bluuebunny/crossref_metadata_2025_split huggingface dataset:
134. Derivation of novel phenotypes of outpatient pediatrician prescribing patterns
Authors: Herigon Joshua C , Hatoun Jonathan , Vernacchio Louis 
Published: January 2021

Abstract

Background
Antibiotics are the most commonly prescribed drugs for children with estimates that 30%-50% of outpatient antibiotic prescriptions are inappropriate. Most analyses of outpatient antibiotic prescribing practices do not examine patterns within individual clinicians’ prescribing practices. We sought to derive unique phenotypes of outpatient antibiotic prescribing practices using an unsupervised machine learning clustering algorithm.

Methods
We extracted diagnoses and prescribing data on all problem-focused visits with a physician or nurse practitioner between 6/11/2018 – 12/11/2018 for a state-wide association of pediatric practices across Massachusetts. Clinicians with fewer than 100 encounters were excluded. The proportion of encounters resulting in an antibiotic prescription were calculated. Proportions were stratified by diagnoses: otitis media (OM), pharyngitis, pneumonia (PNA), sinusitis, skin & soft tissue infection (SSTI), and urinary tract infection (UTI). We then applied consensus k-means clustering, a form of unsupervised machine learning, across all included clinicians to create clusters (or phenotypes) based on their prescribing rates for these 6 conditions. A scree plot was used to determine the optimal number of clusters.

Results
A total of 431 clinicians at 77 practices with 234,288 problem-focused visits were included (Table 1). Overall, 42,441 visits (18%) resulted in an antibiotic prescription. Individual clinician prescribing proportions ranged from 5% of visits up to 44%. The optimal number of clusters was determined to be four (designated alpha, beta, gamma, delta). Antibiotic prescribing rates were similar for each phenotype across AOM, pharyngitis, and pneumonia but differed substantially for sinusitis, SSTI, and UTI (Figure 1). The beta phenotype had the highest median rates of prescribing across all conditions while the delta phenotype had the lowest median prescribing rates except for UTI.
Table 1. Patient demographics and clinician characteristics

Figure 1. Novel phenotypes of antibiotic prescribing practices across six common conditions

Conclusion
Antibiotic prescribing varies by both condition and individual clinician. Clustering algorithms can be used to derive phenotypic antibiotic prescribing practices. Antimicrobial stewardship efforts may have a higher impact if tailored by antibiotic prescribing phenotype.

Disclosures
All Authors: No reported disclosures
1616. Mechanism of Thrombocytopenia Induced by Oxazolidinones Antibiotics (Linezolid, Tedizolid): Demonstration of Impairment of Megakaryocyte Differentiation From Human Hematopoietic Stem Cells associated with Mitochondrial Toxicity
Authors: Tulkens Paul M , Milosevic Tamara V , Vertenoeil Gaëlle , Vainchenker William , Constantinescu Stefan N , Van Bambeke Françoise 
Published: January 2021

Abstract

Background
Linezolid causes thrombocytopenia, which limits its use. In cell culture and in tissues from treated patients, linezolid impairs mitochondrial protein synthesis (due to structural similarities and common binding sites between bacterial and mitochondrial ribosomes). Recent studies have shown that mitochondria act as a key relay in the process leading from activation of the thrombopoietin receptor to megakaryocytes differentiation.

Methods
Validated ex-vivo human model of hematopoietic stem cells (HSC) differentiation for (i) measuring megakaryocytes, granulocyte-monocytes, and burst-forming unit-erythroids colony formation; (ii) differentiation into megakaryocytes (conversion of CD34+ into CD41+/CD42+ cells; morphology) and proplatelets formation, (iii) mitochondrial toxicity (electron microscopy; cytochrome c-oxidase activity [partly encoded by the mitochondrial genome]).

Results
We show that linezolid (and the recently approved tedizolid), both at concentrations corresponding to their human serum concentrations) inhibit the maturation of HSC into fully differentiated megakaryocytes (CD41 and CD42-positive cells) and the formation of proplatelets. Optic and Electron microscopy) showed an impairment of the formation of typical megakaryocytes (lack of large polylobulated nuclei and of intracellular demarcation membrane system [required for platelet formation]), together with disappearance of the internal structure of mitochondria. Biochemical studies showed a complete suppression of the activity of cytochrome c-oxidase (a key enzyme of the mitochondrial respiratory chain).

