bluuebunny/crossref_metadata_2025_split huggingface dataset:
232. Genomic Evidence for Dissemination of Mycobacterium marinum in an HIV Patient with Multifocal Cutaneous Disease
Authors: Dulanto Chiang Augusto , Khil Pavel P , Manion Maura , Sereti Irini , Zelazny Adrian , Dekker John P 
Published: October 2019

Abstract

Background
Hematogenous dissemination has been proposed to explain multifocal cutaneous disease caused by Mycobacterium marinum in certain patients. Treatment duration for disseminated disease is often months longer than for skin infection alone. However, distinguishing multiple independent inoculation events from dissemination has relied primarily on clinical judgement. Additionally, whether temperature-sensitive non-tuberculous mycobacteria such as M. marinum are indeed capable of invading the vascular space at core body temperature is debated. Here we used whole-genome sequencing (WGS) of serial isolates from a single patient with multifocal cutaneous M. marinum infection to distinguish dissemination of a clonal strain from multiple inoculation events.

Methods
A 35-year-old male with HIV (CD4 of 66 cells/µL) presented with a two-month history of a non-healing M. marinum wound on his left elbow (isolate MM0). This was followed a month later after initiation of antiretroviral therapy by a second M. marinum lesion on the right heel (MM1) without history of repeat inoculation, and increased swelling and erythema of the wound on the left arm (MM2) consistent with paradoxical immune reconstitution inflammatory syndrome. A PacBio genome was generated for MM0 and short read Illumina genomes were generated for MM1 and MM2.

Results
All isolates were found to be closely related, with MM1 and MM2 distinguished from MM0 by one and five single-nucleotide variants (SNVs), respectively. Given the substantial genetic heterogeneity among environmental M. marinum strains, such close relatedness of these isolates suggests common origin, and provides strong evidence for dissemination of a clonal strain in this patient. The SNVs included a frameshift mutation in the purT gene, which encodes a formate-dependent phosphoribosylglycinamide formyltransferase involved in de novo purine synthesis, and missense mutations in atsA and the DNA methylase hsdM. All isolates grew at 35°C, compared with the optimal growth temperature of 30°C typically observed for M. marinum, suggesting thermotolerance permissive for dissemination.

Conclusion
These results demonstrate the potential role of WGS for providing supportive evidence of disseminated infection with M. marinum.

Disclosures
All authors: No reported disclosures.
249. Limited Diagnostic Utility of Extended Aerobic Blood Culture Incubation for Fungal Pathogen Detection
Authors: Bourassa Lori , Kates Olivia , Liu Catherine 
Published: October 2019

Abstract

Background
Blood cultures are an important diagnostic tool for the detection of fungemia. At our institution, fungal blood cultures consist of aerobic blood culture with incubation extended from the standard 5 days to 14 days. Orders for fungal blood cultures exist in multiple electronic order sets for selected populations, including oncology and bone marrow transplant services.

Methods
To determine the yield of fungal blood cultures at our institution, a 570-bed tertiary-care referral center, we extracted all fungal blood culture results over a 4.5-year period (January 1, 2014–May 15, 2018) from a Laboratory Information System.

Results
Of the 21,657 fungal blood cultures performed, only 202 (0.9%) demonstrated growth and 189 (0.9%) grew fungal organisms. The majority (90%, n = 182/202) of positive fungal blood cultures grew a Candida or other yeast species. 96% (n = 174/182) of the fungal cultures that grew yeast would have been detected with standard bacterial blood culture. Eight of these cultures became positive during the extended hold period and grew a Candida species. All 8 cultures were collected from patients who had previous positive cultures for the same Candida species detected by standard incubation. Five fungal blood cultures from 4 patients turned positive after 5 days of incubation. Among these, two additional fungal pathogens were identified including 2 cases of Lomentospora prolificans and 2 cases of Fusarium. In both cases of L. prolificans and one case of Fusarium, the patients had previous positive blood cultures that detected the same organism with standard incubation. One patient with Fusarium had no previous positive blood cultures, but had multiple tissue cultures positive for Fusarium. The remaining cultures that turned positive after 5 days of incubation contained bacterial organisms, a number of which were considered clinically insignificant (e.g., Cutibacterium species).

