scholarly journals 930. Clinically Significant CMV Infections in Patients with Lymphoma or Multiple Myeloma

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S557-S558
Author(s):  
Joseph Sassine ◽  
Fareed Khawaja ◽  
Brandon R Shank ◽  
Alexandra Lovell ◽  
Jenessa Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Patient Population ◽  
Panel Member ◽  
Female Gender ◽  
Secondary Prophylaxis ◽  
Cancer Therapies ◽  
Research Support ◽  
New Cancer Therapies ◽  
Clinically Significant

Abstract Background Clinically significant CMV infections (CS-CMVi) among patients with lymphoma and multiple myeloma (MM) have not been clearly defined, especially considering the new cancer therapies that have revolutionized cancer outcomes of these patients. This study aims at describing clinical outcomes of CS-CMVi in this patient population and identify risk factors for CS-CMVi. Methods This is a single-center, cohort study of all patients with lymphoma and MM who developed CS-CMVi between January 2017 and October 2020. Data was collected from the electronic medical records. CMV outcomes were defined according to the standardized definitions for clinical trials. Data was analyzed on IBM® SPSS version 26 using a logistic regression model for multivariate analysis. Results We identified 84 patients; 60 (71%) had lymphoma and 24 (29%) had MM (Table 1). CMV end organ disease was diagnosed in 53 (63%) patients as the initial CMV episode and the most common site was the lungs (68%). In our cohort, 25 (30%) patients had autologous HCT and 14 (17%) had CAR T cells infusions prior to CS-CMVi. Recurrent CS-CMVi occurred in 16 (19%) patients (Table 2). A 100-day all-cause mortality was 55%, at a median of 76 days (range 3 -1330 days) after the initial episode of CS-CMVi. CMV related mortality was 11% amongst patients with end organ disease. In multivariate analysis, female gender was associated with a higher risk of CMV end organ disease (OR 3.42, 95% CI 1.14-10.3) and MM with a lower risk of CMV end organ disease compared to lymphoma (OR 0.27, 95% CI 0.07-0.97) (Table 3). Interestingly, 16 (19%) patients received letermovir as secondary prophylaxis for a median of 94 days (range 5 to 339 days) and only 1 patient had recurrent CS-CMVi while on letermovir. Conclusion CS-CMVi, particularly end organ disease, are not uncommon among patients with lymphoma or MM. Routine CMV surveillance and the use of letermovir for secondary prophylaxis in this patient population should be evaluated in further studies. Disclosures Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Ella Ariza Heredia, MD, Merck (Grant/Research Support) Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support)

scholarly journals 194. Combinatorial Polyfunctionality Analysis of Antigen-specific T-cell Subsets (COMPASS) as a Predictor for Clinically Significant CMV Infection in the Letermovir Era

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S225-S226
Author(s):  
Danniel Zamora ◽  
Elizabeth Duke ◽  
Hu Xie ◽  
Bradley Edmison ◽  
Brenda Akoto ◽  
...  
Keyword(s):  
T Cell ◽  
Panel Member ◽  
T Cell Responses ◽  
Preemptive Therapy ◽  
Cmv Infection ◽  
Research Support ◽  
Review Panel ◽  
Cell Responses ◽  
Cytokine Responses ◽  
Clinically Significant

