bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of Stool Frequency and Abdominal Pain Measures With Simple Endoscopic Score for Crohn’s Disease
Authors: Lewis James D , Rutgeerts Paul , Feagan Brian G , D’haens Geert , Danese Silvio , Colombel Jean-Frederic , Reinisch Walter , Rubin David T , Selinger Christian , Bewtra Meenakshi , Barcomb Lisa , Lacerda Ana P , Wallace Kori , Butler James W , Wu Meijing , Zhou Qian , Liao Xiaomei , Sandborn William J
Published: October 2019

Background

The Crohn’s Disease Activity Index (CDAI) has been criticized for being weakly correlated with bowel inflammation. We assessed correlation between Simple Endoscopic Score for Crohn’s Disease (SES-CD) and individual CDAI items stratified by disease location to better understand this relationship.

Methods

We pooled patient-level data from 3 placebo-controlled Crohn’s disease (CD) trials that tested adalimumab, upadacitinib, and risankizumab. Disease location was defined as ileum only, colon only, or ileocolonic based upon colonoscopy at study entry. Pearson correlation coefficients and linear regression assessed correlations between items of the CDAI and SES-CD.

Results

A total of 353 patients were included (20.7% ileal, 30.6% colonic, 48.7% ileocolonic disease). Crohn’s Disease Activity Index and SES-CD scores were moderately correlated (R = 0.33; P < 0.001). Among CDAI items, the strongest correlations with SES-CD were seen with very soft or liquid stool frequency (SF) and patient-reported outcome 2 (PRO2; which includes SF and abdominal pain score; both R = 0.36; P < 0.001); these correlations were numerically stronger in colonic disease (SF: R = 0.46; P < 0.001; PRO2: R = 0.44; P < 0.001) than in ileal disease (SF: R = 0.14; P = 0.23; PRO2: R = 0.21; P = 0.07), although a test for interaction was not significant. In adjusted linear regression models, the proportion of mucosa that was inflamed and the proportion of mucosa with ulceration were positively correlated, whereas the presence of strictures was inversely correlated with SF.

Conclusions

The SF item of the CDAI is moderately correlated with SES-CD and independently correlated with mucosal ulceration, inflammation, and strictures. Understanding why bowel inflammation as measured endoscopically does not correlate more strongly with patients’ symptoms could help develop scales that link CD pathology to patient experience.
Why do marine endotherms eat gelatinous prey?
Authors: Thiebot Jean-Baptiste , McInnes Julie C
Published: October 2019

There is growing evidence that gelatinous zooplanktonic organisms (“gelata”) are regular prey for marine endotherms. Yet the consumption of gelata is intriguing in terms of the energy reward, because endotherms have a high energy demand and the consumption of gelata provides little energy return. In this paper, we take advantage of recent advances in diet analysis methods, notably animal-borne video loggers and DNA analysis in seabirds, to examine our current understanding of this interaction. We suggest that several hypotheses commonly raised to explain predation on gelata (including increased biomass, reduced prey availability, and secondary ingestion) have already been tested and many lack strong support. We emphasize that gelata are widely consumed by endotherms (121 cases reported across 82 species of seabirds, marine mammals, and endothermic fishes) from the Arctic to the Antarctic but noticeably less in the tropics. We propose that in line with research from terrestrial ecosystems atypical food items might be beneficial to the consumers in a non-energetic context, encompassing self-medication, and responding to homeostatic challenges. Changing the “last resort” context for a “functional response” framework may improve our understanding of widespread predation on gelata. Further biochemical analyses are needed to formally examine this perspective.
Perfectly matched absorbing layer for modelling transient wave propagation in heterogeneous poroelastic media
Authors: He Yanbin , Chen Tianning , Gao Jinghuai
Published: October 2019

The perfectly matched layer (PML) has been demonstrated to be an efficient absorbing boundary for near-field wave simulation. For heterogeneous media, the property of the PML needs to be carefully specified to avoid numerical instability and artificial reflection because part of it lies at the discontinuous interface. Coupled acoustic-poroelastic (A-P) media or coupled elastic-poroelastic (E-P) media often arise in the field of geophysics. However, PMLs that appropriately terminate these heterogeneous poroelastic media are still lacking. The main purpose of this paper is to explore the application of unsplit PMLs for transient wave modeling in infinite, heterogeneous, coupled A-P media or coupled E-P media. To this end, a consistent derivation of memory-efficient PML formulations for the second-order Biot's equations, elastic wave equations and acoustic wave equations is performed based on complex coordinate transformation using auxiliary differential equations. Furthermore, the interface boundary conditions inside the absorbing layer are rigorously derived for the considered A-P and E-P cases. Finally, the weak form of PML formulations for coupled poroelastic problems is presented. The finite element method is used to validate the proposed PML based on several two-dimensional benchmarks. The accuracy and stability of weak PML formulations are investigated. In particular, for coupled acoustic-poroelastic PML, two extreme (open-pore and sealed-pore) interface conditions are considered and PML results are compared with known analytical solutions. This study demonstrates the ability of the PML to effectively eliminate outgoing bulk waves and surface waves in coupled poroelastic media.
The Diverse Upper Reference Limits of Serum Thyroid-Stimulating Hormone on the Same Platform for Pregnant Women in China
Authors: Wang Guocheng , Zhang Guojun
Published: October 2019

Objective

To describe the diverse upper reference limits of serum thyroid stimulating hormone on the same platform for pregnant women in China.

