bluuebunny/crossref_metadata_2025_split huggingface dataset:
840. Clinical Failure Rates Associated with Hemin-induced Metronidazole Resistance in Clostridioides difficile
Authors: Gonzales-Luna Anne J , Shen Wan-Jou , Deshpande Aditi , Dotson Kierra M , Lancaster Chris , Hurdle Julian , Garey Kevin W 
Published: October 2019

Abstract

Background
Current guidelines suggest limiting metronidazole (MTZ) use due to increased treatment failures in patients with Clostridioides difficile infections (CDI). We hypothesized that an increase in the minimum inhibitory concentration (MIC) of MTZ to C. difficile may contribute to these poor response rates. The objective of this study was to examine clinical response rates in patients with CDI based on MTZ MIC and stratified by receipt of MTZ treatment.

Methods
Clostridioides difficile-positive stool samples collected from 2017 to 2018 as part of routine care at two hospital systems in Houston, Texas were collected for MIC determination at 24 h to MTZ by broth microdilution following incorporation of 5 mg/L of hemin. The primary outcome was initial clinical success by Day 7 of treatment in those with MICs ≥1 vs. <1. Results were stratified based on receipt of MTZ within 48 hours of diagnosis. Study objectives were tested using χ 2 and multivariable logistic regression analyses.

Results
A total of 235 C. difficile samples were included, of which 73 (31%) had an MTZ MIC ≥1. Overall, 72% received MTZ within the first 48 hours. Clinical success rates differed based on disease severity (77% in nonsevere, 64% in severe/fulminant; P = 0.03) and infecting ribotype (52% in RT 027, 75% in non-RT 027; P = 0.014). In patients with MTZ receipt, clinical success rates were higher in patients infected with strains with an MTZ MIC < 1 (76%) compared with those with an MIC ≥1 (60%; P = 0.031). The difference in initial clinical success was not different in those that did not receive MTZ (78% for MIC <1 vs. 65% for MIC ≥1, P = 0.28). After controlling for disease severity, treatment failure was higher in patients infected with strains with an MTZ MIC ≥1 and treated with MTZ (OR 2.1; 95% CI, 1.01–4.35; P = 0.048) but not for those with an MIC ≥1 treated with other therapies (OR 1.9; 95% CI, 0.62–5.6; P = 0.27).

Conclusion
This study provides the first preliminary evidence of an association between reduced metronidazole susceptibility and decreased clinical success rates. Larger studies are warranted to validate these findings.

Disclosures
All Authors: No reported Disclosures.
848. Low-Bioavailability vs. High-Bioavailability Oral Antibiotics for the Definitive Treatment of Enterobacteriaceae Bacteremia from Suspected Urine Source in Hospitalized Veterans
Authors: Sutton Jesse D , Chang Nai-Chung N , Stevens Vanessa W , Timbrook Tristan T , Spivak Emily S 
Published: October 2019

Abstract

Background
Limited and conflicting data exist evaluating low-bioavailability oral antibiotics (LOW) for definitive treatment of Enterobacteriaceae bacteremia (EB), and existing dogma limits their use. We compared outcomes for EB from a suspected urine source with LOW vs. high-bioavailability oral antibiotics (HIGH).

Methods
This was a retrospective cohort study across Veterans Affairs hospitals from 2006 to 2015. Inclusion criteria were monomicrobial EB and matching urine culture; receipt of active, empiric parenteral antibiotic(s); and conversion to a single oral LOW or HIGH between treatment day 2 and 6. Exclusion criteria were EB in the previous year, prior urologic abscess, or chronic prostatitis. HIGH included fluoroquinolones or trimethoprim-sulfamethoxazole. LOW included oral β-lactams. The primary outcome was all-cause 30-day mortality or recurrent EB. Patients were weighted using propensity-based overlap weights to make the groups more similar to each other at baseline. Log binomial regression models were used to estimate relative risks and risk differences.