Abstract Background Increased CMV reactivation is observed following discontinuation of letermovir prophylaxis after hematopoietic cellular transplantation (HCT) and decreased CMV-specific polyfunctional T-cell immunity has been proposed as a possible mechanism (BBMT 2020;26:S68). COMPASS is a novel analytical tool that integrates polyfunctional T-cell cytokine responses into a single score value (Nat Biotechnol 2015;33:610). We employed COMPASS for the first time in the HCT setting to determine if CMV-specific immunodeficiency is associated with late CMV events in a prospective cohort of allogeneic HCT recipients receiving either letermovir or preemptive therapy. Methods Peripheral blood mononuclear cells were collected 3 months post-HCT and assessed with a 13-color intracellular cytokine staining (ICS) assay that includes 5 functional markers. Intermediate early-1 (IE-1) antigen and phosphoprotein 65 (pp65) were used to stimulate polyfunctional T-cell responses that were defined using COMPASS generated polyfunctionality scores (PFS). CMV DNAemia was monitored by weekly plasma PCR and patients who reactivated were treated with preemptive therapy per institutional standards. Cumulative incidence of clinically significant CMV infection (cs-CMV; ≥500 IU/mL or CMV disease) by day 270 was assessed. Univariable and multivariable Cox regression were used to estimate the association of polyfunctional T-cell responses (upper quartile versus lower 3 quartiles) with cs-CMV infection by day 270 post-HCT. Results 56 letermovir recipients and 93 preemptive controls were evaluated. Time to first clinically significant CMV (cs-CMV) infection after HCT and among day 100 survivors in both groups is shown in Figure 1. COMPASS PFS at 3 months were significantly lower in letermovir recipients (Figure 2). After adjusting for CMV infection before day 100, CD4 and CD8 PFS to IE-1 and pp65 below the upper quartile were associated with higher risk of late cs-CMV infection, with IE-1 CD8 PFS reaching statistical significance (Figure 3). Conclusion Our findings demonstrate that COMPASS is a valuable tool to evaluate multiple, T-cell cytokine responses to CMV in HCT recipients. COMPASS appears to be useful to identify patients at risk for late cs-CMV infection. Disclosures Elizabeth Duke, MD, Merck (Grant/Research Support) Michael Boeckh, MD PhD, AlloVir (Consultant)EvrysBio (Advisor or Review Panel member, Other Financial or Material Support, share options)Gilead (Consultant, Grant/Research Support)GSK (Consultant)Helocyte (Advisor or Review Panel member, Shareholder)Lophius (Grant/Research Support)Merck (Consultant, Grant/Research Support)SymBio (Consultant)VirBio (Consultant, Grant/Research Support)

scholarly journals 922. The Impact of Clinically Significant CMV Infections on Other Viral Infections in the Era of Letermovir Primary Prophylaxis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S552-S553
Author(s):  
Amy Spallone ◽  
Krithika Srinivasan ◽  
Joseph Sassine ◽  
Terri Lynn Shigle ◽  
Victoria Handy ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Viral Infections ◽  
Univariate Analysis ◽  
Primary Prophylaxis ◽  
Cell Transplant ◽  
Matched Cohort ◽  
Research Support ◽  
Significant Difference ◽  
Clinically Significant ◽  
The Impact

Abstract Background Cytomegalovirus (CMV) is a frequent complication after hematopoietic cell transplant (HCT) and may increase the risk of other viral infections through its immunomodulatory effects. Letermovir, a novel antiviral targeting the viral terminase complex, was approved for primary prophylaxis in CMV-seropositive adult recipients after allogeneic HCT (allo-HCT). Because of its efficacy and safety, letermovir has become the standard of care for primary prophylaxis against CMV during the first 100 days post-transplant. However, its impact on the frequency of other viral infections and non-relapse mortality (NRM), through its reduction in clinically significant CMV infections (CS-CMVi), is not known. Methods This is a single-center, retrospective cohort study of 150 allo-HCT recipients, including controls that were matched by the transplant type (match-unrelated, matched-related, cord, and haploidentical), cared for at our institution between March 2016 and December 2018. Baseline demographics, transplant characteristics, prophylaxis, CMV and other viral infections, and outcomes were collected (Table 1) and analyzed on IBM® SPSS version 26 using a binary logistic regression model for multivariate analysis. For univariate analysis, we used Chi-square and Fischer’s Exact Test. Results In our 2:1 matched cohort analysis, 50 patients received letermovir for primary prophylaxis during the first 100 days post-HCT, and 100 did not. In a univariate analysis with CS-CMVi as the outcome, there was a statistically significant difference in NRM at 24 and 48 weeks. Our data indicated a trend towards a decrease in other viral infections for those without CS-CMVi (Table 2). However, in a multivariate analysis accounting for primary prophylaxis with letermovir as an effect modulator, CS-CMVi did not demonstrate a significant impact on the frequency of other viral infections but was associated with NRM at week 24 and 48 (Table 3). Interestingly, having ALL and donor CMV seropositivity were protective factors against other viral infections (Herpesviridae). Conclusion Our study showed that CS-CMVi is associated with higher 24- and 48-week non-relapse mortality but with no increase in the incidence of other non-respiratory viral infections in this matched cohort of allo-HCT recipients. Disclosures Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Ella Ariza Heredia, MD, Merck (Grant/Research Support) Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support)

scholarly journals 57. Evaluating the Utility of a Penicillin Allergy Reconciliation Program within an Infectious Diseases Consult Population in a Community Health System

