bluuebunny/crossref_metadata_2025 huggingface dataset:
1679. Brucellosis in rural Narok County, Kenya: A Retrospective Review
Authors: Bailey Pamela , Doern Christopher
Published: October 2019

Background

It is well-documented that the country of Kenya is confronted with a heavy burden of brucellosis, presumably related to consumption of unboiled or fermented milk products (maziwa lala). As a developing country, epidemiologic data defining the prevalence of brucellosis is incomplete and particularly lacking in rural areas of the country. The objective of this study was to establish the rate of brucellosis in patients seen in a rural health clinic in Narok County, an area which has not been previously studied.

Methods

This study was performed at the Ewaso Ngiro Health Center, Narok County, Kenya, which serves a catchment area of 6,573 citizens. A retrospective chart review was conducted for 241 patients seen in December 2018 for acute visits. Medical records were reviewed for evidence of joint pain and other symptoms of brucellosis at the time of presentation and for brucellosis antigen testing results.

Results

Of the 241 patient charts reviewed, 78 (71 adult, 7 pediatric) patients had joint pain. Of the 71 adult patients, 21 were male and 49 were female (1 with no gender recorded). 50 patients had Brucella testing performed via serum agglutination, and yielded 14 positive results (13 adult, 1 pediatric). Confirmed brucellosis accounted for 5.8% of all acute visits in December 2018, and 26% of patients presenting with joint pain. In patients with confirmed brucellosis, the average age was 50.2 years (ranging 15–80). There were 8 female cases, 5 male, 1 with gender not recorded. Generalized joint pain was the most common complaint (n = 14), followed by back (n = 6), knee (n = 1), and neck pain (n = 1).

Conclusion

The prevalence of Brucella disease in rural areas of Kenya, specifically Narok County, is not well studied. This study provides insight into the prevalence of brucellosis and shows that over 25% of patients presenting with joint pain, have brucellosis. Furthermore, 5.8% of all patients seen at the Ewaso Ngiro Health Center during the study period had brucellosis and the overall prevalence of disease in patients who were tested specifically for brucellosis (n = 50), was 28%. This study provides preliminary evidence of a heavy burden of Brucella disease in Narok County and suggests that a follow-up study in this area is warranted to be defined the true prevalence of disease over a longer time frame.

Disclosures

All authors: No reported disclosures.
1682. Dengue Fever Outbreak Investigation in Upper Egypt in 2015
Authors: Mohammed. Ibrahim Hamdi , Khalil Mahmoud , Elsawy Mohamed , Samir. Ismail Mohamed , Alfishawy Mostafa
Published: October 2019

Background

Surveillance is the backbone of infectious diseases control but an outbreak of a new pathogen to a developing country may have devastating consequences given less prepared healthcare systems in such countries. In October 2015, there was a sharp rise of febrile illnesses reported in Dairot Fever Hospital which prompted the general department for fever hospitals in the Egyptian ministry of health (MOH) to constitute a scientific committee for field visit study in Dairot fever hospital.

Methods

The committee held meetings at Dairot fever hospital, educated local healthcare providers, examined all isolated patients and requested samples of 118 isolated patients to be sent to central laboratories of MOH. Entomological services were also part of the committee and surveillance was started in the affected area.

Results

Out of 118 samples, 28 came back positive for Dengue virus type 1 by ELISA and PCR. Entomological surveillance revealed the presence of Aedes aegypti larvae and adult mosquito at the sites where cases were living; consequently, entomological control measures for dengue vector were immediately set leading to a dramatic decline in the density of adult mosquito (from 23% to 0%) and larvae (from 25% to 0.5%).

Conclusion

The prompt response of the MOH in Egypt led to rapid control of Dengue fever outbreak but educating healthcare workers about possible imported infectious diseases would have halted the outbreak much earlier which shows the importance of Infectious Diseases training in developing countries.

Disclosures

All authors: No reported disclosures.
1688. Invasive Ocular Candidiasis: Who Is Really at Risk?
Authors: Seidelman Jessica , Fleece Molly E , Yang Wesley Z , Bloom Allison , Lydon Emily , Arnold Christopher , Weber David J , Okeke Nwora L
Published: October 2019

Background

The Infectious Disease Society of America recommends that all patients with candidemia undergo a dilated retinal examination to exclude invasive ocular candidiasis. However, it remains unclear whether there are patients with candidemia who do not warrant routine surveillance because the risk of ocular infection is low.