Methods

The trimester-specific and population-specific TSH reference intervals for pregnant women were established, and then 5 reference intervals on the same platform in China were compared with the reference intervals derived from the present study and the manufacturer.

Results

The most striking difference in the upper reference limits of TSH among 5 reference intervals on the same platform was shown at the first trimester of pregnancy. The calculated regional prevalence rates of subclinical thyroid diseases varied using the data derived from 30,771 pregnant women who visited the largest obstetric center in our district from 2008 to 2018.

Conclusion

We reported differences among 7 reference intervals of TSH on the same platform and showed the changing population factors significantly affected them.
77. Antimicrobial Prescribing Practices for Enteric Bacterial Infections in an Integrated Rural Healthcare System, 2004–2017
Authors: Olson Scott C , Watkins Louise Francois , Watkins Louise Francois , Walter Elaine Scallan , Friedman Cindy R , Friedman Cindy R , McLean Huong
Published: October 2019

Background

Bacterial enteric infections are common in the United States, but few studies have evaluated antibiotic prescribing practices for these illnesses. Unnecessary antibiotics can lead to adverse events and emergence of antimicrobial resistance. We assessed treatment practices among patients with laboratory-confirmed enteric infections in a large regional healthcare system.

Methods

We used electronic health records to identify patients with laboratory-confirmed nontyphoidal Salmonella, Shigella, Shiga toxin-producing E. coli (STEC), and Campylobacter infections from 2004 to 2017. We extracted relevant clinical data, including diagnosis codes for chronic conditions and receipt of immunosuppressive medications in the 60 days before and after the encounter, and antibiotic prescriptions in the 14 days after the encounter. We defined an appropriate treatment based on pathogen, patient characteristics, and IDSA practice guidelines for the study period.

Results

We identified 2,064 patients infected with enteric pathogens: 1,251 (61%) with Campylobacter, 564 (27%) Salmonella, 199 (10%) STEC, and 50 (2%) Shigella. Overall, 425 (20%) patients were immunocompromised, ranging from 17% for Salmonella to 46% for STEC. There were 220 (11%) hospitalizations. The frequency of antibiotic prescribing was highest for Campylobacter (60%), followed by Shigella (50%) and Salmonella (49%). Prescriptions were appropriate for 62% of Campylobacter cases, 92% of Shigella, and 70% of Salmonella. Antibiotics were prescribed for 39% of STEC infections although they are generally not indicated. Appropriate treatment was highest for children with Campylobacter (87%) and lowest for adults ≥50 years with Campylobacter (42%). Among those with Salmonella, appropriate treatment was higher in those with a comorbidity (79% vs. 68% without, P < 0.05). Rates of appropriate use did not improve over time.

Conclusion

Antibiotic prescribing for laboratory-confirmed enteric infections was frequently inappropriate and inconsistent with practice guidelines. Antibiotic stewardship initiatives should address acute bacterial gastrointestinal infections in addition to other common infections.

Disclosures

All Authors: No reported Disclosures.
84. Evaluation of the NHSN Standardized Infection Ratio (SIR) Risk Adjustment for HO-CDI in Oncology and ICU Patients in General Acute Care Hospitals
Authors: Polage Christopher R , Quan Kathleen A , Madey Keith M , Meyers Frank , Krishna Sneha , Grein Jonathan , Gibbs Laurel , Yokoe Deborah S , Mabalot Shannon C , Chinn Raymond , Hallmark Amy , Rubin Zachary A , Fontenot Michael , Cohen Stuart , Wightman Debbra , Birnbaum David , Huang Susan S , Torriani Francesca J
Published: October 2019

Background

The NHSN healthcare-facility onset Clostridioides difficile infection (CDI) standardized infection ratio (SIR) is used to compare hospital quality and set hospital reimbursement but inadequate risk adjustment could penalize hospitals unnecessarily. We hypothesized that general hospitals with large oncology and/or ICU populations were not fully adjusted in the 2015 NHSN acute care hospital CDI Laboratory-Identified (LabID) event prediction model and SIRs would be affected.

Methods

We validated a negative binomial regression HO-CDI event prediction model identical to the 2015 published model and used FY2016 data from eight general hospitals in California to test our hypothesis. We compared HO-CDI events and SIR values, with and without oncology/hematopoietic stem cell transplant or ICU unit events, patient-days, admissions, bed counts, and adjustment parameters included.

Results

Seven major teaching and one nonteaching general acute care hospitals were included (see Table). Eight had oncology/hematopoietic stem cell transplant units; seven had ≥43 ICU beds (median: 134; interquartile range [IQR]: 84–161). The median facility unmodified FacWideIn SIR was 1.23 [IQR: 1.15, 1.29]. Removal of oncology unit data resulted in a 15% median facility decrease in HO-CDI events (IQR: 14%, 21%) and −8% median facility decrease in SIR (IQR: −2%, −14%). Removal of ICU unit data resulted in a 22% median facility decrease in HO-CDI events (IQR: 16%, 26%) and 97% median facility increase in SIR at each facility (IQR: 78%, 105%).

Conclusion

The ICU bed adjustment in the 2015 NHSN SIR is a powerful correction that fully adjusted for ICU HO-CDI events at all hospitals in the study. However, the lack of risk adjustment for oncology/hematopoietic stem cell transplant unit HO-CDI events suggests that the current model unfairly penalizes general acute facilities, many of which also provide specialized oncologic care. Thus, the model needs to be re-adjusted to account for this important specialty care population in general acute care facilities.

