bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.