bluuebunny/crossref_metadata_2025 huggingface dataset:
The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II
Authors: Carnesecchi Julie , Boumpas Panagiotis , van Nierop y Sanchez Patrick , Domsch Katrin , Pinto Hugo Daniel , Borges Pinto Pedro , Lohmann Ingrid
Published: December 2021

Transcription factors (TFs) play a pivotal role in cell fate decision by coordinating gene expression programs. Although most TFs act at the DNA layer, few TFs bind RNA and modulate splicing. Yet, the mechanistic cues underlying TFs activity in splicing remain elusive. Focusing on the Drosophila Hox TF Ultrabithorax (Ubx), our work shed light on a novel layer of Ubx function at the RNA level. Transcriptome and genome-wide binding profiles in embryonic mesoderm and Drosophila cells indicate that Ubx regulates mRNA expression and splicing to promote distinct outcomes in defined cellular contexts. Our results demonstrate a new RNA-binding ability of Ubx. We find that the N51 amino acid of the DNA-binding Homeodomain is non-essential for RNA interaction in vitro, but is required for RNA interaction in vivo and Ubx splicing activity. Moreover, mutation of the N51 amino acid weakens the interaction between Ubx and active RNA Polymerase II (Pol II). Our results reveal that Ubx regulates elongation-coupled splicing, which could be coordinated by a dynamic interplay with active Pol II on chromatin. Overall, our work uncovered a novel role of the Hox TFs at the mRNA regulatory layer. This could be an essential function for other classes of TFs to control cell diversity.
Opioid prescribing practices in chronic kidney disease: a population-based cohort study
Authors: Molnar Amber O , Bota Sarah E , Naylor Kyla , Nash Danielle M , Smith Graham , Suri Rita S , Sood Manish M , Gomes Tara , Garg Amit X
Published: December 2021

Background

Chronic pain is common, and its management is complex in patients with chronic kidney disease (CKD), but limited data are available on opioid prescribing. We examined opioid prescribing for non-cancer and non-end-of-life care in patients with CKD.

Methods

This was a population-based retrospective cohort study using administrative databases in Ontario, Canada which included adults with CKD defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 from 1 November 2012 to 31 December 2018 and estimated the proportion of opioid prescriptions (type, duration, dose, potentially inappropriate prescribing, etc.) within 1 year of cohort entry. Prescriptions had to precede dialysis, kidney transplant or death.

Results

We included 680 445 adults with CKD, and 198 063 (29.1%) were prescribed opioids. Codeine (14.9%) and hydromorphone (7.2%) were the most common opioids. Among opioid users, 24.3% had repeated or long-term use, 26.1% were prescribed high doses and 56.8% were new users. Opioid users were more likely to be female, had cardiac disease or a mental health diagnosis, and had more healthcare visits. The proportions for potentially inappropriate prescribing indicators varied (e.g. 50.1% with eGFR <30 were prescribed codeine, and 20.6% of opioid users were concurrently prescribed benzodiazepines, while 7.2% with eGFR <30 mL/min/1.73 m2 were prescribed morphine, and 7.0% were received more than one opioid concurrently). Opioid prescriptions declined with time (2013 cohort: 31.1% versus 2018 cohort: 24.5%; p <0.0001), as did indicators of potentially inappropriate prescribing.

Conclusions

Opioid use was common in patients with CKD. While opioid prescriptions and potentially inappropriate prescribing have declined in recent years, interventions to improve pain management without the use of opioids and education on safer prescribing practices are needed.
3. Stopping Hospital Infections with Environmental Services (SHINE): A Cluster-Randomized Trial of Intensive Monitoring Methods for Terminal Room Cleaning on Rates of Multidrug-Resistant Organisms (MDROs) in the Intensive Care Unit (ICU)
Authors: Ziegler Matthew J , Babcock Hilary , Babcock Hilary , Welbel Sharon F , Warren David K , Trick William , Reddy Sujan , Tolomeo Pam C , Omorogbe Jacqueline , Garcia Diana , Habrock-Bach Tracey , Donceras Onfofre T , Gaynes Steven M , Cressman Leigh , Burnham Jason P , Pegues David A , Lautenbach Ebbing , Han Jennifer
Published: December 2021

Background

MDROs frequently contaminate hospital environments. We performed a multicenter cluster-randomized, crossover trial of two methods for intensive monitoring of terminal cleaning effectiveness at reducing infection and colonization with MDROs within ICUs.

Methods

Six medical and surgical ICUs at three medical centers received both intensive monitoring interventions sequentially, in a randomized order. The intervention included surveying a minimum of 10 surfaces each in 5 rooms weekly, after terminal cleaning, with adenosine triphosphate (ATP) monitoring or an ultraviolet fluorescent marker (UV/F). Results were delivered to environmental services (EVS) staff in real-time, with failing surfaces recleaned. The primary study outcome was the monthly rate of infection or colonization with MDROs, including methicillin-resistant Staphylococcus aureus, Clostridioides difficile, vancomycin-resistant Enterococcus, and multidrug-resistant gram-negative bacilli (MDR-GNB), assessed during a 12-month baseline comparison period and sequential 6-month intervention periods, separated by a 2-month washout. Outcomes during each intervention period were compared to the combined baseline period plus the alternative intervention period using mixed-effects Poisson regression, with study hospital as a random effect.