Conclusion
These data suggest that extended incubation of aerobic blood culture bottles has limited diagnostic utility beyond standard bacterial blood culture for detection of fungemia. Fungal blood cultures represent an opportunity for improved diagnostic test stewardship, and use should be restricted to selected situations in consultation with Infectious Diseases or Laboratory Medicine.

Disclosures
All authors: No reported disclosures.
251. Implementation of the Sōna Coccidioides Antibody Lateral Flow Assay in the Clinical Laboratory Proves to Reduce Cost and Decrease Turnaround Time When Compared with Send out Immunodiffusion and Complement Fixation Testing
Authors: Candelaria Wesley J 
Published: October 2019

Abstract

Background
Coccidioidomycosis (Valley fever) is an airborne, invasive fungal infection endemic to Arizona, California, Mexico, and Central and South America. The dominant method of diagnosis is serology, which includes complement fixation (CF), immunodiffusion (ID), and enzyme immunoassay (EIA). These serological assays require highly trained personnel and are time consuming, with turnaround times (TAT) that range anywhere from 5 days to 2+ weeks. Due to costs of send outs and long TAT, Valley fever presents a diagnostic challenge to physicians and laboratorians. IMMY developed the sōna Coccidioides Antibody Lateral Flow Assay (LFA), a rapid and simple diagnostic assay that detects anti-Coccidioides antibodies in patient serum in 30 minutes.

Methods
We tested the sōna Coccidioides antibody LFA using 315 patient specimens and compared cost-analysis and TAT to a send out reference lab’s ID and CF assays.

Results
In this study, we found that after implementing the sōna Coccidioides Antibody LFA as a screening test, the cost of send-outs reduced by 84%, and the cost of all testing reduced by 68%. The TAT for sending out testing averaged 5–10 days, whereas the sōna Coccidioides Antibody LFA averaged a total TAT of <24 hours.

Conclusion
The sōna Coccidioides Antibody LFA offers a rapid, simple, and inexpensive method for accurately detecting antibodies against Coccidioides spp. in patient serum.

Disclosures
All authors: No reported disclosures.
258. False Negative Rate of T2Candida Assay in Blood Culture Positive Candidemia
Authors: McCarty Todd , Leal Sixto M , Lee Rachael A , White Cameron , Pappas Peter 
Published: October 2019

Abstract

Background
The T2Candida (T2C) assay is an FDA-approved, non-culture-based rapid diagnostic that utilizes PCR and magnetic resonance technology to detect candidemia in a whole blood specimen. T2C can detect the 5 most common pathogenic species: C. albicans, C. tropicalis, C. parapsilosis, C. krusei, and C. glabrata. The sensitivity of T2C is reported to be 88–94%, varying by the species, based on the original clinical trial from 2015. Only 6 patients with candidemia were included in the study, so it was supplemented with samples spiked with known quantities of Candida spp. In this study, we sought to evaluate the sensitivity of T2C with routine usage in a tertiary-care academic hospital.

Methods
All patients with a blood culture (BC) positive for Candida spp. during the years 2016 through 2018 were identified. Repeat positive cultures of the same species within 30 days of the initial culture were excluded. We then reviewed the medical records of those patients with a T2C collected ±12 hours from the time of the BC collection. Data collection included demographics, time to antifungal therapy, time to culture reported positive, impact of false negative T2C on antifungal therapy, and 30-day mortality.

Results
There were 281 episodes of candidemia (designated as a positive blood culture) in the study period. Forty-four of these episodes had a T2C collected within the specified timeframe (Figure 1). Overall, there were 17 false-negative T2C, reflecting a sensitivity of 61% (27/44). Excluding species not detected by T2C, the sensitivity was 71% (21/38). Of the false-negative group, antifungal therapy was impacted in 8 patients: delayed initiation in 6 patients (1–4 days) and treatment interruption in 2 patients (1 dose each). Demographics, time to treatment, time to culture positivity, and 30-day mortality were similar in the two groups (Table 1).

Conclusion
In spite of the test being readily available and increasingly used, only 44/281 (16%) of patients with a positive BC had a T2C ordered concurrently. Our experience shows a much lower sensitivity than the clinical trial, in part due to species not detected by T2C. Considering only those organisms on the T2C panel, the false-negative rate was 29%. Impact on treatment was limited to half of the false-negative patients with no difference in mortality.

