bluuebunny/crossref_metadata_2025_split huggingface dataset:
2157. Evaluation of the Utility of the MRSA Nasal PCR Assay in a Community Healthcare System
Authors: Hobbs Athena L V , Turner Stephen , Parag Bhavyata , Shea Katherine M , Seligson Nathan 
Published: October 2019

Abstract

Background
The MRSA nasal PCR assay is a rapid, noninvasive test that has demonstrated a strong negative predictive value (NPV), as high as 99%, for ruling out MRSA pneumonia. These findings are based primarily on literature from large academic centers, which have evaluated both the positive predictive value (PPV) and NPV of MRSA nasal PCR assays. Investigators sought to assess the NPV of the MRSA nasal PCR assay to rule out MRSA pneumonia within a community healthcare system. To the best of our knowledge, this is the largest study from a community hospital and the only study from a community healthcare system for the utilization of a nasal PCR assay to rule out MRSA pneumonia.

Methods
This is a multicenter, retrospective study of adult patients with both an MRSA nasal PCR assay and positive respiratory culture (sputum, bronchoalveolar lavage, or endotracheal aspirate). Data were collected from September 2014 through August 2015 at three community hospitals (bed size ranging from 328 to 706) across two states within a healthcare system. The study was approved by the Baptist Memorial Hospital Institutional Review Board. PPV and NPV 95% confidence intervals (95% CI) were calculated as previously described in the literature.

Results
A total of 808 patients were included in the analysis across the three hospitals. The total incidence of MRSA in positive sputum samples was 14.9% across the three facilities. Our study demonstrated an overall NPV of 95.1% (93.2, 96.6%) and a PPV of 65.9% (95% CI 57.2, 73.9%). The high NPV was retained despite unit type, resulting in 94.9% (95% CI 92.7, 96.6%), 96.3% (95% CI 90.8, 99.0%), and 94.7% (95% CI 74.0, 99.9%) for the intensive care units (ICU), medical-surgical units, and the emergency department, respectively (Table 1).

Conclusion
We concluded that the high NPV of a negative MRSA nasal PCR assay to rule out MRSA pneumonia persisted within a community hospital system. With the results of our study, we plan to utilize institution-specific data along with previously published literature to encourage earlier discontinuation of anti-MRSA antibiotics in patients being treated for pneumonia with negative MRSA nasal PCR assays. Our study demonstrates the validity of the assay in the large community hospital setting with similar findings to studies at large academic institutions.

Disclosures
All authors: No reported disclosures.
2173. Detection of Chlamydia psittaci by rtPCR in Outbreak Specimens Tested at CDC—2018
Authors: McGovern Olivia L , Shaw Kelly , Szablewski Christine , Gabel Julie , Holsinger Caroline , Brennan Skyler , Wolff Bernard , Benitez Alvaro J , Diaz Maureen , Thurman Kathleen A , Winchell Jonas , Kobayashi Miwako 
Published: October 2019

Abstract

Background
Psittacosis is a respiratory illness caused by Chlamydia psittaci. The most commonly available diagnostic tests are serologic tests, which have low sensitivity and can cross-react with other chlamydial species. Serologic tests also require paired sera collected weeks apart, which is impractical for patient management. Real-time polymerase chain reaction (rtPCR) testing for C. psittaci is rapid, sensitive, and specific. However, rtRCR testing is only available at the CDC Respiratory Diseases Branch laboratory, and appropriate clinical specimen types need to be validated since psittacosis case detection is infrequent. In 2018, the first large psittacosis outbreak in the United States in 30 years occurred, allowing assessment of rtPCR performance among multiple clinical specimen types.

Methods
rtPCR test positivity rate and turnaround time were determined among 89 specimens tested at CDC from 54 outbreak patients with suspected psittacosis. rtPCR testing was performed on nucleic acid extracted from clinical specimens using oligonucleotides targeting the C. psittaci locus tag CPSIT_RS01985. Clinical information was collected by patient interview and medical record review.

Results
Positivity rates among the most common specimen types were 4.4% (2/46) for nasopharyngeal (NP) swab, 36.4% (8/22) for sputum, and 80.0% (4/5) for stool. Of 21 (24%) specimens with available data, the average time from patient symptom onset to specimen collection was 6 days (range 1–11 days). C. psittaci was detected in specimens from 13 of 54 outbreak patients tested (Table 1); all 13 patients had radiographically-confirmed pneumonia, and 7 were rtPCR-positive from a lower respiratory specimen only. Paired sputum and NP swab specimens were tested for 6 patients; C. psittaci was detected in all sputum but only 1 NP swab. The positive NP swab was from a patient requiring intensive care unit admission and intubation. All results were reported within 1 business day of specimen receipt in the lab.