Results
A total of 4,090 patients met inclusion criteria with 955 LOW and 3,135 HIGH. The median days of parenteral antibiotics before conversion to oral antibiotics were 4 (IQR 3, 5) in LOW and 4 (IQR 3, 4) in HIGH. The composite primary outcome occurred in 42 (4.4%) LOW and 94 (3.0%) HIGH. The adjusted relative risk (aRR) of the composite primary outcome with LOW was 1.28 (95% CI 0.86–1.89; risk difference [RD] 0.9%). Recurrent EB within 30-days occurred in 14 (1.5%) LOW and 12 (0.4%) HIGH (aRR 3.24, 95% CI, 0.46–22.8; RD 1.0%). Thirty-day mortality occurred in 29 (3.0%) LOW and 82 (2.6%) HIGH (aRR 1.0, 95% CI, 0.66–1.52; RD 0%). Similar outcomes were observed at 90 days.

Conclusion
There was no difference in the composite outcome of 30-day mortality and recurrent bacteremia comparing hospitalized patients who received LOW vs. HIGH for the definitive treatment of EB from a suspected urine source. While there was a nonsignificantly higher risk of 30-day recurrent EB with LOW, the absolute risk and risk difference were small, suggesting that definitive therapy with LOW may be considered. Future evaluation is needed to better understand risk factors for recurrent EB and which patients may fail LOW.

Disclosures
All Authors: No reported Disclosures.
885. HIV-1 Treatment Failure and Extensive Drug Resistance in Perinatally Infected Children Failing First-Line Antiretroviral Therapy in Western Kenya
Authors: Nyandiko Winstone , Holland Sabina , Vreeman Rachel , DeLong Allison , Manne Akarsh , Novitsky Vladimir , Coetzer Mia , Ngeresa Anthony , McAteer Carole , Aluoch Josephine , Orido Millicent , Sam Soya , Caliendo Angela , Ayaya Samuel , Hogan Joseph , Kantor Rami 
Published: October 2019

Abstract

Background
Understanding drug resistance in perinatally HIV-infected children (PHIC) when viral load (VL) monitoring is limited is critical for life-long antiretroviral use. Resistance data in PHIC in sub-Saharan Africa are limited. Though guidelines recommend PI-based first-line regimens in PHIC, many worldwide remain on NNRTI-based regimens. We examined treatment failure, resistance, and outcomes in Kenyan PHIC on first-line NNRTI-based therapy.

Methods
PHIC were enrolled in 2010–2013 at the Academic Model Providing Access to Healthcare in Eldoret, Kenya, a large program caring for >160,000 HIV patients; >15,000 PHIC. VL testing, not routinely available then, was done for all, and resistance testing was done in viremic PHIC. Clinical data were derived from medical records. Subtype and resistance interpretation were with Stanford Database tools. Associations between failure (>1,000 copies/mL) or resistance, and demographic, clinical or lab variables were evaluated with Fisher exact and Wilcoxon rank-sum tests.

Results
Of 482 PHIC enrolled, 52% were female, median age 8.4 years (range 1–15), median CD4% 28 (range 0–53), 79% on zidovudine (AZT)/abacavir (ABC)+lamivudine(3TC)+efavirenz (EFV)/nevirapine (NVP) for median 2.3 years. Treatment failure was seen in 31%, associated with low CD4% and count. Genotypes were available in 124, 47% female, median age 8.3 years (range 2–15), median CD4% 22 (range 0–45), 81% on AZT/ABC+3TC+EFV/NVP for median 2.5 years, median VL 7,515 copies/mL. Subtypes were A 76%, C 3%, D 15%, recombinants 6%. Reverse transcriptase mutations were in 93%; 93%-NNRTIs, median 2/patient, most common Y181C (44%); 89%-NRTIs, median 3/patient, most common M184V (85%); 89%-dual class, median 5/patient. Intermediate-high resistance to potential second-line drugs included 62% etravirine, 66% rilpivirine, and 19% tenofovir. Of 92/124 (74%) PHIC with follow-up data, 27% remained on NNRTI-based first-line (median CD4 count 461), of whom 24% had suppressed VL and 48% died; and 73% switched to PI-based second-line (median CD4 count 591), of whom 72% had suppressed VL and 6% died (P < 0.05 for both).