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S49-S50
Author(s):  
Bruce M Jones ◽  
Emily Plauche ◽  
Susan E Smith ◽  
Christopher M Bland
Keyword(s):  
Infectious Diseases ◽  
Health System ◽  
Community Health ◽  
Intervention Program ◽  
Primary Outcome ◽  
Panel Member ◽  
Penicillin Allergy ◽  
Secondary Outcome ◽  
Research Support ◽  
Research Grant

Abstract Background Penicillin allergy reconciliation is an important aspect of antimicrobial stewardship with ~10% of the population reporting a penicillin allergy. Our facility utilizes a Penicillin Allergy Reconciliation Program (PARP) led by an Infectious Diseases (ID) Pharmacist and pharmacy students to identify patients with penicillin allergies to reconcile and intervene when necessary. Information is collected by interview, electronic medical record (EMR) review, prescription outpatient fill history. This study evaluated reconciliations with and without a PARP in patients in a community health system. Methods This was a retrospective study that compared reconciliations performed on adult patients admitted at least once in 2019 with a self-reported penicillin allergy and ID physician consult at a hospital with a PARP (Institution 1) and one without a formal evaluation and intervention program (Institution 2) within the same community health system with same ID physicians. The primary outcome was documented reconciliation of a patient’s penicillin allergy during an inpatient visit in 2019. Reconciliation was defined as an edit or clarification (updating the severity, reaction, or comments section, as well as deleting) to a patient’s penicillin allergy in the EMR. The secondary outcome evaluated the percentage of total and ID consult patients with a penicillin allergy. Results There were 245 patients who met criteria and were included in the study, 113 from Institution 1 and 132 from Institution 2. For the primary outcome, there were 82 (72.6%) reconciliations at Institution 1 and 15 (11.4%) reconciliations at Institution 2 (p < 0.001). Interventions at Institution 1 and 2 resulted in 74 EMR updates and 8 removals and 14 EMR updates and 1 removal, respectively. Reconciliation was performed on the same visit as the ID consult in 59/82 patients (72%) at Institution 1 and 11/15 patients (73.3%) at Institution 2. All reconciliations at Institution 2 were made by pharmacist (10) or nurses (5). For the secondary outcome, 10.9% of patients with an ID consult and 12.6% of all patients admitted in 2019 had a penicillin allergy (p=0.027). Conclusion A PARP led by an ID pharmacist and students was an effective method to perform penicillin allergy reconciliations, even in the presence of active ID consultation. Disclosures Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Christopher M. Bland, PharMD, FCCP, FIDSA, BCPS, ALK Abello, Inc. (Grant/Research Support)Biomerieux (Consultant)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

scholarly journals Pegfilgrastim for primary prophylaxis of febrile neutropenia in multiple myeloma

2021 ◽  
Author(s):  
Claudio Cerchione ◽  
Davide Nappi ◽  
Giovanni Martinelli
Keyword(s):  
Multiple Myeloma ◽  
Febrile Neutropenia ◽  
Supportive Care ◽  
Survival Rates ◽  
Primary Prophylaxis ◽  
Secondary Prophylaxis ◽  
Novel Agents ◽  
Severe Side Effect ◽  
Maximum Benefit ◽  
Long Acting

AbstractMultiple myeloma (MM) survival rates have been substantially increased thanks to novel agents that have improved survival outcomes and shown better tolerability than treatments of earlier years. These new agents include immunomodulating imide drugs (IMiD) thalidomide and lenalidomide, the proteasome inhibitor bortezomib (PI), recently followed by new generation IMID pomalidomide, monoclonal antibodies daratumumab and elotuzumab, and next generation PI carfilzomib and ixazomib. However, even in this more promising scenario, febrile neutropenia remains a severe side effect of antineoplastic therapies and can lead to a delay and/or dose reduction in subsequent cycles. Supportive care has thus become key in helping patients to obtain the maximum benefit from novel agents. Filgrastim is a human recombinant subcutaneous preparation of G-CSF, largely adopted in hematological supportive care as “on demand” (or secondary) prophylaxis to recovery from neutropenia and its infectious consequences during anti-myeloma treatment. On the contrary, pegfilgrastim is a pegylated long-acting recombinant form of granulocyte colony-stimulating factor (G-CSF) that, given its extended half-life, can be particularly useful when adopted as “primary prophylaxis,” therefore before the onset of neutropenia, along chemotherapy treatment in multiple myeloma patients. There is no direct comparison between the two G-CSF delivery modalities. In this review, we compare data on the two administrations’ modality, highlighting the efficacy of the secondary prophylaxis over multiple myeloma treatment. Advantage of pegfilgrastim could be as follows: the fixed administration rather than multiple injections, reduction in neutropenia and febrile neutropenia rates, and, finally, a cost-effectiveness advantage.

