Showing papers by "Steven A. Pergam published in 2021"

Assessment of the Inclusion of Racial/Ethnic Minority, Female, and Older Individuals in Vaccine Clinical Trials.

Abstract: Importance Medical research has not equitably included members of racial/ethnic minority groups or female and older individuals. There are limited data on participant demographic characteristics in vaccine trials despite the importance of these data to current trials aimed at preventing coronavirus disease 2019. Objective To investigate whether racial/ethnic minority groups and female and older adults are underrepresented among participants in vaccine clinical trials. Design, Setting, and Participants This cross-sectional study examined data from completed US-based vaccine trials registered on ClinicalTrials.gov from July 1, 2011, through June 30, 2020. The termsvaccine,vaccination,immunization, andinoculationwere used to identify trials. Only those addressing vaccine immunogenicity or efficacy of preventative vaccines were included. Main Outcomes and Measures The numbers and percentages of racial/ethnic minority, female, and older individuals compared with US census data from 2011 and 2018. Secondary outcome measures were inclusion by trial phase and year of completion. Results A total of 230 US-based trials with 219 555 participants were included in the study. Most trials were randomized (180 [78.3%]), included viral vaccinations (159 [69.1%]), and represented all trial phases. Every trial reported age and sex; 134 (58.3%) reported race and 79 (34.3%) reported ethnicity. Overall, among adult study participants, White individuals were overrepresented (77.9%; 95% CI, 77.4%-78.4%), and Black or African American individuals (10.6%; 95% CI, 10.2%-11.0%) and American Indian or Alaska Native individuals (0.4%; 95% CI, 0.3%-0.5%) were underrepresented compared with US census data; enrollment of Asian individuals was similar (5.7%; 95% CI, 5.5%-6.0%). Enrollment of Hispanic or Latino individuals (11.6%; 95% CI, 11.1%-12.0%) was also low even among the limited number of adult trials reporting ethnicity. Adult trials were composed of more female participants (75 325 [56.0%]), but among those reporting age as a percentage, enrollment of participants who were aged 65 years or older was low (12.1%; 95% CI, 12.0%-12.3%). Black or African American participants (10.1%; 95% CI, 9.7%-10.6%) and Hispanic or Latino participants (22.5%; 95% CI, 21.6%-23.4%) were also underrepresented in pediatric trials. Among trials reporting race/ethnicity, 65 (48.5%) did not include American Indian or Alaska Native participants and 81 (60.4%) did not include Hawaiian or Pacific Islander participants. Conclusions and Relevance This cross-sectional study found that among US-based vaccine clinical trials, members of racial/ethnic minority groups and older adults were underrepresented, whereas female adults were overrepresented. These findings suggest that diversity enrollment targets should be included for all vaccine trials targeting epidemiologically important infections.

Variants of concern are overrepresented among post-vaccination breakthrough infections of SARS-CoV-2 in Washington State.

Abstract: Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOC) and had a median Ct of 20.2 (IQR=17.1-23.3). When compared to 5174 contemporaneous samples sequenced in our laboratory, VOC were significantly enriched among breakthrough infections (p < .05).

Variants of concern are overrepresented among post-vaccination breakthrough infections of SARS-CoV-2 in Washington State

Abstract: Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOC) and had a median Ct of 20.2 (IQR=17.1-23.3). When compared to 5174 contemporaneous samples sequenced in our laboratory, VOC were significantly enriched among breakthrough infections (p < .05).

Predictive Value of 3 Clinical Criteria for Sepsis (Quick Sequential Organ Failure Assessment, Systemic Inflammatory Response Syndrome, and National Early Warning Score) With Respect to Short-term Mortality in Allogeneic Hematopoietic Cell Transplant Recipients With Suspected Infections.