Disclosures

All Authors: No reported Disclosures.
841. Implications of C. difficile Treatment on Environmental Contamination: A Randomized Controlled Trial with Microbiologic, Environmental, and Molecular Outcomes
Authors: Turner Nicholas A , Gergen Maria , Rutala William , Sexton Daniel J , Fowler, Jr. Vance G , Addison Rachel , Anderson Deverick J
Published: October 2019

Background

Clostridioides difficile is a leading cause of healthcare-associated infection. Despite multimodal prevention efforts, in-hospital transmission continues to occur. In this study, we tested whether the choice of treatment can reduce C. difficile shedding and contamination of the inpatient environment.

Methods

We conducted a prospective, unblinded, randomized controlled trial of adult inpatients with C. difficile at Duke University Hospital. Thirty subjects were randomized 1:1:1 to receive metronidazole, vancomycin, or fidaxomicin. Stool specimens and environmental samples from five high-touch surfaces were serially collected throughout each subject’s hospital stay. Each specimen was assessed by quantitative culture and PCR ribotyping. Primary outcomes included the change over time in C. difficile stool burden and environmental contamination relative to treatment choice. As a secondary outcome, we examined the correlation between infecting strains and contaminating strains present in the care environment.

Results

Relative to metronidazole (Figure 1), C. difficile stool shedding decreased more rapidly for patients receiving vancomycin (P = 0.05) and most rapidly with fidaxomicin (P = 0.002). Treatment choice had no significant effect on total C. difficile colony counts across sites sampled over time (Figure 2). However, both vancomycin (P = 0.001) and fidaxomicin (P = 0.01) were associated with lower proportions of positive environmental cultures than metronidazole (Figure 3). Ribotyping of subjects’ stool isolates matched surrounding environmental isolates >90% of the time (Figure 4).

Conclusion

Fidaxomicin and vancomycin reduced C. difficile stool burden more rapidly than metronidazole. Environmental results were mixed: fidaxomicin and vancomycin were associated with fewer positive surface cultures, but no difference in total colony counts. High concordance between stool and environmental ribotypes confirms that most room contamination originated from study subjects, without a significant contribution from any additional sources. Treatment choice may have a role in reducing C. difficile contamination of the hospital environment. Further study is needed to assess for effect on disease incidence.

Disclosures

All Authors: No reported Disclosures.
843. The PALM Consortium: A Multicenter, Multioutbreak Randomized Controlled Trial of Ebola Virus Disease Therapeutics
Authors: Mulangu Sabue
Published: October 2019

Background

Recent outbreaks of Ebola virus disease in the Democratic Republic of the Congo (DRC) reinforce the desperate need to establish definitively the comparative safety and efficacy of different medical countermeasures (MCM).

Methods

Through a multipartner governance framework under WHO coordination, the Institut National de Recherche Biomédicale and NIAID collaborated with clinical partners (the MOH, ALIMA, MSF) to launch a randomized controlled trial in 2018 in the North Kivu/Ituri provinces of DRC. PCR+ participants receiving enhanced supportive care are being randomized 1:1:1:1 to receive either ZMapp™ (control arm), remdesivir, mAb114, or REG-EB3 according to standard treatment regimens. Stratification is by site, country, and baseline nucleoprotein (NP) PCR cycle threshold (CT) ≤ 22 or > 22. The primary objective is a comparison of 28-day mortality relative to the control arm. The planned accrual is for 125 patients per arm. Secondary objectives include an evaluation of the comparative safety and tolerability of the 4 investigational MCMs, relative changes in viral load over time, comparisons of treatment efficacy according to baseline risk categories, 58-day mortality, RNA clearance from semen, and an assessment of the validity of drug-class comparisons, including efficacy. The study is monitored by an independent data and safety monitoring committee (DSMB).

Results

Enrollment commenced in the Ebola Treatment Unit in Beni in November, 2018, with sites in Butembo and Katwa added in early 2019. Time from study concept initiation to study start was only 3.5 months. Ongoing hurdles encountered to date include maintenance of cold chain requirements for the MCMs and marked volatility in the security situation surrounding sites affecting staff and patient safety. Despite these challenges, data quality and completed follow-up have been remarkably high and by mid-April, 2019, accrual to date (see table) had already surpassed the predefined threshold triggering an interim DSMB review.

Conclusion

Scientifically rigorous and ethically sound clinical research can take place during disease outbreaks even within a conflict zone. Results about the relative efficacy of the evaluated investigational MCMs are pending the completion of the trial.

Disclosures

All Authors: No reported Disclosures.
845. Children with Clinical Plasmodium falciparum Infection Have Increased Sharing of Haplotypes with Household Members as well as Temporally Proximal, Symptomatic Peers
Authors: Nelson Cody S , Sumner Kelsey , Freedman Betsy , Obala Andrew , Mangeni Jane , Taylor Steve , O’Meara Wendy
Published: October 2019

Background

Falciparum malaria transmission has failed to decline in proportion to control efforts in certain regions such as Bungoma county, western Kenya. One proposed strategy to eradicate malaria is ring testing and treatment; however, it remains unknown whether infections spread locally or if asymptomatically infected household members are a risk factor for clinical disease.

Methods

From April 2013 to June 2014, we enrolled 442 cases (RDT+ children hospitalized with malaria) and 442 matched controls; all household members of cases and controls were also enrolled and tested, of which 13.6% (n = 608/4449) were RDT+. From each RDT+ participant, parasite gDNA was PCR-amplified at both Pf circumsporozoite protein (csp) and apical membrane antigen 1 (ama1) loci, amplicons sequenced on an Illumina Miseq, and haplotypes inferred using dada2.

