bluuebunny/crossref_metadata_2025_split huggingface dataset:
82. Post-Prescription Review with Threat of Infectious Disease Consultation and Sustained Reduction in Meropenem Use Over Four Years
Authors: Mani Nandita S , Lan Kristine F , Jain Rupali , Kim H Nina , Lynch John B , Krantz Elizabeth M , Bryson-Cahn Chloe , Bryan Andrew , Pottinger Paul , Liu Catherine , Chan Jeannie D 
Published: January 2021

Abstract

Background
Following a meropenem shortage, we implemented a post-prescription review with feedback (PPRF) in November 2015 with mandatory infectious disease (ID) consultation for all meropenem and imipenem courses &gt; 72 hours. Providers were made aware of the policy via an electronic alert at the time of ordering.

Methods
A retrospective study was conducted at the University of Washington Medical Center (UWMC) and Harborview Medical Center (HMC) to evaluate the impact of the policy on antimicrobial consumption and clinical outcomes pre- and post-intervention during a 6-year period. Antimicrobial use was tracked using days of therapy (DOT) per 1,000 patient-days, and data were analyzed by an interrupted time series.

Results
There were 4,066 and 2,552 patients in the pre- and post-intervention periods, respectively. Meropenem and imipenem use remained steady until the intervention, when a marked reduction in DOT/1,000 patient-days occurred at both hospitals (UWMC: percentage change -72.1%, (95% CI -76.6, -66.9), P &lt; 0.001; HMC: percentage change -43.6%, (95% CI -59.9, -20.7), P = 0.001). Notably, although the intervention did not address antibiotic use until 72 hours after initiation, there was a significant decline in meropenem and imipenem initiation (“first starts”) in the post-intervention period, with a 64.9% reduction (95% CI 58.7, 70.2; P &lt; 0.001) at UWMC and 44.7% reduction (95% CI 28.1, 57.4; P &lt; 0.001) at HMC.
Meropenem and Imipenem DOT (January 2013 – November 2019)

Conclusion
Mandatory ID consultation and PPRF for meropenem and imipenem beyond 72 hours resulted in a significant and sustained reduction in the use of these antibiotics and notably impacted their up-front usage.

Disclosures
All Authors: No reported disclosures
1086. Epidemiology, Risk Factors, and Effect of Antifungal Prophylaxis on Early Invasive Fungal Infection in Heart Transplant Recipients
Authors: Yetmar Zachary A , Lahr Brian , Brumble Lisa , Banacloche Juan Gea , Steidley D Eric , Kushwaha Sudhir , Beam Elena 
Published: January 2021

Abstract

Background
Invasive fungal infection (IFI) in heart transplant recipients is associated with increased mortality and poor outcome. Reports have estimated the risk of 1-year IFI to be 3.4-8.6% with renal replacement therapy, delayed chest closure, and reoperation suggested as risk factors. However, the role of antifungal prophylaxis is unclear, though previous studies have suggested a reduced incidence of invasive Aspergillosis. The transplant program in Mayo Arizona provides 6 months of universal azole prophylaxis for Coccidioides, while Rochester and Florida only provide prophylaxis to high risk patients. We sought to define epidemiology and risk factors for 1-year IFI and determine the effect of antifungal prophylaxis.

Methods
We conducted a retrospective cohort study of patients undergoing single-organ heart transplantation at Mayo Rochester, Florida, or Arizona from January 2000 to March 2019. We identified baseline characteristics, details of transplant hospitalization such as need for renal replacement therapy, open chest, reoperation, and operative time, receipt of antifungal prophylaxis, and diagnosis of IFI. Multivariable Cox analysis was performed to identify risk factors of time to 1-year IFI.