Results

The primary outcome rate varied by hospital and ICU (Figure 1). The ATP method was associated with a relative reduction in the incidence rate of infection or colonization with MDROs (incidence rate ratio (IRR) 0.887, 95% confidence-interval (CI) 0.811–0.969, P=0.008) (Table 1), infection with MDROs (IRR 0.924, 95% CI 0.855–0.998, P=0.04), and infection or colonization limited to multidrug-resistant MDR-GNB (IRR 0.856, 95% CI 0.825–0.887, P< 0.001). The UV/F intervention was not associated with a statistically significant impact on these outcomes. Room turn-around time was increased by a median of one minute with the ATP intervention and 4.5 minutes with the UV/F intervention compared to baseline.

Conclusion

Intensive monitoring of ICU terminal room cleaning with an ATP modality is associated with a relative reduction of infection and colonization with MDROs with a negligible impact on TAT.

Disclosures

Hilary Babcock, MD, MPH, FIDSA, FSHEA (nothing to disclose), David K. Warren, MD, MPH, Homburg & Partner (consultant), Ebbing Lautenbach, MD, MPH, MSCE (nothing to disclose), Jennifer Han, MD, MSCE, GlaxoSmithKline (employee, shareholder).
11. Electronic Surveillance Criteria for Non-Ventilator HAP: Empiric testing and Chart Review at Veterans Affairs Facilities
Authors: Stern Sarah , Christensen Matthew A , Nevers McKenna , Ying Jian , Smith Caroline , Jin Robert , Ochoa Aileen , Rhee Chanu , Samore Matthew H , Klompas Michael , Jones Barbara E
Published: December 2021

Background

Surveillance of Non-Ventilator Hospital-Acquired Pneumonia (NV-HAP) is limited by the ambiguity in diagnosing pneumonia. We implemented electronic surveillance criteria for NV-HAP across the VA healthcare system and tested for reliability, validity and meaning of the electronic criteria vs manual chart review.

Methods

We defined NV-HAP surveillance criteria as oxygen deterioration concurrent with fever or abnormal WBC count, ≥3 days of antibiotics, and orders for chest imaging. We applied these criteria to EHR data from all patients hospitalized ≥3 days at all VA acute care facilities from 1/1/2015-12/31/2020 and calculated NV-HAP incidence and inpatient mortality. Clinician reviewers used a consensus review guide to independently review and adjudicate 47 cases meeting NV-HAP surveillance criteria for 1) clinical deterioration, 2) CDC-NHSN pneumonia criteria, 3) treating clinicians’ assessment, and 4) reviewer’s diagnosis. All reviewers subsequently adjudicated all cases and conducted an error analysis to identify sources of discordance.

Results

Among 2.3M hospitalizations, 14,023 met NV-HAP surveillance criteria (0.6 per 100 admissions). Inpatient mortality was 26% (vs 2% for non-flagged hospitalizations). Among 47 hospitalizations flagged by surveillance criteria, 45 (97%) had a confirmed clinical deterioration, (the other 2 were immediate post-operative cases), 20 (43%) met CDC-NHSN pneumonia criteria, 21 (47%) had possible pneumonia per treating clinicians, and 25 (53%) had possible or probable NV-HAP per reviewers. Agreement among the 3 reviewers before adjudication was 51% (Fleiss’ κ 0.43) for CDC-NHSN and 58% (Fleiss’ κ 0.33) for NV-HAP. The most common source of discordance between reviewers was chest imaging classification (15/19 discordant cases).

Conclusion

NV-HAP electronic surveillance criteria demonstrated high precision for identifying clinical deterioration and moderate concordance with CDC-NHSN pneumonia criteria or reviewer diagnosis. Agreement between electronic surveillance criteria vs manual chart review was low but similar to agreement amongst manual reviewers applying NHSN criteria. Electronic surveillance may provide greater consistency than human review while facilitating wide-scale automated surveillance.

Disclosures

Chanu Rhee, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author) Michael Klompas, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author)
27. Co-infections and antimicrobial use in patients hospitalized with COVID-19
Authors: Prasad Prithiv , Zacharioudakis Ioannis , Poles Jordan , Dubrovskaya Yanina , Delpachitra Dinuli , Iturrate Eduardo , Munoz-Gomez Sigridh
Published: December 2021

Background

In-hospital antimicrobial use among COVID-19 patients is widespread due to perceived bacterial and fungal co-infections. We aim to describe the incidence of these co-infections and antimicrobial use in patients hospitalized with COVID-19 to elucidate data for guiding effective antimicrobial use in this population.

Methods

This retrospective study included all patients admitted with COVID-19 from January 1, 2020, to February 1, 2021 at any of the three teaching hospitals of the NYU Langone Health system. Variables of interest were extracted from the health system’s de-identified clinical database. The nadir of hospital admissions between the first and second peaks of hospital admissions in the dataset was used to delineate the First Wave and Late Pandemic periods of observation. A cut-off of 48 hours after admission was used to differentiate Co-infections and Secondary infections respectively among isolates of clinically relevant bacterial or fungal pathogens in blood or sputum samples. Population statistics are presented as median with interquartile range (IQR) or total numbers with percentages.

Results

663 of 7,213 (9.2%) inpatients were found to have a positive bacterial or fungal culture of the respiratory tract or blood during the entire course of their initial admission at our hospitals for COVID-19. Positive respiratory cultures were found in 437 (6.1%) patients, with 94 (1.3%) being collected within 48 hours of admission. Blood culture positivity occurred in 333 patients (4.6%), with 115 (1.6%) identified within 48 hours of admission. Infection-free survival decreased with duration of hospitalization, with rate of secondary infections steadily rising after the second week of hospitalization as seen in Figure 1. 70.2% of inpatients received antimicrobials for a median duration of 6 antimicrobial days (IQR 3.0 – 12.0) per patient. A higher proportion of patients received antimicrobials in the first wave than in the late pandemic period (82.6% vs. 51.8%).