Results

We identified 120 csp and 180 ama1 unique haplotypes (Figure 1). We evaluated the genetic distance between infected individuals using three novel indices: sharing of parasite haplotypes on binary and proportional scales and the L1 norm. Case children median [IQR] binary/proportional sharing of both csp and ama1 haplotypes was significantly increased with members of their origin household (e.g., csp binary sharing: origin = 50.3 [0–87.5] vs. similar household = 0 [0–50.3]; P = 0.01; Wilcoxon sign-rank test), indicating that cases are more likely to share haplotype-identical parasites with members of their own household (Figure 2). We also computed population-level haplotype sharing indices for all pairs of case children and observed no association between genetic relatedness and geographic distance. In contrast, we identified a strong inverse relationship between haplotype sharing and temporal distance, which we exploited to identify the molecular signature of an outbreak (Figure 3).

Conclusion

Overall, these findings suggest that, although haplotype sharing is more common within households, temporal rather than geographic proximity predicts parasite genetic similarity. The observation that identical haplotype combinations are found nearly simultaneously across the study area implies that ring testing approaches may not effectively reduce transmission.

Disclosures

All Authors: No reported Disclosures.
846. Postnatally Acquired Zika Virus (ZIKV) Infection in Infants and Young Children in Guatemala: Serologic and Neurodevelopmental (ND) Evaluation
Authors: Munoz Flor M , Munoz Flor M , Connery Amy , Natrajan Muktha S , Waggoner Jesse , Lamb Molly , Olson Daniel , Paniagua-Avila Alejandra , Bauer Desiree , Anderson Evan J , Mulligan Mark , Calvimontes Mirella , Bolanos Guillermo , Holliday Andrea , Keitel Wendy , El Sahly Hana , Tomashek Kay , Asturias Edwin J
Published: October 2019

Background

Diagnosing ZIKV infection in children in dengue (DENV) endemic regions is challenging. The kinetics and effects of maternal Ab on infant infection responses remain unknown, as do the ND effects of ZIKV acquired in early life.

Methods

This is a population-based prospective cohort study in infant–mother pairs and children <5 years in a rural DENV endemic area of Guatemala evaluating the incidence and ND outcomes of postnatally cquired ZIKV infection. Subjects were followed 1 year for symptoms of flavivirus-like illness (FLI), serologic and virologic evidence of ZIKV or DENV infection and ND outcomes. ZIKV and DENV neutralizing antibodies (NAb) were measured at enrollment and longitudinally. Subjects were classified as ZIKV- or DENV-infected based on NAb. Specimens from acute illnesses were tested for viral RNA by rRT-PCR. ND was assessed at enrollment and longitudinally using an adapted Mullen Scales of Early Learning (MSEL).

Results

In total, 1,371 subjects (374 children 1–5 years, 500 infants, 497 mothers) were enrolled from June 2017 to July 2018. Among 1,335 evaluable subjects, 7.6% (101) had serologic evidence of recent ZIKV infection (NAb >500 or >100 and DENV-neg); 13.2% (176) were DENV-pos only; 44.8% (598) were ZIKV-neg (NAb15 −<100) or low (<500) ZIKV and DENV NAb, suggesting prior flavivirus infection or cross-reactivity (Figures 1 and 2). ZIKV infection alone was more prevalent in children 1–5 years, while infants’ serologic pattern was similar to that of their mothers. One child ZIKV seroconverted. In 391 FLI episodes (67 children 1–5 years and 215 infants with fever, rash, myalgia, and conjunctivitis; 109 mothers with fever, myalgia, and joint pain), acute DENV infections, but not ZIKV, were identified by rRT-PCR. MSEL scores were similar to US norms in infants <12 m (composite mean 94.8, SD 11.9), but lower in children 1–5 years in all domains (mean 75.1, SD 17.4, P < 0.0001) (Figure 3).

Conclusion

Serologic evidence of recent ZIKV infection, but no acute ZIKV, was documented in young children in Guatemala. Infant seroreactivity derives from prior maternal infection and DENV cross-reactivity. Observed substantial differences in ND scores between infants and children 1–5 years challenge the ability to isolate the potential effects of ZIKV infection in early life. NIAID Contract HHSN272201300015I Task Order HHSN27200013. FMM and EJA Co-PIs.

Disclosures

Flor M. Munoz, MD, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor: Royalties, Other Financial or Material Support.
891. Epidemiology and Outcomes of Sepsis in Previously Healthy Patients
Authors: Alrawashdeh Mohammad , Klompas Michael , Simpson Steven Q , Kadri Sameer S , Poland Russell , Sands Kenneth , Rhee Chanu
Published: October 2019

Background

Devastating cases of sepsis in previously healthy patients have received widespread attention and helped catalyze state and national mandates to improve sepsis detection and care. It is unclear, however, what proportion of sepsis cases occur in previously healthy people and how their outcomes compare to patients with comorbidities.

Methods

We conducted a retrospective study of adults admitted from 2009 to 2015 to 373 US hospitals from 3 cohorts using detailed electronic health record data. We identified patients with community-onset sepsis using CDC Adult Sepsis Event criteria and reviewed patients’ ICD-9-CM codes to identify major and minor comorbidities. Generalized linear mixed models were used to identify the association between healthy vs. comorbid status and short-term mortality (in-hospital death or discharge to hospice) among sepsis patients, controlling for demographics and clinical characteristics.

