bluuebunny/crossref_metadata_2025_split huggingface dataset:
1693. Risk Factors Associated with Mortality of Invasive Aspergillosis in King Chulalongkorn Memorial Hospital
Authors: Jutivorakool Kamonwan , Tirastittam Praeopat 
Published: October 2019

Abstract

Background
Invasive aspergillosis is the serious fungal infection that often found in the immunocompromised host such as hematologic malignancy, bone marrow transplantation, organ transplantation, and patient who received chemotherapy. Nowadays the patient who diagnosed with invasive aspergillosis has a high mortality rate of 50–60%. There were some studies about the risk factor of mortality of invasive aspergillosis but most of them were not in Thailand. The objective of this study was to identify risk factors related to mortality and the mortality rate of invasive aspergillosis in King Chulalongkorn Memorial Hospital.

Methods
The retrospective study by collected and analyzed the data from medical record by ICD 10, between 1 January 2012 and 30 October 2017.

Results
Total patients were 176 patients; the mortality rate of invasive aspergillosis patient was 46%. The most common underlying condition was AML (27.8%). The risk of invasive aspergillosis was prolonged neutropenia (31.3%), prolonged corticosteroid therapy 27.8% and induction phase chemotherapy 22.7%. The most infection site was the pulmonary system at 80.1%, sinus 13.6%, and CNS 5.7%. The significant factor which affect the mortality rate was cirrhosis [HR 4.21, 95% CI 1.46–11.69, P = 0.008], HIV infection/AIDS [HR 3.24, 95% CI 1.03–10.24, P = 0.045], tracheal infection [HR 21.81, 95% CI 1.48–320.41, P = 0.025] and empirical treatment with itraconazole [HR 11.65, 95% CI 3.14–43.17, P ≤ 0.001]

Conclusion
The Risk factors associated with mortality of invasive aspergillosis in King Chulalongkorn Memorial Hospital was cirrhosis, HIV infection/AIDS, tracheal infection, and the empirical treatment with itraconazole. The overall mortality rate of invasive aspergillosis was 46%.

Disclosures
All authors: No reported disclosures.
1696. Epidemiology, Clinical Characteristics and Outcomes of Invasive Aspergillosis in a Tertiary Care Hospital in Mexico
Authors: Marina Román-Montes Carla , Gonzalez-Lara María F , Ponce de Leon Alfredo , Valenzuela-Almada Maria O , Rangel-Cordero Andrea 
Published: October 2019

Abstract

Background
Invasive aspergillosis is an important cause of life-threatening infection in immunocompromised patients. The objective was to describe the epidemiology, clinical characteristics, and outcome of patients with invasive aspergillosis (IA) in a tertiary care center in Mexico.

Methods
A laboratory-based survey was done to identify patients with positive Aspergillus culture or galactomannan from 2014 to 2018. The medical records were reviewed to include patients with proven and probable IA, according to the EORTC criteria. Descriptive analysis of clinical characteristics and risk factors for 6-week mortality was made through X2, T-test or Mann–Whitney test. A multivariate logistic regression model including variables with a P-value of <0.2 in univariate analysis was made.

Results
240 cases of IA were identified: 193 (80%) probable, 27 (11%) proven, and 20 (8.3%) not meeting the EORTC criteria but considered infection. 53% were male, median age was 44 years (IQR 28–58), 78 (32.5%) had acute leukemia (AL), 42 (17.5%) hematological neoplasia, 29 (12%) hematopoietic stem-cell transplant (HSCT), 25 (10.4%) solid-organ transplant and 44 (18.3%) autoimmune diseases, 17.5% patients with AL underwent induction remission chemotherapy of which 31% received antifungal prophylaxis. Among patients with IA, 183 (82%) had a positive galactomannan and 109 (45%) had a culture with Aspergillus. Eleven had > 1 species: 55/120 (46%) were A. fumigatus, 18 (15%) A. niger and 18 (15%) A. flavus. Pulmonary disease occurred in 214 (89%). 212 patients (88%) received antifungal treatment with a median duration of 42 days (IQR 20–42). 129 (61%) received voriconazole (VRC), 20 (8.3%) Amphotericin B and 20(8.3%) were randomized to a posaconazole vs. VRC trial. Six-week mortality was 35% (n = 85). Lymphopenia (OR 3.6; 95% CI 1.4–9.0), liver failure (OR 3.3; 95% CI 1.7–6.5) and older age (OR 1.03; 95% CI 1.01–1.05) (marginally) were independently associated with increased 6-week mortality.

