bluuebunny/crossref_metadata_2025_split huggingface dataset:
149. Extraction-free RT-PCR to Detect SARS-CoV-2 Variants of Concern
Authors: Harry Brian L , Qiu Yue , Lu Ling , Couto-Rodriguez Mara , Nagy-Szakal Dorottya , O’Hara Niamh B , Lu Shi-Long 
Published: December 2021

Abstract

Background
SARS-CoV-2 variants of concern (VOC) have challenged real-time reverse transcriptase polymerase chain reaction (RT-PCR) methods for the diagnosis of COVID-19.

Methods
The CDC 2019-Novel Coronavirus real-time RT-PCR panel was modified to create a single-plex extraction-free proxy RT-PCR assay, VOCFast™. This assay uses the nucleocapsid N1 as well as novel primer/probe pairs to target VOC mutations in the Orf1a and spike (S) genes. For analytical validation of VOCFast, synthetic controls for the Wuhan, alpha/B.1.1.7, beta/B.1.351, and gamma/P.1 strains were tested at various concentrations. Clinical validation was performed using patient anterior nares swab and saliva specimens collected in the Denver, CO area between Nov 2020 and Feb 2021 or in March 2021. Orthogonal next-generation sequencing (NGS) was also performed.

Results
Similar N1 quantification cycle (Cq) values corresponding to viral load were observed for all strains, suggesting that VOC mutations do not affect performance of the N1 primer/probe. Orf1a-mut and S1-mut primer/probes generated a stable high Cq value for the Wuhan strain. Conversely, Orf1a-mut Cq values were inversely correlated with viral load for all VOC. The S1-mut Cq was inversely correlated with viral load of the alpha strain, but did not reliably amplify beta/gamma VOC. The limit of detection was 8 copies/uL.
The first set of COVID-19 patient specimens revealed no amplification using Orf1a-mut whereas 53% of specimens collected in Mar 2021 demonstrated amplification by Orf-1a. Orthogonal testing by the SARS-CoV-2 NGS Assay and COVID-DX software demonstrated that 12/12 alpha strains, 2/2 beta/gamma strains, and 33/33 Wuhan strains were correctly identified by VOCFast.

Detection of VOC in clinical specimens and validation by NGS

Conclusion
The combination of the N1, Orf1a-mut, and S1-mut primers/probes in VOCFast can distinguish the Wuhan, alpha, and beta/gamma strains and it consistent with NGS results. Testing of clinical samples revealed that VOC emerged in Denver, CO in March 2021. Future work to discriminate beta, gamma, and emerging VOC is ongoing. In summary, VOCFast is an extraction-free RT-PCR assay for nasal swab and saliva specimens that can identify VOC with a turnaround time suitable for clinical testing.

Disclosures
Brian L. Harry, MD PhD, Summit Biolabs Inc. (Grant/Research Support, Shareholder) Mara Couto-Rodriguez, MS, Biotia (Employee) Dorottya Nagy-Szakal, MD PhD, Biotia Inc (Employee, Shareholder) Niamh B. O’Hara, PhD, Biotia (Board Member, Employee, Shareholder) Shi-Long Lu, MD PhD, Summit Biolabs Inc. (Grant/Research Support, Shareholder)
1302. Duration of Antibiotic Therapy for Pneumonia Among Patients with Advanced Cancer: An Opportunity for Antibiotic Stewardship
Authors: Benson Jemma , Datta Rupak , Quagliarello Vincent , Juthani-Mehta Manisha 
Published: December 2021

Abstract

Background
Antibiotic therapy is common for hospitalized older adults (≥65 years) with advanced cancer.1 Pneumonia is prevalent, but data conflict about the benefits and harms of antibiotics in palliative care settings. To inform antibiotic stewardship protocols, we assessed the duration of therapy for non-ventilator-associated pneumonia (non-VAP) in older adults who received palliative chemotherapy for advanced cancer.

Methods
We identified older adults who received palliative chemotherapy from 1/1/2016 through 9/30/2017 at Yale New Haven Hospital and subsequently developed non-VAP during their index admission following receipt of palliative chemotherapy. Non-VAPs were defined per standardized criteria; 2 complicated pneumonias including those associated with abscess, bacteremia, subsequent VAP, necrotizing and fungal pneumonia, and organizing pneumonia were excluded. We determined the total duration of antibiotics, including both inpatient and post-discharge days of therapy, for each initial episode of non-VAP. Patients were then stratified by total duration of therapy ( &gt;7 days versus ≤ 7 days).