Conclusion
These data suggest that lower respiratory specimens are more sensitive than NP swabs for rtPCR detection of C. psittaci; stool might be a suitable alternative. Widespread implementation of rtPCR testing using appropriate specimen types could improve psittacosis detection and inform timely public health interventions.

Disclosures
All authors: No reported disclosures.
2187. Prediction of Patient Outcome During Febrile Neutropenia Despite Anti-infective Treatment Using Machine Learning Algorithms
Authors: Jakob Carolin , Classen Annika , Stecher Melanie , Fuhrmann Sandra , Franke Bernd , Fuchs Frieder , Walker Sarah , Cornely Oliver , Janne Vehreschild Jörg 
Published: October 2019

Abstract

Background
Clinical management of prolonged febrile neutropenia despite broad-spectrum empirical antibacterial treatment is a clinical challenge, as standard empirical treatment has failed and a broad spectrum of differential diagnoses has to be considered. Growing prevalence of multi-resistant bacteria and fungi has made a balanced choice of effective anti-infective treatment more difficult. A reliable prediction of complications could indicate options for treatment optimization.

Methods
We implemented a supervised machine learning approach to predict death or admission to intensive care unit within 28 days in cancer patients with prolonged febrile neutropenia (neutrophils < 500/mm3 and body temperature ≥ 38°C longer than 3 days). We analyzed highly granular retrospective medical data of the Cologne Cohort of Neutropenic Patients (CoCoNut) between 2008 and 2014. Random forest and 10-fold cross-validation were used for classification. The neutropenic episodes from 2014 were used for evaluation of prediction.

Results
In total, 927 episodes of prolonged febrile neutropenia (median age 52 years, interquartile range 42–62; 562/927 [61%] male; 390/927 [42%] acute myeloid leukemia; 297/927 [32%] lymphoma) with 211/927 (23%) adverse outcomes were processed. We computed 226 features including patient characteristics, medication, clinical signs, as well as laboratory results describing changes of state and interactions of medical parameters. Feature selection revealed 65 features with an area under the receiver operating characteristic curve (AUC) of 0.75. In the validation data set the optimized model had a sensitivity/specificity of 36% and 99% (AUC: 0.68; misclassification error: 0.12) and positive/negative predictive values of 89% and 88%, respectively. The most important features were albumin, age, and procalcitonin.

Conclusion
Structured granular medical data and machine learning approaches are an innovative tool that can be used in a retrospective setting for prediction of adverse outcomes in patients with prolonged febrile neutropenia. This study is the first important step toward clinical decision support based on predictive models in high-risk cancer patients.

Disclosures
All authors: No reported disclosures.
2212. Burden of Community-Acquired Pneumonia Attributable to Co-morbid Conditions in Adults
Authors: Rolfes Melissa A , Jain Seema , Bramley Anna , Self Wesley , Wunderink Richard G , Anderson Evan J , Grijalva Carlos G , Fakhran Sherene , Balk Robert , Zhu Yuwei , Williams Derek , Edwards Kathryn , Reed Carrie 
Published: October 2019

Abstract

Background
Few studies have quantified the risk of community-acquired pneumonia (CAP) among adults with co-morbidities. Combining data from the population-based, prospective Etiology of Pneumonia in the Community study (EPIC) and the nationwide health-related Behavioral Risk Factor Surveillance System (BRFSS) telephone-survey, we estimated the annual risk of hospitalization for CAP among adults with co-morbidities.

Methods
We identified adults hospitalized with radiographic and clinical CAP at hospitals in Chicago, IL and Nashville, TN from July 2010 to June 2012. Using 2011 BRFSS data, we estimated the prevalence of the population with selected co-morbidities (chronic lung disease [CLD], cardiovascular disease [CVD], chronic kidney disease [CKD], or diabetes) in the EPIC study catchment counties, as well as the population without co-morbidities. We estimated the incidence of hospitalized CAP, age-adjusted relative risk (RR) using Poisson regression, and population attributable fraction for each co-morbidity.