Conclusion
Our study provides for the first time insights in the mechanism of thrombocytopenia induced by linezolid and tedizolid, identifying mitochondria as their target and showing that the drugs will impair the differentiation of hematopoietic stem cells into mature platelets-releasing megakaryocytes. It illustrates how mitochondria dysfunction may play a key role in toxicology and diseases, while paving the way for rational approaches for the design and screening of less toxic derivatives for the benefit of future patients.

Disclosures
Paul M. Tulkens, MD, PhD, Bayer (Consultant, Advisor or Review Panel member, Speaker’s Bureau)Menarini (Speaker’s Bureau)Merck (Advisor or Review Panel member, Speaker’s Bureau)Trius (now part of Merck) (Advisor or Review Panel member, Research Grant or Support) Françoise Van Bambeke, PharmD, PhD, Bayer (Speaker’s Bureau)
1624. Real World Experience with Daptomycin (DAP) and Ceftaroline (CPT) Combination Therapy for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia
Authors: Zidaru Andrei , Russo Hannah Ryan , Phe Kady 
Published: January 2021

Abstract

Background
Methicillin-resistant Staphylococcus aureus bacteremia is associated with significant mortality rates up to 30%. Guideline-recommended first-line therapy includes monotherapy with either vancomycin or DAP. Alternative regimens are recommended for persistent MRSA bacteremia of ≥ 7 days or earlier if evident clinical deterioration. The combination of DAP plus CPT has been investigated as salvage therapy due to its synergistic mechanism potential, but real-world data with the combination therapy is limited. The aim of this study was to evaluate the efficacy of DAP plus CPT combination therapy for the treatment of MRSA bacteremia and identify independent predictors of 30-day mortality.

Methods
This was a single center retrospective study of patients receiving DAP-CPT at any point in therapy for the treatment of MRSA bacteremia. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality.

Results
Sixty-five unique patients received DAP-CPT with a median time to combination therapy of 7 days. There were no significant independent predictors of 30-day mortality. The most common reason for combination therapy was persistent bacteremia (80%, 52/65). Bacteremia was cleared in 90.8% (59/65) of patients and the 30-day mortality rate was 15.4% (10/65). Median time to bacteremia clearance after combination switch was 3 days. Eleven patients received DAP-CPT within 72 hours of index culture. Median time to bacteremia clearance for patients switched to DAP-CPT within 72 hours versus after 72 hours did not differ (2 vs 3 days; P = 0.526), however the overall median duration of bacteremia was 4 and 11 days (P = 0.018). In a sub analysis, the median time of bacteremia clearance following combination therapy was significantly longer for patients receiving renal replacement therapy (5 vs 2 days; P = 0.04).

Conclusion
There were no independent predictors of 30-day mortality identified. DAP-CPT combination therapy resulted in clearance of persistent bacteremia and may serve as an effective salvage therapy.

Disclosures
All Authors: No reported disclosures
1626. Synergistic Effect of Cefiderocol with Other Antibiotics Against PER-Producing Acinetobacter baumannii Isolates from the Multinational SIDERO-WT Studies
Authors: Yamano Yoshinori , Takemura Miki , Anan Naomi , Nakamura Rio , Echols Roger 
Published: January 2021

Abstract

Background
Cefiderocol (CFDC), a novel siderophore cephalosporin, showed potent activity at minimum inhibitory concentrations (MICs) of ≤4 μg/mL against ≥99% of Gram-negative isolates in the multinational SIDERO-WT studies. PER-producing Acinetobacter baumannii, mainly from Russia, showed high CFDC MICs of 8– &gt;64 μg/mL. This study evaluated the synergistic effects of CFDC combined with other antibiotics against PER-producing A. baumannii isolates with high CFDC MICs.

Methods
Two isolates of PER-producing A. baumannii with resistance to CFDC (MIC 16 μg/mL), meropenem (MEM; MIC 64 μg/mL), ceftazidime-avibactam (CZA; MIC 64/4 μg/mL), amikacin (AMK; MIC 32 or 64 μg/mL), and ciprofloxacin (CIP; MIC ≥64 μg/mL) were tested. Against ampicillin-sulbactam (SAM), one isolate was resistant (MIC 32/64 μg/mL) and another was susceptible (MIC 8/16 μg/mL). Effects of CFDC combined with other antibiotics were evaluated by checkerboard assay and chemostat model reproducing humanized antibiotic exposure. The checkerboard assay used a single agent (e.g. ceftazidime [CAZ], avibactam [AVI], ampicillin [AMP] or sulbactam [SUL]). Iron-depleted cation-adjusted Mueller‒Hinton broth was used as the standard medium for CFDC, as recommended by the Clinical Laboratory and Standards Institute.