Results
A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62) and 72% male. 444 patients received antifungal prophylaxis which included 32% fluconazole, 34% itraconazole, 18% voriconazole, 15% echinocandin, and &lt; 1% amphotericin or posaconazole. Over 1-year follow-up, 62 patients developed IFI with a cumulative prevalence of 6.4%. The most common organisms were Aspergillus (50%) and Candida (27%). In a multivariable model, factors associated with 1-year IFI were post-transplant renal replacement therapy (HR 3.34, 95% CI 1.69-6.60; P &lt; 0.001) and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96; P=0.042). Operative time, recent hospitalization, open chest, and post-transplant mechanical circulatory support were not associated with 1-year IFI.

Conclusion
Renal replacement therapy after transplantation is associated with 1-year IFI. Antifungal prophylaxis appears to be protective and further prospective study is warranted to verify this finding.

Disclosures
All Authors: No reported disclosures
1087. Evaluation of Risk Factors for Infection among Patients Receiving Ibrutinib
Authors: Tham Kenneth , Prelewicz Stacy , deHoll Sara , Stephens Deborah , Gomez Carlos A 
Published: January 2021

Abstract

Background
Ibrutinib is a small-molecule inhibitor of Bruton tyrosine kinase (BTK) approved for various B-cell malignancies and cGVHD. Rates of serious infection—defined as requiring hospitalization or parenteral antimicrobials— and invasive fungal infection (IFI) in patients on ibrutinib are as high as 11.4% and 4.2% respectively (Varughese T, et al. Clin Infect Dis 2018;67(5):687-92), which may be related to off-target inhibition of interleukin-2-inducible T-cell kinase or macrophage function.

Methods
We retrospectively reviewed infection complications in patients receiving ibrutinib at our institution between 06/01/2014 and 08/31/2019, including patients who received single-agent or combination ibrutinib. In this study, serious infection was defined as above, or a diagnosis of pneumonia regardless of hospitalization or parenteral antimicrobial therapy. Logistic regression was used to identify risk factors.

Results
Baseline characteristics of 134 included patients are in Table 1. Infection and serious infection occurred in 96 (72%) and 48 (36%) patients, respectively. When pneumonia was not included as a criterion for serious infection, the serious infection rate was 22%. Prior allogeneic stem cell transplant (allo-HSCT) (OR 4.50; 95% CI 1.19 – 17.00) and corticosteroid use (OR 5.42; 95% CI 1.49 – 19.82) were significant risk factors for serious infection without pneumonia (Table 2).
Of 37 patients (28%) who received primary HSV/VZV prophylaxis with acyclovir, there was one case of suspected herpes zoster infection (3%). IFI developed in 7 patients (5%): 5 with Pneumocystis jirovecii pneumonia (PJP), 1 with invasive aspergillosis, and 1 with a filamentous fungus, species unknown. Other identified organisms are detailed in Figure 1. Classical risk factors for IFI, including diabetes, allo-HSCT, and concurrent corticosteroid use, were not significant predictors in this group.
Table 1. Baseline Characteristics

Table 2. Risk Factor Analysis

Figure 1. Identified Organisms in Serious Infection

Conclusion
Serious infections developed at a higher rate than previously reported in the literature, with IFI rates similar to those previously described. Prior allo-HSCT and steroid use were found to be risk factors for serious infection without pneumonia. Treating physicians should have a high index of suspicion for pneumonia, IFI, and PJP in this population.

Disclosures
All Authors: No reported disclosures
1090. HHV-6 Encephalitis following Chimeric Antigen Receptor T-cell Therapy: Report of 2 Cases
Authors: Rebechi Melanie T , Bork Jacqueline , Riedel David J 
Published: January 2021

Abstract

Background
Human herpesvirus 6 (HHV-6) is the most common cause of infectious encephalitis following hematopoietic stem cell transplant. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel cancer-directed immunotherapy; chemotherapy conditioning for CAR-T results in prolonged, severe immunosuppression. HHV-6 encephalitis has not been reported in patients after CAR-T therapy.

Methods
We report 2 cases of HHV-6 encephalitis after CAR-T therapy.