Methods

We conducted a retrospective cohort study of all patients with candidemia diagnosed at three academic medical centers (Duke, University of North Carolina and University of Virginia) from 2012 to 2017. We collected risk factors for invasive ocular candidiasis based on previous literature and compared them between patients with and without invasive ocular candidiasis. We then built a multivariate logistic regression model to assess which risk factors were significant for developing invasive ocular candidiasis.

Results

Overall, 942 patients were diagnosed with candidemia over the study period. The mean age was 55.9 years, 56% were men, 25% were non-White. Among these patients, 120 (13%) were also diagnosed with invasive ocular candidiasis, 10% with chorioretinitis and 3% with vitreous involvement. In our logistic regression analysis, central venous catheter presence [OR 8.35 (3.53, 19.77)], intravenous drug use [OR 5.02 (2.63, 9.58)], immunosuppression [OR 2.40 (1.55, 3.70)], total parenteral nutrition [OR 2.28 (1.42, 3.66)], non-White race [OR 1.65 (1.07, 2.55)], older age [OR 1.02 (1.01, 1.03)],and female gender [OR 0.57 (0.37, 0.89)] were risk factors for developing invasive ocular candidiasis. In addition, we found that persons with candidemia due to C. albicans were more likely to have invasive ocular candidiasis [OR 1.86 (1.22, 2.85)].

Conclusion

This cohort represents the largest study of patients with candidemia who developed invasive ocular candidiasis to date. Based on our findings, clinicians should develop targeted and cost-effective strategies for endophthalmitis screening.

Disclosures

All authors: No reported disclosures.
1689. Active, Invasive Fungal Infection, and Hematopoietic Cell Transplantation (HCT) in Chronic Granulomatous Disease (CGD): Presentation, Procedure, and Outcomes
Authors: Parta Mark , Zerbe Christa , Holland Steven M , Malech Harry , Kang Elizabeth M
Published: October 2019

Background

Individuals with CGD develop invasive fungal infections which are often refractory to medical therapy. Disease caused by Aspergillus nidulans (An), Scedosporium apiospermum (Sa), and Aspergillus viridinutans (Av), can be fatal due to involvement of structures contiguous to the primary pulmonary infection. Protocols for managing an active fungal infection during HCT are lacking. Here we describe 5 patients transplanted with active fungal infection and the treatments ancillary to HCT that led to successful outcomes.

Methods

Four males and one female underwent peripheral blood HCT utilizing 3 different transplant platforms. Granulocyte transfusions (GCT) were used in 4 cases.

Results

Antifungal treatment and transplant outcomes are reported in Table 1. Patients 1 (Figure 1) and 4 (previously reported) had Sa infection of the lung and spine and lung and pericardium, respectively. Patients 2 (Figure 2) and 5 had An pneumonia with spinal and sternal involvement, respectively. Patient 3 had Av pneumonia involving the lower lung and diaphragm (Figure 3). The transplant protocol was modified to include a high stem cell dose to facilitate engraftment and post-transplant cyclophosphamide GVHD prophylaxis. No GCTs were used proximal to or during HCT due to the development of antineutrophil antibodies.

Conclusion

Active fungal infection can be managed during HCT. Combination therapy (GCTs and antifungals) lessened the burden of disease prior to and during HCT. All patients had clinical resolution of their infection post-HCT and successful engraftment. Bone disease stabilized post-HCT and remineralization occurred. One patient was successfully transplanted without GCT and its potential complications.

The authors have no conflicts to report.

Disclosures

All authors: No reported disclosures.
1693. Risk Factors Associated with Mortality of Invasive Aspergillosis in King Chulalongkorn Memorial Hospital
Authors: Jutivorakool Kamonwan , Tirastittam Praeopat
Published: October 2019

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

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

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

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

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

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

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

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

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.
1763. The Use of Haploidentical Donors Compared with HLA-Matched Unrelated Donors is Associated with Increased Risk of BK Viruria and Hemorrhagic Cystitis
Authors: Morgan. Scott Mary , Slade Michael , Lawrence Steven
Published: October 2019

Background

BK virus-associated hemorrhagic cystitis (BK-HC) is a common and often serious complication of hematopoietic cell transplantation (HCT). Studies have suggested a higher incidence of BK-HC in patients receiving haploidentical (haplo) HCTs compared with those receiving matched unrelated donor (MUD) transplants.

Methods

We retrospectively identified all adult patients receiving HCT from MUD or haplo donors at Washington University School of Medicine between January 1, 2011 and January 1, 2016. Via informatics queries, we obtained the results of every urine BK test performed on these patients. Patients with BK viruria were then evaluated for BK-HC and graded according to established criteria. The last day of follow-up was April 31, 2017.

