Therapeutic Myths in Solid Organ Transplantation Infectious Diseases.

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.

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients.

BACKGROUND: Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients. METHODS: This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes. RESULTS: A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1-5.6) at LET initiation which increased to 5.1 (3.9-7.2) at the end of follow-up (p <.001). For VGCV controls, WBC was 4.8 (3.4-7.2) at baseline and 5.4 (3.6-7.2) at the end of follow-up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001). CONCLUSION: LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.

Effect of letermovir initiation on tacrolimus concentrations among lung transplant recipients receiving concomitant azole antifungal prophylaxis.

BACKGROUND: The antiviral letermovir has been increasingly used as off-label cytomegalovirus prophylaxis in solid organ transplant recipients. Observational studies have reported notable increases in tacrolimus (FK) exposure following letermovir; however, whether a significant interaction occurs in the setting of existing moderate-to-strong CYP3A4 inhibition is unknown. Therefore, the purpose of this study was to evaluate FK trough changes before and after letermovir among lung transplant recipients receiving azole antifungal prophylaxis. METHODS: This retrospective cohort study included lung transplant recipients newly initiated on letermovir between 2019-2022 following valganciclovir intolerance. Tacrolimus doses and concentrations were collected up to 30 days before and after the letermovir start date. No pre-emptive FK dose adjustments occurred prior to letermovir initiation. Patients admitted to the hospital or lacking an appropriately timed trough in the pre- or post-period were excluded. RESULTS: A total of 78 lung transplant recipients receiving FK (1.5 mg median total daily dose) and itraconazole (56.4%), isavuconazole (25.6%) or posaconazole (17.9%) prophylaxis were included. Letermovir was started at a median of 8.4 months post-transplant. The pre-/post-letermovir median FK trough was 9.6/9.0 ng/mL (p = .151), median dose-corrected trough was 4.2/4.7 ng/mL/mg (+11.9%, p = .032), and median weight-based dose-corrected trough was 362/326 [ng/mL]/[mg/kg/day] (-9.9%, p = .036). There was no significant difference in the proportion of patients within their goal trough range before and after letermovir initiation (62% vs. 72%, p = .229). CONCLUSION: Empiric FK dose adjustments do not appear warranted before letermovir initiation in lung transplant recipients receiving antifungal prophylaxis with moderate-to-strong CYP3A4 inhibitors.

Early Experiences with Intrathecal Administration of Amphotericin B Liposomal Formulation at a Neurosurgical Center.

BACKGROUND: Intrathecal administration of amphotericin B represents an important adjunctive therapy for management of severe fungal meningitis. Intrathecal preparations have traditionally used amphotericin B deoxycholate. Liposomal amphotericin B is an alternative formulation with good clinical outcomes as systemic therapy, but scant data exist investigating intrathecal use. OBJECTIVE: The aim of this exploratory study was to evaluate outcomes following intrathecal administration of liposomal amphotericin B for treatment of severe fungal meningitis. METHODS: A national shortage of amphotericin B deoxycholate necessitated revision of institutional protocols at a southwestern neurosurgical center in Spring 2023. A starting intrathecal daily dose of 0.125-0.5 mg liposomal amphotericin B was recommended (dependent on insertion device), with 0.125-0.25 mg slow titration every 48 h and up to a 2 mg maximum daily dose. RESULTS: Four cases of fungal meningitis treated with adjunctive intrathecal amphotericin B liposomal formulation were reviewed. This included three cases of coccidioidal meningitis and one case of presumed Fusarium solani meningitis following an outbreak. All patients had initial disease improvement following initiation of intrathecal amphotericin B and were able to tolerate long-term therapy. One coccidioidal meningitis patient expired of neurologic complications shortly after being moved from the intensive care unit (ICU) to a floor unit. All other patients were successfully discharged from the hospital. New headache was the only reported adverse effect, which was managed with dose reduction and did not require therapy discontinuation. CONCLUSIONS: Liposomal amphotericin B may be feasibly administered intrathecally for the adjunctive treatment of severe fungal meningitis.

Doxycycline versus cephalexin treatment of presumed streptococcal skin and soft tissue infection among adults presenting to the emergency department.

Among 100 propensity score-matched emergency department patients receiving ≤14 days doxycycline versus cephalexin monotherapy for outpatient treatment of nonpurulent (presumed streptococcal) skin and soft tissue infection, a low rate of 14-day clinical failure was observed [6% each group; odds ratio (OR), 1.34 (0.21-8.69); P = 0.745], defined as hospital admission, i.v. antibiotic therapy, or change in oral antibiotic. Doxycycline may represent a reasonable therapeutic alternative for this indication in regions with low tetracycline resistance.

Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis.

BACKGROUND: Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. OBJECTIVES: To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection. METHODS: A systematic review and individual patient data meta-analysis. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023. STUDY ELIGIBILITY CRITERIA: (a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis. PARTICIPANTS: SOT recipients. INTERVENTION: TMP-SMX prophylaxis versus no prophylaxis. ASSESSMENT OF RISK OF BIAS: Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies. METHODS OF DATA SYNTHESIS: For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100). CONCLUSIONS: In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.

Can fluconazole be used for inpatient re-treatment of coccidioidomycosis among patients with past fluconazole exposures?

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.

Adherence and outcomes of a surgical prophylaxis guideline promoting cephalosporin use among patients with penicillin allergy.

BACKGROUND: The study purpose was to assess adherence to a local surgical prophylaxis guideline in patients with reported penicillin allergies, which recommends cephalosporins as first-line prophylaxis. METHODS: Adult patients with penicillin allergies admitted for a surgical procedure from July 2020 to June 2021 were retrospectively screened, and the first surgery per admission was included. The primary outcome was the proportion of surgeries using ß-lactam prophylaxis. Additional outcomes included prophylaxis timing, hypersensitivity reactions, acute kidney injury, infectious complications, duration of stay, and 30-day mortality or readmission. RESULTS: Among 597 procedures, 504 patients (84.4%) received a ß-lactam for surgical prophylaxis, including 494 (82.3%) who received a cephalosporin. Patients in the non-ß-lactam group were more likely to have a type I IgE-mediated penicillin allergy (48.4% vs 31.7%, P = .002); however, the majority with type I reactions still received ß-lactams (78.0%), including in the setting of anaphylaxis or angioedema to penicillin (67.7%). Zero allergic reactions to prophylaxis antibiotics were reported in either group, and there were no significant differences in the proportion of patients receiving drugs associated with the management of allergic reactions. Receipt of non-ß-lactams was associated with inappropriate prophylaxis timing (9.7% vs 3.2%, P = .005) and postprocedural acute kidney injury (7.5% vs 0.6%, P < .001). All other outcomes were nonsignificant between the groups. CONCLUSION: Among surgical patients with a documented penicillin allergy, most received cephalosporin prophylaxis as recommended by institutional guidelines, with zero allergic reactions. Receipt of non-ß-lactam prophylaxis was associated with worsened outcomes. Cephalosporin prophylaxis should be preferred for surgical patients, including in the setting of true penicillin allergy.

Outcomes of nontuberculous mycobacteria isolation among lung transplant recipients: A matched case-control with retrospective cohort study.

PURPOSE: Lung transplant recipients are at increased risk for acquiring nontuberculous mycobacteria (NTM), but the clinical significance of NTM isolation, particularly among patients not meeting guideline-endorsed diagnostic criteria for NTM pulmonary disease, is unclear. METHODS: A case-control study of lung transplant recipients culture-positive for NTM at a large transplant center during a 7-year period (2013-2019) was performed. RESULTS: Twenty-nine cases were matched 1:2 to non-NTM controls. The median time to NTM isolation was 10.7 months post transplant. Only 34.5% of all cases, and half of treated cases, met diagnostic criteria for NTM pulmonary infection. All-cause mortality at 12 months was numerically higher among NTM cases versus controls (20.7% vs 8.6%, P = 0.169); however, no deaths were attributed to NTM. No increase in the 12-month rate of acute rejection was observed (27.6% vs 36.2%, P = 0.477). Recent augmented immunosuppression was associated with increased odds of NTM isolation, while azithromycin prophylaxis was associated with reduced odds of NTM isolation and was not associated with macrolide resistance. Both adverse events and actual or potential drug-drug interactions occurred in more than 90% of treated cases; these events included ocular toxicity, hearing loss, and supratherapeutic calcineurin inhibitor concentrations. Eight of the 14 treated cases (57.1%) required early antibiotic discontinuation due to adverse events or drug-drug interactions. CONCLUSION: Among lung transplant recipients, most patients with NTM isolation did not meet guideline criteria for infection and had outcomes similar to non‒NTM-infected patients, which may reflect transient lung colonization by NTM rather than true disease. As adverse events are common with NTM therapy, limiting unnecessary antibiotic treatment represents an area for future antimicrobial stewardship efforts.

Universal Lifelong Fungal Prophylaxis and Risk of Coccidioidomycosis in Lung Transplant Recipients Living in an Endemic Area.

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.