Conclusion
240 patients with IA were identified in a 5-year period in a tertiary care center. Most had hematological neoplasias and low prevalence of antimold prophylaxis due to economical reasons. Six-week mortality was 35%, nonsurvivors had liver failure and lymphopenia more often. Increased awareness to prevent IA is needed.

Disclosures
All authors: No reported disclosures.
1706. Use of Management Bundles as a Checklist for Candidemia: Impact of Compliance on Clinical Outcomes in a Multicenter Study in Japan
Authors: Ueda Takashi , Takesue Yoshio , Nakajima Kazuhiro , Miyazaki Taiga , Nakada-Motokawa Nana , Mikamo Hiroshige , Yamagishi Yuka , Nagao Miki , Kawamura Hideki , Kakeya Hiroshi , Yamada Koichi , Miyazaki Yoshitsugu 
Published: October 2019

Abstract

Background
We previously developed management bundles for candidemia and beneficial effects on clinical outcomes were shown in compliant patients (JAC 2015). However, there is a risk for bias because some elements cannot be achieved in patients who have an early death.

Methods
Patients with candidemia who were treated at six medical centers between 2015 and 2017 were prospectively evaluated. Bundle elements consisted of removal of central venous catheters within 24 hours, initial appropriate selection and dosing of antifungals, an ophthalmological examination, follow-up blood cultures, consideration of alternative antifungals on the 3rd to 5th days, and at least 2 weeks of therapy. To exclude bias by early death, we investigated the clinical results in patients who survived ≥2 weeks.

Results
Among 221 patients with candidemia, 190 patients were analyzed (31 patients were excluded because of early death). Clinical success and the 28-day mortality rate were 77.4% (171/221) and 22.2% (49/221) in all patients with candidemia and 88.9% (167/190) and 9.5% (18/190) in eligible patients, respectively. Compliance in achieving all bundle elements was accomplished in 67.9% of eligible patients. In multivariate analysis, compliance with the bundles was an independent factor for 28-day mortality (4.7% vs. 19.7%, odds ratio 0.19, 95% confidence interval 0.05–0.63). However, compliance did not affect clinical success (92.2% vs. 82.0%, odds ratio 2.13, 95% CI 0.77–5.86). Non-Candida albicans, disseminated candidiasis, and total parenteral nutrition were independent factors for poor clinical success. Severe severity and total parenteral nutrition were independent factors for 28-day mortality.

Conclusion
With prospective use of bundles as a checklist in patients with candidemia, compliance of bundles has a beneficial effect on clinical outcomes. This research was supported by AMED (JP18fk0108045).

Disclosures
All authors: No reported disclosures.
1719. Incidence and Characterization of Invasive Fungal Infections (IFIs) in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Ibrutinib (IBR)
Authors: Frei Michael , Aitken Samuel L , Aitken Samuel L , Jain Nitin , Thompson Philip , Wierda William G , Kontoyiannis Dimitrios P , DiPippo Adam 
Published: October 2019

Abstract

Background
IBR is a Bruton’s tyrosine kinase inhibitor, and plays a key role in the treatment of CLL. In randomized clinical trials, <1% of IBR-treated CLL patients developed IFIs. However, several IFIs were reported with real-life use of IBR.

Methods
This is a retrospective observational study of all CLL patients (> 18 years) treated with IBR (2/2014–8/2018) at MD Anderson Cancer Center. We excluded patients with active IFI (proven and probable, EORTC/MSG criteria) at the start of IBR and patients with <6 months of follow-up.

Results
Of the 821 CLL IBR-treated patients, 24 developed probable or proven IFI (2.9%). Of these infections, 21 occurred within 30 days (d) of last IBR dose, while 3 IFIs occurred at 94, 135 and 221 d post IBR, respectively. The majority of patients with IFI were male (83%) with a median age of 66 years at IFI diagnosis. The median prior lines of therapy for CLL was 1 (range 0–7), with 29% receiving IBR as frontline treatment. Five patients had evidence of Richter’s transformation at the time of IFI diagnosis, while two patients had prior stem cell transplant. The average time from start of IBR to diagnosis of IFI was 338 d, with only 7 cases of IFI within the first 3 months of IBR. The majority of IFIs were proven/probable aspergillosis (63%), including 9 cases of Aspergillus fumigatus. The remaining infections consisted of Cryptococcus neoformans (21%), Fusarium spp. (8%), with one case each of candidiasis, histoplasmosis, mucormycosis, and Pneumocystis jiroveci pneumonia. Three patients had evidence of poly-fungal IFI. The sites of infection were pulmonary (88%), blood (13%), CNS (13%), and sinus (8%). Five patients were diagnosed with disseminated IFI, including Cryptococcus spp. (2 cases), Rhizopus spp., Aspergillus spp., and Candida spp. The 42-day mortality rate post IFI diagnosis was 25%.