Abstract: Background Sepsis, a life-threatening immunological response to an infection, disproportionality affects allogeneic hematopoietic cell transplant (HCT) recipients and is challenging to define. Clinical criteria that predict mortality and intensive care unit endpoints in patients with suspected infections (SI) have been adopted in sepsis definitions, but their predictive value among immunocompromised populations is largely unknown. Here, we evaluate three criteria among allogeneic HCT recipients. Methods We evaluated Systemic Inflammatory Response Syndrome (SIRS), quick-Sequential Organ Failure Assessment (qSOFA), and National Early Warning Score (NEWS) criteria in relation to short-term mortality among HCT recipients with SIs. Data from the first 100-days post-transplant were analyzed for patients transplanted between September 2010 - July 2017. We used the following cut-points (qSOFA/SIRS: 2+; NEWS: 7+) and restricted to first SI per hospital encounter. Results Of the 880 HCT recipients who experienced ≥ 1 SI, 58 (6.6%) died within 28 days and 22 (2.5%) within 10 days of a SI. In relation to 10-day mortality, SIRS was the most sensitive: 91.3% (95% CI:72.0 - 98.9%) but least specific: 35.0% (32.6 - 37.5%) whereas qSOFA was the most specific: 90.5% (88.9 - 91.9%) but least sensitive: 47.8% (26.8 - 69.4%). NEWS was moderately sensitive 78.3% (56.3 - 92.5%) and specific 70.2% (67.8 - 72.4%). Conclusion NEWS outperformed qSOFA and SIRS, but all three criteria had low to moderate predictive accuracy and the magnitude of the known predictive limitations of qSOFA and SIRS were at least as large as in general populations. Our data suggest that population-specific sepsis criteria are needed for immunocompromised patients.

Cocooning against COVID-19: The argument for vaccinating caregivers of patients with cancer.

Abstract: Current national COVID‐19 vaccination guidelines and recommendations focus vaccine guidance on patients with cancer. In this COVID‐19 vaccination race, “cocoon vaccination” strategies which include informal caregivers and household contacts as priority groups for SARS‐CoV‐2 vaccination could be an additional strategy used to protect patients with cancer who may have limited immune responses to current vaccinations. Medical systems specializing in cancer care should support education and vaccination campaigns which target informal caregivers and household contacts in addition to cancer patients.

Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy: a prospective observational study.

Abstract: Recipients of chimeric antigen receptor-modified T (CAR-T) cell therapies for B cell malignancies have profound and prolonged immunodeficiencies and are at risk for serious infections, including respiratory virus infections. Vaccination may be important for infection prevention, but there are limited data on vaccine immunogenicity in this population. We conducted a prospective observational study of the humoral immunogenicity of commercially available 2019-2020 inactivated influenza vaccines in adults immediately prior to or while in durable remission after CD19-, CD20-, or B cell maturation antigen-targeted CAR-T-cell therapy, as well as controls. We tested for antibodies to all four vaccine strains using neutralization and hemagglutination inhibition (HAI) assays. Antibody responses were defined as at least fourfold titer increases from baseline. Seroprotection was defined as a HAI titer ≥40. Enrolled CAR-T-cell recipients were vaccinated 14-29 days prior to (n=5) or 13-57 months following therapy (n=13), and the majority had hypogammaglobulinemia and cellular immunodeficiencies prevaccination. Eight non-immunocompromised adults served as controls. Antibody responses to ≥1 vaccine strain occurred in 2 (40%) individuals before CAR-T-cell therapy and in 4 (31%) individuals vaccinated after CAR-T-cell therapy. An additional 1 (20%) and 6 (46%) individuals had at least twofold increases, respectively. One individual vaccinated prior to CAR-T-cell therapy maintained a response for >3 months following therapy. Across all tested vaccine strains, seroprotection was less frequent in CAR-T-cell recipients than in controls. There was evidence of immunogenicity even among individuals with low immunoglobulin, CD19+ B cell, and CD4+ T-cell counts. These data support consideration for vaccination before and after CAR-T-cell therapy for influenza and other relevant pathogens such as SARS-CoV-2, irrespective of hypogammaglobulinemia or B cell aplasia. However, relatively impaired humoral vaccine immunogenicity indicates the need for additional infection-prevention strategies. Larger studies are needed to refine our understanding of potential correlates of vaccine immunogenicity, and durability of immune responses, in CAR-T-cell therapy recipients.

Seroprevalence of Measles and Mumps Antibodies Among Individuals With Cancer.