Results
Among 2,061 adult patients enrolled in EPIC, 1,428 (69%) had at least one selected co-morbidity, most commonly CLD (42%) and CVD (35%). Among the adult population in the EPIC catchment area, 17% had ≥1 selected co-morbidity. The overall incidence of hospitalized CAP was 24.8/10,000, 118.7/10,000 among adults with ≥1 co-morbidity, and 11.2/10,000 among adults without a co-morbidity. Compared with patients without co-morbidities, the incidence of hospitalization for CAP was higher among patients with CLD (aRR: 20.7 [95% confidence interval [CI]: 20.0–21.5]), CKD (aRR: 14.5 [CI: 13.8–15.1]), CVD (aRR: 14.0 [CI: 13.5–14.6]), and diabetes (aRR: 6.2 [CI: 5.9–6.4]). While CLD and CVD accounted for high proportions of the incidence of CAP hospitalizations in the study population, the contribution of the selected co-morbidities varied by age groups (figure).

Conclusion
There is an increased risk of hospitalization for CAP among adults with co-morbidities, particularly chronic lung and cardiovascular disease. As a large portion of CAP is attributable to these co-morbidities, targeted public health interventions, such as vaccination and risk communication, need to be reinforced among these high-risk groups.

Disclosures
All authors: No reported disclosures.
2227. Outcomes in Patients with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane–Tazobactam (C/T) Treatment of Nosocomial Pneumonia (ASPECT-NP)
Authors: Huntington Jennifer A , Yu Brian , Li Linping , Jensen Erin , Bruno Christopher , Rhee Elizabeth G 
Published: October 2019

Abstract

Background
ASPECT-NP, a phase 3, randomized, double-blind study, evaluated C/T (at double the approved dose for other indications) vs. meropenem (MEM) in adults with ventilated nosocomial pneumonia. We compared safety and efficacy outcomes from this trial among patients with and without renal impairment (RI).

Methods
Patients were stratified by age and diagnosis and were randomized 1:1 to intravenous (IV) C/T 3 g every 8 h or IV MEM 1 g every 8 h. Study drug was administered for 8–14 days; doses were adjusted for moderate and severe RI. Eligible patients were mechanically ventilated; those on renal replacement therapy or with creatinine clearance (CrCL) < 15 mL/minute were excluded. Key efficacy endpoints included clinical cure rates at the test of cure (TOC) visit in the intent-to-treat (ITT) and clinically evaluable (CE) populations and Day 28 all-cause mortality (ACM) in the ITT population. In this analysis, patients were stratified based on renal function for outcome comparisons: normal renal function (CrCL ≥ 80 mL/minute); mild RI (CrCL > 50 to < 80 mL/minute); moderate RI (CrCL ≥ 30 to ≤ 50 mL/minute); and severe RI (CrCL ≥ 15 to < 30 mL/minute).

Results
A total of 726 patients were enrolled (C/T, N = 362; MEM, N = 364). Clinical cure rates at the TOC visit (CE and ITT populations) were robust across CrCL subgroups in both treatment arms and were similar based on 95% confidence intervals for treatment differences that included 0 (table). Day 28 ACM rates for patients with moderate and severe RI were numerically higher than those with mild RI in the MEM treatment arm. Rates of treatment-emergent adverse events (TEAEs) were similar in both treatment arms and across CrCL subgroups, with rates generally increasing with increasing RI severity. Rates of treatment-related TEAEs were low across treatment arms and CrCL subgroups with no treatment-related deaths reported.

Conclusion
Similar clinical cure and Day 28 ACM rates at the TOC visit were found across treatment groups for all CrCL subgroups, consistent with the overall primary and key secondary efficacy results for the ASPECT-NP study. Both drugs were well-tolerated. The results of this analysis indicate that the use of dose-adjusted C/T is appropriate in patients with nosocomial pneumonia and moderate or severe RI.

Disclosures
All authors: No reported disclosures.
2246. Improved Outcomes for Cancer Patients Treated With Ceftazidime–Avibactam vs. Polymyxin-Containing Regimens for Carbapenem-Resistant Enterobacteriaceae Bacteremia
Authors: Borjan Jovan , Shelburne Samuel A , Shelburne Samuel A , Bhatti Micah M , Aitken Samuel L , Aitken Samuel L 
Published: October 2019

Abstract

Background
Outcomes are improved with ceftazidime–avibactam (CZA) compared with polymyxin-based regimens (PBR) for carbapenemase-producing carbapenem-resistant Enterobacteriaceae. It is unclear whether this finding is true in non-carbapenemase (non-CP) producing CRE. The purpose of this study was to compare the efficacy and safety of CZA-based and PBR for CRE bacteremia in cancer patients with a high prevalence of non-CP CRE.