Conclusion
We report the largest single-center cohort of CLL patients on IBR to date. The IFI incidence of 2.9% (24/821) is consistent with most previous reports estimating a 0.5–4% incidence. In contrast to published reports, close to 1/3 of our patients with IFI received IBR as frontline therapy and most IFIs (71%) were diagnosed > 3 months after starting IBR. We are currently conducting a case–control comparison with IBR–treated CLL patients with no infection to uncover risk factors associated with IFIs in these patients.

Disclosures
Samuel L. Aitken, PharmD, Melinta Therapeutics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.
1741. Invasive Fungal Infections in Patients with Multiple Myeloma in the Era of Novel Therapies
Authors: Baneman Emily , Chari Ajai , Rana Meenakshi , Dunn Dallas , Sullivan Timothy , Taimur Sarah , Sanchez Larysa , Jacobs Samantha E 
Published: October 2019

Abstract

Background
Rapid advances in multiple myeloma (MM) therapy have led to improved survival, yet the impact of novel agents on the risk of invasive fungal infection (IFI) is largely unknown. We aim to describe the epidemiology of IFIs in MM patients in the current era of chemotherapy.

Methods
We performed a retrospective chart review of MM patients at Mount Sinai Hospital in New York, NY who entered care between December 2009 and October 2016 and had proven or probable IFI between January 2011 and October 2017. Probable and proven IFIs were defined by revised EORTC/MSG criteria. Descriptive statistics are reported as median (range). We evaluated factors associated with mortality by univariate analysis using Fisher’s exact and Mann–Whitney U tests.

Results
2,960 MM patients entered care during the study period. We identified 30 episodes of IFI among 29 patients. Median age was 59 (42–80) years and 21 (70%) were men. IFI occurred at a median of 3.7 (0.3–18) years from MM diagnosis. At the time of IFI diagnosis, patients had received a median of 4 (1–12) lines of chemotherapy, 18 (60%) had undergone autologous stem cell transplant (ASCT), and 21 (70%) had progressive disease status. Agents received immediately prior to IFI were immunomodulators (n = 14), proteasome inhibitors (n = 14), conventional chemotherapy (n = 11), monoclonal antibodies (n = 6), checkpoint inhibitors (n = 3) and other (n = 3). Twenty-two (73%) patients received corticosteroids in the prior 30 days. Neutropenia and lymphopenia were present in 12 (40%) and 13 (43%) patients, respectively. There were 9 proven and 21 probable IFIs: invasive aspergillosis (n = 19), candidemia (n = 5), cryptococcosis (n = 3), talaromycosis (n = 1), mucormycosis (n = 1) and other (n = 2). Bacterial and viral respiratory co-infections occurred in 7 and 4 patients, respectively. Eight (27%) patients required ICU admission and 9 (30%) died within 30 days of IFI diagnosis. In univariate analysis, number of lines of chemotherapy (P = 0.05), progressive disease status (P = 0.03), and prior ASCT (P = 0.004) were associated with 30-day mortality.

Conclusion
IFIs are uncommon in MM patients receiving newer agents but are associated with significant morbidity and mortality. Further study is needed to identify high-risk subgroups that may benefit from antifungal prophylaxis or increased surveillance.

Disclosures
All authors: No reported disclosures.
1743. Impact of Cytomegalovirus Serostatus on Allograft Loss and Mortality within the First Year after Kidney Transplantation: An Analysis of the National Transplant Registry
Authors: Bruminhent Jackrapong , Dajsakdipon Thanate , Watcharananan Siriorn 
Published: October 2019

Abstract

Background
Cytomegalovirus (CMV) infection is one of the leading causes of morbidity and mortality in kidney transplant (KT) recipients. We investigated the association of CMV serostatus and allograft outcome within the first year after KT.

Methods
All KT recipients from 2007 to 2017 were derived from the Thai Transplant Registry. The prevalence of allograft loss and mortality within the first year after KT was estimated by Kaplan–Meier analysis. CMV serostatus of the donor (D) and the recipient (R) was assessed as a prognostic factor of allograft loss and mortality by Cox proportional hazards models.