scholarly journals Relative Frequency and Risk Factors of COVID-19 Related Headache in a Sample of Egyptian Population: A Hospital-Based Study

Pain Medicine ◽  
2021 ◽  
Author(s):  
Mona Hussein ◽  
Wael Fathy ◽  
Ragaey A Eid ◽  
Hoda M Abdel-Hamid ◽  
Ahmed Yehia ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Platelet Count ◽  
Relative Frequency ◽  
Clinical Laboratory ◽  
Primary Headache ◽  
Female Gender ◽  
Imaging Data ◽  
Laboratory Findings ◽  
Neutrophil Lymphocyte Ratio ◽  
The Impact

Abstract Objectives Headache is considered one of the most frequent neurological manifestations of coronavirus disease 2019 (COVID-19). This work aimed to identify the relative frequency of COVID-19-related headache and to clarify the impact of clinical, laboratory findings of COVID-19 infection on headache occurrence and its response to analgesics. Design Cross-sectional study. Setting Recovered COVID-19 patients. Subjects In total, 782 patients with a confirmed diagnosis of COVID-19 infection. Methods Clinical, laboratory, and imaging data were obtained from the hospital medical records. Regarding patients who developed COVID-19 related headache, a trained neurologist performed an analysis of headache and its response to analgesics. Results The relative frequency of COVID-19 related headache among our sample was 55.1% with 95% confidence interval (CI) (.516–.586) for the estimated population prevalence. Female gender, malignancy, primary headache, fever, dehydration, lower levels of hemoglobin and platelets and higher levels of neutrophil/lymphocyte ratio (NLR) and CRP were significantly associated with COVID-19 related headache. Multivariate analysis revealed that female gender, fever, dehydration, primary headache, high NLR, and decreased platelet count were independent predictors of headache occurrence. By evaluating headache response to analgesics, old age, diabetes, hypertension, primary headache, severe COVID-19, steroid intake, higher CRP and ferritin and lower hemoglobin levels were associated with poor response to analgesics. Multivariate analysis revealed that primary headache, steroids intake, moderate and severe COVID-19 were independent predictors of non-response to analgesics. Discussion Headache occurs in 55.1% of patients with COVID-19. Female gender, fever, dehydration, primary headache, high NLR, and decreased platelet count are considered independent predictors of COVID-19 related headache.

scholarly journals 1608. Efficacy of Ceftolozane/Tazobactam for Multidrug-Resistant Gram-Negative Infections in Multiple Urban Hospitals

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S798-S799
Author(s):  
Nicolo Cabrera ◽  
Truc T Tran ◽  
Travis J Carlson ◽  
Faris Alnezary ◽  
William R Miller ◽  
...  
Keyword(s):  
Research Study ◽  
Clinical Success ◽  
Significant Proportion ◽  
Scientific Research ◽  
Panel Member ◽  
Multidrug Resistant ◽  
Outcome Data ◽  
Research Support ◽  
Gram Negative ◽  
Study Investigator

Abstract Background Ceftolozane/tazobactam (C/T) is a novel cephalosporin/beta-lactamase inhibitor combination developed for use against multidrug-resistant (MDR) Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T is approved for complicated urinary tract and intraabdominal infections as well as hospital-acquired/ventilator-associated bacterial pneumonias. However, comprehensive clinical characterization of patients treated with C/T in non-FDA-approved indications is limited. Methods Patients ≥18 years who received C/T for ≥48 hours while hospitalized in 9 acute care centers in Houston, TX from January 2016 through September 2018 were included. Demographic, microbiologic, treatment and clinical outcome data were retrospectively collected by chart review. In patients who received multiple inpatient courses of C/T, only the first course with C/T was assessed. Results 210 patients met inclusion criteria: 58% were non-white, 35% were female and 13% were immunocompromised. Median age was 61 years (IQR, 48 to 69). Median Charlson comorbidity index was 5 (IQR, 2 to 6). At the onset of the index episode, a significant proportion of patients required intensive care unit admission (44%), mechanical ventilation (37%) and pressor support (22%). Respiratory sources were the most common (50%) followed by urine (15%). Positive cultures were documented in 93% of the cases and PA was found in 86%. Majority (95%) of PA which were MDR. C/T use was guided by susceptibility testing of the index isolate in ca. 52%. In 5.7% of cases, C/T was used to escalate therapy without any documented C/T-susceptible organism. Half (51%) of the cohort received initial dosing appropriate for renal function while 36% receiving a lower than recommended dose. Clinical success (i.e., recovery from infection-related signs and symptoms) occured in 77%. The in-hospital mortality rate in our cohort was 15% with 26 of 31 deaths deemed infection-related. Conclusion We report a large multicenter observational cohort that received C/T. A 77% clinical success with the use of C/T was documented. These data support the use of C/T in critically ill patients infected with MDR PA. Disclosures William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Laura A. Puzniak, PhD, Merck (Employee) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

