bluuebunny/crossref_metadata_2025_split huggingface dataset:
1710. Profiling Patients with Rare Mucormycosis Infections Using Real-world Data
Authors: Sung Anita H , Rubinstein Emily , Benigno Michael , Chambers Richard , Aram Jalal A 
Published: October 2019

Abstract

Background
Invasive mucormycosis (IM) is universally fatal if untreated and is a challenge to assess due to its rarity. Diagnosis is difficult and can be missed due to a low index for suspicion. IM prevalence may be increasing with medical advances, especially in neutropenia management, leading to improved survival and expansion of the at-risk patient group. Large administrative databases contain patient-level chart information and may offer a way to describe IM patients in a representative sample of the population.

Methods
A retrospective observational study was conducted using US data from the deidentified Optum Electronic Health Record database between January 2007 and June 2018. Patients with any fungal infection and IM specifically were defined by ICD9 (110–119, 117.7) or ICD10 (B35-49, B46) codes. Descriptive statistics were used to assess demographics, comorbidities, and antifungal agents (AF) prescribed among IM patients with an underlying diagnosis of hematologic malignancy (HM). Restricting to an at-risk population minimized possible false IM coding in the sample.

Results
Of the approximately 97 million patients in the database, about 5 million had a fungal infection diagnosis and 5,208 had an IM diagnosis (0.005% overall, 0.11% of fungal infection). Among those with underlying HM (n = 698,187), 641 IM cases were observed (0.09%); of whom, 46% were male, 82% were over 40 years of age, and 77% were in the Midwest region of the United States. They were 83% Caucasian, 7% African American, 2% Asian, and 8% other/unknown race or ethnicity. The mean Charlson Comorbidity Index score was 3 ± 2 and the top comorbidities, aside from malignancy, were diabetes (24%, n = 151), chronic pulmonary disease (22%, n = 141), and renal disease (11%, n = 69). Not all IM patients were treated. There were 376 AF prescriptions, of which 35% were for fluconazole, 28% for posaconazole, and 14% for voriconazole, followed by 7–8% each for isavuconazole and amphotericin formulations.

Conclusion
A sizable number of IM patients were identified from a large US electronic medical records database. More work is needed to understand the data. Given the significant challenges in prospectively identifying IM patients, a large database may allow for a broader insight into patients at risk and potential predictors of IM.

Disclosures
All authors: No reported disclosures.
1711. Histoplasmosis-Associated Hemophagocytic Lymphohistiocytosis: A Case Series and Review of the Literature
Authors: Jabr Ra’ed , El Atrouni Wissam , Male Heather , Hammoud Kassem 
Published: October 2019

Abstract

Background
Histoplasmosis is an endemic fungal disease with a spectrum of presentations from asymptomatic, mild to disseminated infections. Histoplasmosis-associated hemophagocytic lymphohistiocytosis (HLH) is a rare disorder with limited data regarding treatment and outcome. We described the clinical features, treatment, and outcomes of five patients. This review also summarized the current literature about presentation, treatment, and outcome of this infection-related HLH entity.

Methods
We searched the electronic medical records for patients with histoplasmosis-associated HLH at our institution from January 1, 2006 to September 30, 2017. Diagnosis of HLH was confirmed and by chart review according to HLH-04 criteria. We also searched the current literature for case reports and case series of this entity.

Results
We reported five cases of histoplasmosis-associated HLH during this period. All patients were diagnosed after 2010, this may be explained in part by increased awareness of this entity. The literature review yielded 60 cases of histoplasmosis-associated HLH. Among all patients (65 patients), the most common underlying condition was HIV in 61% of all patients. The majority of histoplasmosis patients were treated with amphotericin B formulation in 81%. The specific treatment for HLH was as follows: nine patients received steroids only, six patients received intravenous immunoglobulin (IVIG) only, three patients received dexamethasone and etoposide, two patients received etoposide, dexamethasone, and cyclosporine, two patients received steroids and IVIG, and one patient received Anakinra and IVIG. The inpatient mortality rate was 31% with most of the deaths occurring within 2 weeks of hospital admission.

Conclusion
Histoplasmosis-associated HLH among adults is an uncommon but aggressive disease with multiorgan involvement. Early antifungal therapy with a lipid formulation amphotericin B is the most important part of the management. Initial HLH-specific immunosuppressive therapy with regimens such as the HLH-94 protocol is usually individualized.