Results

503 MUDs and 140 haplos were identified for inclusion in the study. Haplo patients were significantly more likely to be nonwhite (21% vs. 5%, P < 0.001) and were younger (median age: 51.5 vs. 55, P = 0.01). Conditioning regimens were also significantly different; haplos were less likely to receive myeloablative conditioning (44% vs. 57%, P < 0.001) and busulfan-based conditioning (13% vs. 39%, P < 0.001), but were more likely to receive total body irradiation-based conditioning (83% vs. 26%, P < 0.001). Haplos were also more likely to have undergone previous allogeneic HCT (26% vs. 6%, P < 0.001). The cumulative incidence of both BK viruria and BK-HC were significantly higher in haplos (both P < 0.001). This was observed at 100 days, 180 and 365 days (Table 1).

Conclusion

We found a significantly higher incidence of both BK viruria and BK-HC in patients receiving haplo HCT compared MUD HCT. Significant demographic and clinical imbalances exist between our two cohorts and attribution of increased risk for BK-HC to donor type vs. other factors should be further explored.

Disclosures

All authors: No reported disclosures.
1767. Incidence of Respiratory Syncytial Virus Infection among Adults Undergoing Hematopoietic Stem Cell Transplantation: A Prospective Study from India
Authors: Abdul Samad Sameer , Dar Lalit , Kumar Lalit , Brijwal Megha , Choudhary Aashish , Ray Animesh , Jethani Jyoti
Published: October 2019

Background

Respiratory Syncytial Virus (RSV) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients; progression from Upper Respiratory Tract Infection (URI) to Lower Respiratory Tract Infection (LRTI) may occur in 30%–40% of transplant recipients with associated high fatality. Data on disease burden due to RSV among adult HSCT recipients is limited with no earlier reports from India.

Methods

We prospectively studied 50 HSCT recipients who underwent hematopoietic stem cell transplantation at our institute from January 2017 onwards. Patients were followed up for a period of 18 months post-transplant, initially during stay in transplant unit and subsequently on out-patient basis and telephonically for any episode of acute respiratory tract infection. Information on symptoms and signs at presentation as well as basic hematological and radiological investigations were collected. Nasal and throat swabs from symptomatic patients were taken in viral transport medium and tested for RSV by real-time RT–PCR. As per institute policy patients had received prophylaxis with acyclovir and itraconazole till day +30 post-transplant.

Results

A total of 68 episodes of acute respiratory tract infection were tested for RSV during the follow-up period (mean ± standard deviation = 12 ± 5 months; 11 patients expired during follow-up period). Of these 21 were URI episodes, 46 were acute bronchitis episodes and 1 was a pneumonia episode. Two episodes tested positive for RSV in two autologous HSCT recipients, both belonging to RSV-B subtype, one from a URI episode on day 163 of HSCT and the other from a pneumonia episode on day 8 after HSCT. Both recovered without specific targeted treatment against RSV. The incidence of RSV infection in post-HSCT adult patients calculated from this study is 4% per year.

Conclusion

There is significant incidence of RSV infection among post-HSCT adults in India. Nevertheless, institution of targeted treatment options depends on weighing the cost and risk against benefit of using them. RSV-B subtype as seen in this study also is less virulent and less likely to lead to LRTI compared with RSV-A. Clinical predictors of poor outcomes can also help to decide upon prophylaxis. Larger studies focusing on preventing progression to LRTI need to be done.

Disclosures

All authors: No reported disclosures.
1784. The Value of a Systematic Screening of Influenza Virus and Vaccination on Emergent Admissions to a Cardiac Intensive Care Unit (C-ICU)
Authors: Galar Alicia , Vicent Lourdes , Sousa-Casasnovas Iago , Valerio Maricela , Juárez Miriam , Catalán Pilar , Devesa-Cordero Carolina , Bruña Vanesa , Martínez-Sellés Manuel , Bouza Emilio , Muñoz García-Paredes Patricia
Published: October 2019

Background

Influenza is a potential inducer of acute cardiac events. However, the incidence of influenza in patients admitted to a C-ICU, the accuracy of clinical suspicion and the compliance of influenza vaccination of high-risk patients, are not well known. Objectives: To evaluate the incidence of influenza at C-ICU admission during influenza season, the potential underdiagnosis and the vaccination rate.

