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Background Methods Results Conclusion Coccidioidomycosis may cause severe disseminated disease and mortality among lung transplant recipients. A strategy of lifelong azole prophylaxis was previously associated with low rates of coccidioidomycosis. Whether lung transplant recipients relocating to the Coccidioides endemic region are also at risk and would benefit from antifungal prophylaxis is unknown.Lung transplant recipients transplanted at an outside center with low Coccidioides endemicity before relocating for post‐transplant follow‐up at a transplant center in Phoenix, Arizona from January 2013 to March 2024 were included. The primary outcome was proven or probable coccidioidomycosis per Mycoses Study Group consensus definitions.Forty lung transplant recipients were included, with 62.5% not receiving antifungal prophylaxis at the time of transfer. The median time from transplant to relocation was 34 months. Of those not on prophylaxis, 96% were initiated on azole therapy at the first clinic visit, with 72% prescribed itraconazole. Coccidioides serologic testing was performed in 30% of the cohort, most often in the context of a broad diagnostic work‐up for suspected infection during hospitalization. After a median follow‐up of 31 months, one case (2.5%) of proven pulmonary coccidioidomycosis was identified, occurring 4.8 years post‐transplant and >2 years post‐transfer in a cystic fibrosis patient who had a pause in fluconazole prophylaxis for >1 month prior to diagnosis due to gastrointestinal intolerance and access issues. The patient was treated and maintained on isavuconazole without complications.Azole antifungal prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients relocating to the highly endemic region. [ABSTRACT FROM AUTHOR]

Infection management in solid organ transplantation poses unique challenges, with a diverse array of potential pathogens and associated antimicrobial therapies. With limited high-quality randomized clinical trials to direct optimal care, therapeutic "myths" may propagate and contribute to suboptimal or excessive antimicrobial use. We discuss 6 therapeutic myths with particular relevance to solid organ transplantation and provide recommendations for infectious diseases clinicians involved in the care of this high-risk population. [ABSTRACT FROM AUTHOR]

The 2023 ACCP Research Affairs Committee was charged with developing a commentary to address best practices in pharmacy resident research and quality improvement projects and to consider methods to overcome the challenges encountered in conducting these projects. Literature regarding best practices was evaluated, and approaches were recommended that might help (1) advance the value of the projects to stakeholders; (2) overcome limited preparation for research by residents and mentors, including writing skills and dissemination experience; (3) overcome challenges related to resources (e.g., time and mentors); and (4) avoid burnout among residents and mentors. Although there are many challenges to completing projects and disseminating the results, studies have provided useful recommendations to help circumvent the barriers. [ABSTRACT FROM AUTHOR]

Background: Coccidioides spp. may cause significant disease requiring hospitalisation, but optimal antifungal therapy among inpatients following outpatient fluconazole exposures is unknown. Objectives: The objective of this study is to describe the effectiveness of fluconazole among patients hospitalised for coccidioidomycosis despite recent outpatient fluconazole treatment. Patients/Methods: Patients were admitted to an academic medical center in Phoenix, Arizona from 1 January 2013 through 31 December 2020 for coccidioidomycosis following at least 30 days of outpatient treatment and re‐initiation of fluconazole upon admission. The primary outcome was the proportion of patients with an improved response per the change in the modified Mycosis Study Group (MSG) score (a composite of symptoms, serology and radiographic findings) and clinician impressions. Results: Sixty‐seven patients were included, with most (54%) admitted to the intensive care unit. Meningitis was the most common infectious presentation (55%), 17 patients (25%) had multiple infection sites, and 23 (34%) were culture‐positive for Coccidioides. Upon admission, the median (IQR) MSG score was 11 (9–14), which dropped to 4 (1–7) at end of therapy or last follow‐up. Overall, after initiation of fluconazole therapy at a median daily dose of 800 mg, 48 patients (72%) improved in overall status, 10 (15%) showed stable disease and 9 (13%) were unresponsive. Improved response rates were high across all infection sites, including meningitis (68%) and bone infection (71%). There was no significant difference in response rates between patients with and without reported outpatient fluconazole nonadherence. Conclusions: The majority of patients admitted to the hospital for coccidioidomycosis appeared responsive to fluconazole therapy despite past outpatient exposures. [ABSTRACT FROM AUTHOR]