Results

The cohort included 6,715,286 adult hospitalizations, of which 337,983 (5%) met community-onset sepsis criteria. Most (329,052; 97.4%) sepsis patients had at least one comorbidity (96.1% major, 1.2% minor, 0.1% pregnant) whereas the minority (8,931; 2.6%) were previously healthy. Hospitalized patients without sepsis, by contrast, tended to be healthier (6.2%, Figure 1). Compared with sepsis patients with comorbidities, previously healthy sepsis patients were younger (mean 48.3 + 20 vs. 66.9 + 16.5 years, P < 0.001) and less likely to require ICU care on admission (30.9% vs. 50.5%, P < 0.001). Previously healthy patients were more likely to be discharged home vs. subacute facilities compared with sepsis patients with comorbidities but had higher short-term mortality rates (22.7% vs. 20.8%, P < 0.001) (Figure 2). The increased risk of short-term death in healthy patients persisted on multivariate analysis (adjusted odds ratios 1.36–1.79, P < 0.001).

Conclusion

The vast majority of patients who develop community-onset sepsis have pre-existing conditions. However, previously healthy patients may be at higher risk for death due to sepsis compared with patients with comorbidities. These findings provide context for high-profile reports about sepsis deaths in previously healthy people and underscore the importance of early sepsis recognition and treatment for all patients.

Disclosures

All Authors: No reported Disclosures.
900. Effect of Influenza Vaccine Priming on Current Season Vaccine Effectiveness among Children and Adolescents, US Flu VE Network 2014–2015 Through 2017–2018
Authors: Chung Jessie R , Flannery Brendan , Gaglani Manjusha , Reis Evelyn , Hickey Robert , McLean Huong , Jackson Michael L , Belongia Edward , Smith Michael , Martin Emily T , Monto Arnold , Thompson Mark G , Kim Sara S , Patel Manish
Published: October 2019

Background

Studies have demonstrated that optimal protection against childhood influenza requires two “priming” doses of influenza vaccine in the first season of vaccination. Two doses of influenza vaccine are recommended for US children aged 6 months-8 years who received ≤1 dose in prior seasons. We examined risk of influenza among children fully or partially vaccinated during study seasons and vaccine effectiveness (VE) by the number of priming doses.

Methods

Analyses included children aged 6 months-17 years enrolled during outpatient visits for acute illness for ≤7 days with cough in the US Influenza Vaccine Effectiveness Network during 2014–2015 through 2017–2018. Participants’ respiratory specimens were tested for influenza by rRT-PCR. Vaccination histories back to birth year were obtained from electronic immunization records. VE was calculated by comparing vaccination odds among influenza-positive cases to test-negative controls, as 100 × (1 − odds ratio) adjusted for season, site, age, high-risk status, and calendar time.

Results

Of 7,583 children, 6,362 (84%) had received ≥1 dose in their lifetime. Among vaccinated children, 90% were primed prior to the enrollment season, and 80% were primed prior to age 2 years. Most (55%) received two priming doses in their first season. Among children recommended to receive two priming doses in the enrollment season, receipt of two doses vs. one was associated with a lower risk of influenza illness (aOR: 0.60; 95% CL: 0.36, 1.00). VE of ≥1 dose in the enrollment season against any influenza among unprimed children was 53% (95% CL: 36, 66). VE of ≥1 dose in the enrollment season was similar among children primed with one dose in their first season (46%; 95% CL: 34, 55) and among those primed with two doses (46%; 95% CL: 35, 55). Overall results were similar when stratified by age and for A/H3N2 viruses, which predominated during study years.

Conclusion

Among the US children recommended to receive two priming doses of vaccine in the enrollment season, receipt of two doses provided optimal protection. VE in seasons after the priming did not differ by the number of priming doses. Results were driven by predominance of A/H3N2 viruses and may not be similar for A/H1N1pdm09 or B viruses. Current US influenza vaccine recommendations for children are effective and appropriate.

Disclosures

All Authors: No reported Disclosures.
966. A Closer Look at Antibiotic Prescribing for Upper Respiratory Illnesses (URI) in People with HIV Compared with People Without HIV
Authors: Abbas Anum , Keintz Mackenzie R , Lyden Elizabeth , Ma Jihyun , Bares Sara H , Van Schooneveld Trevor C , Marcelin Jasmine R , Marcelin Jasmine R
Published: October 2019

Background

Antibiotic overuse is widespread, increasing healthcare cost and promoting antimicrobial resistance. People with HIV (PWH) who develop URIs may be assumed “higher risk,” compared with non-PWH, but comparative antibiotic use evaluations have not been performed. We evaluated antibiotic prescribing patterns for URI diagnoses (cough, sinusitis, bronchitis, and cold) in PWH and non-PWH.

Methods

This was an observational, single-center study comparing PWH and non-PWH diagnosed with URI (using ICD 10 codes for URI syndromes: cough, sinusitis, bronchitis, and cold) between January 1, 2014 and April 30, 2018. Patients were empaneled in an outpatient primary care clinic or specialty care clinic in one healthcare system. Appropriateness of antibiotic prescribing was defined based on published guidelines. Fisher’s exact test compared categorical variables with antibiotic prescribing patterns. Each encounter was considered an independent event.