Methods

Prospective study at a tertiary institution including all patients admitted to a C-ICU during 2017–2018 flu season. A nasopharyngeal swab was collected at admission from all patients who consented (198/201, 98.5%) and tested using Xpert® Flu/RSV assay. Clinical data were registered.

Results

Influenza was detected in 14/198 (7.1%) patients (11 FluA, 3 FluB) and initially suspected by the cardiologist in 57.1% cases. When compared with patients without influenza, flu-positive patients had more respiratory (21.4% vs. 6.0%, P = 0.03) or neurologic diseases (21.4% vs. 4.3%, P < 0.01), contact with relatives with flu-like illnesses (35.7% vs. 14.4%, P = 0.03), antimicrobials use (71.4% vs. 36.4%, P = 0.01) and need for mechanical ventilation (28.6% vs. 3.3%, P < 0.01). Reasons for C-ICU admission between both groups were similar. All patients promptly received oseltamivir and no patient with flu died (0 vs. 3.8%, P = 0.46) despite a high rate of severe presentations (85.7%) and related complications (78.6%). Seasonal flu vaccination was received by 44.9% of the patients admitted to the C-ICU and 52.0% of patients who had indication for flu vaccination. The incidence of influenza in the vaccinated and non-vaccinated population (with flu vaccine indication) was, respectively 12.6% vs. 4.1% (P = 0.08). Flu episodes in vaccinated patients required less mechanical ventilation (20% vs. 75%, P = 0.05) and showed a trend toward shorter length of in-hospital stay (6 vs. 15d, NS). Risks factors for no vaccination despite indication were: younger age (67 vs. 75y-o, P < 0.05) and less comorbidity (Charlson index 4 vs. 5, P < 0.01).

Conclusion

Seven percent of patients admitted to the C-ICU had influenza, only half of the influenza cases diagnosed were suspected at admission and only half of the patients with indication for flu vaccination, received the vaccine. A clinical score to recognize influenza in these patients is needed.

Disclosures

All authors: No reported disclosures.
1786. An Automated Method to Assess Oligonucleotide Primer and Probe Complementarity to Genomic Targets in Infectious Disease qPCR Assays
Authors: Sinha Rohita , Wissel Mark , Bartlett Katelyn , Grantham James , Kleiboeker Steve
Published: October 2019

Background

Success of real-time TaqMan PCR (qPCR) in detecting pathogen targets and quantifying pathogen load is dependent upon frequent assay monitoring. This is due to i) the high degree of complementarity needed between primers / probes and genomic targets for assay accuracy and ii) natural pathogen variation and evolution. Failure to monitor and refine may result in false negativity or under quantification. Here we present a bioinformatics tool to identify potential problems resulting from newly discovered genomic mutations in primer/probe regions.

Methods

The tool performs an unbiased and automated search of the NCBI database, collects relevant genomic sequences based on user-defined Taxon-ID and executes a Python program to discard synthetic sequences. A profile of primer-probe sequence complementarity to targets is then generated. While the tool can be used for any microbe, here we present results for our laboratory’s cytomegalovirus (CMV) qPCR primer-probe analysis. In addition, our laboratory’s traditional approach utilizing alignment software was performed (download of all CMV sequences (~10,000) followed by iterative alignment building of these against our primers and probes). The amount of time to perform the automated and manual methods was recorded.

Results

The tool retrieved 8,732 sequences from NCBI and compared these to the CMV qPCR primers and probes. The tool found 2,501 alignments between the primers / probes and the downloaded genomic data (~15 minutes to finish (6 CPUs)). A total of 64% (1,624/2,501) of BLASTn alignments were exact matches between all primers / probes and viral genomic sequences. 17.5% (439/2,501) of alignments had 1 mismatch at either 5’ or 3’ terminus, and 1% (25/2,501) of alignments had two mismatches with the primers / probes. Similar results were found using a primarily manual approach (which took approx. 5 hours computing time and 20 hours of labor).

Conclusion

This new bioinformatics approach performed indistinguishably vs. a manual approach and did so in minutes rather than days. Both methods led to the conclusion that, by virtue of our design involving overlapping primers and probes, none of the identified mismatches are predicted to lead to false negativity or under quantification in our current CMV qPCR assay.

