Shawn R , Berkow Elizabeth L
Published: January 2021

Background

Many U.S. clinical laboratories lack capacity to definitively identify fungi or perform antifungal susceptibility testing (AFST). To expand testing access, CDC’s Antibiotic Resistance Laboratory Network (AR Lab Network) provides Candida species identification and AFST to U.S. facilities for clinical and public health purposes. We describe the first three years of Candida AR Lab Network resistance data.

Methods

Isolates from any body site with species identification and AFST performed July 2016–June 2019 are included. Submissions were based on clinical and public health need. Patients may have multiple isolates. The 7 AR Lab Network regional laboratories used matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) or DNA sequencing for species identification. AFST was performed using broth microdilution for azoles and echinocandins (anidulafungin and micafungin) and Etest for amphotericin B. This analysis focuses on non-albicans Candida species with Clinical and Laboratory Standards Institute M60 minimum inhibitory concentration breakpoints and C. auris, which has CDC-proposed tentative breakpoints.

Results

Participation increased from healthcare facilities from 2 states submitting in 2016 to 35 states in 2019. Species identification was performed on 5,234 non-albicans isolates. AFST was performed on 4,222 (81%) isolates, including 2,395 C. glabrata, 815 C. auris, 267 C. parapsilosis, 125 C. tropicalis, 35 C. guilliermondii, and 32 C. krusei. Of isolates with AFST and body site indicated, 22% (900/4,102) were from blood. We found 85% of C. auris, 8% of C. glabrata, and 5% of C. parapsilosis isolates were resistant to azoles; 33% of C. auris isolates were resistant to amphotericin B; and 2% of C. glabrata, 1% of C. auris, and 1% of C. parapsilosis isolates were resistant to echinocandins. Although intrinsically resistant to fluconazole, C. krusei isolates were not resistant to voriconazole. Multidrug resistance was present in 32% of C. auris and 1% of C. glabrata isolates.

Conclusion

AR Lab Network has expanded access to rapid Candida testing, including AFST, and provides real-time surveillance. Results can be used to detect emerging species and resistance and guide public health action and healthcare practices.

Disclosures

All Authors: No reported disclosures
156. How Does Exposure to C. Diffogenic Antibiotics Impact Multidrug-resistant Organism Colonization and Environment Contamination in Nursing Homes?
Authors: Gontjes Kyle J , Gibson Kristen , Lansing Bonnie , Mantey Julia , Jones Karen , Cassone Marco , Wang Joyce , Mills John , Mody Lona , Patel Payal K
Published: January 2021

Background

Antimicrobial stewardship program (ASP) outcomes are often measured in the acute care setting, less is known about the effect of acute care antibiotic exposures on multidrug-resistant organism (MDROs) colonization of nursing home (NH) patients. We assessed exposure to antibiotics commonly associated with Clostridioides difficile (C. diffogenic agents) on post-acute care patient colonization and room environment contamination (Figure 1).

Figure 1. Conceptual Diagram of Hospital Antibiotic Exposure’s Influence on Patient Colonization and Room Environment Contamination with Multidrug-Resistant Organisms

Methods

MDRO surveillance of post-acute care patients in 6 NHs between 2013–16. We screened patient hands, nares, oropharynx, groin, perianal area, and high-touch room environment surfaces for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and resistant Gram-negative bacilli (rGNB). C. diffogenic agents were defined as fluoroquinolones, 3rd/4th generation cephalosporins, penicillin combinations, lincosamides, and carbapenems. Multivariable logistic regression was used to assess whether hospital antibiotic exposure is an independent risk factor for MDRO colonization and room environment contamination on study enrollment.

Results

We enrolled 618 patients: average age was 74.4 years; 57.4% female; 62.3% white; 9.9% had indwelling devices (Table 1). Three hundred-fifty patients (56.6%) were MDRO colonized on enrollment: 98 (15.9%), MRSA; 208 (33.7%); VRE; 196 (31.7%), rGNB. Sixty-eight percent of patient rooms were MDRO contaminated: 166 (26.9%), MRSA; 293, (47.4%). VRE; 182 (29.5%), rGNB.

A majority (59.4%) of patients were exposed to an antibiotic before admission. Of which, 239 (65.1%) were exposed to a C. diffogenic antibiotic. In multivariable analysis, C. diffogenic antibiotic exposure was an independent risk factor for MDRO colonization (OR, 1.94; 95% CI, 1.35–2.79), MDRO room environment contamination (OR, 1.94; 95% CI, 1.43–2.63), VRE colonization (OR, 4.23; 95% CI, 2.59–6.90), and VRE room environment contamination (OR, 2.58; 95% CI, 2.00–3.33).

Table 1. Clinical Characteristics and MDRO Burden on Study Enrollment, Stratified by Hospital Antibiotic Exposure Status

Multivariable Analysis of Hospital Antibiotic Exposure Status as Risk Factor for Proximal and Distal MDRO Outcomes

Conclusion

Hospital exposure to antibiotics is associated with an increased risk of VRE colonization and room environment contamination on NH study enrollment. These observations highlight the potential influence of hospital-based ASPs on MDRO prevalence and transmission in NHs.