Abstract: Importance Although patients with cancer are at an increased risk of infection-related complications, few studies have characterized their vulnerability to measles and mumps. Given the recent outbreaks and increased community vaccine hesitancy, understanding measles and mumps immunity within this population is vital. Objectives To identify a point prevalence estimate of protective measles and mumps antibodies among ambulatory patients with cancer. Design, setting, and participants In this cross-sectional study, residual clinical plasma samples were obtained from consecutive patients with cancer at Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center in Seattle, Washington, in August 2019. These samples were tested for measles and mumps IgG using a commercial enzyme-linked immunosorbent assay. Patients without cancer were excluded from the analysis. Exposures Patient age, sex, self-reported race and ethnicity, primary disease, receipt of chemotherapy in the past 30 days before sample collection, hematopoietic cell transplant (HCT) history, and date of most recent intravenous immunoglobulin treatment were abstracted from electronic medical records. Main outcomes and measures Measles and mumps IgG seroprevalence, defined as the proportion of patients with positive antibody test results, was measured overall and among the subgroups. Results Of the 959 patients included in the analysis, 510 (53%) were male individuals and the mean (SD) age at sample collection was 60 (15) years. Most patients (576 [60%]) had a malignant solid tumor, and 383 patients (40%) had a hematologic malignant neoplasm; 146 patients (15%) had an HCT history. Overall, the seroprevalence of measles antibodies was 0.75 (95% CI, 0.72-0.78), and the seroprevalence of mumps antibodies was 0.62 (95% CI, 0.59-0.65). The lowest seroprevalences were among patients with a hematologic malignant neoplasm (0.63 for measles and 0.48 for mumps), those with a history of HCT (0.46 for measles and 0.29 for mumps), and those aged 30 to 59 years (0.49-0.63 for measles and 0.41-0.58 for mumps). Conclusions and relevance In this study, 25% of ambulatory patients with cancer lacked protective antibodies for measles and 38% lacked protective antibodies for mumps. Deficits in protective antibodies underscore patients' increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population.

Blood and marrow transplantation during the emerging COVID-19 pandemic: the Seattle approach.

Abstract: On January 20, 2020, the first patient with coronavirus disease 2019 (COVID-19) in the United States of America was diagnosed in Washington state, which subsequently experienced rapidly increasing numbers of COVID-19 cases, hospitalizations, and deaths. This placed the Seattle Blood and Marrow Transplant Program at Fred Hutchinson Cancer Research Center (Fred Hutch) in the national epicenter of this pandemic. Here, we summarize the experience gained during our rapid response to the COVID-19 pandemic. Our efforts were aimed at safely performing urgent and potentially life-saving stem cell transplants in the setting of pandemic-related stresses on healthcare resources and shelter-in-place public health measures. We describe the unique circumstances and challenges encountered, the current state of the program amidst evolving COVID-19 cases in our community, and the guiding principles for recovery. We also estimate the collateral impact of directing clinical resources toward COVID-19-related care on cancer patients in need of stem cell transplantation. Although our experience was influenced by specific regional and institutional factors, it may help inform how transplant programs respond to COVID-19 and future pandemics.

Cytomegalovirus (CMV) management in allogeneic hematopoietic cell transplantation: Pre-transplant predictors of survival, reactivation, and spontaneous clearance

Abstract: BACKGROUND: Cytomegalovirus (CMV) reactivation is a frequent complication after allogeneic hematopoietic cell transplant (alloHCT). METHOD: We analyzed 159 alloHCT recipients with 4409 quantitative CMV viral loads to determine pre-transplant predictors of CMV reactivation, clinically significant CMV infection (cs-CMVi, defined as CMV viral load >1000 IU/mL), CMV disease, kinetics of spontaneous clearance of CMV, and survival using a standardized pre-emptive therapy approach to identify at-risk groups to target prevention strategies. RESULTS: Cs-CMVi was most common in D-/R+ unrelated donor transplants (URD). Spontaneous CMV clearance occurred in 26% of patients who reached a viral load of 56-137 IU/mL, 6% at 138-250 IU/mL and in one patient >250 IU/mL. Median time between the first CMV reactivation (>56 IU/mL) and a viral load >250 IU/mL was 13 days, whereas the time from the first viral load >250 IU/mL to reach a vial load >1000 IU/mL was 4 days. Cs-CMVi was associated with a significant increase in non-relapse mortality (NRM) on multivariate analysis. CONCLUSIONS: Overall, this study indicates that D-/R+ URD recipients are at high-risk for cs-CMVi- and CMV-related mortality, and are potential candidates for targeted CMV prophylaxis. Spontaneous clearance of CMV beyond a viral load of 250 IU/mL is uncommon, suggesting that this could be used as an appropriate threshold to initiate pre-emptive therapy.

Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy

Abstract: Recipients of chimeric antigen receptor-modified T (CAR-T) cell therapies for B-cell malignancies are immunocompromised and at risk for serious infections. Vaccine immunogenicity is unknown in this population. We conducted a prospective observational study of the humoral immunogenicity of 2019-2020 inactivated influenza vaccines (IIV) in children and adults immediately prior to (n=7) or 13-57 months after (n=15) CD19-, CD20-, or BCMA-targeted CAR-T-cell therapy, as well as controls (n=8). Individuals post-CAR-T-cell therapy were in remission. We tested for antibodies to 4 vaccine strains at baseline and ≥1 time point after IIV using neutralization and hemagglutination inhibition assays. An antibody response was defined as a ≥4-fold titer increase from baseline at the first post-vaccine time point. Baseline A(H1N1) titers in the CAR-T cohorts were significantly lower compared to controls. Antibody responses to ≥1 vaccine strain occurred in 2 (29%) individuals before CAR-T-cell therapy; one individual maintained a response for >3 months post-CAR-T-cell therapy. Antibody responses to ≥1 vaccine strain occurred in 6 (40%) individuals vaccinated after CAR-T-cell therapy. An additional 2 (29%) and 6 (40%) individuals had ≥2-fold increases (at any time) in the pre- and post-CAR-T cohorts, respectively. There were no identified clinical or immunologic predictors of antibody responses. Neither severe hypogammaglobulinemia nor B-cell aplasia precluded antibody responses. These data support consideration for vaccination before and after CAR-T-cell therapy for influenza and other relevant pathogens such as SARS-CoV-2, irrespective of hypogammaglobulinemia or B-cell aplasia. Larger studies are needed to determine correlates of vaccine immunogenicity and durability in CAR-T-cell therapy recipients. Key Points Influenza vaccination was immunogenic pre- and post-CAR-T-cell therapy, despite hypogammaglobulinemia and B-cell aplasia. Vaccination with inactivated vaccines can be considered before CAR-T-cell therapy and in individuals with remission after therapy.

Development and Validation of a Machine Learning Model to Estimate Bacterial Sepsis Among Immunocompromised Recipients of Stem Cell Transplant.

Abstract: Importance Sepsis disproportionately affects recipients of allogeneic hematopoietic cell transplant (allo-HCT), and timely detection is crucial. However, the atypical presentation of sepsis within this population makes detection challenging, and existing clinical sepsis tools have limited prognostic value among this high-risk population. Objective To develop a full risk factor (demographic, transplant, clinical, and laboratory factors) and clinical factor-specific automated bacterial sepsis decision support tool for recipients of allo-HCT with potential bloodstream infections (PBIs). Design, setting, and participants This prognostic study used data from adult recipients of allo-HCT transplanted at the Fred Hutchinson Cancer Research Center, Seattle, Washington, between June 2010 and June 2019 randomly divided into 70% modeling and 30% validation data sets. Tools were developed using the area under the curve (AUC) optimized SuperLearner, and their performance was compared with existing clinical sepsis tools: National Early Warning Score (NEWS), quick Sequential Organ Failure Assessment (qSOFA), and Systemic Inflammatory Response Syndrome (SIRS), using the validation data set. Data were analyzed between January and October of 2020. Main outcomes and measures The primary outcome was high-sepsis risk bacteremia (culture confirmed gram-negative species, Staphylococcus aureus, or Streptococcus spp bacteremia), and the secondary outcomes were 10- and 28-day mortality. Tool discrimination and calibration were examined using accuracy metrics and expected vs observed probabilities. Results Between June 2010 and June 2019, 1943 recipients of allo-HCT received their first transplant, and 1594 recipients (median [interquartile range] age at transplant, 54 [43-63] years; 911 [57.2%] men; 1242 individuals [77.9%] identifying as White) experienced at least 1 PBI. Of 8131 observed PBIs, 238 (2.9%) were high-sepsis risk bacteremia. Compared with high-sepsis risk bacteremia, the full decision support tool had the highest AUC (0.85; 95% CI, 0.81-0.89), followed by the clinical factor-specific tool (0.72; 95% CI, 0.66-0.78). SIRS had the highest AUC of existing tools (0.64; 95% CI, 0.57-0.71). The full decision support tool had the highest AUCs for PBIs identified in inpatient (0.82; 95% CI, 0.76-0.89) and outpatient (0.82; 95% CI, 0.75-0.89) settings and for 10-day (0.85; 95% CI, 0.79-0.91) and 28-day (0.80; 95% CI, 0.75-0.84) mortality. Conclusions and relevance These findings suggest that compared with existing tools and the clinical factor-specific tool, the full decision support tool had superior prognostic accuracy for the primary (high-sepsis risk bacteremia) and secondary (short-term mortality) outcomes in inpatient and outpatient settings. If used at the time of culture collection, the full decision support tool may inform more timely sepsis detection among recipients of allo-HCT.