Results
Case 1: A 69 year old man underwent CAR-T therapy after fludarabine/cyclophosphamide (Flu/Cy) conditioning for relapsed diffuse large B cell lymphoma (DLBCL). His course was complicated by cytokine release syndrome (CRS) requiring tocilizumab and neurotoxicity requiring high dose dexamethasone. On day 29 he was febrile to 39.3℃, confused, and had difficulty speaking. Mental status (MS) worsened, so LP and MRI of the brain were performed. HHV-6 CSF PCR was positive, and ganciclovir (GCV) was started. He improved gradually over 10 days. At follow up, he reported mild short term memory difficulty but no focal deficits.
Case 2: A 57 year old man underwent CAR-T therapy after Flu/Cy conditioning for refractory DLBCL. His course was complicated by CRS requiring tocilizumab. On day 6, he had difficulty concentrating, slowed thinking, stuttering and repetitive speech. MS continued to worsen, and dexamethasone and siltuximab were given for CAR-T neurotoxicity. After 1 week he was following commands. By week 3 he remained intermittently confused and agitated, so MRI and LP were performed. HHV-6 PCR was positive in the CSF. He was started on GCV and improved gradually over the next 2 weeks but remained dysarthric with slowed speech. On day 55, HHV-6 remained detectable in CSF but not quantifiable and GCV was discontinued despite persistent cognitive deficits.
Table 1: Demographics and clinical characteristics of 2 patients with HHV-6 encephalitis following CAR-T therapy

Conclusion
Diagnosing HHV-6 encephalitis can be challenging after CAR-T therapy because altered MS is often attributed to CAR-T associated neurotoxicity. It is important to maintain a high index of suspicion for infectious causes of altered MS after CAR-T therapy, including HHV-6 encephalitis, especially in patients treated with further immunosuppression for CRS and CAR-T related neurotoxicity.

Disclosures
All Authors: No reported disclosures
1091. Incidence of Post-Transplant Lymphoproliferative Disorders among Epstein-Barr Virus Donor Positive, Recipient Negative Adult Solid Organ Transplant Recipients
Authors: Limaye Abhijit P , Heldman Madeleine R , Edlefsen Kerstin L , Kapnadak Siddhartha G , Rakita Robert M , Fisher Cynthia E 
Published: January 2021

Abstract

Background
Epstein-Barr virus (EBV) donor positive (D+), recipient negative (R-) serostatus is a major risk factor for post-transplant lymphoproliferative disorder (PTLD) in adult solid organ transplant recipients (SOTR). Few studies have systematically characterized absolute organ transplant type-specific incidence, timing, and outcomes of PTLD in adult EBV D+R- SOTR.

Methods
We retrospectively assessed the incidence, timing, and associated morbidity and mortality of biopsy-confirmed PTLD (WHO classification) among consecutive adult SOTR between Jan 1, 2000 and Apr 30, 2018 at a single university center, and who had a minimum 2 years of follow-up. Antibodies to EBV (viral capsid antigen and nuclear antigen) were assessed in candidates and donors by FDA-cleared ELISA assay. Donors with unknown serology were considered seropositive based on the known prevalence of &gt;93% seropositivity in this donor population.

Results
Among 4,923 SOTR, prior to transplant, 4,770 (96.9%) were R+ (regardless of donor status), 144 (2.9%) were D+R-, and 9 (0.2%) were D-R-. PTLD incidence by last follow-up was higher among D+R- (15/144 [10.4%]) than R+ (61/4,770 [1.2 %]), P &lt; 0.0001, and occurred earlier after transplant (median 9.6 months [IQR 6.1-34.2] versus 35.1 months [IQR 7.1-73.1]), P= 0.003, respectively. Among D+R-, incidence was higher among recipients of non-kidney versus kidney organs (13/89 [14.6%] vs. 2/55 [3.6%], P = 0.05, respectively). Incidence in rank order was: pancreas (2/9 [22.2%]), lung (6/29 [20.7 %]), heart (2/21 [9.5%]), and liver (3/30 [6.7%]). PTLD histopathology was monomorphic in 9/15 [60%] and EBV-encoded RNA-1 (EBER-1) positive in 12/12 evaluable cases. Outcomes among the 15 PTLD cases included: graft failure without transplant in 3 (20%), graft failure with re-transplant in 2 (13.3%), and death within 6 months in 3 (20%).
Table 1: Characteristics of the EBV Donor seropositive, Recipient seronegative (D+R-) cohort