Conclusion
PHIC in western Kenya on NNRTI-based first-line regimens had high treatment failure rates and extensive drug resistance with poor clinical outcomes, demanding urgent interventions.

Disclosures
All Authors: No reported Disclosures.
889. Impact of an Infectious Disease Telehealth (IDt) Service on S. aureus Bacteremia (SAB) Outcomes in 15 Small Community Hospitals
Authors: Gabrellas Alithea D , Veillette John J , Webb Brandon J , Stenehjem Edward A , Grisel Nancy A , Vento Todd J 
Published: October 2019

Abstract

Background
Infectious diseases (ID) consultation improves SAB readmission rates, compliance with care bundles and mortality. Small community hospitals (SCHs) (which comprise 70% of US hospitals) often lack access to on-site ID physicians. IDt is one way to overcome this barrier, but it is unknown if IDt provides similar clinical benefits to traditional ID consultation. Our study aims to evaluate the impact of IDt on patient outcomes at 15 SCHs (bed range: 16–146) within the Intermountain Healthcare system in Utah.

Methods
Baseline demographics, Charlson Comorbidity Index (CCI), hospital length of stay (LOS), and mortality (in-hospital, 30- and 90-day) were collected using an electronic health record database and health department vital records on all patients with a positive S. aureus blood culture from January 1, 2009 through December 31, 2018. Data from January 2014 through Sep 2016 were excluded to avoid potential influence of a concurrent antimicrobial stewardship study. Starting in October 2016 an IDt program (staffed by an ID physician and pharmacist) provided consultation for SCH providers and patients using electronic consultation and encrypted two-way audiovisual communication.Statistical analyses were performed using Fisher’s exact test or χ 2 test for categorical variables and Mann–Whitney U test for nonparametric continuous data.

Results
In total, 625 patients with SAB were identified: 127 (20%) received IDt and 498 (80%) did not (non-IDt). The two groups (IDt vs. non-IDt) were similar in median age (66 vs. 62 years; P = 0.76), percent male (62% vs. 58%; P = 0.35), and median baseline CCI (4 vs. 4; P = 0.54). There were no statistically significant differences in median LOS (5 vs. 5 days; P = 0.93) or in-hospital mortality (2% in both groups). The IDt group had a lower 30-day (9% vs. 15%; P = 0.049) and 90-day mortality (13% vs. 21%; P = 0.034).

Conclusion
IDt consultation was associated with a decrease in 30- and 90-day mortality for SCH SAB cases. Early transfer of critically ill patients might have affected LOS and in-hospital mortality. Post-discharge care factors might also contribute to 30- and 90-day mortality. While more work is needed to identify other factors associated with the effect of IDt on SAB, these data support the use of IDt to increase access to care and improve SAB outcomes in SCHs.

Disclosures
All Authors: No reported Disclosures.
894. Universal Decolonization in Nursing Homes: Effect of Chlorhexidine and Nasal Povidone–Iodine on Prevalence of Multi-Drug-Resistant Organisms (MDROs) in the PROTECT Trial
Authors: Miller Loren G , McKinnell James A , Singh Raveena , Gussin Gabrielle , Kleinman Ken , Saavedra Raheeb , Mendez Job , Catuna Tabitha D , Felix James , Heim Lauren , Franco Ryan , Estevez Marlene , Lewis Brian , Shimabukuro Julie , Evans Kaye , Bittencourt Cassiana , Lee Eunjung , He Jiayi , Tjoa Thomas , Baesu Christine , Robinson Philip A , Tam Steven , Park Steven , Steinberg Karl , Beecham Nancy , Montgomery Jocelyn , Walters DeAnn , Stone Nimalie D , Huang Susan S 
Published: October 2019

Abstract

Background
The prevalence of MDROs in nursing homes (NH) is much higher than that of hospitals. Decolonization to reduce the reservoir of MDRO carriage in NH residents may be a strategy to address MDRO spread within and among healthcare facilities.