scholarly journals 1012. Efficacy, safety and tolerability of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in HIV-1 infected virologically-suppressed older adults in a real-world setting

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S534-S535
Author(s):  
Charlotte-Paige M Rolle ◽  
Vu Nguyen ◽  
Kiran Patel ◽  
Dan Cruz ◽  
Federico Hinestrosa ◽  
...  
Keyword(s):  
Older Adults ◽  
Drug Interactions ◽  
Real World ◽  
Research Study ◽  
Panel Member ◽  
Median Number ◽  
Research Support ◽  
Review Panel ◽  
Study Investigator ◽  
Hiv 1

Abstract Background Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Efforts are ongoing to identify antiretrovirals associated with fewer drug-drug interactions (DDIs) and long-term side effects in this group. Clinical trials of B/F/TAF demonstrated favorable efficacy and safety in older adults, however, data from real-word settings are needed to validate these results. Methods This retrospective analysis evaluated records from PLWH aged ≥ 50 years at the Orlando Immunology Center who were switched to B/F/TAF between 2/7/2018 and 5/31/2019. Eligible patients had baseline HIV-1 RNA< 50 copies/mL and were followed for 48 weeks post-switch. The primary endpoint was maintenance of HIV-1 RNA< 50 copies/mL at week 48. The impact of switching to B/F/TAF on DDIs, adverse events (AEs) and safety parameters were analyzed throughout the study. Results 306 patients met inclusion criteria. 62 (20%) were female, 126 (41%) were non-white, median age was 58 years (range [r] 50-81), median duration of HIV infection was 19.5 years (r 2-40), median number of chronic co-morbid conditions was 5 (r 0-20), and median number of baseline concomitant medications was 4 (r 0-23). 159 (52%) patients were switched from regimens containing ritonavir or cobicistat. The most commonly documented reason for switch was simplification (Table 1). At Week 48, 287 (94%) patients maintained an HIV-1 RNA< 50 copies/ml and 19 (6%) had an HIV-1 RNA between 50-200 copies/mL (Figure 1). 1 patient discontinued due to lack of efficacy. A total of 123 potential DDIs were identified in 104 (34%) patients taking a boosting agent or rilpivirine at baseline (Table 2). At Week 48, there was a significant median decline in total cholesterol (15.5 mg/dL, 95% confidence interval [CI]: 9.5; 21.5), LDL cholesterol (9.5 mg/dL, 95% CI: 4; 15.5) and triglycerides (20 mg/dL, 95% CI: 9.5; 32.5), and median weight increased by 2.5 pounds (95% CI: 1.5; 3.5). Treatment-related AEs occurred in 33 (11%) patients (all Grade 1-2) and led to 7 (2%) discontinuations. Table 1-Baseline demographic and clinical characteristics Table 2-Avoidance of Drug-Drug Interactions (DDIs) following switch to B/F/TAF Figure 1-Subgroup analysis of virologic outcomes at Week 48 Conclusion In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, improvement in lipid parameters, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Speaker’s Bureau)Merck (Speaker’s Bureau)Theratechnologies (Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Advisor or Review Panel member)

scholarly journals 1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S582-S583
Author(s):  
Eleni Karantoni ◽  
Yiqi Su ◽  
Anat Stern ◽  
Phaedon D Zavras ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
T Cell ◽  
Panel Member ◽  
Multivariable Model ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Advisory Boards ◽  
Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

scholarly journals 652. Comparison of fosfomycin (FOF) activity and prevalence of subpopulations between Escherichia coli (EC) and Klebsiella pneumoniae (KP) during susceptibility testing