Disclosures
All authors: No reported disclosures.
262. Assessment of Serum Galactomannan Test Results of Pediatric Patients with Hematologic Malignancies According to Different Threshold Levels and Consecutive Positivity in Terms of Invasive Aspergillosis Diagnosis: Cross-Sectional Research in a Tertiary Care Hospital
Authors: Çağlar İlknur , Özkerim Duygu , Tahta Neryal , Düzgöl Mine , Bayram Nuri , Demirağ Bengü , Hilkay Karapınar Tuba , Sorguç Yelda , Gözmen Salih , Dursun Vecihe , Oymak Yeşim , Vergin Canan , devrim İlker 
Published: October 2019

Abstract

Background
The aim of this study was to evaluate the diagnostic utility of serum galactomannan (GM) test by investigating the impact of positivity according to different threshold levels and consecutiveness in terms of invasive aspergillosis (IA) in pediatric hematology-oncology patients.

Methods
Positive GM test results between January 2015 and August 2017 were reviewed, retrospectively. The children with hematological malignancies and GM positivity were included in the study and grouped according to the presence of IA. Impact of single and consecutive (3-day interval) GM positivity on IA diagnosis were evaluated according to different galactomannan index (GMI) threshold values of >0.5, >0.7, >1.0, and >1.5.

Results
There were 104 positive GM results from 70 patients. Forty-one patients (58.6%) had no clinical evidence of IA and categorized as the non-IA group. Invasive aspergillosis diagnosis was identified in 29 (41.4%) of the patients; 2 of them were proven and 27 were probable. Demographic characteristics and clinical findings of the patients were reviewed in Tables 1 and 2. According to different cutoff GMI values, the number of positive results was 104 for >0.5, 76 for >0.7, 57 for >1.0 and 32 for >1.5. The PPVs were low at a single GMI of >0.5 (39.4%) and reached to 50.0% with single GMI of >1.0. There was not a statistically significant difference between IA and non-IA groups in terms of different thresholds of a single GM positivity (P > 0.05) (Table 3). The number of two consecutive positive results was 34 for GMI of >0.5, 20 for GMI of >0.7, 13 for GMI of >1.0 and 4 for GMI of >1.5. In the IA group, GM positivity of consecutive results was significantly higher than non-IA group (P < 0.05). The PPVs of two consecutive positive results for GMI >0.5, GMI >0.7, GMI >1.0, and GMI >1.5 were 58.8%, 65.0%, 84.6%, and 100.0%, respectively. The effect of the GMI increase between two consecutive GM results on IA diagnosis (GM2-GM1 >0.5) was also evaluated and the PPV was found 53.8% without a statistical significance between two groups (Table 4).

Conclusion
When evaluated with consecutive GM positivity, the GM assay would have higher PPVs independently from the GMI cutoff value chosen. Since it may be more effective on IA diagnosis, consecutive sampling should be performed in pediatric patients at high risk.

Disclosures
All authors: No reported disclosures.
265. Clinical Epidemiology of Invasive Fungal Infection with Aspergillus and Mucor Species in a Tertiary Children’s Hospital
Authors: Oikonomopoulou Zacharoula , Patel Sameer , Toia Jacquie , Muller William 
Published: October 2019

Abstract

Background
Patients undergoing hematopoietic stem cell transplantation and patients with hematologic malignancies are at increased risk for acquiring invasive fungal infection (IFI) due to immune system impairment from chemotherapy. Affected patients require prolonged antifungal therapy with the risk of associated toxicity and extended hospitalization due to delay of accurate diagnosis. There is a lack of effective serologic biomarkers and hesitancy to proceed with tissue diagnosis due to thrombocytopenia or other associated risks. Mortality in oncology patients with invasive mycoses is high, with pediatric mortality rates of 30–40% at 12 weeks following diagnosis.

Methods
All patients that were admitted to Lurie Children’s Hospital between January 2014 and December 2018 and received voriconazole, ambisome, posaconazole and isavuconazole were identified. The following data were retrospectively collected: CT chest and sinus, (1,3)-β-d-Glucan and Aspergillus galactomannan, ANC and ALC at diagnosis, blood next-generation sequencing, tissue 18s rRNA, fungal culture, duration of neutropenia and lymphopenia, site of infection, time between underlying diagnosis and development of IFI, surgical intervention and associated mortality.