Methods
PROTECT is an 18-month cluster randomized trial of 1:1 universal decolonization vs. routine care in 28 NHs in California. Decolonization consists of chlorhexidine (CHG) bathing plus twice daily nasal iodophor on admission and Monday–Friday biweekly. We assessed pre- vs. post-intervention MDRO prevalence by sampling 50 randomly selected residents at each NH as an outcome unrelated to the trial’s primary intent (infection, hospitalization reduction). NH residents had nasal swabs cultured for methicillin-resistant S. aureus (MRSA), and skin (axilla/groin) swabs taken for MRSA, vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase producers (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE). Generalized linear mixed models (GLM) assessed the difference in differences of MDRO prevalence using an arm by period interaction term, clustering by NH.

Results
Four NHs dropped from the trial. Among the 24 NHs that remained, MDRO colonization at baseline was 49.4% and 47.5% of residents in control (N = 650) vs. decolonization (N = 550) NHs, with no difference in MRSA, VRE, ESBL, and CRE (Table 1). Among remaining NHs, decolonization was associated with 28.8% raw decrease in MDRO prevalence in decolonization sites (GLM OR = 0.51, P < 0.001), 24.3% raw decrease in MRSA (OR = 0.66, P = 0.03), 61.0% raw decrease in VRE (OR = 0.17, P < 0.001), and 51.9% raw decrease in ESBL (OR = 0.40, P < 0.001). CRE increased, but numbers were small (Control arm: 10 in baseline, 4 in intervention; intervention arm: 1 in baseline, 2 in intervention, P = NS).

Conclusion
Universal NH decolonization with CHG bathing and nasal iodophor resulted in a marked decrease in Gram-positive and Gram-negative MDRO prevalence. This decrease may lower MDRO acquisition, infection, and antibiotic use within NHs, as well as regional MDRO spread to other healthcare facilities.

Disclosures
All Authors: No reported Disclosures.
895. Impact of Measurement and Results Feedback of Chlorhexidine Gluconate (CHG) Skin Concentrations in Medical Intensive Care Unit (MICU) Patients Receiving CHG Bathing
Authors: Rhee Yoona , Hayden Mary K , Simms Andrew T , Yelin Rachel D , Lolans Karen , Bell Pamela B , Schoeny Michael , Baker Arthur W , Baker Meghan A , Gohil Shruti K , Rhee Chanu , Talati Naasha , Warren David K , Welbel Sharon F , Dangana Thelma E , Majalca Thelma , Bravo Heilen , Cass Candice , Nelson Alicia , Tolomeo Pam C , Wolf Robert , Lin Michael Y 
Published: October 2019

Abstract

Background
Higher CHG skin levels may be needed to adequately control infection and transmission of pathogens in the ICU. We assessed whether measurement and feedback of patient CHG skin concentrations could improve CHG bathing quality and identified factors associated with higher CHG skin concentrations.

Methods
We conducted 6 one-day surveys from January 2018 to February 2019 in 7 academic hospital MICUs with established daily CHG bathing. Adults admitted >1 day were assessed for CHG skin levels with a semi-quantitative colorimetric assay using swabbed 25 cm2 areas of anterior neck, axilla, and inguinal skin. Prior to survey 4, results from the first 3 surveys (baseline) were reported to ICU leadership and front-line staff to retrain and reeducate on bathing technique. Feedback of results from prior surveys also occurred before surveys 5 and 6. For statistical analysis, mixed-effects models accounted for clustering of CHG measurements within patients and ICUs. We categorized CHG product type as “cloth” for no-rinse 2% CHG-impregnated cloth and “liquid” for 4% CHG liquid or foam.