Figure 1: Cumulative Incidence of PTLD among the EBV D+R- cohort (all organs)

Figure 2: Incidence of PTLD among the D+R- cohort, stratified by organ transplant type

Conclusion
Although rare overall, we identified a specific subgroup of adult SOT patients (EBV D+R- non-kidney recipients) whose absolute PTLD incidence and associated morbidity and mortality are high, and who should be targeted for future mechanistic or therapeutic studies.

Disclosures
All Authors: No reported disclosures
1092. Increased Risk of Serious Infections in Mantle Cell Lymphoma Versus Other Hematologic Malignancies in Patients on Ibrutinib
Authors: Holowka Thomas , Cheung Harry , Malinis Maricar F , Perreault Sarah , Isufi Iris , Azar Marwan M 
Published: January 2021

Abstract

Background
Ibrutinib, a tyrosine kinase inhibitor used for treatment of hematologic malignancies, is associated with an increased risk of infection including invasive fungal infections (IFI). However, the risk of infection may vary across different types of malignancies. The primary aims of our study were to determine the incidence of serious infection and associated risk factors in different hematologic malignancies while on ibrutinib.

Methods
We performed a retrospective analysis of patients prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital between January 2014 and July 2019 by chart review. We collected demographic, and clinical data along with oncologic history, and identified serious infections defined as those requiring inpatient management. Chi-squared tests were used to determine characteristics associated with an increased risk of infection.

Results
A total of 254 patients on ibrutinib were identified including 156 with CLL, 89 with NHL including 20 with Mantle Cell Lymphoma (MCL) and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. Of 51 patients with serious infections, 10 (20%) had MCL, 11 (20.3%) had other NHLs, 28 (54.9%) had CLL and 2 (3.9%) had other malignancies. The relative frequency of serious infections was higher in MCL than non-MCL (50% vs. 17.1%). More MCL patients experienced IFI (1 pulmonary cryptococcosis, 2 pulmonary aspergillosis), compared to non-MCL patients (2 pulmonary aspergillosis; 15% vs. 0.9%). Risk factors associated with serious infection in MCL included maximum ibrutinib dose of 560 mg (OR 16.4, p &lt; 0.001), other concurrent chemotherapy (OR 8.2, p &lt; 0.001), prior HSCT (OR 5.9, p &lt; 0.001), concurrent steroid use (≥ 10 mg prednisone for ≥ 2 weeks; OR 2.4, p &lt; 0.05), lymphopenia (OR 2.4, p &lt; 0.05) a history of prior chemotherapy (OR 0.2, p &lt; 0.05) and ECOG score ≥ 2 (OR 3.2, p &lt; 0.01).

Conclusion
In this study of hematologic malignancy on ibrutinib, MCL patients had a greater risk of serious infection. This increased risk in MCL could be associated with more prolonged and intense immunosuppression rather than underlying disease pathogenesis. Antimicrobial prophylaxis should be considered in MCL patients on ibrutinib to mitigate risk of infection.

Disclosures
All Authors: No reported disclosures
83. Staff Pharmacist-driven Prospective Audit and Feedback at a Community Hospital: Assessing an all Hands on Deck Approach to Antimicrobial Stewardship
Authors: Dempsey Casey J , Weiner Natasha , Riccardi Michele , Linder Kristin 
Published: January 2021

Abstract

Background
Facilities with robust antimicrobial stewardship programs often have infectious disease (ID) pharmacists with devoted time to complete antimicrobial stewardship initiatives. Smaller facilities with limited resources or lacking ID pharmacists, may encounter challenges meeting antimicrobial stewardship regulatory requirements. The goal of this study is to assess the impact of a staff pharmacist-driven prospective audit and feedback program in a small community hospital.