Disclosures
All authors: No reported disclosures.
1712. Candida auris: A Case Series at a Large Tertiary Care Medical System
Authors: Yeturu Preethi , Harrington Amanda , Reid Gail 
Published: October 2019

Abstract

Background
Candida Auris has become one of the most feared pathogens globally in a relatively short period of time and, despite increased awareness, its incidence continues to rise. Recently there has been growing concern regarding drug resistance, difficulty in identification, as well as problems with eradication.

Methods
Loyola Medicine includes Loyola University Medical Center, a large tertiary care transplant center, and Gottlieb Memorial Hospital, a community-based medical center. Both hospitals have reported cases of Candida auris infection. We reviewed the microbiology laboratory data and clinical information of all positively identified cases over a 17-month period.

Results
Candida auris was isolated from 14 patients in cultures from blood, urine, wounds, and respiratory secretions. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS; Burker, Biotyper RUO) was used for identification in all of the cases and susceptibility testing was performed using microbroth dilution (Sensititre, YeastOne) for all isolates. 7/14 isolates (50%) were considered resistant to fluconazole; however, none were multi-drug resistant. All 14 isolates (100%) were considered susceptible to echinocandins. In addition, all patients were critically ill and had multiple comorbidities.

Conclusion
Candida auris is an emerging global health threat with increasing incidence of infection. Awareness of the pathogen, appropriate contact precautions, and laboratory methods of identification are necessary. Given increasing drug resistance, we recommend susceptibility testing on all isolates.

Disclosures
All authors: No reported disclosures.
1718. The Natural History of Chronic Pulmonary Coccidioidomycosis in the Pre-Antifungal Era
Authors: Freifeld Alana J , Bays Derek , Thompson George R , Reef Susan , Snyder Linda , Galgiani John N 
Published: October 2019

Abstract

Background
Prior studies to characterize pulmonary coccidioidomycosis (CM) have been limited by small samples. The historical VA-Armed forces CM patient group provides a unique cohort of patients not treated with conventional antifungals to better characterize and describe chronic pulmonary CM with an emphasis on chronic nodules and cavities.

Methods
A retrospective study of 374 VA-Armed forces non-disseminated CM patients diagnosed between 1955 and 1958 and followed to 1966. Patients had a pulmonary nodule or a pulmonary cavity secondary to CM. Basic demographic information, complement fixation serology, and details regarding the nodules and cavities were investigated.

Results
The studied population had a median age of 34 with 97% men and 84% white. Eighty percent had no underlying pulmonary disease and concurrent tuberculosis was the most common comorbid pulmonary condition (11%). Patients with cavities had a median complement fixation (CF) serology of 1:2 (interquartile range (IQR) negative 1:8). Patients with nodules had a median CF serology of negative (IQR negative 1:2). The median number of pulmonary nodules was 1 with a median size of 1–1.9 cm. Sixty-nine percent of the nodules had a sharp, well-defined border, while 10% had a calcified border. The median number of cavities was 1 with a median size of 3–3.9 cm. Forty-five percent of the cavity walls were thin, 31% were thick, and 19% were variable in size. Twenty-six percent of the cavities developed during acute infection with 46% developing without a prior history of primary infection. Twenty-nine percent of the cavities were stable in size, 20% increased in size, 5% disappeared, 4% ruptured, and 2% decreased in size.

Conclusion
This study helps further characterize chronic pulmonary nodules and cavities caused by CM. To the best of our knowledge, this is the largest study of the natural history of chronic CM pulmonary cavities and nodules providing valuable descriptive features.

Disclosures
All authors: No reported disclosures.
1729. Profiling Human Neutrophil Functional Responses From Solid-Organ and Stem Cell Transplant Recipients to Candida albicans
Authors: Barros Nicolas , Alexander Natalie , Viens Adam , Hopke Alex , Knooihuizen Sally , Scherer Allison , Dagher Zeina , Irimia Daniel , Mansour Michael 
Published: October 2019

Abstract

Background
Solid-organ (SOT) and stem cell transplant (SCT) recipients are at increased risk of invasive fungal disease despite normal neutrophil counts in peripheral blood. However, the neutrophils function against fungi has not been completely defined. In this study, we measure human neutrophil anti-candida activity in SOT and SCT recipients.