Clinical and Virologic Characteristics and Outcomes of Coronavirus Disease 2019 at a Cancer Center

Abstract: Background High morbidity and mortality have been observed in patients with cancer and coronavirus disease 2019 (COVID-19); however, there are limited data on antimicrobial use, coinfections, and viral shedding. Methods We conducted a retrospective cohort study of adult patients at the Seattle Cancer Care Alliance diagnosed with COVID-19 between February 28, 2020 and June 15, 2020 to characterize antimicrobial use, coinfections, viral shedding, and outcomes within 30 days after diagnosis. Cycle threshold values were used as a proxy for viral load. We determined viral clearance, defined as 2 consecutive negative results using severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction results through July 30, 2020. Results Seventy-one patients were included with a median age of 61 years; 59% had a solid tumor. Only 3 patients had documented respiratory bacterial coinfection. Empiric antibiotics for pneumonia were prescribed more frequently early in the study period (February 29-March 28, 2020; 12/34) compared to the later period (March 29-June 15, 2020; 2/36) (P = .002). The median number of days from symptom onset to viral clearance was 37 days with viral load rapidly declining in the first 7-10 days after symptom onset. Within 30 days of diagnosis, 29 (41%) patients were hospitalized and 12 (17%) died. Each additional comorbidity was associated with 45% lower odds of days alive and out of hospital in the month following diagnosis in adjusted models. Conclusions Patients at a cancer center, particularly those with multiple comorbidities, are at increased risk of poor outcomes from COVID-19. Prolonged viral shedding is frequently observed among cancer patients, and its implications on transmission and treatment strategies warrant further study.

Association of Physician Orders for Life-Sustaining Treatment With Inpatient Antimicrobial Use at End of Life in Patients With Cancer.

Abstract: Background Antimicrobial utilization at end of life is common, but whether advance directives correlate with usage is unknown. We sought to determine whether Washington State Physician Orders for Life Sustaining Treatment (POLST) form completion or antimicrobial preferences documented therein correlate with subsequent inpatient antimicrobial prescribing at end of life. Methods This was a single-center, retrospective cohort study of adult patients at a cancer center who died between January 1, 2016, and June 30, 2019. We used negative binomial models adjusted for age, sex, and malignancy type to test the relationship between POLST form completion ≥30 days before death, antimicrobial preferences, and antimicrobial days of therapy (DOT) per 1000 inpatient-days in the last 30 days of life. Results Among 1295 eligible decedents with ≥1 inpatient-day during the last 30 days of life, 318 (24.6%) completed a POLST form. Of 318, 120 (37.7%) were completed ≥30 days before death, 35/120 (29.2%) specified limited antimicrobials, 55/120 (45.8%) specified full antimicrobial use, and 30/120 (25%) omitted antimicrobial preference. Eighty-three percent (1070/1295) received ≥1 inpatient antimicrobial. The median total and intravenous (IV) antimicrobial DOT/1000 inpatient-days were 1077 and 667. Patients specifying limited antimicrobials had significantly lower total antimicrobial DOT (adjusted incidence rate ratio [IRR], 0.68; 95% CI, 0.49-0.95; P = .02) and IV antimicrobial DOT (IRR, 0.57; 95% CI, 0.38-0.86; P = .008) compared with those without a POLST. Conclusions Indicating a preference for limited antimicrobials on a POLST form ≥30 days before death may lead to less inpatient antimicrobial use in the last 30 days of life.