Methods
A pre- and post-intervention study was performed to assess the primary outcome of days of therapy per 1,000 patient days (DOT) for targeted antimicrobials (ciprofloxacin, levofloxacin, piperacillin/tazobactam, cefepime, ceftazidime). Secondary outcomes were antibiotic expenditures and rates of Clostridioides difficile infection (CDI).

Results
Significant decreases in DOT were observed for piperacillin/tazobactam (29.88 vs. 9.25; p &lt; 0.001), ciprofloxacin (23.22 vs. 9.97; p &lt; 0.001), levofloxacin (11.2 vs. 5.07; p &lt; 0.001) and overall antipseudomonal DOT (62.91 vs. 51.67; p &lt; 0.001). There was no difference in ceftazidime DOT (8.75 vs. 6.47; p= 0.083) and an increase in cefepime DOT (20.47 vs. 34.35; p &lt; 0.001). A trend towards decreased rates of CDI was seen (4.9/10,000 patient days vs. 2.64/10,000 patient days; p= 0.931). There were significant decreases in antibiotic expenditures for piperacillin/tazobactam ($52,498 vs. $10,937; p &lt; 0.001), levofloxacin ($2,168 vs. $672; p &lt; 0.001), ciprofloxacin ($6,700 vs. $1,954; p &lt; 0.001). Lower expenditures for ceftazidime were seen ($9,952 vs. $7,457; p= 0.29). Cefepime expenditures increased ($25,638 vs. $40,097; p= 0.001). An overall decrease in the expenditure for the targeted antibiotics was seen ($95,715 vs. $62,837; p &lt; 0.001).

Conclusion
Implementation of a staff pharmacist-driven prospective authorization and feedback program led to a significant decrease in DOT and antibiotic expenditures for several targeted antibiotics and a trend towards decreased rates of CDI. Despite increased DOT and expenditures for cefepime, there was an overall decrease amongst the targeted antibiotics. With proper implementation, staff pharmacists can significantly benefit antimicrobial stewardship initiatives.

Disclosures
All Authors: No reported disclosures
1099. Opportunistic Infections Among Long Term Survivors of Kidney Transplantation: Defining Risk Factors
Authors: Cheung Harry , Azar Marwan M , Gan Geliang , Deng Yanhong , Cohen Elizabeth A , Kulkarni Sanjay , Malinis Maricar F 
Published: January 2021

Abstract

Background
Opportunistic infections (OIs) in kidney transplant recipients (KTR) most commonly occur in the early post-transplant period or with increased immunosuppression, largely as a result of impaired T-cell function. Additionally, age confers susceptibility to infection independent of time post-transplant. The combined impact of cumulative immunosuppression and immunosenescence on infection risk of long-term KT survivors has not been well described.

Methods
We performed a retrospective chart review of patients age ≥ 18 years who underwent KT between 2003 to 2009 and who survived ≥ 10 years post-KT, in order to evaluate the risk factors for OIs. Demographics, comorbidities, immunosuppression, and clinical data for OIs occurring ≥ 10 years of KT were collected. AST ID Working Group on Infectious Disease Monitoring definitions for OIs was used. Risk factors for OIs were assessed by simple logistic regression.