Table 1.

Table 2

Figure 1

Infection free survival represented as duration of admission in days on the X-axis, and proportion of admitted patients remaining infection-free in the Y-axis. The blue line represents blood cultures and the orange line represents sputum cultures.

Conclusion

There was a very low incidence of co-infection with SARS-CoV-2 infection at admission. A longer duration of hospitalization was associated with an increased risk of secondary infections. Antimicrobial use far exceeded the true incidence and detection of co-infections in these patients.

Disclosures

All Authors: No reported disclosures
29. Sustained Recovery in Patients Admitted to Hospital With COVID-19
Authors: Moestrup Kasper S , Zucco Adrian G , Reekie Joanne , MacPherson Cameron , Otrowski Sisse R , Niemann Carsten Utoft , Lundgren Jens , Helleberg Marie
Published: December 2021

Background

Several interventional Coronavirus Disease 2019 (COVID-19) studies assess outcomes at day 28, but this follow-up time can be too short, since COVID-19 often cause protracted disease. Further, data on mortality and readmissions after discharge are scarse.

Methods

Patients aged 18-100 years and hospitalized with COVID-19 in Eastern Denmark between March 18th, 2020 and January 12th, 2021, were followed for 91 days after admission. Patients were stratified in a first and second wave, by admissions before or after June 15th, 2020, app. when remdesivir and dexamethasone were introduced as standard of care. Sustained recovery was defined as the first date, achieving 14 consecutive days after hospital discharge without an event of readmission or death. Cumulative incidences of sustained recovery were estimated in both waves and in subgroups based on the patient’s maximum level of respiratory support in the first 14 days of admission as a proxy for disease severity. Risk factors for poor outcomes were assessed in a multivariable cox proportional hazards model.

Results

Overall 3,386 patients were included in the study; 1,137 and 2,249 patients were admitted in the first and second wave, respectively (Table 1). The cumulative incidence of sustained recovery at day 91 was higher in the second (0.79, 95% CI: 0.77,0.81) than in the first wave (0.72, 95% CI: 0.70, 0.75) (Fig. 1A). In both waves, those with more severe disease recovered at a slower rate (Fig. 2B). There were no differences in cumulative incidences of readmissions or deaths at day 91 after discharge between the two waves, cumulative incidence (0.20, 95% CI: 0.19,0.21) and (0.11, 95% CI: 0.09,0.12), respectively (Fig 1C, Fig 1D). Male sex, high age, cardiovascular disease, diabetes, chronic pulmonary disease, renal disease, malignancies and neurological disease were associated with lower rates of sustained recovery (Table 2).

Conclusion

A follow-up period of 28 days in clinical trials for COVID-19 treatments is too short, especially for patients with severe disease. Rates of adverse outcomes after hospital discharge are non-neglible. In-hospital mortality was reduced with improvements in treatment, but post discharge mortality and readmissions rates did not change significantly.

Disclosures

Carsten Utoft Niemann, PhD MD, Abbvie (Grant/Research Support, Advisor or Review Panel member)Astra Zeneca (Grant/Research Support, Advisor or Review Panel member, teaching)CSL Behring (Consultant)Genmab (Grant/Research Support)Gilead (Grant/Research Support)Janssen (Grant/Research Support, teaching)Novo Nordisk Foundation (Grant/Research Support)Roche (Grant/Research Support)Sunesis (Grant/Research Support)
45. COVID-19 Vulnerability and Data Reporting in Africa: Reflections from Cameroon
Authors: Judson Seth D , Njabo Kevin , Torimiro Judith
Published: December 2021

Background

At the beginning of the COVID-19 pandemic there were many questions about vulnerability and data reporting among African countries. We previously found that policymakers in Cameroon value region-specific risk maps for emerging diseases. Therefore, we created regional vulnerability indices for COVID-19 in Cameroon. As the pandemic grew, we aimed to compare how these predictions related to reported COVID-19 cases in Cameroon and whether additional African countries had available data to assess vulnerability for COVID-19.

Methods

Using data from the Cameroon 2018 Demographic and Health Survey (DHS), we had constructed an epidemiological vulnerability index based on comorbidities potentially associated with COVID-19 severity. Similarly, we had created a healthcare access index. We then compared these indices with regional COVID-19 cases per population from weekly situation reports in Cameroon. Finally, we identified the availability of DHS data and COVID-19 reporting systems in other African countries.

Vulnerability Indices for COVID-19 in Cameroon

The epidemiological and healthcare access vulnerability indices constructed for Cameroon are shown along with COVID-19 cases per population.

Results

Adjusting for data reporting limitations, regions in Cameroon that scored higher on the epidemiological vulnerability index were associated with greater COVID-19 cases per population. We also identified regions with mismatches between high epidemiological vulnerability and low healthcare access. COVID-19 data reporting systems varied among African countries. 29/54 (53.7%) of African countries had recurrent situation reports or online dashboards with subnational COVID-19 data in 2020. Meanwhile, 36/54 (66.7%) of African countries had DHS data reported in the last decade.

Conclusion

We found that vulnerability indices could be a rapid way of identifying populations at risk for emerging diseases such as COVID-19. This method could be used in other countries that have both recent health surveys from programs such as the DHS and subnational reporting of COVID-19 cases. Indices could be useful for decision-making, but they will need to be refined with national expert input. National situation reports and online dashboards provided subnational COVID-19 data in approximately half of African countries. Therefore, increased baseline health surveys as well as expanded reporting of COVID-19 case data could inform future vulnerability assessments in other countries.