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S384-S384
Author(s):  
Jadyn C Anderson ◽  
Amanda R Krueger ◽  
Elizabeth C Smith ◽  
Morgan L Bixby ◽  
Hunter V Brigman ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Inhibitory Concentration ◽  
Panel Member ◽  
Colony Growth ◽  
The United States ◽  
Research Support ◽  
Review Panel ◽  
Agreement Rate ◽  
Future Studies ◽  
Agar Dilution

Abstract Background In the United States, interpretive criteria for FOF are established only for EC, yet those criteria are often extrapolated to KP. Recent studies have highlighted both inferior clinical outcomes after FOF treatment and difficulties in interpretation of inner colony subpopulations, the presence of which may affect clinical efficacy. We sought to compare FOF activity against EC and KP and to determine the prevalence of inner colony subpopulations following disk diffusion (DD) testing of the two species. Methods A convenience collection of 73 KP and 42 EC isolates from 3 U.S. institutions were included. Minimal inhibitory concentration (MIC) testing was performed in duplicate on separate days using agar dilution (AD) and DD as recommended by the Clinical and Laboratory Standards Institute guidelines, with application of EC susceptibility (≤ 64mg/L) breakpoints. The frequency and counts of inner colonies observed during DD testing was calculated, and colonies were subcultured for use in future studies. Results MIC50/90 values were 1/16 mg/L and 32/256 mg/L for EC and KP respectively. All EC isolates were considered susceptible and therefore categorical agreement was 100%. The majority of KP isolates were considered susceptible (83.6% with AD and 86.3% with DD) and categorical agreement between the methods was 84.9%. Inner colonies were observed during DD testing in 88.1% of EC isolates and 80.8% of KP isolates during at least one replicate, with 47.6% of EC isolates and 39.7% of KP isolates showing inner colony growth during both DD test replicates. More than 10 inner colonies were observed in 50% of EC isolates compared to 12.3% of KP isolates. Conclusion KP isolates demonstrated considerably higher FOF MIC values compared to EC, as evidenced by MIC50/90 values 4-5 dilutions higher than those for EC. The categorical agreement rate was higher among EC than KP, highlighting concerns regarding the practice of extrapolating FOF susceptibility breakpoints for EC to KP. The high frequency of inner colonies observed in DD for both species necessitates further studies to determine best practices for interpreting their relevance, fitness, and resistance in order to identify potential impacts to clinical efficacy of FOF. Disclosures Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)

scholarly journals 108. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S183-S183
Author(s):  
Rajesh Gandhi ◽  
Joshua Cyktor ◽  
Ronald Bosch ◽  
Hanna Mar ◽  
Gregory Laird ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Panel Member ◽  
Plasma Viremia ◽  
Research Support ◽  
Review Panel ◽  
Proviral Dna ◽  
Hiv 1 ◽  
Over Time ◽  
Residual Plasma Viremia ◽  
Research Grant

Abstract Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well-defined in people on ART. Methods We separately quantified intact and defective proviruses (using an intact proviral DNA assay), residual plasma viremia, and markers of inflammation and activation in people on long-term ART. Longitudinal measurements were done at three timepoints: timepoint 1 was a median of 7.1 years on ART; timepoint 2 was a median of 3.7 years later; timepoint 3 was a median of 5.5 years after timepoint 1 and a median 12 years after starting ART (Figure 1). Figure 1: Study timepoints Results Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life 7.1 years; 95% confidence interval [CI], 3.9, 18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6, 75). When we evaluated the change in proviral DNA per year, intact proviral DNA declined significantly more (p< 0.001) than defective proviral DNA (the latter did not change) (Figure 2). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART timepoint to about 5% at the last timepoint (Figure 3). At timepoint 1, intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation. Figure 2: Percent change in HIV-1 proviral DNA per year Figure 3: Total HIV-1 proviruses (grey bars) and the percentage of intact proviruses (red lines, displaying median, Q1, Q3) by timepoint. Conclusion Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion. Disclosures Rajesh Gandhi, MD, Merck (Advisor or Review Panel member) Gregory Laird, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Albine Martin, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Bernard Macatangay, MD, Gilead (Grant/Research Support) Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV Healthcare (Consultant, Research Grant or Support) Janet Siliciano, PhD, Gilead (Advisor or Review Panel member)US Military HIV Research Program (Advisor or Review Panel member) John Mellors, MD, Abound Bio (Shareholder)Accelevir Diagnostics (Consultant)Co-Crystal Pharmaceuticals (Shareholder)Gilead (Consultant, Grant/Research Support)Merck (Consultant)

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