Results
Of 332 KTR, 16 (4.8%) had an OI with 18 total episodes. Of 16 KTR, half were white, 10 (62.5%) were male, median age at time of transplant was 43 (range 25-72) and the median post-transplant follow-up was 14.2 years (range 10.3-37.6). The mean Charlson Comorbidity Index (CCI) at diagnosis was 5.6 (S.D. 3.6). Ten patients (62.5%) were on mycophenolate-based regimens. The mean absolute lymphocyte count (ALC) at the time of OI was 0.78 x 103/µL (S.D. 0.43). Two (12.5%) had acute rejection within 1 year of OI. Of 18 OI episodes, there were 6 PJP, 2 candida esophagitis, 3 CMV (2 viremia, 1 colitis), 2 cryptococcal infections (1 meningitis, 1 myositis/disseminated), 2 adenovirus (pneumonia, colitis), 2 VZV (herpes zoster) and 1 HSV (esophagitis). Two patients had 2 concurrent OIs (1 had PJP and cryptococcus and 1 had HSV and candida esophagitis). Three died within 30-days of OI diagnosis. OI incidence was associated with years from date of transplant [OR 1.3, p=0.002], cerebrovascular disease [OR 4.45, p=0.02], and lower ALC [OR 5.9, p &lt; 0.05]. CCI also trended towards association [OR 1.24, p=0.09].
Table 1: Demographics, comorbidities, immunosuppression, and clinical data for patients with OIs

Table 2: Detailed characteristics of each patient with opportunistic infections

Conclusion
OIs were infrequently observed beyond 10 years of transplant among long-term survivors of KT. However, OI incidence was associated with poor outcome. Low ALC and a higher burden of comorbidities were risk factors for very late occurrence of OIs in this population.

Disclosures
All Authors: No reported disclosures
1100. Outcomes of HIV-Associated Lymphoma Treatments: A Contemporary Single Center Cohort Study
Authors: Mousa Rinda , Song Xing , Clough Lisa A , Dias Ajoy , Merino Fernando , El Atrouni Wissam 
Published: January 2021

Abstract

Background
There is a paucity of outcome studies on HIV-associated lymphoma treated with chemotherapy with or without autologous hematopoietic stem cell transplantation (autoHSCT) in comparison to HIV-uninfected individuals with similar histology.

Methods
In our retrospective matched cohort study, we enrolled adult HIV-positive patients with lymphoma treated with chemotherapy with (group 2) or without autoHSCT (group 1) between January 1, 2007 to December 31, 2018 at the University of Kansas Medical Center and followed until May 1, 2020. Group 1 were matched 1:1 to HIV-negative patients based on age, gender, lymphoma histology, stage at diagnosis, year of lymphoma diagnosis, and Group 2 were matched 1:2 to HIV-negative patients based on age at autoHSCT, gender, lymphoma histology, stage at diagnosis and year of transplantation. Overall survival (OS) and progression-free survival (PFS) at 2 years were calculated using Kaplan-Meier (KM) analysis, and adjustment for ECOG and IPI/IPS scores was done using multivariate Cox model.

Results
We had 37 HIV+ patients with lymphoma in our cohort: 9 Hodgkin’s disease (HD), 28 Non Hodgkin’s Lymphoma (NHL). Eleven underwent autoHSCT (3 HD, 8 NHL). The majority were white (76.2%), non-hispanic (92.9%), males (90.5%) and mean age was 46 years. Median CD4 was 172.5, HIV viral load was &lt; 50 copies/mL in 43..2%, and 76.2% were on antiretroviral therapy (ART) at diagnosis. ART was interrupted in 14.6% and adjusted in 40.5% of patients. After excluding rare histological types, 22 in group 1 and 9 in group 2 were included in the matched analysis. On KM survival at 2-years, group 1 had worse OS (75% vs 95%, p=0.02), and a trend for worse PFS (75% vs 90%, p=0.07) than the matched referent group, while group 2 had similar OS (100% vs 94%, p= 0.47) and better PFS (100% vs 70%, p=0.02) than the matched referent group. On Cox models adjusting for ECOG and IPI/IPS, HIV status was no longer independently associated with OS in group 1 or PFS in group 2.
Group 1 HIV lymphoma cases and controls characteristics

Group 2 HIV lymphoma with HSCT cases and controls characteristics

Conclusion
In patients with HIV and lymphoma treated with chemotherapy with or without autoHSCT, the outcomes are comparable to those without HIV in our single center contempory cohort.

Disclosures
Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)