Disclosures

All Authors: No reported disclosures
47. Impact of COVID-19 Pandemic on an Emergency Department Opt-out HIV Screening Program: An Interrupted Time Series Analysis
Authors: Niu Jianli , Eckardt Paula
Published: December 2021

Background

The coronavirus disease 2019 (COVID-19) pandemic has posed tremendous challenges to health care systems, including emergency department (ED) priorities and visits. We describe the impact of COVID-19 pandemic on ED-based “Opt-out” HIV testing at a public healthcare system in South Florida.

Methods

The programmatic data of ED-based HIV testing from July 2018 to March 2021 at the Memorial Regional Hospital, Hollywood, Florida was retrospectively analyzed. Interrupted time series (ITS) analysis models were developed to evaluate the immediate and gradual effects of the pandemic on the monthly number of HIV tests over time, with an interruption point at March 2020.

Results

45,185 HIV tests were recorded between July 2018 and March 2021. A mean of 1,745 (SD, 266) HIV tests per month before the COVID-19 pandemic (July 2018 to Feb 2020) and a mean of 791 (SD, 187) HIV tests per month during the pandemic period (March 2020 to March 2021) was seen (p< 0.0001). As shown in Table 1, there was a slight decline trend in the number of monthly HIV test before the pandemic (estimate -10.29, p=0.541). We estimated a significant decrease in monthly HIV tests (estimate -678.48, p = 0.008), whereas the slope change after the pandemic was non-significant (estimate 4.84, p = 0.891). The number of monthly HIV tests declined significantly during the early phase of the pandemic, particularly between March 2020 and September 2020 (all p< 0.05), with an estimated 48.0% decrease in the March 2020 (estimate -678.48, p = 0.007), 43% in the April 2020 (estimate -673.65, p=0.007), and 50.7% in the May 2020 (estimate -668.83, p=0.009), compared with the same month of the pre-pandemic period (Figure 1). This decline in number of monthly HIV tests is consistent with the first wave of the COVID-19 pandemic in South Florida. Number of decreased monthly HIV tests from October 2020 through March 2021 was less pronounced (all p >0.05) and returned to pre-pandemic levels.

Conclusion

The COVID-19 pandemic led to a significant and immediate decline in monthly number of ED-based HIV tests. Disruption of basic health services by the COVID-19 pandemic is a public health concern. Strategies to develop an infrastructure to meet the demands of HIV testing should be implemented to ensure the current HIV prevention during the COVID-19 period.

Disclosures

All Authors: No reported disclosures
49. Effects of Maternal SARS-CoV-2 Infection on Neonatal Discharge Planning and Care: Exacerbation of Racial and Ethnic Healthcare Disparities
Authors: Jubulis Jennifer , Goddard Amanda , Dibrigida Sarah , McCarthy Carol A
Published: December 2021

Background

SARS-CoV-2 has exacerbated healthcare disparities. Maine’s population of 1.3 million is comprised of only 6% Black, Indigenous, People of Color (BIPOC); however, statewide 18% of SARS-CoV-2 infections have occurred in this group. This study examines newborn care inequities for infants born to mothers with SARS-CoV-2.

Methods

This study was conducted at Maine Medical Center in Portland, the largest hospital in Maine. Maternal SARS-CoV-2 infections from March 15, 2020 through April 1, 2021 were identified by PCR near time of delivery. Cases were matched to uninfected women by date of delivery. Chart review was conducted assessing demographic and clinical characteristics, comparing SARS-CoV-2 exposed and unexposed infants. The subset of SARS-CoV-2 exposed infants was further analyzed for trends in care by race. Protocol was exempt by MaineHealth IRB.

Results

Twenty four women and their infants were identified with maternal positive SARS-CoV-2 PCR just prior to delivery. An additional 24 unexposed infants were enrolled. When compared to unexposed infants, SARS-CoV-2 exposed were more likely to be racial minorities (63% vs 21%, p = 0.003), to have foreign-born mothers (58% vs 0.4%, p< 0.05) or to receive health care in a language other than English (29% vs 0.4%, p =0.02). For infants born to SARS-CoV-2 infected mothers, only 29% had initial follow up visit in person with their primary care provider (13% of BIPOC infants vs 56% of non-BIPOC infants, p = 0.03). Time to in-person follow up for exposed infants varied by race, with median time of 21 days (range 2-53 days) for racial minorities and 7.5 days (range 2-30 days) for non minorities. All families were discharged with a thermometer and scale for home management. No infants required re-admission during the month after discharge. One exposed infant tested positive for SARS-CoV-2.

Conclusion

The American Academy of Pediatrics recommends evaluation of newborns 3-5 days after discharge to identify maternal and child health factors affecting newborn well-being. The SARS-CoV-2 pandemic has made this challenging for patients, particularly for racial minorities. BIPOC pediatric patients were disproportionately affected by the pandemic in Maine, and were disproportionately affected by care discrepancies even when the infant was uninfected.

Disclosures

All Authors: No reported disclosures
53. Sex and Race Disparities in Premature Mortality among People with HIV: A 21-Year Observational Cohort Study
Authors: Pellegrino Rachael , Rebeiro Peter F , Turner Megan , Davidson Amber , Best Noelle , Shaffernocker Chandler , Sterling Timothy , Castilho Jessica L
Published: December 2021

Background

Since the availability of antiretroviral therapy, mortality rates among people with HIV (PWH) have decreased; however, this trend may fail to quantify premature deaths among PWH. We assessed trends and disparities in all-cause and premature mortality by sex, HIV risk factor, and race, among PWH receiving care at the Vanderbilt Comprehensive Care Clinic from January 1998 – December 2018.

