Beta Lactam and Other Antibiotic Allergies in Solid Organ and Hematopoietic Cell Transplant Recipients

Thesis (Master's)--University of Washington, 2019Background Patients with reported beta lactam antibiotic allergies (BLA) are more likely to receive broad-spectrum antibiotics and experience adverse outcomes. Data on the burden of beta lactam and other antibiotic allergies among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients are limited. Methods We reviewed records of first-time adult SOT or allogeneic HCT recipients from 1/1/2013-12/31/2017 to characterize allergy labels at time of transplant. Days of hospitalization and inpatient antibiotic use for pre-specified antimicrobials were examined for the first 100 days post-transplant. Incidence rate ratios (IRR) comparing antibiotic use in BLA and non-BLA groups were calculated using negative binomial models for two metrics: days of therapy (DOT)/1000 inpatient days and percentage of antibiotic exposure days, both adjusted for transplant type, age, and cystic fibrosis diagnosis. Results Among 2153 SOT (65%) and HCT (35%) recipients, 634 (29%) reported any antibiotic allergy and 347 (16%) reported BLAs. BLA patients had significantly higher DOT for vancomycin (IRR 1.4 [1.2 – 1.7], p<0.001), clindamycin (IRR 7.6 [2.2 – 32.4], p=0.001), aztreonam in HCT (IRR 9.7 [3.3 – 35.0], p<0.001), fluoroquinolones in SOT (IRR 2.9 [2.1 – 4.0], p<0.001) and lower DOT for ampicillin-sulbactam (IRR 0.1 [0.0 – 0.4], p<0.001) and piperacillin-tazobactam (IRR 0.4 [0.2 – 0.6], p<0.001) compared to non-BLA patients; these findings were consistent when using percentage of antibiotic exposure days. Conclusions Transplant recipients have a high burden of reported antibiotic allergies, and reported BLA was significantly associated with altered post-transplant antibiotic prescribing. Pre-transplant allergy evaluation may optimize antibiotic stewardship in this population

Risk factors for infection in HIV-infected patients

Background: Clostridium difficile infection is a healthcare-associated infection resulting in significant morbidity. Although immunosuppression is associated with Clostridium difficile infection acquisition and adverse outcomes, the epidemiology of Clostridium difficile infection in HIV-infected patients has been little studied in the era of antiretroviral therapy. This study identifies the risk factors for acquisition of Clostridium difficile infection in HIV-infected patients. Methods: A retrospective, propensity score–matched case–control study design was employed, with patients selected from our institution’s outpatient HIV clinic. Clostridium difficile infection cases were defined as having positive stool testing plus an appropriate clinical presentation. The propensity score was generated via multiple logistic regression from year of HIV diagnosis, age at first contact, duration of follow-up, gender, and initial CD4 count. Results: The 46 cases included were matched to a total of 180 controls. Prior antibiotic treatment was a significant predictor of Clostridium difficile infection (odds ratio: 13, 95% confidence interval: 3.49–48.8, p  < .001) as was number of hospital admissions in the preceding year (odds ratio: 4.02, confidence interval: 1.81–8.94, p  < .001). Having both proton pump inhibitor use and CD4 count <200 cells/µL significantly increased odds of Clostridium difficile infection in the multivariable model (odds ratio: 15.17, confidence interval: 1.31–175.9, p  = .021). Conclusion: As in the general population, frequent hospitalizations and exposure to antimicrobials are independent predictors of Clostridium difficile infection acquisition in patients with HIV. Additionally, low CD4 count and proton pump inhibitor use are new potentially modifiable variables that can be targeted for prevention of Clostridium difficile infection in future interventional studies

Evaluation of foliar-applied insecticides to control insect pests of alfalfa in Illinois, 2008

Annual summary of field crop insect management trials, Department of Crop Services, University of Illinois. Providing accurate and unbiased evaluations of insect control products and management strategies to assist growers in Illinois.University of Illinois Extension and Department of Crop Science

493. Incidence and Characterization of Chronic Active COVID Among Patients Infected with the Novel Coronavirus (COVID-19) Receiving B-cell Depleting Therapies (BCDTs)

BACKGROUND: There have been reports of COVID-19 infection characterized by prolonged viral replication [chronic active COVID-19 (CAC)] among immunocompromised patients, including those receiving B-cell depleting therapies (BCDTs). We aimed to characterize the severity and incidence of CAC among patients on BCDTs with COVID-19, and to identify associated risk factors. METHODS: We retrospectively reviewed all patients who received an anti-CD20 BCDT within 1 year of a positive COVID test at University of Utah Health. Demographics, comorbidities, indications, and timing of BCDT were documented. Chart review was performed to characterize the clinical course, including need for hospitalization, COVID-specific therapies, need for ICU and ventilatory support, and mortality. We defined CAC as: (1) despite initial clinical improvement, progression of illness extending beyond 14 days, characterized by ongoing fevers or progressive respiratory failure; or (2) ongoing symptoms with demonstration of absent seroconversion ≥ 14 days into illness. In some patients the diagnosis of CAC was supported by low viral PCR crossing thresholds that occurred ≥ 14 days into illness. Logistic models were used to identify risk factors for CAC among the cohort of patients who survived through the initial period of infection. RESULTS: We identified 66 individuals who received a BCDT within 1 year of a positive COVID test; 29 (44%) were hospitalized, 4 (6%) required ventilation, and 7 (11%) died within 60 days. Among 63 patients who survived their initial COVID course, 16 (25%) had courses compatible with CAC. Nine (56%) who received a BCDT within 1 month before or 2 weeks after their COVID diagnosis developed CAC; OR 7.4 (95% CI 1.7, 31.6, p=0.002). [Image: see text] [Image: see text] CONCLUSION: We clinically observed COVID-19 infection lasting longer than the typical course and propose a definition for CAC. Incidence of CAC was highest among patients who received BCDT within 30 days before or 2 weeks after COVID-19 diagnosis. High suspicion for CAC is warranted among patients receiving these therapies. Additional study is needed to better define risk for CAC among varying immunosuppressed populations and determine whether COVID-specific treatments early in disease may benefit these patients. DISCLOSURES: Hannah Imlay, MD, MS, Gilead Sciences, Inc. (Scientific Research Study Investigator

Identifying causes of persistent HIV viremia in adult patients at an academic medical center

Objectives: Despite many advances in medicine, not all individuals with HIV are able to achieve complete virologic suppression. This retrospective study identifies variables associated with persistent HIV viremia in an academic clinic. Methods: We studied 66 HIV-infected patients with a viral load of >200 copies/mL over 1 year, with controls matched 1:1 via a propensity score utilizing age at diagnosis, era of diagnosis, gender, and initial CD4 count. We collected data on multiple variables including medications, adherence, comorbidities, hospitalizations, and insurance status. Conditional logistic regression was used for unadjusted and adjusted analyses. Results: A total of 66 viremic cases/matched controls were included. Fewer viremic patients were on antiretroviral therapy for all 12 months (45% vs 77%; odds ratio: 0.33, p  = .018) and fewer were of white race (52% vs 70%; odds ratio: 0.49, p  = .053). Hospitalization (11% vs 3%; odds ratio: 10, p  = .028), underinsurance (20% vs 1%; odds ratio: 5.87, p  = .022), and conflicting personal beliefs about their disease (17% vs 3%; odds ratio: 5.5, p  = .027) were more common in viremic patients. Psychiatric illness increased the odds of viremia in patients who had four or more visits (odds ratio: 1.63/6.64 with four/five clinic visits, respectively). Conclusion: Psychiatric illness is an important contributor to the presence of persistent viremia in HIV-infected patients and deserves further study

Positivity of repeat nasal MRSA PCR screening: a single-center experience

Repeating nasal methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reactions (PCRs) within 14 days may increase healthcare costs and inform anti-MRSA antibiotic therapy without known benefit. Within an inpatient admission, our retrospective, single-center evaluation found that conversion from negative to positive on repeat nasal MRSA PCR screen was uncommon (2%)

Comparison of Short-Term Outcomes in Kidney Transplant Recipients from SARS-CoV-2-Infected versus Noninfected Deceased Donors.

BACKGROUND: Acceptable posttransplant outcomes were reported in kidney transplant recipients from donors with coronavirus disease-2019 (COVID-19), however, there are no comparative studies with well-matched controls. METHODS: This multicenter, prospective observational study, which included three transplant centers in the US, enrolled 61 kidney recipients from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected deceased donors. Using optimal matching methods, we matched every recipient to three comparators receiving kidneys from SARS-CoV-2-negative deceased donors with otherwise highly similar characteristics within the same transplant centers to compare 6-month eGFR. RESULTS: Among recipients of SARS-CoV-2-infected donor kidneys, one recipient died with a functional graft within 6 months. Mean 6-month eGFR was not significantly different between SARS-CoV-2-infected and non-infected donor groups (55±21 and 57±25 mL/min/1.73m2; p=0.61). Six-month eGFR in recipients from SARS-CoV-2-infected donors who died from reasons other than COVID-19 was not significantly different from those from SARS-CoV-2-negative donors (58±22 and 56±25 mL/min/1.73m2; p=0.51). However, recipients from donors who died from COVID-19 had significantly lower 6-month eGFR that those from SARS-CoV-2-negative donors (46±17 and 58±27 mL/min/1.73m2; p=0.03). No donor-to-recipient SARS-CoV-2 transmission was observed. CONCLUSIONS: Six-month eGFR was not significantly different between recipients of kidneys from SARS-CoV-2-infected and non-infected donors. However, those receiving kidneys from donors who died from COVID-19 had significantly lower 6-month eGFR. Donor-to-recipient SARS-CoV-2 transmission was not observed

Consensus Definitions of BK Polyomavirus Nephropathy in Renal Transplant Recipients for Clinical Trials

Abstract Background BK polyomavirus (BKPyV) infection and BK polyomavirus nephropathy (BKPyVAN) are important causes of allograft dysfunction and premature allograft loss in renal transplant recipients. Results and Discussion Controlled clinical trials to evaluate new agents for prevention and treatment are needed but are hampered by the lack of outcome measures that accurately assess the effect of the intervention, are clinically relevant, and are acceptable from a regulatory perspective. Methods To facilitate consistent end points in clinical trials and to support clinical research and drug development, definitions of BKPyV infection and disease have been developed by the BK Disease Definitions Working Group of the Transplantation Associated Virus Infection Forum with the Forum for Collaborative Research, which consists of scientists, clinicians, regulators, and industry representatives. Conclusions These definitions refine established principles of “proven” BKPyV disease and introduce a “probable” disease category that could be used in clinical trials to prevent or treat BKPyVAN in renal transplant recipients