Disclosures

All authors: No reported disclosures.
1788. The Utility of Next-Generation Sequencing for Detection of Candidate Pathogens in Bronchoalveolar Lavage Fluid from Pediatric Patients with Respiratory Failure
Authors: Takeuchi Suguru , Kawada Jun-ichi , Horiba Kazuhiro , Okuno Yusuke , Okumura Toshihiko , Suzuki Takako , Torii Yuka , Kawabe Shinji , Wada Sho , Ikeyama Takanari , Ito Yoshinori
Published: October 2019

Background

In the field of infectious diseases, identification of etiologic pathogen is essential for definitive diagnosis and decisions regarding appropriate management. Bronchoalveolar lavage fluid (BALF) is considered a sterile type of specimen that is suitable for detecting pathogens of respiratory infections. Recently, next-generation sequencing (NGS) has been applied in the field of infectious diseases and has enabled us to identify pathogenic microorganisms comprehensively. The aim of this study was to comprehensively identify pathogens using NGS in BALF samples from immunocompetent pediatric patients with respiratory failure.

Methods

Ten patients hospitalized in the pediatric intensive care unit with respiratory failure were included. BALF samples obtained in the acute phase were used to prepare DNA- and RNA-sequencing libraries. The libraries were sequenced on MiSeq, and the sequence data were analyzed using metagenome analysis tools.

Results

A mean of 2,041,216 total reads were sequenced for each library. A significant number of four types of bacterial reads was detected in three BALF samples with DNA-sequencing, whereas pathogenic respiratory viruses were detected in seven of 10 patients with RNA-sequencing.Candidate pathogens were detected in three patients in whom etiologic agents were not identified by conventional methods. A summary of the detected pathogens is listed in Table 1. Sequence coverage and depth of each reference bacterial and viral genome are shown in Figures 1 and 2, respectively. The complete genome of enterovirus D68 was identified in two patients without underlying diseases, and phylogenetic analysis suggested that both strains belong to subclade B3, which is an epidemic strain that has spread worldwide in recent years.

Conclusion

We demonstrated the utility of the NGS-based approach for detection of candidate pathogens in BALF from pediatric patients with severe respiratory failure. Our results suggest that NGS can be applied for comprehensive molecular diagnostics as well as surveillance of pathogens in the field of infectious diseases.

Disclosures

All authors: No reported disclosures.
1991. Implementation of Rapid Turnaround PCR Bacterial/Viral Panel Testing in Community-acquired Pneumonia Decreases LOS, Antibiotic Cost, Antibiotic Charges, and Antibiotic Use
Authors: Shadowen Rebecca D , Doshi Akash , Ndzi Rene , Kazimuddin Faraaz
Published: October 2019

Background

Community-acquired pneumonia (CAP) is a significant infection contributing to hospitalization, morbidity, mortality, intensive care, antibiotic use, and healthcare costs. Antibiotic stewardship aims to improve appropriate antibiotic use which addresses these same issues. Accurate, confirmed diagnosis upon presentation of CAP patients using Respiratory Bacteria/Viral (RBVP) Polymerase Chain Reaction (PCR) panels can significantly impact outcomes in the CAP patient population.

Methods

In this cross-sectional study, commercially available RBVP PCR panels were used. Comparison of CAP patient populations was done before PCR use (2014–2015 control group) and after implementation (2016–2017 intervention group) using a provider choice intervention following education and order availability. Providers were educated via multiple means with lectures, individual meetings, online brief presentation, and group discussions. A nursing computer-based learning module was also developed and required to be completed. Independent sample t-test and binary logistic regression were used to analyze data.

Results

Out of total 2,523 observations in the study, 1,994 (79.03%) were in the control group and 529 (20.96%) were in the intervention group. An independent sample t-test showed significant differences in the mean of length of stay (LOS) (P = 0.04, 95% CI: 8.67–9.36), total antibiotic cost (TAC) (P = 0.000, 95% CI: 486.61–550.45), antibiotic charges (ACH) (P = 0.048, 95% CI: 1,815.79–2,009.75), and antibiotic defined daily doses (DDD) (P = 0.039, 95% CI: 6.84–7.42). Binary logistic regression results revealed statistical significance in LOS (P = 0.01, 95% CI: 0.9251–0.9902) and TAC (P = 0.000, 95% CI: 0.9989–0.9994). Actual savings per patient were LOS 0.88 days, TAC $202.73, ACH $240.23, and DDD 0.77.

Conclusion

The use of RBVP PCR panel testing in CAP patients decreases antibiotic use, LOS, and cost of care. This correlated with antibiotic de-escalation providing a significant contribution to antibiotic stewardship. PCR panel testing with rapid turnaround is widely available and cost effective.

Disclosures

All authors: No reported disclosures.