Methods
Adult cancer patients with first occurrence of CRE (i.e., meropenem non-susceptible) bacteremia treated with either CZA or PBR as directed therapy were included. Day 14 integrated benefit-risk outcomes based on desirability of outcome ranking (DOOR; (1) cured and discharged home, (2) cured and hospitalized, (3) cured and hospitalized with renal failure, (4) not cured, (5) dead) were used. DOOR is a recently developed statistical approach designed to unify important patient and clinician outcomes. Inverse probability of treatment weighted (IPTW) ordered logistic regression was used to model the odds of moving down ranked DOOR categories (i.e., having a worse outcome). The probability of a patient treated with CZA or a PBR having a worse DOOR category was also calculated. IPTW logistic regression was used to model the odds of 14-day mortality.

Results
43 patients (CZA, n = 24; PBR, n = 19) with similar demographics and relative illness were included. Klebsiella pneumoniae (n = 21) and Escherichia coli (n = 16) were most common. 16/43 (37%) were CP CRE, 19/43 (44%) were non-CP CRE, and the remainder were unknown. The probability of a better DOOR for patients treated with CZA was 58% (95% CI 53% - 62%). Patients treated with CZA had an 81% reduction in IPTW-adjusted odds of a worse DOOR (OR 0.19, 95% CI 0.05 – 0.76; P = 0.02). 14-day mortality was 2/24 (8%) for patients receiving CZA vs. 5/19 (26%) for patients treated with PBR (IPTW-adjusted OR 0.12, 95% CI 0.02 – 0.82, P = 0.03).

Conclusion
These data suggest that CZA-based treatment, compared with PBR, has a superior integrated benefit-risk profile for the treatment of CRE bacteremia in cancer patients with a high burden of non-CP CRE. These findings build upon available data and suggest that CZA is preferred to PBR for CRE with heterogenous resistance mechanisms.

Disclosures
Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.
2249. Impact of Minimum Inhibitory Concentration on Clinical Outcomes of Daptomycin for VRE Bloodstream Infection Among Neutropenic Oncology Patients
Authors: Caulder Elisabeth , Palavecino Elizabeth , Beardsley James , Johnson James , Luther Vera , Ohl Christopher , Williamson John 
Published: October 2019

Abstract

Background
Vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) is a significant cause of morbidity and mortality in immunocompromised patients. This study aimed to assess the impact of daptomycin (DAP) MIC on outcomes of treatment for VRE BSI in neutropenic oncology patients.

Methods
This was a retrospective, observational, single-center, cohort study at an academic medical center. Included: age ≥ 18, neutropenia, admitted to oncology unit, and DAP for VRE BSI. Excluded: death within 24 hours after initiation of DAP, polymicrobial BSI, and linezolid use for > 48 hours before DAP initiation. Patients with VRE BSI 2008–2018 were identified using a report from the micro lab. Data were collected by electronic medical record review. The primary outcome of the study was clinical success, defined as culture sterilization, hypotension resolution, defervescence, and no need to change DAP due to persistent signs/symptoms of infection. Patients were analyzed according to DAP MIC ≤ 2 vs. ≥ 4 mg/L. Multivariable logistic regression analysis was performed to identify factors associated with clinical success.

Results
44 patients met study criteria (MIC ≤ 2, n = 26; MIC ≥ 4, n = 18). Mean age was 58 years, 59% were male, and median ANC was 0. Median Charlson Comorbidity Index Score and Pitt Bacteremia Score (Pitt) were 5 and 1, respectively. 34% required ICU admission. More patients achieved clinical success with MIC ≤ 2 (88% vs. 56%; P = 0.03). Time to success (2.4 vs. 4 days, P = 0.02) and time to culture sterilization (2.2 vs. 2.9 days, P = 0.24) were shorter with MIC ≤ 2. Mortality was similar between groups (31% vs. 33%). Time to culture sterilization (P = 0.008), neutropenia resolution (P = 0.02), MIC group (P = 0.096), and Pitt (P = 0.52) were included in the multivariable model.

Conclusion
DAP MIC should be considered when choosing therapy for VRE BSI among neutropenic oncology patients, particularly those expected to have prolonged neutropenia and those with persistently positive cultures.

Disclosures
All authors: No reported disclosures.
2251. Estimating the Need for Novel Gram-Negative Active Antibiotics in US Hospitals
Authors: Strich Jeffrey R , Warner Sarah , Ling Lai Yi , Demirkale Cumhur Y , Powers John H , Danner Robert L , Kadri Sameer S 
Published: October 2019

Abstract

Background
Assessing the unmet need for novel antibiotics could inform appropriate utilization, enrollment in trials and ensure balance in aligning incentives and investments in therapeutic development.