Results
We identified a total of 118 older adults who developed non-VAP during their index admission following receipt of palliative chemotherapy (Figure). Median age was 77.6 (range, 65.2 to 92.5), 37.2% were female sex, and the most common malignancies included lung (n=42/118; 35.5%), hematologic (n=28/118; 23.7%), gastrointestinal (n=17/118; 14.4%), and genitourinary (n=17/118; 14.4%) tumors. Overall, 83.0% (n=98/118) were prescribed &gt;7 days of therapy.

Figure. Duration of therapy for non-VAP

Conclusion
83.0% of older adults who developed non-VAP during the index hospitalization following receipt of palliative chemotherapy received a duration of antibiotics that exceeded guideline recommendations. This finding provides an opportunity for intervention to improve patient care and antibiotic stewardship in patients receiving palliative chemotherapy. Future studies are needed in larger cohorts to evaluate the implications of guideline-discordant therapy on readmissions and mortality.
References
1. Marra et al. Antibiotic use during end-of-life care: A systematic literature review and meta-analysis. ICHE 2021;42:523-9.
2. CDC NHSN Patient Safety Component Manual, 2021.

Disclosures
All Authors: No reported disclosures
1303. A Rare Case of Legionella micdadei Lung Abscess in an Immunocompromised Patient
Authors: Samaan Fadi , Barchuk Andriy , Bata Yasmin , Biancuzzo Rachael , Jabbour Elias , Zainah Hadeel 
Published: December 2021

Abstract

Background
Legionella micdadei is the most common legionella species causing infection after L. pneumophila. It usually causes infection in immunocompromised hosts and leads to nodules with tendency to cavitate. It is difficult to culture which makes diagnosis challenging. We report a case or L. micdadei in an immunocompromised host with cavitary pneumonia.

Methods
Case Report. An 82 year-old female presented with upper abdominal pain for one day duration. She has history of hypertension, coronary artery disease, hyperlipidemia, heart failure, and hypothyroidism. She was diagnosed with hypersensitivity pneumonia 5 months prior, treated with prednisone (40 mg daily). The pain was not associated with nausea, vomiting or diarrhea. She was found with hypoxia despite she denied shortness of breath, cough, hemoptysis or chest pain. There was no fever, chills, headache, myalgia or upper respiratory symptoms. She was afebrile, tachycardic 134/min and hypoxic to 88% on room air. White cell count was 22x10(3) /mcL (90% neutrophils), hemoglobin was 10.4 g/dL, creatinine was 1.23 mg/dL and lactic acid was 3.6 mmol/L. Chest CT scan showed left lower lobe cavitary lesion with surrounding infiltrates (image 1). Quantiferon gold, serum galagtomannan, B-D-glucan, and vasculitis work-up were negative. Bronchoscopy showed a patent airway. Bronchial smears and cultures were negative for bacteria, fungi and mycobacteria. The patient was treated with ceftriaxone and metronidazole with de-escalation to amoxicillin/clavulanate. Bronchial culture was positive for legionella micdadei after discharge, azithromycin was added.
Image 1. Cavitary lesion on thoracic CT

Results
Our patient was considered immunocompromised given steroid use, predisposing her for L. micdadei infection. L. micdadei is considered an opportunistic infection and was reported in hematologic malignancy population. It can cause an invasive lung disease with lung cavities. It needs special media for growth making it difficult to diagnose especially it is not detected by legionella urine antigen.

Conclusion
L. micdadei should be considered in the differential diagnosis for cavitary lung lesions in immunocompromised patients.

Disclosures
All Authors: No reported disclosures
1304. Antimicrobial Management of Stenotrophomonas maltophilia Pneumonia: Does TMP-SMX Dose Affect Treatment Failure?
Authors: Keck J Myles , Perkins Nicholson , Adams Delaney , Warner Mia , McCommon Julanne , Hobbs Athena L 
Published: December 2021

Abstract

Background
Limited literature exists to guide the appropriate antimicrobial choice, dose, and duration for Stenotrophomonas maltophilia (S. maltophilia) pneumonia.

Methods
This multi-center, retrospective cohort study was conducted in adults diagnosed with S. maltophilia pneumonia in eight hospitals between March 1, 2014 and August 31, 2020. Patients were enrolled into one of two arms: those treated with TMP-SMX and those treated with alternative antibiotics. The primary outcome was a composite of treatment failure, defined as the need for alternative antibiotics with in vitro activity against S. maltophilia, isolation of S. maltophilia on repeat cultures drawn greater than 72 hours from the index culture, or in-hospital mortality. Other clinical outcomes that were accessed include the TMP-SMX dosing regimen, and 30- and 90-day mortality rates. This study was approved by the local Institutional Review Board (IRB).