Results

The two groups (PWH and non-PWH) were similar, with 34% of subjects in both groups being female. PWH had median CD4+ count of 610 cells/mm3 with 91% on antiretrovirals and 77% with HIV RNA < 20 copies/mL. Overall, 37% of visits resulted in antibiotic prescriptions, 92% of which were inappropriate (discordant with guidelines). Antibiotics were prescribed slightly more frequently in non-PWH (40% vs. 33%, P = 0.056; Figure 1) and inappropriate more often in non-PWH (37% vs. 30%, P = 0.029). Over 20% of PWH antibiotic prescriptions were too long, and 22% of non-PWH received the wrong drug (Figure 2; P = 0.011). 47% of the non-PWH receiving antibiotics for URI had private insurance (compared with other payers; P < 0.0001) vs. 33% in PWH (P = 0.32) (Figure 3).

Conclusion

Outpatient antibiotic overuse remains prevalent among patients evaluated for URIs. This is the first study, to our knowledge, comparing antibiotic use for URIs in PWH compared with non-PWH. Counterintuitively, we found less-frequent inappropriate antibiotic use in PWH. We speculate that PWH are more likely to be evaluated by infectious disease/HIV specialists, possibly explaining the lower rate of antibiotic prescriptions for URIs in this population. Future analyses will evaluate the association between provider specialty and inappropriate antibiotic use.

Disclosures

All Authors: No reported Disclosures.
968. Effect of Outpatient Antibiotic Ordering Restrictions on Antibiotic Prescribing Patterns at a State-wide VA Healthcare System
Authors: Dave Rohini , Bork Jacqueline
Published: October 2019

Background

Approximately 30% of antibiotics prescribed in the outpatient setting are inappropriate, mostly due to unnecessary prescriptions (Rx) for upper respiratory infections. Ordering restrictions is one approach to curtail inappropriate use. However, this approach may cause unintended consequences, such as increases in Rx of higher level antibiotics. This study evaluated the downstream effect of an azithromycin (AZM) ordering restriction.

Methods

This was a pre–post evaluation of the impact of an AZM removal (October 2017) on prescribing patterns of common outpatient antibiotics at the VA Maryland Healthcare System. AZM restriction was placed >10 years ago for concerns of emerging AZM resistance and overuse. During the study period, fluoroquinolone (FQ) use was scrutinized due to increasing toxicity risk. The proportion of several outpatient antibiotic Rx were compared between October 2017 and September 2018 (FY17) and October 2018 and September 30, 2018 (FY18) using χ 2 and logistic regression. FQ and AZM Rx were also stratified by location of prescribing clinic (urban vs. rural) and duration (≤14 days vs. >14 days).

Results

There were 15,972 and 14,451 prescriptions in FY17 and FY18, respectively. AZM Rx increased from 1,247 (7%) Rx in FY17 to 1,734 (11%) in FY18 (P < 0.0001) with an OR of 1.8 (95% CI 1.65–1.94). There was a greater effect on shorter than longer duration (OR 1.9 vs. 1.3, P < 0.0001), but no significant effect difference for urban and rural clinics (OR 1.8 vs. 1.9, P = 0.6). Conversely, FQ Rx decreased from 2,414 (15%) in FY17 to 1,731 (11%) in FY18 (P < 0.0001) with an OR of 0.7 (95% CI 0.66–0.76). There was a greater effect on shorter than longer duration (0.6 vs. 1.2, P < 0.0001) and also a greater effect on urban than rural clinics (OR 0.6 vs. 0.97, P < 0.0001). Doxycycline, amoxicillin–clavulanate and trimethoprim–sulfamethoxazole did not change significantly.

Conclusion

Removal of AZM restriction led to a significant decrease in FQ Rx, with greater effect in shorter duration and urban clinics, and an increase in AZM Rx, with greater effect in shorter duration, but no difference in clinic setting. Disparity of rural prescribers needs further exploration, as do other interventions outside of restrictive ordering, which needs periodic evaluation of risk and benefit if implemented.

Disclosures

All Authors: No reported Disclosures.
969. Antibiotic Prescribing in a Large Retail Health Clinic Chain: Opportunities for Stewardship
Authors: Fleming-Dutra Katherine E , King Laura M , Boghani Safia , Hicks Lauri , Hou John , Kirkham Heather S
Published: October 2019

Background

Retail health is a growing outpatient setting. Research using claims data found that antibiotics were linked with 46% of urgent care, 17% of medical office, and 14% of retail health visits for acute respiratory infections (ARIs) for which antibiotics are not needed. We aimed to quantify antibiotic prescribing rates to adult patients in a large retail health clinic chain using electronic health records and to identify future stewardship targets.

Methods

We included visits by adults ≥18 years to network retail health clinics from 2012 to 2016. We classified diagnoses by ICD codes. We calculated the percent of visits with systemic antibiotics prescribed among all visits, by individual diagnosis, and for ARIs as a group (e.g., pneumonia, sinusitis, pharyngitis, acute otitis media [AOM], bronchitis, and viral upper respiratory infections [URI]). We also assessed the percent of visits for sinusitis and pharyngitis with first-line antibiotics prescribed.

Results

Of 2,893,413 visits by adults during 2012–2016, 1,866,145 (66%) resulted in antibiotic prescriptions. ARIs accounted for 2,039,423 (72%) of visits and 1,475,069 (79%) of antibiotic prescriptions. The most common diagnoses regardless of antibiotic prescription were sinusitis (31% of visits), pharyngitis (15%, of which 81% were coded as streptococcal pharyngitis), urinary tract infection (9%), viral URI (8%), AOM (7%), and bronchitis (5%). Antibiotics were frequently prescribed for sinusitis, urinary tract infection, pharyngitis, and AOM but not for viral URI and bronchitis (Figure 1). First-line antibiotics were prescribed in the majority of sinusitis and pharyngitis visits (Figure 2).