Methods
The Cerner Healthfacts electronic health record repository was queried to identify inpatient treatment opportunities for Gram-negative active agents (GNAA) displaying either difficult-to-treat resistance (DTR; resistance to all β-lactams including carbapenems and fluoroquinolones) or extended-spectrum cephalosporin resistance (ECR). The former was quantified by aggregating episodes of confirmed DTR infection (i.e., DTR strain isolated and concomitant antibiotic(s) received) or suspected (i.e., 1–2 days of empiric colistin/polymyxin-B or aminoglycosides and no DTR pathogen isolated). Aggregate days of therapy (DOT) were reported as a range, multiplying episodes by site-specific or uniform 14-day treatment durations, respectively. Recursive partition and cluster analyses were performed for hospital characteristics and contributions of outbreaks to DTR treatment opportunities, respectively.

Results
Between 2009 and 2015, across 2,996,271 encounters, 1,352 episodes of potential targeted treatment were identified, which combined with empiric treatment episodes, represent 39–138 DOT/10,000 encounters for a DTR-GNAA. Similarly, 9,535 episodes of potential targeted therapy for an ECR-GNAA were identified (representing 211-466 DOT/10,000 encounters). The most common candidate site and pathogens for DTR-GNAA were lower respiratory and A. baumannii and P. aeruginosa respectively; DTR bloodstream infections displayed the highest crude mortality at 45%. Enterobacteriaceae urinary infections dominated the ECR group. Teaching hospitals with ≥100 beds were the most likely to encounter a DTR infection; potential outbreaks contributed to 10.6% of DTR treatment opportunities.

Conclusion
The candidate population for new antibacterials directed against highly resistant GN infections with limited treatment options is small but critical, indicating a role for non-revenue-based strategies to develop more effective antibiotics, as well as mechanisms to support trials that address real-world unmet needs.

Disclosures
All authors: No reported disclosures.
2252. Patient Preferences for Triazole Antifungals in the Treatment of Invasive Mold Infection: A Discrete Choice Experiment
Authors: Bhagat Hardik , Xu Yanqing , Spalding James , Song Yan , Zhao Jing , Zhou Mo , Fadli Ela , Yang Hongbo 
Published: October 2019

Abstract

Background
Invasive mold infections (IMIs) are an increasing cause of morbidity and mortality worldwide.1 Pharmacological differences among the currently available mold-active triazoles make treatment selection complex.1 To the best of our knowledge, this is the first study to assess patient preferences for mold-active triazoles in IMI treatment.

Methods
Patients were included if they were aged ≥ 18 years with investigator-confirmed invasive aspergillosis or invasive mucormycosis; had received voriconazole, isavuconazonium sulfate or posaconazole within ≤ 1 week previously; and were outpatients for ≥ 3 weeks. Participants were presented with 14 choice cards, each with two hypothetical treatments with varying levels of attributes, and asked to select their preferred treatment. Preference weights for attribute levels were analyzed using conditional logit regression and used to calculate the impact of changes in attribute levels on patient choices; relative attribute importance (RAI); and patient willingness to pay (WTP; monthly out-of-pocket cost) for an attribute improvement.

Results
Of 50 participants, 52% were female and the mean age was 47.3 years; 40%, 40%, and 28% had used posaconazole, voriconazole and isavuconazonium sulfate, respectively (Figure 1). Route of administration (27% RAI), treatment duration (22% RAI), and chance of symptom relief after treatment (20% RAI) were the most important attributes for patients (Figure 2). The odds ratios for patients choosing oral suspension or tablets/capsules over IV infusion were 5.6 and 4.5, respectively (P < 0.001) (Figure 3); patients were willing to pay an additional $205/month or $180/month out of pocket for these respective routes of administration over IV (Figure 4). The odds ratio for patients choosing a 30-day over a 90-day treatment were 4.1 (P < 0.001) (Figure 3); this decrease in duration was valued by patients at $168/month (Figure 4). For a 50% vs. 30% chance of symptom relief, the odds ratio was 3.5 (P < 0.001) (Figure 3) and WTP was $147.89/month (Figure 4).

Conclusion
Patients considered route of administration, treatment duration and chance of symptom relief to be the most important IMI treatment attributes among mold-active triazoles.
1Jenks JD et al. (2019) Med Mycol 57:S168–S178

Disclosures
All authors: No reported disclosures.