Results
A total of 94 unique patients that received voriconazole were identified. There were 8 proven cases of invasive Aspergillus infection the past 5 years, 50% male, mean age 14 years. Only 25% of patients had positive serum Aspergillus galactomannan and 37.5% had positive β-d-Glucan. Seven cases were due to Aspergillus fumigatus and one case was due to Aspergillus flavus. There were 9 patients with mucormycosis and all but one were culture positive. Three patients with Mucor had mold identification in blood next-generation sequencing prior to surgery. Mucor associated mortality was 22.2%.

Conclusion
The majority of pediatric patients with invasive aspergillosis did not have characteristic chest CT imaging findings and serum Aspergillus galactomannan was usually negative.The was no associated mortality in invasive Aspergillus cases, whereas the mortality rate of invasive mucormycosis was 22.2%. Although we have a small sample size, this is significantly lower compared with published literature.

Disclosures
All authors: No reported disclosures.
304. Hepatocellular Carcinoma Occurs Frequently and Early After Treatment in HCV Genotype 3 Infected Persons Treated with DAA Regimens
Authors: Un Nabi Tayyab Ghias , Rasool Shafqat , Nasir Bilal , Butt Adeel A 
Published: October 2019

Abstract

Background
Treatment of HCV with directly acting antiviral agents (DAAs) is associated with a significant reduction in cardiovascular, metabolic and cancer risk. However, there are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after DAA treatment. Risk of HCC in HCV genotype 3 infected persons after DAA therapy is not well known.

Methods
We prospectively studied HCV-infected persons initiated on treatment between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. The occurrence of HCC was confirmed based on radiologic findings on a triphasic CT on 64 slice MDCT scanner. The treatment regimen was at the discretion of clinical care providers, taking into account the national guidelines and patient preferences. Patients were followed for 24 weeks after the completion of therapy. Informed consent was obtained from all participants.

Results
A total of 662 persons were initiated on treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic with 90% of cirrhotics having compensated cirrhosis. 91% were genotype 3 and SVR was attained in 91.9%. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCL), 10.6%; SOF/DCL, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the six month period after treatment completion, and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85) while SOF/RBV/DCL regimen (compared with SOF/RBV/PEG-IFN) was associated with an increased risk of HCC (HR, 95% CI: 17.32, 2.14,140.36). In K-M plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCL, or SOF/DCL regimens had shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen. (See figure)

Conclusion
In a predominantly genotype 3 cohort, incident HCC occurs commonly and early after treatment completion, and exclusively in those with pretreatment cirrhosis. SVR reduces but does not completely eliminate the risk of HCC. Treating HCV-infected persons before the development of cirrhosis may reduce future risk of HCC.

Disclosures
All authors: No reported disclosures.
309. Should Primary Care Practitioners Follow Hepatitis C Exposed Infants?
Authors: Merjaneh Nawal , Smotherman Carmen , Maraqa Nizar , Mirza Ayesha 
Published: October 2019

Abstract

Background
Hepatits C virus (HCV) infection in pregnancy is estimated between 1–4% and risk of vertical transmission ~5%. While the benefits of HCV testing for perinatally exposed infants under a year is debatable, a strategy for follow-up (F/U) is important. We instituted interventions to improve the F/U rate for HCV exposed infants in December 2012. Pediatric infectious diseases (PID) service was consulted in the newborn period to establish care. Perinatal HCV exposure was added to the infant’s electronic record. Educational brochures were given to guardians at discharge. We aimed to assess the efficacy of the interventions in improving the F/U rate.

Methods
A retrospective chart review of 227 HCV exposed infants born between January 2013 and December 2016 was done after obtaining IRB. Infant charts were reviewed for maternal age, race, insurance, HCV risk factors, HIV and Hep B co-infection, third trimester HCV PCR, delivery type, gestational age, birth weight and infant custody. Based on 2002 NIH guidelines: first visit at 6–8 weeks, second at 6–8 months, final visit ≥18 months of age. Maternal HCV infection is positive HCV antibody (Ab) during pregnancy, medical care defined as at least one infant PID clinic visit, and appropriate F/U as an 18-month visit for HCV (Ab) check. Univariate analysis is used for demographics, descriptive summaries were recorded as frequencies and percentages.