Outcomes of Hematopoietic Cell Transplantation in Patients with Mixed Response to Pretransplantation Treatment of Confirmed or Suspected Invasive Fungal Infection

Abstract: Patients with hematologic malignancy or bone marrow failure are typically required to achieve radiographic improvement or stabilization of invasive fungal infection (IFI) before hematopoietic cell transplantation (HCT) owing to a concern for progression before engraftment. Refractory IFI with a mixture of improvement and progression on serial imaging (ie, mixed response) poses a clinical dilemma, because a delay in HCT may allow for a hematologic relapse or other complications. Furthermore, HCT itself may yield the immune reconstitution necessary for clearance of infection. We sought to describe the characteristics and outcomes of patients who underwent HCT with mixed response IFI. We performed a chart review of all patients who underwent HCT between 2014 and 2020 in whom imaging within 6 weeks before HCT indicated a mixed response to treatment of a diagnosed IFI. Fourteen patients had evidence of a mixed response in low-to-moderate burden of diagnosed IFI by imaging before HCT, including 9 with pulmonary aspergillosis, 2 with hepatosplenic candidiasis (1 also with aspergillosis), and 4 with pulmonary nodules of presumed fungal etiology. Five had refractory severe neutropenia at evaluation for HCT (median, 95 days). All 14 patients showed radiographic stability or improvement in imaging following engraftment; no IFI-related surgeries were required, and no IFI-related deaths occurred. For patients without relapse who underwent HCT more than 1 year earlier, 7 of 8 (88%) were alive at 1 year. Our findings suggest that low-to-moderate burden IFI with mixed response is unlikely to progress on appropriate therapy before engraftment during allogeneic HCT.

Cannabis and the Cancer Patient.

Abstract: Session 2 of the National Cancer Institute's Cannabis, Cannabinoids, and Cancer Research Workshop opened with testimony from a lymphoma survivor who detailed medicinal cannabis-related improvements in nausea, low appetite, insomnia, and mental health and the limited clinical counsel she received regarding cannabis use. Discussion next turned to the evolution of the legal landscape of cannabis in the United States, one in which state and federal laws frequently conflict and the Controlled Substance Act renders cannabis Schedule I. This legal climate creates conundrums for US medicinal cannabis researchers who contend with limited funding opportunities, avenues to source trial drug, and procedural red tape and for oncology clinicians who recommend medicinal cannabis to patients with some frequency while perceiving themselves as ill equipped to make such clinical recommendations. Ultimately, it creates challenges for cancer patients who find themselves turning to nonmedical and anecdotal information sources. The risks of cannabis use by the cancer patient were discussed next. These include infection, pharmacodynamic and pharmacokinetic drug-botanical interactions, cyclic nausea and vomiting, e-cigarette or vaping product use-associated illness, legal issues, and high cost. The session concluded with a broad survey of the research supporting oncologic cannabinoid use, conclusive evidence for chemotherapy-induced nausea and vomiting, and suggestive evidence for cancer-related pain.

Advanced practice providers in the infectious disease workforce: A Nationwide utilization survey

Abstract: Background Shortages of infectious disease (ID) physicians is an identified workforce problem. The COVID-19 pandemic has exacerbated this care gap, leaving many communities without access to an ID physician. More advanced practice providers (APPs), specifically nurse practitioners and physician assistants, work as healthcare extenders, yet are not well described in ID. Purpose Evaluate collaboration between ID physicians and APPs, and potential barriers to utilization of APPs. Methods Anonymous and voluntary surveys; one for physicians, another for APPs. We collected experience, practice setting, familiarity regarding APPs in ID, use of APPs, and perceived barriers/concerns for utilization of APPs. Discussion Nationwide, 218 ID physicians and 93 APPs in ID responded. 71% (155) of ID physicians use APPs. Of APPs, 53% (49) had > 5 years ID experience. Responses highlighted opportunities for dedicated ID education, collaboration, and clarification of practice scope. Conclusion APPs are an experienced group who provide ID care, working alongside physicians to meet ID workforce needs.