Results
Overall, 213 patients were included; 100 (46.9%) received TMP-SMX, and 113 (53.0%) received alternative therapy. Though there was no difference in treatment failure between the two groups, more patients in the “alternative” antibiotic group required mechanical ventilation (57% vs. 31%, respectively; p &lt; 0.001) (Table 1). 74% of patients who received TMP-SMX received a “low-dose” regimen, characterized by &lt; 10 mg/kg/day. When evaluating treatment failure based on “high” or “low-dose” TMP-SMX, there was no difference in treatment failure. However, we noted that physicians were more likely to utilize an alternative agent in addition to TMP-SMX (p=0.001) compared to an alternative agent. When removing this confounder from the composite endpoint, high-dose TMP-SMX was associated with significantly less treatment failure compared to low dose 23% vs. 49%, respectively (p=0.023). The average TMP-SMX dose of patients in the “low-dose” group was 5 + 2.2 mg/kg/day vs. 13.9 + 3.5 mg/kg/day in the “high-dose group. Moreover, when serum creatinine was evaluated at baseline, day 3, day 5, and day 7, no increase was seen in patients who received high dose TMP-SMX (Table 1).
Table 1: Clinical Outcomes

Conclusion
These preliminary results suggest that appropriate dosing of TMP-SMX may be more important for clinical success in patients with S. maltophilia pneumonia than the choice of agent.

Disclosures
All Authors: No reported disclosures
1306. Early Transition to Oral Antibiotics, Including Fluoroquinolone Therapy, for Streptococcus milleri Empyema Following Video-Assisted Thoracoscopic Surgery
Authors: Ovalle Anais , Alsalman Ahmad , Millington Timothy , Zuckerman Richard A 
Published: December 2021

Abstract

Background
Pleural empyema from Streptococcus milleri (SM) is often complex and requires a combination of surgery and intravenous (IV) antibiotics. There is a paucity of data on the efficacy of oral (PO) treatment due to concerns about the development of resistance, particularly to fluoroquinolones (FQ). We report outcomes of postoperative antibiotic treatment for SM empyema over 3 years, including PO therapy.

Methods
A single-center retrospective chart review was performed of 20 patients treated with video-assisted thoracoscopic surgery (VATS) from October 2015 to March 2018 and SM diagnosed by thoracentesis or operative culture. We reviewed clinical factors, route and duration of antibiotics, complications (empyema recurrence, repeat surgery, 30-day readmission due to empyema), and mortality (30-day and 1-year)

Results
Of the 20 patients, 12 (60%) received all IV and 8 (40%) transitioned to PO therapy (Table 1). Median age was 60 and 58 in the IV and PO group, respectively. IV treated patients had more comorbidities. Cultures were primarily monomicrobial. Isolates tested were susceptible (S) to penicillin (Table 1), Of 10 tested specimen, all had moxifloxacin MIC &lt; 0.19 μg/mL
and 8/8 specimens tested were S to levofloxacin. The average duration of antibiotic therapy in the IV group was 34 days and 32 days in the PO group. There were no complications in the IV group: however, there were 2 deaths (1 patient died from comorbid complications and 1 patient was readmitted and died due to MSSA endocarditis). There were no complications or deaths in patients treated PO.

Conclusion
Our review suggests that early transition to PO antibiotics may be a viable option for operatively managed empyema caused by SM in certain patients. FQs have been generally avoided due to concerns about the rapid development of resistance that has been shown in-vitro; however, no in-vivo data have been reported regarding this concern. We show excellent outcomes with the use of PO therapy in susceptible isolates, particularly FQs, with no failure or reported resistance in patients with SM empyema treated with VATS. Further study is needed to validate these findings and determine optimal patient characteristics for transition to PO therapy.

Disclosures
All Authors: No reported disclosures
1307. The Mycoplasma Conundrum
Authors: Rand Kenneth 
Published: December 2021

Abstract

Background
Lockdown for Covid 19 between March 15 - 30, 2020 lead to sudden closures of schools, public gatherings, all but essential businesses, and stay-at-home orders. Between then and the end of April 2020, literally all enveloped respiratory viruses declined to virtually undetectable levels, suggesting a successful interruption of transmission. Weekly percentage positivity rates for M. pneumoniae and all other respiratory viruses from BioFire Syndromic Trends for weeks ending 3/7/2020- 4/24/2020.

Weekly percentage positive rates are shown, with the Rhinovirus/Enterovirus rate divided by 3 and the M. pneumoniae rate multiplied by 10 to fit on the same scale.