Results
In total, 681 of 704 (97%) patients were enrolled. Three ICUs used CHG cloth, 3 ICUs used CHG liquid, and 1 ICU switched from liquid to cloth after the second survey. Median CHG skin concentrations were higher in both the baseline and feedback period for institutions using CHG cloth, as compared with liquid (table). Across all time points, axillary and inguinal regions had higher skin CHG concentrations than the neck (median 39.1, 78.1, 19.5 µg/mL, respectively, P < 0.001). After controlling for age, mechanical ventilation, presence of a central venous catheter, body site, and hours since last CHG bath, institutions that used CHG cloth had a 3-fold increase in adjusted CHG skin concentrations in the feedback period compared with the baseline period (P = 0.001, Figure). There was no significant change in CHG skin concentrations from baseline to feedback period for institutions that used liquid CHG.

Conclusion
CHG skin concentrations on MICU patients receiving daily CHG bathing varied by body site and CHG product type. The use of CHG cloth was associated with higher CHG skin levels, compared with CHG liquid. For ICUs using CHG cloth, feedback of CHG skin concentration results to ICU staff improved CHG bathing quality.

Disclosures
All Authors: No reported Disclosures.
961. Prevalence and Macrolide Resistance of Mycoplasma genitalium After Initiation of HIV Preexposure Prophylaxis
Authors: Van Praet Jens , Steyaert Sanne , Vandecasteele Stefaan , Van Den Bergh Barbara , Mahieu Hilde , De Buyser Stefanie , Grootaert Veerle , Descheemaeker Patrick , Reynders Marijke 
Published: October 2019

Abstract

Background
Recent evidence shows that patients using HIV preexposure prophylaxis (PrEP) have an increased rate of bacterial sexually transmitted infections (STIs), including syphilis, chlamydia, and gonorrhea. The rate of Mycoplasma genitalium infections and the susceptibility of M. genitalium in patients on PrEP have been less well described.

Methods
We studied all patients who started on PrEP in the AZ Sint-Jan Hospital Bruges from January 6, 2017 to January 4, 2019. Patients were screened for M. genitalium and other bacterial STIs with rectal swabs, pharyngeal swabs, first-voided urine and blood collections at baseline and quarterly intervals after initiating PrEP. TaqMan array card technology was used to detect M. genitalium and determine macrolide-resistance mediating mutations in the region V of the 23S rRNA gene (A2058G, A2059G, A2058C, and others). Patients with an STI were treated based on a national guideline. Proportions were estimated using a Generalized Estimating Equations model with independent correlation structure.

Results
A total of 136 males and 1 female (median age, 40 years (interquartile range (IQR), 20–79)) were included in the study. All men were gay or bisexual. The median follow-up time was 11.3 months (IQR, 4.7–15.3). In total, 117 patients (85%) used PrEP daily at their last visit. The estimated proportion of patients with M. genitalium at baseline, 3 months, 6 months, 9 months, and 12 months was 7% (95% CI 4–13), 12% (95% CI 7–20), 7% (95% CI 4–15), 6% (3–15), and 6% (2–15). Thirty-two patients (23%) tested at least once positive for M. genitalium during the study period. The estimated percentage of macrolide resistance increased from 40% (95% CI 16–70) at baseline to 71% (95% CI 44–89), 67% (95% CI 27–92), 80% (95% CI 31–97), and 75% (95% CI 24–97) at 3 months, 6 months, 9 months, and 12 months, respectively.

Conclusion
After initiation of PrEP, the prevalence of M. genitalium in our cohort at quarterly screening was not increased compared with baseline. However, a nonsignificant trend of an increased percentage of macrolide-resistant strains was observed.

Disclosures
All Authors: No reported Disclosures.
970. Antibiotic Use Variability Among US Nursing Homes—2016
Authors: Kabbani Sarah , Wang Stanley , Ditz Laura , Palms Danielle , Rowe Theresa , Hyun David Y , Chi Nancy , Stone Nimalie D , Hicks Lauri 
Published: October 2019

Abstract

Background
Antibiotics are frequently prescribed in nursing homes (NH). National data describing facility-level antibiotic use (AU) in NH are lacking. The objectives of this analysis were to use NH electronic health records (EHR) to describe AU in NH and variability in AU rates across NH.