Results
Against both isolates, synergy with CFDC was seen for two β-lactamase inhibitors, AVI and SUL, with a fractional inhibitory concentration (FIC) index of 0.026–0.033 and 0.26–0.27, respectively. A synergistic to additive effect was seen for MEM and AMK, with an FIC index of 0.53–0.75 and 0.25–0.52, respectively. In the chemostat model, regrowth during 24-h treatment was observed with single agents (CFDC 2 g, q8h, 3-h infusion; MEM 2 g, q8h, 1-h infusion; CZA 2 g, q8h, 2-h infusion; SAM 3 g, q8h, 3-h infusion; AMK 15 mg/kg, q8h, 3-h infusion) for both isolates, including the SAM-susceptible isolate. However, no regrowth was seen when CFDC was combined with CZA, MEM, SAM or AMK.

Conclusion
The most potent synergy was seen between CFDC and AVI against PER-producing A. baumannii with a decreased MIC to ≤1 µg/mL for all isolates, followed by SUL and MEM. Under humanized pharmacokinetic exposure, combination of CFDC and CZA, MEM, SAM or AMK is expected to be effective against PER-producing A. baumannii in spite of high CFDC MICs.

Disclosures
Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Naomi Anan, MSc, Shionogi & Co., Ltd. (Employee) Rio Nakamura, BSc, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant)
1639. Lung Transplant Outcomes in Patients with Chronic Respiratory Disease and Pre-Operative Nontuberculous Mycobacterial Disease
Authors: McGuffin Sarah , Lease Erika D , Bartlett Lauren E , Goss Chris , Johnson Luke M , Jamali Haya 
Published: January 2021

Abstract

Background
Pulmonary infection secondary to nontuberculous mycobacteria (NTM) is associated with significant morbidity and mortality, especially in individuals with underlying structural lung disease. Such infections are challenging to treat due to high virulence, antibiotic resistance, and the lack of effective and tolerable therapies. At many transplant centers, the isolation of NTM may be considered a contraindication for lung transplantation.

Methods
Institutional and referral medical records, microbiology, radiology and pathology databases were reviewed for patients who underwent lung transplantation at the University of Washington between 2006-2020. 8 patients with NTM disease were identified according to the American Thoracic Society (ATS) guidelines. 9 patients with sputum cultures positive for NTM, but not diagnosed with NTM disease were also evaluated.

Results
Patients with NTM disease continued antimycobacterial therapy pre- and post-operatively. NTM organisms isolated included M avium complex, M fortuitum, M abscessus, M kansasii, and M fortiutum.
In the cohort with NTM-disease, one patient died within a year of transplantation (14%), three died within 1-5 years (43%), and four (51%) are still alive 1-9 years post-transplantation. Only one patient clearly died as a direct cause of the NTM infection, and this occurred early post-transplantation due to disseminated M abscessus infection. Of the other deceased patients with pre-existing NTM disease, one died due to graft rejection at 3 years, one died due to graft rejection with concomitant non-NTM pneumonia at 2 years, and one died due to cardiac arrest at 4 years. In the cohort without NTM disease, none died within 1 year of transplantation, 22% died within 1-5 years, 11% died more than 5 years post-transplant, and 66% are still alive 1-14 years post-transplant.
The probability of survival more than 1 year and more than 5 years post-transplant and 38% in patients with NTM-disease, and 100% and 56% in patients without NTM disease.

Conclusion
NTM infection in the lung transplant candidate is uncommon and challenging, however successful treatment can occur, perhaps in the setting of certain subspecies and with prolonged combination antimicrobial therapy.

Disclosures
All Authors: No reported disclosures
137. Evaluating a Novel Antibiogram Format for use in Wisconsin Nursing Homes
Authors: Taylor Lindsay N , Howe Michael , Crnich Christopher J 
Published: January 2021

Abstract

Background
Nursing homes (NHs) increasingly use antibiograms to track antibiotic-related outcomes and guide antibiotic choice. Creation of a facility-specific antibiogram is hampered by low number of cultures collected in NHs. A weighted-incidence syndromic combination antibiogram (WISCA) is an alternative approach that may provide more stable estimates of antibiotic activity. In this study, we compare traditional antibiograms and WISCAs in a sample of Wisconsin NHs.