Results
During a 10-year study period, the population consisted of 4,556 KT recipients with a mean ± SD age of 43 ± 14 years and 63% were male. Fifty-two percent underwent deceased donor KT and 58% received induction therapy. Among 3,907 evaluable patients, the CMV seroprevalence were D+/R+ (88.9%), D+/R− (6.1%), D−/R+ (2.9%), and D−/R− (1.9%). The estimated prevalence of allograft loss and mortality within the first year were 3.8 and 2.8%, respectively. In univariate analysis, CMV D+/R- was significantly associated with mortality within the first year after KT [hazard ratio (HR), 2.10; 95% confidence interval [CI], 1.18–3.75 (P = 0.01)] however not with an allograft loss [HR, 1.51; 95% CI, 0.85–2.66 (P = 0.16)]. In multivariate analysis, CMV D+/R- serostatus was associated with mortality within the first year after KT [HR, 2.04; 95% CI, 1.05–3.95 (P = 0.04)]. Other independent prognostic factors for mortality were older recipient age, deceased donor KT, and hemodialysis after KT (Table 1).

Conclusion
In the setting where the donor and recipient CMV seropositivity is predominant, CMV seromismatch still negatively affects patient survival within the first year after KT.

Disclosures
All authors: No reported disclosures.
1744. CMV Infection and Management Among Pediatric Solid-Organ Transplant Recipients
Authors: Sharova Anna , Galetaki Despoina M , Hayes Molly , Gianchetti Lauren , Vella Laura A , Downes Kevin J , Downes Kevin J 
Published: October 2019

Abstract

Background
Our institution provides universal CMV prophylaxis (PPX) for all high (D+/R-) and medium risk (R+) solid-organ transplant (SOT) recipients. We sought to evaluate this practice by assessing CMV infection and disease within the first year of SOT.

Methods
Retrospective cohort study of all children undergoing first SOT at Children’s Hospital of Philadelphia from January 2012 to October 2017. We identified recipients with CMV infection (detection of CMV DNA in body fluid/tissue with or without symptoms) and disease (symptomatic or tissue-invasive infection) in the first year after SOT. We calculated the rate of CMV infection and compared CMV-free survival based on SOT type and CMV risk using log-rank tests.

Results
244 children received 246 SOTs: 90 liver, 70 kidney, 59 heart, 27 lung. In total, 39 children (16%) had 49 CMV infections in the first year after SOT, including 29% of high (n = 21/72) and 23% of medium risk recipients (n = 16/69). The fraction of each organ type with CMV infection was similar (Figure 1, P = 0.33). Among high and medium risk recipients, all of whom received PPX, the incidence rate of CMV infection in the first year post-SOT was similar: 10.1 vs. 7.8/10,000 days (P = 0.22). There were no differences in CMV-free survival by organ (Figure 2, log-rank P = 0.25) or between high and medium risk recipients (Figure 3, log-rank P = 0.46). In total, 22% (n = 10/45) of CMV infections in high/medium risk patients occurred while on PPX; half were in the setting of reduced PPX dosing or within 2 weeks of SOT. Of the 35 CMV infections post-PPX, the median time to detection of CMV after PPX was 39 days (IQR 28–98). There were 11 cases (6 high, 5 medium risk) of CMV disease: 6 CMV syndrome, 2 hepatitis, 2 pneumonitis, 1 GI disease. Valganciclovir was more often used for treatment of asymptomatic infections than for CMV disease (79% vs. 33%, P = 0.03). All-cause mortality in the first year post-SOT was similar among those with and without CMV infections (7.7 vs. 6.3%, P = 0.76) and among those with and without CMV disease (9.1 vs. 5.2%, P = 0.57).

Conclusion
CMV infection was common in high and medium risk SOT recipients in the first year following SOT, and most infections occurred off of PPX. Our data suggest that the highest risk period for CMV infection is in the first months after PPX, and that monitoring may be most useful after PPX has been stopped or when PPX doses are reduced.

Disclosures
Kevin J. Downes, MD, Merck: Grant/Research Support, Research Grant; Pfizer: Grant/Research Support.
1752. Differential Degree and Duration of Cytomegalovirus (CMV) Viremia Between WHO International Standard-Calibrated Quantitative CMV Nucleic Acid Tests: Implications for Clinical Care
Authors: Meesing Atibordee , Yao Joseph D , Germer Jeffrey , Gartner Michelle , Digmann Benjamin , Razonable Raymund R 
Published: October 2019

Abstract

Background
Quantitative nucleic acid amplification (QNAT) tests are cornerstone for the management of CMV disease after organ transplantation. We assessed the potential impact of viral load results obtained by two commercial WHO international standard-calibrated NAT in solid-organ (SOT) and hematopoietic stem cell transplant (HSCT) recipients.