Limits of the Glasgow Coma Scale When Assessing for Sepsis in Allogeneic Hematopoietic Cell Transplant Recipients.

Abstract: Background The well-documented association between acute mental status changes and sepsis development and progression makes acute mental status an attractive factor for sepsis screening tools. However, the usefulness of acute mental status within these criteria is limited to the frequency and accuracy of its capture. The Glasgow Coma Scale (GCS) score-the acute mental status indicator in many clinical sepsis criteria-is infrequently captured among allogeneic hematopoietic cell transplant recipients with suspected infections and its ability to serve as an indicator of acute mental status among this high-risk population is unknown. Objective We evaluated the GCS score as an indicator of acute mental status during the 24 hr following suspected infection onset among allogeneic hematopoietic cell transplant recipients. Methods Using data from the first 100 days posttransplant for patients transplanted at a single center between September 2010 and July 2017, we evaluated the GCS score as an indicator of documented acute mental status during the 24 hr following suspected infection onset. From all inpatients with suspected infections, we randomly selected a cohort based on previously published estimates of GCS score frequency among hematopoietic cell transplant recipients with suspected infections and performed chart review to ascertain documentation of clinical acute mental status within the 24 hr following suspected infection onset. Results A total of 773 patients had ≥1 suspected infections and experienced 1,655 suspected infections during follow-up-625 of which had an accompanying GCS score increase. Among the randomly selected cohort of 100 persons with suspected infection, 28 were accompanied with documented acute mental status including18 without a recorded GCS. In relation to documented acute mental status, the GCS had moderate to high sensitivity and high specificity. Discussion These data indicate that among allogeneic hematopoietic cell transplant recipients with suspected infections, the GCS scores are infrequently collected and has a moderate sensitivity. If sepsis screening tools inclusive of acute mental status changes are to be used, nursing teams need to increase measurement of GCS scores among high sepsis-risk patients or identify a standard alternative indicator.

Dynamics of Epstein Barr virus on post-transplant lymphoproliferative disorders after anti-thymocyte globulin-conditioned allogeneic hematopoietic cell transplant

Abstract: BACKGROUND: The use of antithymocyte globulin (ATG) in allogeneic hematopoietic cell transplant (HCT) is associated with an increased risk of Epstein-Barr virus (EBV) reactivation and post-transplant lymphoproliferative disorders (PTLD). The dynamics and outcomes of EBV-DNAemia are not well described in this population. METHODS: We retrospectively assessed the kinetics of EBV-DNAemia after ATG conditioning of HCT recipients. Receiver operating characteristic (ROC) curves were used to assess EBV-DNAemia to predict EBV-PTLD in this group. RESULTS: A total of 174/405 (43%) consecutive HCT recipients from two centers met inclusion criteria of ATG conditioned, non-B-cell lymphoma patients. Of these with EBV-DNA measured using standardized IU/ml, 78.6% (92/117) developed EBV-DNAemia: 62% spontaneously resolved; 19% cleared after preemptive rituximab, and 13% developed EBV-PTLD. ROC curve analysis using maximum pre-EBV-PTLD EBV-DNAemia, demonstrated an AUC of 0.912 with EBV-DNAemia of 9782 IU/ml, associated with 82.6% sensitivity and 94.4% specificity for development of EBV-PTLD. Median time for EBV-DNAemia to increase from initial detection to >1000 IU/ml was 7 days; to >10 000 IU/ml, 12 days; and to >100 000 IU/ml, 18 days. Median EBV-DNAemia level prior to administration of rituximab was significantly lower in patients with successful preemptive treatment, compared with those who developed EBV-PTLD (3.41 log10 IU/ml [3.30-3.67] vs. 4.34 log10 IU/ml [3.85-5.13], p = .002; i.e., 2628 IU/ml vs. 21 965 IU/ml, respectively). CONCLUSIONS: EBV-DNAemia >10 000 IU/ml was the strongest predictor of the development of EBV-PTLD, and progression to this level was rapid in ATG-conditioned HCT recipients. This information may guide EBV-PTLD management strategies in these high-risk patients.