Methods
We created urine-specific antibiograms using traditional and WISCA approaches at facility and regional levels using culture data collected in study NHs from 01/01/2018 – 12/31/2018. Susceptibility results were standardized across laboratories using CLSI breakpoints. Traditional antibiograms were deemed reliable when ≥ 20 isolates were recovered for at least one species and species exceeding this threshold comprised 75% of all isolates. WISCAs were deemed reliable if ≥ 20 urinary isolates were recovered. Bootstrapped regional mean susceptibilities and confidence intervals for traditional antibiograms and WISCAs were calculated. Susceptibilities calculated at the facility-level were compared to regional estimates. Facility-level susceptibility estimates were deemed concordant if within 1 SD, moderately discordant if between 1 and 2 SDs, and severely discordant if greater than 2 SDs of the regional estimate.

Results
462 urine isolates were obtained from 23 NHs in 2 regions. None of the facility-specific traditional antibiograms met reliability criteria. 10 of 23 facility-specific WISCAs were reliable and increased to 19 of 23 when 2-years of microbiology data were utilized (table). Severe discordance between facility-specific and regional estimates was identified with 62/107 NH species-antibiotic means and 98/119 NH urine isolate-antibiotic means falling outside of 2 SD of corresponding bootstrap regional susceptibility means (figure).
Table. Reliability analysis of facility-specific urinary WISCAs and traditional antibiograms. 2-year projection was created using the assumption of similar culture results over 2-years.

Figure. Proportion of concordant, moderately discordant, and severely discordant NH mean susceptibilities in comparison to bootstrap regional mean susceptibilities for traditional antibiograms and WISCAs. NH mean susceptibilities from 5 isolates of more were included.

Conclusion
WISCAs are more reliable than traditional antibiograms for estimating antibiotic susceptibilities using facility-specific data. The high degree of discordance observed between facility-specific and regional antibiograms raises concerns about pooling culture data from multiple facilities.

Disclosures
All Authors: No reported disclosures
1640. A Clinical Audit and Cost Analysis of Tuberculosis Management at a Tertiary Referral Centre in the Republic of Ireland
Authors: O’Connell James A , de barra Eoghan , McConkey Samuel 
Published: January 2021

Abstract

Background
Ireland is a low tuberculosis (TB) incidence country. Effective TB services are important in the efforts to meet WHO End TB Targets. A dedicated TB clinic was established in our tertiary referral centre in 2018. Our aim is to describe the patients with TB attending our service and evaluate the care provided to them in terms of cost and clinical effectiveness.

Methods
We performed a retrospective review of patients attending our service from 01/07/2018-31/12/2019. We included patients who were referred for assessment of symptoms of active tuberculosis. We collected data on patients risk factors for TB, time from illness onset to diagnosis and resources utilized (including hospital admissions, outpatient appointments, investigations and drug treatment). We estimated the productivity losses due to TB in our cohort following the Hanover Consensus. Using national TB notifications data we used our estimate treatment cost and productivity losses to estimate the total national cost of TB in Ireland in 2019.

Results
Fifty-four patients were assessed for TB in our clinic. Most patients (68.5%) referred had a diagnosis of TB made, 5.6% had a non-tuberculosis mycobacterial infection and the remainder had no mycobacterial infection diagnosed. Over half (51.4%) of patients with TB had respiratory TB. The most prevalent risk factor was being from a country of high TB incidence (59.5% of TB patients). Five patients (13.5%) had drug resistance. Patients were referred most frequently from the emergency department (54.1%). The median time from symptom onset to diagnosis was 14.1 weeks (IQR 5.3-30) in patients with respiratory TB compared to 25.9 weeks (IQR 6.3-55.9) in patients with non-respiratory TB. Out of 35 patients who remained within our service 97.1% (34/35) completed treatment and 2.9% (1/35) are still on treatment.
We estimate that the median cost of managing a case of TB in our centre was €6088 (€1,003-17,588). The estimated cost of managing all 267 cases of TB in Ireland in 2019 was €9,048,380 which incurred productivity losses of €791,421. The total cost of TB to Ireland in 2019 was €9,839,801.

Conclusion
Our clinic had a high rate of treatment success. Interventions to reduce diagnostic delay and cost are needed.