Methods
SOT and SCT patients were identified and consented from September 2018 until April 2019. Healthy control patients (HC) were identified at primary care clinics. EDTA-anticoagulated peripheral blood was obtained from healthy and transplant patients 2–4 months post-transplant. Neutrophils were isolated by negative selection. C. albicans was incubated for 2 hours with and without human neutrophils at multiplicity of infection (MOI) of 10, 5 and 1. Following neutrophil cell lysis, percent remaining live Candida was measured using a viability dye. In addition, growth inhibition of C. albicans by neutrophil swarming to C. albicans spotted onto glass slide arrays was also assessed by live cell imaging.

Results
22 SOT (15 kidneys, 7 livers), 20 SCT (allograft) and 22 HC were enrolled. Neutrophils from SCT and SOT had lower C. albicans killing percentages compared with HC at MOI 10 (HC: 47%, SOT: 29%, SCT 24% P = 0.0041); MOI 5 (HC: 72%, SOT: 35%, SCT 38% P < 0.0001) and MOI 1 (HC: 91%, SOT: 48%, SCT: 45% P < 0.0001). Neutrophil swarming and fungal control of C. albicans spots was significantly inhibited by neutrophils from SCT when compared with SOT and controls (P <0.0001). Analysis of medications, including tyrosine kinase inhibitor (TKI) use, did not demonstrate significant differences of a specific drug class when patient groups are compared (SCT vs. SOT).

Conclusion
Our study indicates that despite normal circulating numbers, neutrophils from SOT and SCT recipients are dysfunctional and show profoundly impaired anti-Candida activity. There were no medications or laboratory values that predicted functional neutrophil outcome. These data strongly support the use of functional neutrophil profiling to risk stratify those individuals at higher risk for invasive fungal infections.

Disclosures
All authors: No reported disclosures.
1734. Antifungal Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience in Colombia
Authors: Estacio Mayra , Rosales Joaquin , Jaramillo Francisco , Sanz Ana-Maria , Vélez Juan D , Moncada Pablo A , Rosso Fernando 
Published: October 2019

Abstract

Background
Invasive fungal infections (IFI) are significant causes of morbidity and mortality among patients with hematopoietic stem cell transplantation (HSCT). Primary antifungal prophylaxis has lowered the IFI cases however there is no clear guidance regarding which mold active agent is most useful if mold-active prophylaxis. We aim to present the incidence of IFI in patients with allogeneic HSCT, and the impact of primary antifungal prophylaxis regimen.

Methods
Retrospective cohort study. We included patients older than 18 years, with allogeneic HSCT from Fundación Valle del Lili, between January 2008 and April 2017. The patients received antifungal prophylaxis with fluconazole, itraconazole, or posaconazole from conditioning day to +100 post-transplant day. The prophylactic antifungal agent was selected according to the initial diagnosis, transplant type, conditioning regimen and the risk of developing GVHD. All patients received myeloablative conditioning regimens and were hospitalized in laminar airflow rooms during their period with neutropenia. The cases were defined according to the EORTC/MSG Consensus Group. We analyzed patients with probable or confirmed IFI, in the first 120 post-transplant days.

Results
We enrolled a total of 101 patients who received HSCT over the course of the study. The median age was 32 (23–43). Posaconazole prophylaxis was used in 73%, fluconazole in 18% and itraconazole 10% of the patients. The IFI incidence was 3.9% (4 cases) and the median time from HSCT to the diagnosis of IFI was 60 days. The percentages of patients who experienced probable IFI in the itraconazole arm was 22% (2/9 patients) and in the fluconazole arm 11.1% (2/18), there was no infection in the posaconazole group (P = 0.001). Donor sources were HLA-matched sibling (42%), Haploidentical (48%), and cord blood (10%). The cumulative incidence of grade I–IV aGVHD was 63.4% and that of grade III–IV aGVHD was 37.5%.

Conclusion
In patients undergoing HSCT posaconazole prevented invasive fungal infections more effectively than did either fluconazole or itraconazole.

Disclosures
All authors: No reported disclosures.
1747. Impact of Inappropriately Low Cytomegalovirus (CMV) Prophylaxis Dosing on CMV Outcomes Among Lung Transplant (LT) Recipients
Authors: Watts Corey , Blumberg Emily , Lee James , Claridge Tamara , Crespo Maria , Anesi Judith A , Anesi Judith A 
Published: October 2019

Abstract

Background
Valganciclovir (VGCV) and ganciclovir (GCV) are commonly used to prevent CMV in at-risk lung transplant recipients (LTRs). Because renal function changes frequently in the post-transplant setting, antiviral under-dosing may occur. We sought to determine the frequency of GCV/VGCV under-dosing and its impact on CMV-related outcomes among LTRs.