Background Lung transplant recipients residing in the endemic region are vulnerable to severe morbidity and mortality from Coccidioides. As infection risk persists beyond the first posttransplant year, investigations evaluating extended prophylaxis durations are needed. The purpose of this study is to assess the incidence of coccidioidomycosis among lung transplant recipients receiving universal lifelong azole antifungal prophylaxis. Methods Patients receiving transplants from 2013–2018 and initiated on azole antifungal prophylaxis at a lung transplant center in Arizona were included and followed through 2019 or until death, second transplant, or loss to follow-up. Recipients who died or received treatment for coccidioidomycosis during the transplant admission, or who had received a previous transplant, were excluded. The primary outcome was proven or probable coccidioidomycosis with new asymptomatic seropositivity assessed secondarily. Results A total of 493 lung transplant recipients were included, with 82% initiated on itraconazole prophylaxis, 9.3% on voriconazole, and 8.5% on posaconazole. Mean age at transplant was 62 years, 77% were diabetic, and 8% were seropositive for Coccidioides pretransplant. After a median follow-up of 31 months, 1 proven infection and 1 case of new asymptomatic seropositivity (1/493 each, 0.2% incidence) occurred during the study period. The single coccidioidomycosis case occurred 5 years posttransplant in a patient who had azole prophylaxis stopped several months prior. Although within-class switches were common throughout the study period, permanent discontinuation of azole prophylaxis was rare (1.4% at end of follow-up). Conclusions Universal lifelong azole prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients residing in endemic regions. [ABSTRACT FROM AUTHOR]

Introduction: National pharmacy organizations advocate for training relating to the investigation and evaluation of scientific evidence. Accordingly, most postgraduate year 1 (PGY1) residents conduct longitudinal research. However, residents typically report low confidence in their research abilities and may benefit from structured training within the residency program. The purpose of this study was to assess how PGY1 programs promote research on their websites, including the proportion offering resident research training. Methods: PGY1 residency programs were identified using the American Society of Health‐System Pharmacists residency directory. Community‐based, managed care, or PGY1/postgraduate year 2 (PGY2) combined programs were excluded. Study data were extracted using the residency directory and program websites and included program characteristics, research requirements, dedicated research time, promotion of past research, research mentorship and support, and research training. Characteristics of the programs with and without research training were compared. Results: Of 1139 PGY1 residency program websites, 3.0% had a highly prominent research section, 19.7% had a clear paragraph relevant to research information, 63.4% had minimal information on research, and 14.0% offered no research information. Forty‐one percent of PGY1 residency programs required dissemination of research findings via poster presentation, platform presentation, or completed manuscript. Fifty‐one programs (4.5%) provided research development training through seminars, a development program, or a certificate program. Compared with programs without research training, these programs were more likely to be fully accredited (100% vs 92.2%, P =.028), offer five or more PGY1 positions (25.5% vs 14.0%, P =.037), and offer one or more PGY2 specialty residencies (60.8% vs 35.6%, P <.001). Conclusion: Most PGY1 program websites had minimal information related to resident research. Although the presentation and dissemination of research was a commonly listed residency requirement, less than 5% of programs indicated that they provide resident research development. Residency program directors should ensure that their program websites accurately reflect their residents' research experience, including development opportunities. [ABSTRACT FROM AUTHOR]

Exosomes isolated from plasma of lung transplant recipients with allograft injury contain donor‐derived lung self‐antigens (collagen V and Kα1 tubulin) and human leukocyte antigen (HLA) molecules. We present a case of a 76‐year‐old, female lung transplant recipient treated for acute cellular rejection with methylprednisolone and anti‐thymocyte globulin, who subsequently contracted SARS‐CoV‐2 and developed a sharp increase in the mean fluorescent intensity of anti‐HLA antibodies. Analysis of circulating exosomes during rejection, but before SARS‐CoV‐2 infection, revealed the presence of lung self‐antigens and HLA class II molecules. After the patient contracted SARS‐CoV‐2, exosomes with the SARS‐CoV‐2 spike protein were also found. After resolution of infectious symptoms, exosomes with SARS‐CoV‐2 spike protein were no longer detected; however, exosomes with lung self‐antigens and HLA class II molecules persisted, which coincided with a progressive decline in spirometric flows, suggesting chronic lung allograft dysfunction. We propose that the analysis of circulating exosomes may be used to detect allograft injury mediated by both rejection and infection. Furthermore, the detection of exosomes containing viral proteins may be helpful in identifying allograft injury driven by viral pathogens. [ABSTRACT FROM AUTHOR]