Disclosures
All Authors: No reported disclosures
1652. Diagnoses of Non- Tuberculosis Mycobacterium (NTM) in patients with granuloma on lung biopsy
Authors: Singh Vansha , Kim Angela , Hayes Lisa , Rasul Rehana , Schwartz Rebecca , Epstein Marcia , Epstein Marcia 
Published: January 2021

Abstract

Background
The prevalence of non-Tuberculous mycobacteria (NTM) lung disease has increased from 8.7 to 13.9/100,000 from 2008-2013 making NTM lung disease a rising public health problem. Patterns of infection include fibrocavitary, bronchiectatic or nodular. Diagnosis of NTM may be incidental after surgical resection performed during malignancy work up. We aimed to identify the proportion of NTM in resected lung lesions (both nodules and masses) with granulomas (GL) both necrotizing (NGL) and non-necrotizing (n-NGL) on pathology and to compare differences in characteristics of patients with NTM versus those without NTM.

Methods
This was a retrospective chart review of patients who underwent resection of lung nodules and/or a lung mass during malignancy work up from January 2013 through March 2019 including only those with granulomatous inflammation on pathology. 497 patients met these criteria and their electronic medical records were reviewed. Findings of culture-confirmed NTM on tissue, bronchoalveolar lavage or sputum (at time of resection) were classified as “NTM” group; and those with no NTM diagnoses were classified as “Non-NTM” group. Patients with NTM and another diagnoses were classified within the NTM group. Study variables were compared by the dichotomous NTM group using Chi-square test for categorical variables and T-test for continuous variables.

Results
Among all patients, the most common diagnosis was lung cancer (21.93%). There were 81 (16.3%) patients with NTM (Table 1). Within the NTM group, percentage of Asians, presence of NGL, placement on airborne precautions and prior history of tuberculosis were significantly higher. The NTM group also had a higher proportion of both COPD and lung cancer as their underlying condition (Table 2). 161 patients had non-diagnostic biopsies.
Table 1

Table 2

Table 2

Conclusion
Mycobacterial infections made up a significant percentage of resected lung nodules and/or lung masses for malignancy evaluation. NTM were isolated with greater frequency than M. Tuberculosis even with NGL on lung pathology. This reflects the changing epidemiology of NTM. The significant proportion of Asians with NTM compared with GL found during a malignancy work up without NTM is interesting and deserves further investigation.

Disclosures
All Authors: No reported disclosures
1665. Using Electronic Health Records to Describe TB in Community Health Settings: a Cohort Analysis in a Large Safety-Net Population
Authors: Todd Jonathan , Puro Jon , Jones Matthew , Oakley Jee , Vonnahme Laura A , Ayers Tracy 
Published: January 2021

Abstract

Background
Over 80% of tuberculosis (TB) cases in the United States are attributed to reactivation of latent TB infection (LTBI). Eliminating TB in the United States requires expanding identification and treatment of LTBI. Centralized electronic health records (EHRs) are an unexplored data source to identify persons with LTBI. We explored EHR data to evaluate TB and LTBI screening and diagnoses within OCHIN, Inc., a U.S. practice-based research network with a high proportion of Federally Qualified Health Centers.

Methods
From the EHRs of patients who had an encounter at an OCHIN member clinic between January 1, 2012 and December 31, 2016, we extracted demographic variables, TB risk factors, TB screening tests, International Classification of Diseases (ICD) 9 and 10 codes, and treatment regimens. Based on test results, ICD codes, and treatment regimens, we developed a novel algorithm to classify patient records into LTBI categories: definite, probable or possible. We used multivariable logistic regression, with a referent group of all cohort patients not classified as having LTBI or TB, to identify associations between TB risk factors and LTBI.

Results
Among 2,190,686 patients, 6.9% (n=151,195) had a TB screening test; among those, 8% tested positive. Non-U.S. –born or non-English–speaking persons comprised 24% of our cohort; 11% were tested for TB infection, and 14% had a positive test. Risk factors in the multivariable model significantly associated with being classified as having LTBI included preferring non-English language (adjusted odds ratio [aOR] 4.20, 95% confidence interval [CI] 4.09–4.32); non-Hispanic Asian (aOR 5.17, 95% CI 4.94–5.40), non-Hispanic black (aOR 3.02, 95% CI 2.91–3.13), or Native Hawaiian/other Pacific Islander (aOR 3.35, 95% CI 2.92–3.84) race; and HIV infection (aOR 3.09, 95% CI 2.84–3.35).

Conclusion
This study demonstrates the utility of EHR data for understanding TB screening practices and as an important data source that can be used to enhance public health surveillance of LTBI prevalence. Increasing screening among high-risk populations remains an important step toward eliminating TB in the United States. These results underscore the importance of offering TB screening in non-U.S.–born populations.

Disclosures
All Authors: No reported disclosures