Are hematopoietic cell transplant recipients with Gram-negative bacteremia spending more time outpatient while on intravenous antibiotics? Addressing trends over 10 years at a single center.

Abstract: Introduction The increasing proportion of outpatient allogeneic hematopoietic cell transplants (HCTs) coupled with increased access of once-daily broad-spectrum antibiotics and evidence that outpatient antibiotic treatment may be safer and less costly than inpatient treatment, suggest that allogeneic HCT recipients with Gram-negative rod bacteremia (GNRBs) are increasingly being treated in ambulatory care settings. Methods Using data from the first GNRB event that occurred within the first 100 days posttransplantation among allogeneic HCT recipients transplanted at a single center between 2007 and 2016, we estimated the temporal trends in GNRB incidence and treatment management of GNRBs and identified if patient or infection characteristics impacted observed trends. Results A total of 11% (238/2165) of the observed allogeneic HCT recipients experienced ≥1 GNRB with available resistance data and contributed antibiotic treatment time. Patients, on average, received 55.1% of their antibiotic treatment in an outpatient setting and we observed a significant decline in the proportion of treatment time spent outpatient (crude: -3.3% [95% confidence interval: -5.0, -1.6%]). We observed similar declines in the proportion of treatment time spent outpatient among patients with similar GNRB and pretransplant complexity factors but not among patients with similar posttransplant complications (p value: .165). Conclusion These results suggest that, despite increased availability of outpatient suitable treatment options, allogeneic HCT recipients with GNRBs received less treatment in outpatient settings. However, among patients with similar posttransplant complications, the lack of significant decline suggests that treatment location decisions remained consistent for patients with similar posttransplant complications. These findings suggest the need for additional interventions targeting outpatient antibiotic treatment among allogeneic HCT recipients with GNRBs.

Infection-Related Mortality in Adults and Children Undergoing Allogeneic Hematopoietic Cell Transplantation: An Australian Registry Report.

Abstract: Infection-related mortality (IRM) is the most common non-relapse-related cause of death reported after allogeneic hematopoietic cell transplantation (HCT). Information on the incidence and timing of specific infective organisms and the risk factors for IRM is essential to developing prevention strategies. This report provides the first account of IRM in adults and children undergoing HCT in Australia. Between 2013 and 2018, 2705 adult and 689 pediatric first HCTs were identified from the Australasian Bone Marrow Transplant Recipient Registry database, associated with 1075 (39.7%) total overall deaths in adults and 134 (19.4%) in children. Demographics and causes of death, including infectious etiology and causative organisms, were extracted from the database for adults and children for analysis. At day +100 and 1 year post-HCT, IRM was the leading cause of early post-HCT mortality in adults, accounting for 6.2% and 9.8%, respectively; in children, IRM was the leading cause of post-HCT mortality at day +100 at 2.5% and the second highest cause of post-HCT mortality at 1 year post-HCT at 4.9%, following relapse at 5.8%. In adults, older age, transplantation not in a first complete remission (non-CR1), the use of antithymocyte globulin (ATG) or alemtuzumab, donor-positive/recipient-negative cytomegalovirus (CMV) serostatus, and acute graft-versus-host disease were significant risk factors for IRM. However, in children, age >5 years, acute lymphocytic leukemia as the primary disease, and mismatched unrelated or haploidentical donor source were predictive of IRM. Of the deaths in which an infectious etiology was reported in adults (52.4%), 49.3% were attributed to bacteria, 25.3% to fungus, 21.7% to viruses, and 3.6% to post-transplantation lymphoproliferative disorder (PTLD). The most common organisms were Pseudomonas spp, Enterococcus spp, Candida spp, Aspergillus spp, and CMV. In children where an infectious etiology was reported (64%), 13% were attributed to bacteria, 26% to fungus, 45% to viruses, and 16% to PTLD. This report highlights that IRM was the leading cause of death early post-HCT in Australia. Strategies to reduce IRM, such as individualized pre-transplantation infection risk assessment, rapid diagnostics, and prevention management strategies should be explored to determine whether these outcomes can be improved. In addition, improving the completeness and accuracy of reported data, particularly for infectious pathogens, could assist in directing management strategies to reduce IRM in HCT.