Methods
We used the percentage positivity rates from BioFire Syndromic Trends and from GenMark Diagnostics to examine the post lockdown response of M. pneumoniae versus other respiratory viruses on the Respiratory Virus Panel (RP 2.0)

Results
As has been reported (Nawrocki J., et al, OFID 2021) and as shown in Figure 1, there was a rapid drop in the positivity rate for all enveloped respiratory viruses by 85.6% from an average rate of 2.014% positive for the week ending 3/14/20 to 0.29% for the week ending 4/18/20, while the positivity rate for M. pneumoniae actually increased by 44% from 0.536 % to 0.772%. The increase in M. pneumoniae positivity rate from its baseline of 0.51 ± 0.38 between 1/25/20 - 3/21/20 vs 0.71 ± 0.09 between 3/28/20 - 4/25/20 was significantly higher by t test, p=0.00574. Data from GenMark was available only monthly but also showed an upward rise from march to April, 2020.

Conclusion
It is well documented that M. pneumoniae is transmitted through respiratory mechanisms, yet lockdown measures sufficient to dramatically reduce ordinary respiratory virus transmission had no comparable effect on transmission of Mycoplasma pneumoniae. It is also well known that M. pneumoniae persists in the respiratory tract as long as months after an infection. Therefore, it is possible that this reservoir continued to be a source of transmission for M. pneumoniae, even though lockdown measures effectively interrupted the enveloped respiratory viruses.

Disclosures
Kenneth Rand, M.D., BioFire Diagnostics (Advisor or Review Panel member, Research Grant or Support)
150. Updated Clinical Guidelines for Treatment and Prophylaxis of Plague
Authors: Nelson Christina , Cooley Katharine , Fleck-Derderian Shannon 
Published: December 2021

Abstract

Background
Plague still occurs naturally in the western United States, Latin America, Asia, and Africa. Yersinia pestis, the causative agent of plague, is a Tier 1 bioterrorism agent due to its potential for aerosol release and high fatality rates. Recommendations for treatment and post-exposure prophylaxis (PEP) of plague were published in 2000 and included limited first-line options for treating plague, namely streptomycin or gentamicin. Doxycycline or ciprofloxacin were recommended for PEP. However, since 2000 new human clinical data and animal data have become available, and the FDA has approved additional antimicrobials for plague.

Methods
CDC developed updated, evidence-based guidelines for treatment and prophylaxis of plague using a comprehensive process. To collect evidence on relative efficacy of various antimicrobials for treatment of plague, the guidelines team conducted systematic literature reviews and analyzed U.S. surveillance data. Results of these investigations were published in Clinical Infectious Diseases in 2020. We also hosted several meetings with subject matter experts and clinical organizations (IDSA, AAP, etc.), federal agencies, and others to review relevant data and gather individual input on treatment and prophylaxis of plague.

Results
The forthcoming plague guidelines will include several important updates. First-line treatment options have been expanded to include ciprofloxacin, levofloxacin, and moxifloxacin in addition to streptomycin and gentamicin. For PEP, levofloxacin and moxifloxacin are now first-line options in addition to doxycycline and ciprofloxacin. Trimethoprim-sulfamethoxazole is now one of several new alternative options for PEP. The updated guidelines also include recommendations for treatment of clinical forms of plague other than pneumonic. Additional special populations such as immunocompromised persons and neonates are also covered.

Conclusion
Plague remains a threat, both as a naturally occurring disease and as a potential bioterrorism weapon, and preparedness and early recognition are key to effective response. The updated clinical guidelines will be a useful tool for clinicians to manage antimicrobial treatment and PEP for plague.

Disclosures
All Authors: No reported disclosures
1310. Provider and Facility Variation in Empiric Broad-Spectrum Antibiotic Use for Hospitalization Pneumonia: A Mixed Methods Study of Veterans Affairs Facilities
Authors: Jones Barbara E , Taber Peter , Ying Jian , Butler Jorie M , Nevers McKenna , Jones Makoto M , Greene Tom , Stevens Vanessa W , Zickmund Susan , Weir Charlene , Samore Matthew 
Published: December 2021

Abstract

Background
We previously found widespread variation in the empiric use of antibiotics against methicillin-resistant Staph aureus (anti-MRSA) and Pseudomonas aeruginosa (anti-PAER) for patients hospitalized for pneumonia. To explore this variation further, we conducted (1) quantitative analyses of facility-level versus provider-level variation, and (2) qualitative interviews with emergency department providers.