Methods
We conducted a retrospective cohort study of all adult LTRs with a CMV seropositive donor (D+) between 2014 and 2016 at the Hospital of the University of Pennsylvania. Exposed patients were those with exposure to inappropriately low-dose GCV/VGCV. Unexposed patients were those whose antiviral dosing was consistently appropriate for their creatinine clearance. We employed a multivariable Cox proportional hazard analysis to determine the impact of low-dose prophylaxis on time to CMV infection post-transplant; prophylaxis dosing was incorporated as a time-varying covariate in this survival analysis.

Results
108 adults underwent CMV D+ LT during the study period. 46 (43%) experienced low prophylaxis dosing at some point during their prophylaxis course. 47 (43%) LTRs developed CMV viremia, of which 10 (9%) were still on prophylaxis. 20 (19%) LTRs developed CMV disease and 6 (6%) had ganciclovir-resistant CMV. In the multivariable Cox analysis, we found that there was not a significant association between exposure to any low-dose prophylaxis and the hazard of CMV infection (HR = 1.001, 95% CI 0.99–1.01, P = 0.75; Table 1), even among CMV seronegative recipients (D+/R−) (HR = 1.002, 95% CI 0.99–1.01, P = 0.68). When only those who received > 28 days of low-dose prophylaxis (N = 6, 6%) were evaluated, there was a trend toward an increased hazard of CMV infection (HR = 1.001, 95% CI 0.999–1.004, P = 0.18; Table 2).

Conclusion
CMV D+ LTR are frequently exposed to inappropriately low CMV prophylaxis dosing. This does not appear to significantly increase the risk for CMV infection, though prolonged subtherapeutic exposure merits further exploration as a risk factor for CMV outcomes in higher-risk patients.

Disclosures
All authors: No reported disclosures.
1748. Incidence of Cytomegalovirus Disease and Viral Replication Kinetics in Intermediate Risk Liver Transplant Recipients Managed According to a Preemtive Therapy Algortihm
Authors: Fernández Oscar , Cuellar-Rodríguez Jennifer , Sifuentes-Osornio Jose , García Ignacio , Belaunzarán Pablo 
Published: October 2019

Abstract

Background
Cytomegalovirus (CMV) is an important opportunistic pathogen in liver transplant recipients (LTR). Risk of invasive disease is determined by CMV donor/recipient (D/R) serostatus, immunosuppression, and use of antiviral prophylaxis. Viral replication kinetics that can predict the development of CMV disease in transplant recipients are a high maximal viral load (VL) and a fast replication velocity. At our institution LTR at intermediate risk for CMV disease (CMV D/R+) are managed following a preemptive therapy algorithm (the pre-established cutoff for treatment initiation is 4,000 IU/mL). The primary endpoint of this study was to determine the incidence of early CMV disease in CMV D/R+ LTR. Secondary endpoints were to calculate the period of maximal VL and viral kinetic parameters.

Methods
We performed a retrospective observational study of CMV D/R+ LTR. Patients were followed for 6 months after transplantation. We calculated the incidence of CMV disease. Viral kinetic parameters calculated were the VL duplication time (Td) and the basic reproductive number (R0). For the assessment of viral kinetics we used the maximal VL of 10 patients who had a VL determined within the previous week.

Results
Forty CMV D/R+ LTR were included. The median age was 52 years, 65% were women. The mean MELD score was 18, 83% of patients had decompensated cirrhosis. No patient developed CMV disease during the first 6 months after LT. Nineteen patients (47%) had CMV DNAemia, but only 8 (20%) required antiviral therapy. The highest VLs were observed during the second month after transplant. The median duplication time was 2.14 days. The median R0 was 1.46.

Conclusion
Although limited by our sample size, our algorithm appears useful for discriminating the patients who need antiviral treatment from those who will only have asymptomatic DNAemia. The study population VL, Td and R0 behave as described by other groups, which emphasizes the need for frequent monitoring. This is a challenge for CMV prevention in resource-limited countries.