Methods

We examined mortality trends across calendar eras using person-time from clinic entry to date of death or December 31, 2018. We compared mortality rates by demographic and clinical factors and calculated adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) using multivariable Poisson regression. For individuals who died, years of potential life lost (YPLL) were obtained from the expected years of life remaining by referencing US sex-specific period life tables at age and year of death; age-adjusted YPLL (aYPLL) rates were also calculated. We examined patient factors associated with YPLL using multivariable linear regression.

Results

Among the 6,531 individuals (51% non-Hispanic [NH] White race, 40% NH Black race, 21% female) included, 956 (14.6%) died. Mortality rates dramatically decreased during the study period (Figure). After adjusting for calendar era, age, injection drug use, hepatitis C virus (HCV), year of HIV diagnosis, history of AIDS-defining illness, CD4 cell count, and HIV RNA at clinic entry, only female sex (aIRR=1.32, 95% CI: 1.13–1.55 vs. males) but not NH Black race (aIRR=1.02, 95% CI: 0.88–1.17 vs. NH White race) was associated with increased mortality. In contrast, aYPLL per 1,000-person years was significantly higher for both female and NH Black PWH (Table 1). In adjusted models including CD4 cell count, HIV RNA, HCV, and year of clinic entry, higher YPLL remained associated with NH Black race, female sex regardless of HIV risk factor, and younger age at HIV diagnosis (Table 2).

Conclusion

Despite marked improvement over time, sex disparities in mortality as well as sex and race disparities in YPLL remained among PWH in care in this cohort. YPLL is a useful measure for examining persistent gaps in longevity and premature mortality among PWH.

Disclosures

Peter F. Rebeiro, PhD, MHS, Gilead (Other Financial or Material Support, Single Honorarium for an Expert Panel)
58. Cost-Effectiveness of Emerging Antibiotic Strategies for the Treatment of Drug-Use Associated Infective Endocarditis
Authors: Adams Joella W , Savinkina Alexandra , Gai Mam Jarra , Hill Allison , Hudspeth James , Jawa Raagini , Kimmel Simeon D , Marks Laura , Linas Benjamin P , Barocas Joshua
Published: December 2021

Background

Drug use-associated infective endocarditis (DUA-IE) is typically treated with 4-6 weeks of in hospital intravenous antibiotics (IVA). Outpatient parenteral antimicrobial therapy (OPAT) and partial oral antibiotics (PO) may be as effective as IVA, though long-term outcomes and costs remain unknown. We evaluated the clinical outcomes and cost-effectiveness of four antibiotic treatment strategies for DUA-IE.

Methods

We used a validated microsimulation model to compare: 1) 4-6 weeks of inpatient IVA along with opioid detoxification, status quo (SQ); 2) 4-6 weeks of inpatient IVA along with inpatient addiction care services (ACS) which offers medications for opioid use disorder (SQ with ACS); 3) 3 weeks of inpatient IVA with ACS followed by OPAT (OPAT); and 4) 3 weeks of IVA with ACS followed by PO antibiotics (PO). We derived model inputs from clinical trials and observational cohorts. All patients were eligible for either in-home or post-acute care OPAT. Outcomes included life years (LYs), discounted costs, incremental cost-effectiveness ratios (ICERs), proportion of DUA-IE cured, and mortality attributable to DUA-IE. Costs (&US) were annually discounted at 3%. We performed probabilistic sensitivity analyses (PSA) to address uncertainty.

Results

The SQ scenario resulted in 18.64 LY at a cost of &416,800/person with 77.4% hospitalized DUA-IE patients cured and 5% of deaths in the population were attributable to DUA-IE. Life expectancy was extended by each strategy: 0.017y in SQ with ACS, 0.011 in OPAT, and 0.024 in PO. The PO strategy provided the highest cure rate (80.2%), compared to 77.9% in SQ with ACS and 78.5% in OPAT and X in SQ. OPAT was the least expensive strategy at &412,300/person, Compared to OPAT, PO had an ICER of &141,500/LY. Both SQ strategies provided worse clinical outcomes for money invested than either OPAT or PO (dominated). All scenarios decreased deaths attributable to DUA-IE compared to SQ. Findings were robust in PSA.

Table 1

Selected cost and clinical outcomes comparing treatment strategies for drug-use associated infective endocarditis including the status quo, status quo with addiction care services, outpatient parenteral antimicrobial therapy, and partial oral antibiotics.

Conclusion

Treating DUA-IE with OPAT along with ACS increases the number of people completing treatment, decreases DUA-IE mortality, and is cost-saving compared to the status quo. The PO strategy also improves clinical outcomes, but may not be cost-effective at the willingness-to-pay threshold of &100,000.