Methods
For each hospitalization, we predicted the probability of anti-MRSA and anti-PAER use by fitting machine learning models from 75 patient variables. We estimated the predicted risk of anti-MRSA/anti-PAER and facility features among patients hospitalized at upper versus lower 10% facilities after controlling for patient characteristics. We plotted density curves with the variance attributed to facility and provider alone and together. We then interviewed 16 emergency department (ED) providers at 8 VA facilities using a cognitive task analysis.

Results
Among 215,803 hospitalizations at 128 VA facilities 1/1/2006-12/31/2016, 31% received empiric anti-MRSA and 29% received empiric anti-PAER antibiotics. Hospitalizations at upper-decile facilities had a 50% and 45% adjusted probability of receiving anti-MRSA and anti-PAER antibiotics, compared to 15% and 20% in the lower-decile facilities. Facility features most predictive of anti-MRSA or anti-PAER use after adjusting for patient characteristics were complexity level (33% and 30% in high versus 15% and 20% in low complexity facilities). Variation in empiric anti-MRSA and anti-PAER use was almost completely at the facility level (Figure 1). Providers reported social influences from the opinions of other providers during decision-making and a high trust in guidelines and order sets. Consideration of pathogens was not mentioned by any providers at high-prescribing facilities.

Conclusion
Variation in empiric use of anti-MRSA and anti-PAER antibiotics in pneumonia clustered nearly completely at the facility level. ED providers report social influences during decision-making and a high trust in guidelines and order sets. Guidelines, order sets, and facility-level clinical champions that promote consideration of pathogens could be important strategies for de-adoption.

Disclosures
All Authors: No reported disclosures
1314. Descriptive Epidemiology of 30-day Readmissions among Survivors of Hospitalization with Bacterial Nosocomial Pneumonia in the US, 2012-2019
Authors: Zilberberg Marya , Nathanson Brian , Puzniak Laura A , Zilberberg Noah , Shorr Andrew F 
Published: December 2021

Abstract

Background
Nosocomial pneumonia (NP) remains associated with excess morbidity and mortality. The effect of NP on other measures of outcome and quality, such as re-admission at 30 days, remains unclear. Moreover, differing types of NP may have varying impacts on re-admissions.

Methods
We conducted a multicenter retrospective cohort study within the Premier Research database, a source containing administrative, pharmacy, and microbiology data. The rate of rehospitalization at 30 days following the index discharge served as our primary endpoint. We compared NP patients readmitted with pneumonia (RaP) as the principal diagnosis to those readmitted for other reasons (RaO). We also compared readmission rates as function of the type of NP: ventilator-associated bacterial pneumonia (VABP), ventilated hospital-acquired bacterial pneumonia (vHABP), and non-ventilated HABP (nvHABP).

Results
Among 17,819 patients with NP, 14,123 (79.3%) survived to discharge, of whom 2,151 (15.2%) required an acute readmission within 30 days of index discharge. Of these, 106 (4.9%) were RaP, and the remainder were RaO. At index hospitalization, RaP patients were older (mean age (SD) 67.4 (13.9] vs. 63.0 (15.2) years), more likely medical (44.3% vs. 36.7%), and less chronically ill (median [IQR] Charlson scores (3 [2-5] vs. 4 [2-5]) than persons with RaO. Bacteremia (10.4% vs. 17.5%), need for vasopressors (15.1% vs. 20.0%), dialysis (9.4% vs. 16.5%), and/or sepsis (9.4% vs. 16.5%) or septic shock 14.2% vs. 17.1%) occurred less frequently in the RaP group. With respect to NP type, nvHABP was most common in RaP (47.2%) and VABP in RaO (38.1%).

Conclusion
One in seven survivors of a hospitalization complicated by NP requires an acute rehospitalization within 30 days. However, few of these readmissions had a principal diagnosis of pneumonia, irrespective of NP type. This suggests that short-term readmission does not capture the quality of care initially delivered to patients for their NP. Of the 5% of NP subjects with RaP, the plurality initially suffered from nvHABP.

Disclosures
Marya Zilberberg, MD, MPH, Cleveland Clinic (Consultant)J&J (Shareholder)Lungpacer (Consultant, Grant/Research Support)Merck (Grant/Research Support)scPharma (Consultant)Sedana (Consultant, Grant/Research Support)Spero (Grant/Research Support) Brian Nathanson, PhD, Lungpacer (Grant/Research Support)Merck (Grant/Research Support)Spero (Grant/Research Support) Laura A. Puzniak, PhD, Merck & Co., Inc. (Employee) Andrew F. Shorr, MD, MPH, MBA, Merck (Consultant)