Disclosures
All authors: No reported disclosures.
1759. Incidence of Hospitalizations and Emergency Department Visits for Herpes Zoster in Immunocompromised and Immunocompetent Adults in Ontario, Canada, 2002–2016
Authors: Buchan Sarah , Wang John , Wilson Sarah , Wormsbecker Anne E , Garber Gary , Daneman Nick , Deeks Shelley 
Published: October 2019

Abstract

Background
Adults with immunocompromising conditions are at increased risk of herpes zoster (HZ) infection and related complications. We aimed to assess the incidence of HZ seen in hospital or emergency department in immunocompromised populations and compare it to that of immunocompetent populations.

Methods
Using healthcare administrative data, we calculated incidence rates (IR) of HZ in Ontario, Canada between April 1, 2002 and August 31, 2016 in adults ≥18 years categorized as immunocompromised or immunocompetent. We repeated these analyses by type of immunocompromising condition and provided incidence rate ratios (IRR) comparing to immunocompetent adults. We also calculated IRs and IRRs of HZ complications by immunocompromised status.

Results
There were 120,654 incident cases of HZ seen in hospital or emergency department during the study period. Immunocompromised adults accounted for 13% of these cases despite representing only 3% of the population. The risk of HZ was higher for immunocompromised adults compared with immunocompetent (IRR = 2.8, 95% CI 2.8–2.9) and ranged across type of immunocompromising condition (from 2.4 [95% CI 2.3–2.5] in those with a solid tumor malignancy to 11.0 [95% CI 10.0–12.0] in those who had undergone a hematopoietic stem cell transplant). The risk of any HZ complication was also higher in immunocompromised adults (IRR = 3.5, 95% CI 3.4–3.6) and was highest for disseminated zoster (IRR = 31.5, 95% CI 26.3–37.5).

Conclusion
The risk of HZ and related complications was higher in immunocompromised populations compared with immunocompetent. Our findings underscore the high-risk nature of this population and the potential benefits that may be realized through HZ vaccination of this group.

Disclosures
All authors: No reported disclosures.
1765. BK Polyomavirus Reactivation Outcomes After Renal Transplantation in Association With Adherence to a Standardized BK Polyomavirus Screening Protocol: A Multi-Center Collaboration
Authors: Rogers Ralph , Chobanian Michael , Gilligan Hannah , Goyal Nitender , Rodig Nancy , Rossi Ana , Sabrina Tan Chen , Pavlakis Martha 
Published: October 2019

Abstract

Background
Reactivation of BK polyomavirus (BKPyV) due to immunosuppression after renal transplantation can lead to allograft nephropathy (BKAN) or even allograft loss. Many transplant centers implement screening protocols in an attempt to detect BKPyV reactivation before progression to BKAN, although the frequency and duration of screening vary widely among centers.

Methods
The New England BK Consortium (NEBKCON), a collaboration of 12 transplant centers in the northeastern United States, has adopted a standard BKPyV screening protocol (screening monthly for the first 6 months followed by screening every 3 months until 2 years after transplantation). Participating members implemented this screening protocol at their centers, and later measured adherence to the protocol as part of a NEBKCON quality improvement project. This study retrospectively analyzes BKPyV-specific outcomes in association with adherence to this protocol.

Results
Six centers reported data on 472 subjects who received a renal transplant between January 2016 and December 2017. Adherence to the screening protocol during the first 12 months (7.1–76.7%, mean 56.1%) and 24 months (2.9–52.5%, mean 36.8%) after transplant varied between centers. Rates of BKPyV viremia (3.6–28.2%, mean 20.6%) as well as BKAN (0–4.5%, mean 3.2%) also varied among centers. Adherence to the screening protocol was associated with a decrease in the magnitude of the initial viral load detected (3.29 vs. 3.74 log10 copies/mL, P = 0.065), but was not associated with peak viral load (3.95 vs. 4.14 log10 copies/mL, P = 0.47), viremia duration (179 vs. 196 days, P = 0.74), or incidence of BKAN among viremic subjects (15.3 vs. 16.0%, P = 0.91).

Conclusion
Even with a uniform screening protocol for BKPyV in place, adherence to this protocol varied widely among centers. More research is needed to determine patient-level and center-level barriers to adherence, as well as to determine optimal screening practices to further reduce the incidence of BKAN.

Disclosures
All authors: No reported disclosures.