Disclosures

Simeon D. Kimmel, MD, MA, Abt Associates for a Massachusetts Department of Public Health project to improve access to medications for opioid use disorder in nursing facilities (Consultant)
62. Follow-Up Blood Culture Practices for Gram-Negative Bloodstream Infections in Immunocompromised Hosts at a Large Academic Medical Center
Authors: Groft Lauren , Mease James , Bork Jacqueline , Bernhardi Ciera L , Kristie Johnson J , Claeys Kimberly C
Published: December 2021

Background

Routine follow-up blood cultures (FUBC) are strongly recommended for Staphylococcus aureus and Candida spp. bloodstream infections (BSI), but the role of FUBC in Gram-negative (GN) BSI remains controversial. Factors that may result in persistent GN BSI include critical illness, endovascular infection, lack of source control, multidrug resistant organisms (MDRO), end-stage renal disease, or immunocompromised status. As such, FUBC in patients with any of these factors may be warranted to improve clinical outcomes, but the true balance of benefit versus harm remains unknown. Our objective was to evaluate the role of FUBC in immunocompromised patients with GN BSI.

Methods

This was a retrospective observational cohort of adult, immunocompromised patients treated for confirmed GN BSI between January 2019 and December 2020 at University of Maryland Medical Center. Immunocompromise was defined as active hematologic or solid tumor malignancy at time of BSI diagnosis, history of hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), or absolute neutrophil count (ANC) < 1000 cells/mm3 at any time 30 days prior to BSI diagnosis. FUBC were defined as blood cultures drawn between 24 hours and 7 days from index blood culture, within the same hospital encounter. Positive FUBC was defined as a FUBC with same pathogenic GN organism identified. Comparison of patient and microbiologic characteristics was made between patients with and without FUBC.

Results

A total of 146 patients with GN BSI were included. Baseline characteristics are reported in Table 1. FUBC were collected in 129 (88.4%) patients. Neutropenia (49.6% vs. 19.4%, P=0.122), presence of central line (69.8% vs. 30.2%, P=0.061), and hospital-acquired origin of BSI (63.6% vs. 36.4%, P=0.395) resulted in increased frequency of FUBC. Patients with FUBC had a significantly longer post-BSI mean (SD) length of stay (17.3 [35.4] vs. 6.5 [6.0] days; P=0.005). Positive FUBC occurred in only 2 cases (1.4%) and both patients had persistent fevers at time of FUBC.

Table 1. Baseline Characteristics

Conclusion

Positive FUBC were uncommon in this immunocompromised cohort with GN BSI, which challenges the need for routine collection of FUBC in this patient population.

Disclosures

Ciera L. Bernhardi, PharmD, Servier Pharmaceuticals (Advisor or Review Panel member) J. Kristie Johnson, PhD, D(ABMM), GenMark (Speaker’s Bureau) Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)
66. Utilizing ceftazidime/avibactam therapeutic drug monitoring in the treatment of neurosurgical meningitis caused by Difficult-to-treat resistant (DTR)-Pseudomonas aeruginosa and KPC-producing Enterobacterales
Authors: Yasmin Mohamad , nutman Amir , Wang Lu , Marshall Steven , Yahav Dafna , Chen Ke , Wang Jiping , Li Jian , Bonomo Robert A
Published: December 2021

Background

Central nervous system (CNS) infections caused by carbapenem-resistant Enterobacterales (CRE) and Difficult-to-treat resistant (DTR)-Pseudomonas aeruginosa (PA) are a therapeutic challenge. Data demonstrating the pharmacokinetic/pharmacodynamic (PK/PD) properties of newer beta-lactamase inhibitors remains scarce. A clinical challenge lies in selecting an antimicrobial regimen that diffuses across the blood brain barrier and maintains concentrations to achieve PD targets associated with bacterial killing. These complexities compelled us to quantify the pharmacological properties of ceftazidime/avibactam (CZA). Utilizing therapeutic drug monitoring (TDM), we evaluated the adequacy of therapy and aimed to guide precise CNS dosing in the treatment of three patients with neurosurgical meningitis.

Methods

Bacterial identification and susceptibility testing were performed using MicroScan. TDM of CZA was implemented using a dose of 2.5 g infused intravenously over 2-hours, every 8 hours. The concentrations of ceftazidime and avibactam were determined by liquid chromatography/mass spectrometry. For patients 2 and 3, four unique CSF and plasma samples spanning the dosing interval were obtained; including trough values. (See table)

Results

Bacterial identification and CZA MICs for patients 1, 2, and 3 revealed blaKPCKp (0.25μg/mL), DTR PA (4 μg/mL), and blaKPCE. cloacae (0.25 μg/mL), respectively. Measured plasma and CSF concentrations of avibactam (AVI) and ceftazidime (CAZ) are shown in Table 1.

Table 1a. Therapeutic Drug Monitoring of CAZ-AVI depicting dosing, time of samples, and measured concentrations in CSF and Human Plasma (HP)

Table 1b. Therapeutic Drug Monitoring of CAZ-AVI concentrations in CSF and Human Plasma (HP) pertaining to patient 2 and 3

Conclusion

Measuring CZA concentration levels in CSF was achieved in 3 patients with complicated CNS infections. Post-infusion concentrations indicated that adequate CAZ and AVI exposures were attained in the CSF. Notably, avibactam was shown to achieve concentrations ≥1 µg/ml in the CSF throughout the dosing interval. For avibactam and ceftazidime, the PK/PD target correlated with bacterial killing is ~50% fT >MIC. In 2 out of 3 patients, concentrations were determined to be above the respective MICs throughout the entire dosing interval in the CSF. All patients attained clinical and microbiological cure. A novel CZA TDM method was successfully employed to establish that CZA maintains therapeutic CSF concentrations that exceed the MIC throughout the dosing interval.