Results
214 infants included in analysis (1 deceased and 12 adopted and left area). Baseline characteristics of those who had medical care vs. not were similar except for infant custody and HIV co-infection 94/214 (44%) had medical care. Of those, 32/94(34%) had appropriate F/U while 62/94(66%) did not 31/214 infants were followed by primary care practitioners (PCPs) at our institution. Of those 24/31(77.5%) were either tested inappropriately or lost to F/U HIV co- infection and custody by a relative (not mom) increase the likelihood of F/U (P 0.003 and 0.002, respectively) 5 infants contracted HCV infection. One infant who lost to F/U was diagnosed incidentally in the ER.

Conclusion
Appropriate F/U for HCV exposed infants poses challenges despite established systems of care. Because current guidelines recommend antibody testing at 18 months, educating PCPs who are more likely to establish regular F/U is important for appropriate testing.

Disclosures
All authors: No reported disclosures.
318. Tenofovir Alafenamide (TAF) vs. Tenofovir Disoproxil Fumarate (TDF) in Hispanic/Latinx and Black Participants: Efficacy, Bone and Renal Safety Results from a Pooled Analysis of 7 Clinical Trials
Authors: DeJesus Edwin , Federico Andrade Villanueva Jaime , Ramon Arribas Lopez Jose , Brinson Cynthia , Crofoot Gordon , Daar Eric S , Koenig Ellen , Podzamczer Daniel , Ramgopal Moti , Santana Jorge , Santiago Lizette , Tebas Pablo , Zorrilla Carmen , Guo Susan , Liu Ya-Pei , Zhong Lijie , Brainard Diana M , Carter Christoph C , Temme Lauren , Das Moupali 
Published: October 2019

Abstract

Background
People of color are underrepresented in clinical trials. TAF has shown improved renal and bone safety vs. TDF. We pooled 7 studies to evaluate efficacy/safety of TAF vs. TDF for ART initiation/switch in Hispanic/Latinx and Black participants.

Methods
Data from Hispanic/Latinx and Black adults who initiated/switched to TAF or TDF in 7 randomized trials (2 treatment-naïve, 5 suppressed switch) were analyzed. TAF-based regimens (elvitegravir/cobicistat/emtricitabine [FTC]/TAF, rilpivirine/FTC/TAF, FTC/TAF, or bictegravir/FTC/TAF) were compared with TDF-based regimens. Virologic suppression (VS; HIV-1 RNA < 50 c/mL, FDA snapshot) and % change in bone mineral density (BMD) and renal tubular biomarkers urine β-2-microglobulin (B2M):creatinine (Cr) ratio and retinol binding protein (RBP):Cr ratio are reported at W96.

Results
The pooled population (N = 5,825) included 1138 Hispanic/Latinx and 1324 Black participants. Treatment-naïve participants (n = 1,733) were 15% female, 25% Black, 19% Hispanic/Latino, with median age 34 years, HIV-1 RNA 4.6 log10 c/mL, CD4 405 cells/mm3. Switch participants (n = 4,092) were 13% female, 22% Black, 20% Hispanic/Latino, median age 45 years, CD4 653 cells/mm3. There was no difference in VS rate with TAF vs. TDF in any group. VS rate (TAF vs. TDF) in naïve participants: 88% vs. 84% (Hispanic/Latinx); 78 vs. 79% (Black); 87% vs. 85% (overall). VS (TAF vs. TDF) was well maintained in switch participants: 91% both arms (Hispanic/Latinx); 86% vs. 87% (Black); 90% vs. 88% (overall). TAF and TDF were well tolerated with few discontinuations due to adverse events (0.6–2%) in all groups. At W96 there was less impact on renal biomarkers in all groups initiating TAF (P < 0.001; table), and decreases in BMD were smaller (P < 0.005; table) vs. TDF. All groups switching from TDF to TAF experienced decreases in tubular proteinuria and improvements in BMD (both P < 0.001; table) at W96.

Conclusion
Hispanic/Latinx and Black participants who initiated/switched to TAF had significantly improved bone and renal parameters vs. TDF, with similar VS rates at W96. Efficacy and biomarkers were similar to the overall study population. These data in >2,400 Hispanic/Latinx and Black PLH demonstrate noninferior efficacy and safety advantages with TAF vs. TDF.

Disclosures
All authors: No reported disclosures.