Methods
Sixty-four patients (36 SOT and 28 HSCT) had plasma CMV viral load assessed using the COBAS AmpliPrep/COBAS TaqMan CMV Test (CAP/CTM; lower limit of quantification [LLoQ] at 137 IU/mL) and cobas 6800 System (cobas CMV; LLoQ at 35 IU/mL). Viral load values were correlated with clinical course and outcomes.

Results
Forty-three of 64 patients (67.2%) had CMV infection or disease (asymptomatic, 67.4%; gastrointestinal disease, 16.3%; pneumonitis 4.7%) at median of 4.4 months (IQR 1.4 to 7.7) from transplantation. At CMV infection diagnosis, viral load results (mean ± SD) were almost two-fold higher when measured by cobas CMV (19,456 ± 51,618 IU/mL) compared with CAP/CTM (10,504 ± 27,744 IU/mL; P = 0.04). Time to onset of CMV viremia was significantly shorter (11.5 days; P < 0.001) while viral clearance was significantly longer (12.75 days; P < 0.001) by cobas CMV when compared with CAP/CTM. Persistent viremia was observed with cobas CMV in 44% of patients at the time of first negative results by CAP/CTM. Patients with negative results by cobas CMV at the end of antiviral treatment had a significantly lower need for re-treatment (OR 0.26, 95% CI 0.04 to 0.99, P = 0.05).

Conclusion
Our study highlights significant differences between CMV QNAT assays despite calibration to the WHO-international standard. The significant differences in the degree (almost two-fold), time to onset (12 days difference) and clearance (13 days difference) of CMV viremia between two automated commercial QNAT assays have direct implications in the care of transplant recipients. Persistence of low-level viremia was observed in samples that reached negative threshold by CAP/CTM, when tested using the more sensitive cobas CMV. Clearance of CMV viremia, when assessed by the more sensitive cobas CMV, was significantly associated with a lower need for re-treatment.

Disclosures
All authors: No reported disclosures.
1762. Genotype Prevalence and Molecular Characteristics of Human Adenovirus in Pediatric Hematopoietic Stem Cell Transplant Recipients
Authors: Blumenstock Jesse , Galetaki Despoina M , Boge Craig L K , Shuster Sydney G , Seif Alix , Petersen Hans , Maria Cardenas Ana , Fisher Brian T , Kajon Adriana 
Published: October 2019

Abstract

Background
Human adenovirus (HAdV) is a documented source of morbidity and mortality after hematopoietic cell transplant (HCT); however, there are limited data documenting HAdV species and type in this population. Understanding the molecular characteristics of HAdV could inform the development and assessment of interventions. The species and type of HAdV-positive specimens are detailed using an archived convenience sample of specimens obtained in pediatric HCT recipients.

Methods
The cohort included autologous and allogeneic HCT recipients between January 2000 and December 2013. An archived clinical repository of frozen specimens was interrogated to identify residual HAdV-positive specimens, which were sent to Lovelace Respiratory Research Institute (LRRI) to determine species and type. Medical chart review was performed to determine whether an isolate was related to HAdV disease or HAdV-attributable death.

Results
There were 547 HAdV PCR-positive clinical specimens from 87 HCT recipients. Of the 547 specimens, 289 were identified from an archived repository and sent to LRRI to determine species and type, and HAdV was successfully isolated and typed from 61 (Figure 1). Species C was the most common species (59.0%) with C2 being the most frequent type (34.4%). Of the 15 recipients with type C2, plasma was the most common specimen source (57.1%). Three recipients with C2 had this species and type detected from multiple sources (Tables 1 and 2). Among those with a typing result, type C2 also was responsible for 33.3% of all HAdV-attributed disease and 38.1% of all HAdV-attributed death.

Conclusion
Species C was the most common species to be isolated in a convenience sample of HAdV-positive clinical specimens from a single-center cohort of pediatric HCT recipients. Type C2 was most commonly associated with HAdV disease and attributable death. These results suggest HAdV species and type influence the impact of HAdV in this patient population. The findings need to be confirmed in prospective cohorts but suggest real-time molecular typing may be relevant and provide possible targets for the development of future interventions. These results must be interpreted with caution; not all clinical specimens were available for molecular typing, and it is possible C2 is easier to isolate from archived specimens.

Disclosures
All authors: No reported disclosures.