Disclosures

Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)
68. Comparison of Cardiovascular Risk Assessment Calculators in the US Military HIV Natural History Study
Authors: Wyatt Andrew C , Xu Xiaohe , Daniels Colton , Sunil Thankam , Grance Melissa , Bohidar Niraja , Batzlaff Caitlin G , Ganesan Anuradha , Agan Brian , Larson Derek , Okulicz Jason , Markelz Ana E
Published: December 2021

Background

People living with HIV (PLHIV) have increased risk of cardiovascular disease (CVD), however CVD risk assessment can be challenging as HIV-related factors are not included in most calculators. We compared CVD risk calculators in US Military HIV Natural History Study (NHS) participants.

Methods

The NHS database was screened for participants enrolled between 2009-2019 who were ≥ 40 years of age with no previous history of CVD or statin use. Of the 399 participants meeting criteria, 385 (96.5%) had available data to assess 3 CVD risk calculators: Atherosclerotic CVD risk calculator (ASCVD), Framingham Risk Calculator (FRC), and the Data Collection on Adverse Eﬀects of Anti-HIV Drugs Study (DAD) risk calculator. Risk calculators were applied cross-sectionally at the first available time point at or after age 40 years and calculators were compared using a Wilcoxon signed rank test. Demographic and HIV-related characteristics were analyzed as independent variables.

Results

Participants were predominantly male (91.1%), mostly White (49.6%) or Black/African American (44.7%), and commonly had a history of tobacco use (38.9%). The mean age at HIV diagnosis and at CVD risk calculation was 33 and 41.8 years, respectively (Table 1). Overall, there was significant variability between calculators with mean scores of 3.66%, 2.50% and 1.38% for ASCVD, FRC, and DAD, respectively for all pairwise comparisons (p< 0.001; Table 2). When assessing those with CVD risk ≥ 7.5%, a clinically relevant threshold, the proportion of individuals with risk ≥ 7.5% varied for the ASCVD (10.4%), FRC (7.5%), and DAD (< 0.8%) calculators. Associations or trends toward higher CVD risk was observed among the various calculators for race/ethnicity and both age < 30 years and CD4 ≤ 350 cells/uL at HIV diagnosis (Table 2).

Conclusion

Since significant variability among CVD risk calculators was observed in the NHS cohort, it may be challenging to apply overall CVD risk calculators in a clinically relevant manner. HIV-related factors, such as duration of HIV infection and CD4 nadir, are not accounted for in CVD calculators and may be indicators of increased CVD risk. Future studies are warranted in order to determine the optimal clinical use of CVD risk calculators for PLHIV.

Disclosures

All Authors: No reported disclosures
70. Changes in Invasive Pneumococcal Disease among Adults Living with HIV Following Introduction of 13-Valent Pneumococcal Conjugate Vaccine, 2008–2018
Authors: Matanock Almea , Li Jianmin , Adih William , Xing Wei , Schaffner William , Alden Nisha B , Harrison Lee , Petit Susan , Baumbach Joan , Reingold Arthur , Almendares Olivia , Gierke Ryan , Holtzman Corinne , Farley Monica M , Thomas Ann , Pilishvili Tamara , Kobayashi Miwako
Published: December 2021

Background

People living with HIV (PLHIV) are at increased risk of invasive pneumococcal disease (IPD). The 13-valent pneumococcal conjugate vaccine (PCV13) was recommended for children in 2010, and for immunocompromised adults (including PLHIV) in series with 23-valent polysaccharide vaccine (PPSV23) in 2012. We evaluated changes in IPD incidence in adults ≥19 years old by HIV status after PCV13 introduction and proportion of remaining IPD due to serotypes included in the 15- (PCV15) and 20-valent (PCV20) conjugate vaccines expected to be licensed in 2021.

Methods

IPD cases were identified through CDC’s Active Bacterial Core surveillance (ABCs). HIV status was obtained from medical records. Isolates were serotyped by Quellung reaction, or whole-genome sequencing and grouped into PCV13-types, PPV11-types (unique to PPSV23), or non-vaccine types. We estimated IPD incidence (cases per 100,000 people) using national projections of ABCs cases as numerators and national case-based HIV surveillance (PLHIV) or US census data (non-PLHIV) as denominators. We compared IPD incidence in 2011–12 and 2017–18 to pre-PCV13 baseline (2008–09) by serotype groups. We assessed the proportion of IPD due to serotypes included in PCV15 and PCV20.

Results

Overall IPD incidence at baseline was 306.7 for PLHIV and 15.2 for non-PLHIV. From baseline to 2017–18, IPD incidence declined in PLHIV (-40.3%; 95% CI: -47.7, -32.3%) and non-PLHIV (-28.2%; 95% CI: -30.9, -25.5%). The largest reductions were in PCV13-type IPD during both periods (-44.2% for PLHIV and -42.2% for non-PLHIV in 2011–12; -72.5% for PLHIV and -62.2% for non-PLHIV in 2017–18) compared to baseline (Figures 1, 2). In 2017–2018, overall IPD and PCV13-type rates were 16.8 (95% CI: 15.1, 18.5) and 12.6 (95% CI: 9.9, 15.3) times as high in PLHIV vs non-PLHIV, respectively; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2% and 16.5% of IPD in PLHIV.

IPD incidence rates among adults aged ≥19 years old by serotype group in PLHIV, 2008–2018

IPD incidence rates among adults aged ≥19 years old by serotype group in non-PLHIV, 2008–2018

Conclusion

IPD rates declined significantly in both PLHIV and non-PLHIV during the study period due to reductions in PCV13-type IPD; however, IPD rates remained 17-fold higher in PLHIV compared to non-PLHIV, mainly due to non-PCV13 types. Higher-valent pneumococcal conjugate vaccines provide opportunities to reduce some of the remaining IPD burden in PLHIV.