Methods
We analyzed antibiotic orders for 309,884 residents in 1,664 US NHs using one EHR company in 2016. We calculated AU rates as antibiotic days-of-therapy (DOT) per 1,000 resident-days and compared by the type of stay (short-stay (SS) ≤ 100 days vs. long-stay (LS) >100 days). We also examined prescribing indications and the duration of nursing home-initiated antibiotic orders. We assessed facility-level correlates of AU using resident health and NH facility characteristics publically available through NH Compare and LTCfocus using a univariate linear regression.

Results
In 2016, 57% of NH residents received at least one systemic antibiotic; overall rate of AU was 90 DOT/1,000 resident-days. The median facility-level AU rate was 64 DOT/1,000 resident-days (IQR 36–104). The median proportion of SS residents at a facility was 74% (IQR 60–84%). The SS and LS AU rates were 241 DOT/1,000 resident-days (IQR 173–342) and 24 DOT/1,000 resident-days (IQR 14–37), respectively. Overall, the three most common antibiotic classes prescribed were fluoroquinolones (18%), cephalosporins (18%), and extended-spectrum β-lactams (10%). Antibiotics were most frequently prescribed for urinary tract infections, and the mean duration of an antibiotic order was 9 days (range 1–365). Higher facility AU rate correlated positively with the following facility characteristics; proportion of SS residents, urban location, proportion of residents with mild cognitive impairment and lower activities of daily living scores, presence of ventilator beds, proportion of LS residents with urinary catheters or pressure ulcers, facility case-mix index, and not-for-profit ownership and multiorganization facilities.

Conclusion
Significant variability in NH AU rates exist, and SS residents have higher AU rates. Identifying NH with high rates of AU after adjusting for facility-level predictors of AU may identify opportunities for targeting efforts to improve prescribing practices.

Disclosures
All Authors: No reported Disclosures.
973. Single-cell RNA Sequencing Analysis of Zika Virus Infection in Human Stem Cell-Derived Cerebral Organoids
Authors: Ocwieja Karen , Stanton Alexandra , Richards Alexsia , Antonucci Jenna , Hughes Travis , Shalek Alex , Jaenisch Rudolph , Gehrke Lee 
Published: October 2019

Abstract

Background
The molecular mechanisms underpinning the neurologic and congenital pathologies caused by Zika virus (ZIKV) infection remain poorly understood. One barrier has been the lack of relevant model systems for the developing human brain; however, thanks to advances in the stem cell field, we can now evaluate ZIKV central nervous system infections in human stem cell-derived cerebral organoids which recapitulate complex 3-dimensional neural architecture.

Methods
We apply Seq-Well—a simple, portable platform for massively parallel single-cell RNA sequencing—to characterize cerebral organoids infected with ZIKV. Using this sequencing method, and published transcriptional profiles, we identify multiple cellular populations in our organoids, including neuroprogenitor cells, intermediate progenitor cells, and terminally differentiated neurons. We detect and quantify host mRNA transcripts and viral RNA with single-cell resolution, defining transcriptional features of uninfected cells and infected cells.

Results
In this model of the developing brain, we identify preferred tropisms of ZIKV infection and pronounced effects on cell division, differentiation, and death. Our data additionally reveal differences in cellular populations and gene expression within organoids infected by historic and contemporary ZIKV strains from a variety of geographic locations. This finding might help explain phenotypic differences attributed to the viruses, including variable propensity to cause microcephaly.

Conclusion
Overall, our work provides insight into normal and diseased human brain development, and suggests that both virus replication and host response mechanisms underlie the neuropathology of ZIKV infection.

Disclosures
All Authors: No reported Disclosures.