Disclosures

All Authors: No reported disclosures
159. efficacy of CD377, a Novel Antiviral Fc-conjugate, Against Seasonal Influenza in Lethal Mouse Infection Models
Authors: Levin James , Amundson Karin , Shathia Kim , Borchardt Allen , Lam Thanh , Brady Tom , Noncovich Alain , Tari Les
Published: January 2021

Background

Cidara’s AVCs (antiviral Fc-conjugates) are novel conjugates of potent, antiviral agents with the Fc domain of human IgG1. CD377 is an AVC development candidate for prevention and treatment of influenza that has broad anti-neuraminidase activity in both enzymatic and cell-based assays and the potential to engage the immune system, as well as a long half-life.

Methods

Efficacy studies were conducted in BALB/c mice lethally challenged intranasally at 3x the LD95 with influenza A (H1N1, H3N2) and influenza B (both lineages). CD377 was administered as a single dose subcutaneously (SC) 2 hours after viral challenge. Body weights (BW) and health scores were monitored daily, with 20% BW loss recorded as a mortality.

Results

In mice challenged with a lethal dose of an H1N1 strain (A/California/12/2012), a single 0.3 mg/kg dose of CD377 administered 2 hours post-challenge was fully protective (P=0.0015 relative to vehicle) (Fig 1A). In a similar study against a mouse-adapted H3N2 subtype (A/Hong Kong/1/1968), a single dose of CD377 at 0.1 mg/kg was fully protective (P=0.0025) (Fig 1B). In both studies, only a transient loss of BW was observed before mice began recovering weight.

The activity of CD377 was also evaluated against both lineages of influenza B (Fig 1C, 1D). Against influenza B/Colorado/06/2017 (Victoria), a single CD377 dose of 0.3 mg/kg was fully protective (P=0.0035) while the Fc-only control dosed at 1 mg/kg was not, as expected. Against the Yamagata lineage (B/Florida/4/2006), CD377 demonstrated full protection at a dose of only 0.03 mg/kg (P=0.0023).

Conclusion

A single dose of CD377 (0.3 mg/kg or less) was protective against lethal challenge with several seasonal influenza A/B subtypes. The exceptional PK profile of CD377 combined with potent broad-spectrum activity highlight its potential for use as a long-term preventative against seasonal influenza.

Seasonal influenza efficacy

Disclosures

James Levin, PhD, Cidara Therapeutics (Shareholder) Karin Amundson, BSc, Cidara Therapeutics (Shareholder) Allen Borchardt, PhD, Cidara Therapeutics (Employee) Thanh Lam, PhD, Cidara Therapeutics (Shareholder) Tom Brady, PhD, Cidara Therapeutics (Shareholder) Alain Noncovich, PhD, Cidara Therapeutics (Shareholder) Les Tari, PhD, Cidara Therapeutics (Shareholder)
161. impact of State Childcare and School Hepatitis a Vaccination Requirements on Coverage of Hepatitis a Vaccines in the United States
Authors: Choi Yoonyoung , Bhatti Alexandra , Liu Zhiwen , Goveia Michelle , Simon Jakub
Published: January 2021

Background

Widespread Hepatitis A (Hep A) outbreaks in the United States (US) have raised the importance of vaccination. Vaccination requirements for childcare and school entry could be an effective strategy to ensure compliance to recommended vaccination schedule. We assessed the association between state childcare and school entry requirements for Hep A vaccination and vaccine coverage rate among children and adolescents in the US.

Methods

We conducted a cross-sectional cohort study using National Immunization Survey-Child and Teen dataset between 2008 and 2017. We included children aged 19–35 months and adolescents aged 13–17 years residing in states with childcare entry requirement only (C); school entry requirement only (S); childcare AND school entry requirement (C+S); and neither of requirements in place in the survey year (Control). We developed a multivariate logistic regression model adjusting for demographics, survey year, state’s CDC vaccination recommendation status, stringency of requirement, and history of Hep A outbreak, accounting for the survey design.

Results

We included 150,653 children and 119,265 adolescents in the analysis. Vaccination initiation rate was 53.9% and 72.6% (C), 48.3% and 74.9% (S), 48.2% and 83.9% (C+S) in pre- and post-requirement periods, respectively. In multivariate analysis, all state requirements were associated with higher Hep A vaccination initiation compared to control states (C: odds ratio 1.51, 95% confidence interval 1.37–1.66; S: 1.82, 1.49–2.23; and C+S: 1.49, 1.38, 1.62). Predictors for high vaccination initiation included vaccine recommendation since 1999 vs 2006 (2.87, 2.63–3.13); exemption of enforcement (most restrictive vs lenient: 2.10, 1.68–2.63). In addition, non-White, Hispanic children aged between 19–35 months with insurance, >$75,000 family income household, mothers having college degree were more likely to initiate Hep A vaccination. The associations were similar for Hep A vaccination completion.

Figure 1. Hep A vaccination initiation and completion rates between pre- and post-requirement periods (C=childcare entry requirement only; S=school entry requirement only; and C+S=childcare AND school entry requirement)

Table 1. Multivariate association between state policy and vaccination initiation and completion rate

Conclusion

States with childcare and school entry requirements are more likely to initiate and complete Hep A vaccine compared to those without such policy. This interventional policy may help to control and prevent Hep A outbreaks in states where it is applied.

Disclosures

Yoonyoung Choi, PhD, MS, RPh, Merck (Employee) Alexandra Bhatti, JD, MPH, Merck (Employee) Zhiwen Liu, PhD, Merck & Co., Inc., (Employee) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) Jakub Simon, MD, MS, Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder)