Overall Infectious Complications Related to Belatacept Conversion in Comparison to Tacrolimus in Kidney Transplant Recipients.

Introduction: Belatacept has demonstrated effectiveness for preventing rejection in kidney transplant and has a favorable side effect profile. Studies assessing long-term infectious complications with belatacept compared to tacrolimus are limited. Project Aims: The purpose of this program evaluation was to determine the proportion of patients who developed an infection when converted to belatacept compared to those on tacrolimus. Design: In this retrospective evaluation, kidney transplant recipients receiving belatacept were matched 1:1 to those receiving tacrolimus, based on transplant date, age, induction immunosuppression, and cytomegalovirus risk. Data collection was initiated in tacrolimus patients on the date of belatacept conversion in the belatacept-matched patients. Data were extracted until study conclusion, death, or discontinuation of belatacept. Patients were stratified into 3 groups based on time of conversion posttransplant, which included early, late, and very late conversion. The primary outcome was the proportion of patients with an infection in belatacept compared to tacrolimus. Outcome data were calculated using chi-square, Fisher's exact test, student's t-test or Mann-Whitney U test where appropriate. Results: A total of 328 matched patients were included in the analysis. More patients on belatacept developed an infection compared to tacrolimus (42.7% vs 29.9%, P = 0.02), which was primarily driven by pneumonia (6.1% vs 0.5%; P = 0.01). Higher incidences of infections were identified in those converted within 6 months from transplant. Conclusions: Belatacept was associated with a higher proportion of patients with infections compared to tacrolimus, particularly in those converted within 6 months from time of transplant.

Rectal screening for azole non-susceptible Candida species in patients undergoing liver transplantation.

INTRODUCTION: Candidiasis is the most common invasive fungal infection in solid organ transplant recipients, and liver transplant (LT) recipients are at heightened risk. We hypothesized that pre-transplant screening for azole non-susceptible Candida (ANSC) allows for tailored antifungal prophylaxis to reduce the incidence of post-LT ANSC infection. METHODS: We performed a retrospective chart review of adult (age ≥18 years) patients who underwent LT at Yale New Haven Hospital from April 2019 to March 2021. Screening for ANSC, defined as Candida glabrata or Candida krusei, was performed using a rectal swab prior to or at the time of LT. RESULTS: During the study period, ANSC screening was performed in 47 patients who underwent a total of 48 LTs, with 46/48 (96%) primary LTs and two re-transplantations. Ten of 48 screened cases (21%) had ANSC-positive rectal swabs. Only seven of 10 ANSC-colonized patients received appropriate antifungal prophylaxis (i.e., anidulafungin), and one of these seven patients developed candidemia within 30 days of LT. The median number of candidiasis risk factors was one, and 29% of the cohort had two or more risk factors. DISCUSSION: Routine ANSC screening of LT candidates may assist in selecting appropriate antifungal prophylaxis but may be insufficient to prevent infection in those with multiple risk factors for Candida infection.

Genetic and Epidemiologic Analyses of an Outbreak of Pneumocystis jirovecii Pneumonia Among Kidney Transplant Recipients in the United States.

BACKGROUND: Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. METHODS: Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. RESULTS: Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. CONCLUSIONS: Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.

Review and drug therapy implications of glucose-6-phosphate dehydrogenase deficiency.

PURPOSE: The pathophysiology, diagnosis, and medication-use implications of glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzyme deficiency in humans, are reviewed. SUMMARY: Originally identified as favism in patients who experienced hemolysis after ingestion of fava beans, G6PD deficiency results from an X-linked chromosomal mutation that leads to reduced activity of the enzyme responsible for the final step of the pentose phosphate pathway, through which reduced nicotinamide adenine dinucleotide phosphate required for protection of cells from oxidative stress is produced. G6PD deficiency affects about 400 million people worldwide. Diagnosis of G6PD can be made through detection of enzymatic activity (by spectrophotometric testing, fluorescence testing, or formazan-based spot testing) or molecular analysis to detect known mutations of the gene encoding G6PD. Most individuals with G6PD deficiency are asymptomatic throughout life. Symptoms of acute hemolysis associated with G6PD deficiency include anemia, fatigue, back or abdominal pain, jaundice, and hemoglobinuria. The most common precipitators of oxidative stress and hemolysis in G6PD deficiency include medication use and infection. CONCLUSION: G6PD deficiency should be considered in patients who experience acute hemolysis after exposure to known oxidative medications, infection, or ingestion of fava beans. A diagnosis of G6PD deficiency is most often made through enzymatic activity detection, but molecular analysis may be required in females heterozygous for the disorder. When clinically feasible, rasburicase, primaquine, dapsone, pegloticase, and methylene blue should not be used until a G6PD diagnostic test has been performed.

Impact of A Collaborative Strategy to Reduce the Inappropriate Use of Acid Suppressive Therapy in Non-Intensive Care Unit Patients.

BACKGROUND: Stress ulcer prophylaxis (SUP) is inappropriately prescribed in more than 30% of non-intensive care unit (ICU) patients, leading to unnecessary adverse events as well as increases in economic burden. OBJECTIVE: There was an increasing trend in the prophylactic use of acid suppressive therapy (AST) in non-critically ill patients at our institution, which prompted this initiative aimed at reducing the inappropriate use of AST in non-ICU patients. METHODS: This was a retrospective interventional study that consisted of formulation of a guideline, education to the hospitalist service, and intervention by clinical pharmacists. All adult non-ICU patients admitted to the hospitalist service who were newly initiated on AST were considered for inclusion. The primary outcome was a comparison of the proportion of inpatient days with inappropriate AST. Secondary outcomes included a comparison of patients discharged on inappropriate AST and drug acquisition costs, successful pharmacy interventions, hospitalist interventions, incidence of Clostridium difficile infection (CDI) or gastrointestinal (GI) bleeding, and drug costs averted through pharmacy intervention. RESULTS: There were 61 patients in the historical group and 81 patients in the interventional group. This intervention resulted in a 31% absolute reduction in inappropriate patient days of AST and a 24% absolute reduction in patients discharged on inappropriate AST. There were 23 successful interventions. There were no cases of CDI and 1 GI bleed. This intervention resulted in an 87% reduction in drug acquisition costs per patient. CONCLUSIONS: A collaboration between clinical pharmacists and a hospitalist service can significantly reduce the inappropriate use of AST in non-ICU patients.