Disclosures

William Schaffner, MD, VBI Vaccines (Consultant) Lee Harrison, MD, GSK, Merck, Pfizer, Sanofi Pasteur (Consultant)
88. Review of nursing home antibiotic stewardship citation deficiencies to identify opportunities to improve antibiotic stewardship implementation, 2018-2019
Authors: Gouin Katryna A , Cool Andrea J , Stone Nimalie D , Hicks Lauri , Jacobs Slifka Kara M , Almendinger Katherine , Harmon Holly , Gifford David , Truscott Pamela , Kabbani Sarah
Published: December 2021

Background

Centers for Medicare & Medicaid Services (CMS) set standards for nursing homes (NH) and conduct inspections to assess adherence to regulatory requirements, including antibiotic stewardship implementation. NHs not meeting requirements are issued a citation. We reviewed text summaries for citations related to antibiotic stewardship to assess implementation in NHs.

Methods

We obtained publicly available antibiotic stewardship deficiency citations issued to NHs from 9/2018—7/2019 and NH characteristics data from CMS Nursing Home Compare. We used the χ2 test to compare characteristics of NHs with and without citations.

We did a qualitative review of a randomly selected subset (318/635) of antibiotic stewardship citations and classified citations into one or more of four categories based on Centers for Disease Control and Prevention’s Core Elements of Antibiotic Stewardship: 1) Leadership & Accountability, 2) Action, 3) Tracking & Reporting, 4) Education (Fig 1). We developed subcategories based on our iterative review process to further describe the citations. Each citation was reviewed by two reviewers and yielded 95% agreement in categorization. Discordant citations were reviewed by a third reviewer, and core element categories with agreement by ≥2/3 reviewers were assigned, resulting in 99% agreement.

Antibiotic Stewardship Citation Deficiency Category Common Themes and Examples from Citation Text from Qualitative Review of Antibiotic Stewardship Citation Deficiencies.

Results

There were 635 NH stewardship citation deficiencies across 44 states from 9/2018—7/2019. NHs with a citation were more likely to have < 100 beds (60% vs. 50%) and for-profit ownership (75% vs. 70%) (Table 1).

Of the 318 reviewed citations, Action was cited in 67% of NHs; 115/213 had missing or incomplete criteria documented for antibiotic initiation. Tracking & Reporting was cited in 40% of NHs; 117/126 had missing or incomplete antibiotic or infection tracking logs. Leadership & Accountability was cited in 23% of NHs; 41/72 NHs had no stewardship policy available. Education was cited in 13% of NHs (Fig 2).

Table 1. Characteristics of US Nursing Homes With and Without an Antibiotic Stewardship Citation Deficiency from 9/2018-7/2019.

Figure 2. Types of Antibiotic Stewardship Citation Deficiencies in US Nursing Homes, 2018-2019, N=318.

Conclusion

The most common opportunities for improvement fell under appropriate assessment and documentation of criteria for antibiotic initiation at the resident and facility-level. Training NH staff to use available resources for antibiotic stewardship activities may improve implementation. Further evaluation to identify barriers to implementation is needed.

Disclosures

David Gifford, MD, MPH, American Healthcare Association (Employee)
92. Characteristics and Outcomes of Deep Brain Stimulation Device Related Infections: Experience from Quaternary Centers
Authors: Tabaja Hussam , Tai Don Bambino Geno , Corsini Campioli Cristina G , Chesdachai Supavit , DeSimone Daniel , Mahmood Maryam
Published: December 2021

Background

Increasing use of deep brain stimulation (DBS) over the past 20 years is paralleled by a rise in DBS infections. There is a paucity of data on the diagnosis, management, and outcomes in such infections. We describe our center’s experience with DBS infections.

Methods

Adults ( >18 years) diagnosed with DBS associated infection between January 1, 2000 and May 1, 2020 were retrospectively reviewed. Data on patient demographics, clinical presentation, microbiology, and management was collected.

Results

Seventy cases were identified (table 1). The mean age at diagnosis was 58.9 ± 16.5 years. The bulk were free of comorbidities. Parkinson’s disease and essential tremors were the most common indications for DBS placement. The median time from implantation to infection was 4 months [IQR 1,24]. The neurotransmitter and extension wires were the most frequently infected parts. A microbiological diagnosis was made in 89% of cases, 47% of which were polymicrobial. The most commonly identified organisms were Staphylococcus aureus, Cutibacterium acnes, and coagulase-negative staphylococci. For patients with deep infection, 71% had complete device extraction, 20% partial extraction, and 9% device retention; clinical cure at 3 months occurred in 97%, 64% and 100%, respectively (figure 1). On the other hand, 93% of patients with superficial infection had device retention; cure at 3 months was seen in 64% (figure 2). Suppressive oral antibiotics were rarely used, 45% of patients with partial extraction and 26% with device retention. DBS was reimplanted in 71% of patients after complete extraction and led to reinfection in 30% at 1 year follow up. Median time to reimplantation was 2.7 months. All patients who failed at 3 months in the partial extraction and device retention cohorts subsequently underwent complete device removal leading to clinical cure sustained at 1 year follow up.

Conclusion

All patients who had complete extraction achieved clinical cure at 3-months follow-up, while high failure rates occurred in those with device retention. Most infections were polymicrobial and predominantly caused by gram-positive pathogens. Thirty percent of patients with re-implantation after complete device extraction developed re-infection within 1 year.

Disclosures

All Authors: No reported disclosures