Conclusion

ARIs are major drivers of visits by adult patients and of antibiotic prescribing to adults in this retail clinic network. Inappropriate antibiotic use was low in this setting for viral URI and bronchitis and first-line antibiotic selection was high for sinusitis and pharyngitis, although additional opportunities for improvement exist. Future antibiotic stewardship efforts may target examining adherence to guideline-recommended diagnostic criteria for sinusitis, AOM, and pharyngitis and increasing use of watchful waiting for sinusitis and AOM.

Disclosures

All Authors: No reported Disclosures.
1820. Efficacy of Pulse-Taper Corticosteroid Adjunctive Therapy for Refractory Non-HIV Cryptococcal Meningoencephalitis
Authors: Anjum Seher , Williamson Peter R , Bielekova Bibiana , Kosa Peter
Published: October 2019

Background

Cryptococcal meningoencephalitis (CM) affects individuals with AIDS, transplants recipients and those previously healthy, with 30–50% mortality in most groups despite anti-fungal treatment. In the previously healthy, a post-infectious inflammatory response syndrome (PIIRS) analogous to cryptococcal IRIS in AIDS patients has recently been described. PIIRS is defined as a deterioration in mental status and/or audio-visual capacity despite optimal treatment for CM and negative CSF cultures. Pathophysiology is related to excessive T-cell responses to lysed fungal cells during therapy but data on effective treatment regimens are limited.

Methods

Between March 2015 and February 2019, 11 consecutive patients with PIIRS who evidenced clinical deterioration over a period of up to 10 weeks despite effective antifungals were referred to the NIH clinical center. Patients were prospectively treated with adjunctive pulse solumedrol 1 g daily for 1 week followed by prednisone 1 mg/kg/day, tapered based on clinical and radiological response plus oral fluconazole. Montreal cognitive assessments (MOCA) scores at baseline and 1 month were the primary endpoints and CSF parameters including WBC, glucose, HLA DR4+ CD4 and CD8 cells and cytokines were also determined at baseline and after 1 week of solumedrol. Paired nonparametric t-tests were conducted using GraphPad Prism 7.0.

Results

All patients demonstrated clinical improvement despite 7 being initiated at the point of stupor and 6 having received ventriculoperitoneal shunts without clinical response. MOCA scores at 1 month showed significant improvement (P = 0.002), accompanied by significant improvements in CSF: serum glucose ratios, CSF WBC, protein and HLADR4 positive T cells 1 week after receiving corticosteroids (P < 0.02). Patients with hearing or visual deficits exhibited clinical improvement. CSF cultures remained negative.

Conclusion

Our findings in this small observational cohort of refractory non-HIV CM with PIIRS demonstrated significant clinical benefit of high dose adjunctive pulse-taper corticosteroids. The study also demonstrates the utility of physiology-based immunophenotyping to guide therapy in neuroinflammation associated with infectious diseases.

Disclosures

All Authors: No reported Disclosures.
1821. Evaluation of Cerebrospinal Fluid White Blood Cell Count Criteria for Use of the BioFire® FilmArray® Meningitis/Encephalitis Panel in Immunocompetent Patients
Authors: McCreery Randy , Nielsen Lindsey E , Clarey Dillon , Murphy Caitlin N , Van Schooneveld Trevor C
Published: October 2019

Background

In 2016, our academic medical center implemented the BioFire® FilmArray® Meningitis/Encephalitis Panel (MEP), which detects 14 viral, bacterial, and fungal pathogens. Institutional guidelines recommended the test be used in nonimmunocompromised patients age ≥2 years only if the cerebrospinal fluid (CSF) white blood cell (WBC) count was >10 cells/mm3.

Methods

We reviewed all MEP performed at our institution over 2 years (January 1, 2017 to December 31, 2018). We collected CSF WBC count, protein, and glucose; MEP results; CSF culture results; and demographics. We excluded children age <2 years, immunocompromised patients, those without a CSF WBC count, and duplicate tests during the same illness.

Results

Of 453 patients, 311 met inclusion criteria. The median age was 51, 51% male. Median CSF indices: WBC/mm3 = 4, protein = 57 mg/dL, glucose = 66 mg/dL. MEP positivity rate = 12% (37/311): viruses (29/37), bacteria (7/37), and fungi (1/37). Positive bacterial/fungal MEP results compared with CSF culture are summarized in Table 1. No clinically significant discordant negative MEP results occurred compared with CSF culture, cryptococcal antigen, or other viral PCR testing. Of the 311 patients, 184 (59%) had ≤10 CSF WBC/mm3. Of these, 4 had positive MEP results: 1 enterovirus, 1 human herpes virus 6 (HHV-6) and 2 varicella zoster virus (VZV). The HHV-6 was judged clinically insignificant. The 2 VZV cases had concomitant shingles and were already on acyclovir. No clinically significant MEP results occurred in 110/311 (35%) patients with ≤ 2 CSF WBC/mm3.

Conclusion

In nonimmunocompromised patients, age ≥ 2, with ≤ 10 CSF WBC/mm3 on lumbar puncture, positive MEP results were rare and the clinical significance of the 4 positives was debatable. A hard-stop restriction in this setting could have reduced overall use by up to 59% and resulted in significant cost savings. Lower CSF WBC/mm3 cut-offs could be considered and still improve MEP utilization.