Background: Lung transplant recipients are at heightened risk for nocardiosis compared to other solid organ transplant recipients, with incidence rates as high as 9% and up to 30% associated mortality. No controlled studies assessing risk factors for nocardiosis in this high‐risk population have been reported. Methods: Patients undergoing lung transplantation at a single center between 2012 and 2018 and diagnosed with nocardiosis post‐transplant were matched 1:2 to uninfected control subjects on the basis of age, transplant date, and sex. Results: The incidence of nocardiosis in this lung transplant population was 3.4% (20/586), occurring a median of 9.4 months (range 4.4‐55.2) post‐transplant. In multivariable analysis, consistent use of trimethoprim/sulfamethoxazole (TMP/SMX) in the 12 weeks prior to diagnosis was independently associated with protection against nocardiosis (OR 0.038; 95% CI 0.01‐0.29; P =.002). Augmented immunosuppression in the 6 months prior to diagnosis was independently associated with the development of nocardiosis (OR 9.94; 95% CI 1.62‐ 61.00; P =.013). Six case patients (30%) had disseminated disease; all‐cause 6‐month mortality was 25%. The most common species was Nocardia farcinica (7/17 isolates), which was associated with dissemination and mortality. The most active antibiotics were TMP/SMX (100%), linezolid (100%), and amikacin (76%). Imipenem was only active against 4/17 isolates (24% susceptibility), with two isolates becoming non‐susceptible later in therapy. Conclusions: Trimethoprim/sulfamethoxazole prophylaxis was shown to be protective against nocardiosis in lung transplant recipients, while augmented immunosuppression conferred increased risk. Institutional epidemiologic data are needed to best guide empiric therapy for Nocardia, as historical in vitro data may not predict local susceptibilities. [ABSTRACT FROM AUTHOR]

The article provides advice to residents embarking on their first post-residency job to help them transition to their new clinical position. Topics discussed include the significance of taking on small additional tasks early, opportunity for new practitioners to learn more about their specific site through involvement in clinical research, and development of a sustainable work-life balance.

Introduction: The 2013 pooled cohort equations (PCE) may misestimate cardiovascular event (CVE) risk, particularly for black patients. Alternatives to the original PCE (O-PCE) to assess potential statin benefit for primary prevention-a revised PCE (R-PCE) and US Preventive Services Task Force (USPSTF) algorithms-have not been compared in contemporary US patients in routine office-based practice.Methods: We performed retrospective, cross-sectional analysis of a nationally representative, US sample of office visits made from 2011 to 2014. Sampling criteria matched those used for PCE development: aged 40 to 79 years, black or white race, no cardiovascular disease. Original PCE, R-PCE, and USPSTF algorithms were applied to biometric and demographic data. Outcomes included estimated 10-year CVE risk, percentage exceeding each algorithm's statin-treatment threshold (>7.5% risk for O-PCE and R-PCE, and >10% O-PCE plus >1 risk factor for USPSTF), and percentage prescribed statin therapy.Results: In 12 556 visits (representing 285 330 123 nationwide), 10.8% of patients were black, 27.1% had diabetes, and 15.7% were current smokers. Replacing O-PCE with R-PCE decreased mean (95% confidence interval [CI]) estimated CVE risk from 12.4% (12.0%-12.7%) to 8.5% (8.2%-8.8%). Significant (P < 0.05) racial disparity in the rate of CVE risk >7.5% was identified using O-PCE (black and white patients [95% CI], respectively: 58.8% [54.6%-62.9%] vs 52.8% [51.1%-54.4%], P = .006) but not R-PCE (41.6% [37.6%-45.7%] vs 39.9% [38.3%-41.5%], P = .448). Revised PCE and USPSTF recommendations were concordant for 90% of patients. Significant racial disparity in guideline-concordant statin prescribing was found using O-PCE (black and white patients, respectively, 35.0% [30.5%-39.9%] vs 41.8% [39.9%-44.4%], P = .013), but not R-PCE (40.6% [35.0%-46.6%] vs 43.0% [40.0%-45.9%], P = .482) or USPSTF recommendations (39.0% [33.8%-44.5%] vs 44.4% [41.5%-47.5%], P = .073).Conclusions: Use of an alternative to O-PCE may reduce racial disparity in estimated CVE risk and may facilitate shared decision-making about primary prevention. [ABSTRACT FROM AUTHOR]