Disclosures

All Authors: No reported Disclosures.
1826. Impact of Rapid Diagnostics and Ceftazidime–Avibactam on Mortality after Bacteremia Caused by Carbapenem-Resistant Enterobacteriaceae
Authors: Satlin Michael J , Chen Liang , Weston Gregory , Gomez-Simmonds Angela , Bhowmick Tanaya , Seo Susan K , Sperber Steven , Kim Angela , Eilertson Brandon , Jenkins Stephen , Levi Michael , Uhlemann Anne-Catrin , Weinstein Melvin P , Tang Yi-Wei , Hong Tao , Juretschko Stefan , Walsh Thomas J , Westblade Lars , Kreiswirth Barry
Published: October 2019

Background

Patients with bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) have long delays until receipt of appropriate antimicrobial therapy and high mortality rates. Rapid molecular diagnostics and novel therapies, such as ceftazidime–avibactam (CAZ-AVI), offer promise to improve outcomes, but their clinical impact is unclear.

Methods

We conducted an observational study of patients with CRE BSI from January 2016 to June 2018 at 8 New York and New Jersey medical centers. Patient demographics, comorbidities, clinical presentations, diagnostic methods, and treatments were compared between patients who died within 30 days of BSI onset and survivors. Independent risk factors for mortality were identified using logistic regression. We then compared time to receipt of active antimicrobial therapy between patients whose positive blood culture bottles underwent testing for the Klebsiella pneumoniae carbapenemase gene (blaKPC PCR) and patients where this test was not used.

Results

We identified 178 patients with CRE BSI (K. pneumoniae: n = 104, 58%; Enterobacter cloacae: n = 26, 15%; Escherichia coli: n = 26, 15%). The 30-day mortality rate was 38%. An increasing Acute Physiology and Chronic Health Evaluation II score (adjusted odds ratio [aOR] 1.06, P = 0.005) was independently associated with increased 30-day mortality; whereas, use of blaKPC PCR (aOR 0.31, P = 0.005), urinary tract source (aOR 0.12, P = 0.001), and source control (aOR 0.25, P = 0.001) were independently associated with survival. Initial targeted therapy with CAZ-AVI was associated with a 28% 30-day mortality rate, compared with a 49% 30-day mortality rate among patients who received a polymyxin or aminoglycoside (P = 0.036). Patients whose blood culture underwent blaKPC PCR were more likely to receive active antimicrobial therapy within 24 hours of BSI onset (42% vs. 28%; P = 0.07) and had a decreased median time until receipt of active therapy (25 hours vs. 46 hours; P = 0.07), although these differences did not achieve statistical significance.

Conclusion

The use of PCR to rapidly identify blood cultures with blaKPC and definitive therapy with CAZ-AVI instead of polymyxins or aminoglycosides were associated with decreased mortality after CRE bacteremia.

Disclosures

All Authors: No reported Disclosures.
1829. The Paradox of KPC Bearing Strains of Klebsiella pneumoniae with the D179Y Substitution: Resistance to Ceftazidine/Avibactam (CZA) and Susceptibility to Meropenem (MEM)
Authors: Barnes Melissa D , Taracilla Magdalena A , Rutter Joseph D , Nguyen Minh-Hong , Shields Ryan K , Clancy Cornelius J , Bonomo Robert A
Published: October 2019

Background

Resistance to CZA is a serious limitation of treatment for KPC bearing Enterobacteriaceae infections. Recently, a single amino acid substitution (D179Y) was described in KPC-2 and KPC-3 bearing CZA-resistant K. pneumoniae recovered from patients failing treatment. In class A β-lactamases the D179 residue is located at the neck of the omega loop and is critical for KPC catalytic activity. In attempts to understand the evolution of substrate specificity in KPC-2, the D179Y variant of KPC-2 was shown to be resistant to CZA (ceftazidime forms a long-lived acyl enzyme with in KPC-2), but susceptible to MEM. A similar observation was made in clinical and laboratory-generated K. pneumoniae and E. coli strains bearing D179Y KPC-3. We were compelled to explore the catalytic mechanisms of susceptibility to MEM of the D179Y variants in KPC-2 vs. KPC-3.

Methods

KPC-2, KPC-3, and D179Y in the respective KPC were cloned into an expression vector and the β-lactamase proteins were purified. 5 mg of each β-lactamase with and without MEM (1:1 molar ratio) was incubated for the time indicated and analyzed using the Quadrupole Time-of-Flight (QTOF) timed mass spectrometry for the reaction intermediates. To assess thermal stability, denaturation melting curves were run for 2 hours using 12 µM β-lactamase.

Results

The D179Y variant forms prolonged acyl-complexes with meropenem in KPC-3 and KPC-2, which can be detected up to 24 hours (Figure 1). This prolonged trapping of meropenem by D179Y variants is not evident with the respective KPCs. Further, the tyrosine substitution at the D179 position (Tm = 48–52°C) destabilizes the KPC β-lactamases (TmKPC-2/3 = 52–56°C).

Conclusion

These data suggest that MEM acts as a covalent β-lactamase inhibitor more than as a substrate for KPC-2 and -3. The mechanistic basis of paradoxical susceptibility to carbapenems provides an impetus to develop better therapeutic approaches to the increasing threat of carbapenem resistance and highlights how the rational design of novel β-lactam/β-lactamase inhibitors must consider mechanistic bases of resistance.

Disclosures

All Authors: No reported Disclosures.