Pharmacist-provided SARS-CoV-2 testing targeting a majority-Hispanic community during the early COVID-19 pandemic: Results of a patient perception survey.

BACKGROUND: Racial and ethnic minority groups are disproportionally represented among U.S. coronavirus disease (COVID-19) cases, owing to long-standing systemic inequities in the social determinants of health. Among Hispanic populations, a lack of access to testing sites has resulted in delayed time to diagnosis, risking increased spread within high-risk communities. The accessibility and expertise of community pharmacists support expanded pharmacist roles in public health and pandemic response, including point-of-care (POC) diagnostic testing. OBJECTIVE: To determine the local impact of community pharmacist-provided COVID-19 testing among a majority-Hispanic, lower income population during the early COVID-19 pandemic, as assessed by a patient satisfaction survey. METHODS: A 10-question Likert-type questionnaire was administered in English and Spanish to patients who received a pharmacist-provided POC COVID-19 test at a large-chain community pharmacy in Arizona between May 1, 2020 and June 14, 2020. Questions surrounded patient perceptions of the testing process and subsequent pharmacist counseling on their test results. RESULTS: A total of 622 patients completed the survey (94.1% participation rate among successful contacts, representing 28.3% of all eligible patients). The mean age was 42 years, 51% were female, and 64% of patients identified as Hispanic. More than 97% of surveyed patients either agreed or strongly agreed that receiving a pharmacist-provided COVID-19 test at a community pharmacy was a comfortable experience, expanded their access to care, and allowed them to receive their test results in a timely manner. In addition, more than half of surveyed patients "did not know" where they would have alternatively sought testing if the community testing site was not available. Overall, the results of this study demonstrated highly favorable patient perceptions of pharmacist-provided POC testing for COVID-19, with more than 99% of surveyed patients satisfied with their testing experience. CONCLUSION: Among patients in a lower income majority-Hispanic community, pharmacist-provided POC testing services for COVID-19 were well received and expanded patient access to testing during the early pandemic.

Impact of the COVID-19 Pandemic on the Emotional Intelligence of Student Pharmacist Leaders.

Objective. To assess changes in Emotional Intelligence Appraisal (EIA) scores following the COVID-19 pandemic for pharmacy students within a voluntary cocurricular leadership development program.Methods. Participants from the class of 2021 (pandemic group) completed an EIA self-assessment near the beginning of the leadership program in August 2019 (pre-pandemic) and at the end of the program in July 2020 (during peak first-wave COVID-19 activity) and wrote an accompanying self-reflection. To determine changes in students' emotional intelligence potentially attributable to COVID-19, differences in EIA scores from the pandemic group were compared to the pooled results of previous program cohorts (classes of 2017-2019). Prevalent themes in student self-reflections were also highlighted.Results. Thirty-five student leaders comprised the pandemic group, with 166 students included within the control group. The proportion of students with final EIA scores indicating high emotional intelligence was greater within the pandemic group (74.3% vs 50.6%). While both groups had increased final EIA scores compared to baseline values, score increases were significantly higher among students in the pandemic group with respect to overall emotional intelligence and relationship management. Students commented that the pandemic highlighted the importance of emotional intelligence during stressful situations, although the lack of in-person interaction was noted as a limitation for social development.Conclusion. Pharmacy students participating in a leadership development program during the COVID-19 pandemic experienced greater increases in emotional intelligence than did the program's pre-pandemic cohorts. This may support the ability of health professional students to maintain resiliency through the pandemic and develop both personal and interpersonal relationship-building skills.

Unexplained mortality during the US COVID-19 pandemic: retrospective analysis of death certificate data and critical assessment of excess death calculations.

OBJECTIVES: Cause-of-death discrepancies are common in respiratory illness-related mortality. A standard epidemiological metric, excess all-cause death, is unaffected by these discrepancies but provides no actionable policy information when increased all-cause mortality is unexplained by reported specific causes. To assess the contribution of unexplained mortality to the excess death metric, we parsed excess deaths in the COVID-19 pandemic into changes in explained versus unexplained (unreported or unspecified) causes. DESIGN: Retrospective repeated cross-sectional analysis, US death certificate data for six influenza seasons beginning October 2014, comparing population-adjusted historical benchmarks from the previous two, three and five seasons with 2019-2020. SETTING: 48 of 50 states with complete data. PARTICIPANTS: 16.3 million deaths in 312 weeks, reported in categories-all causes, top eight natural causes and respiratory causes including COVID-19. OUTCOME MEASURES: Change in population-adjusted counts of deaths from seasonal benchmarks to 2019-2020, from all causes (ie, total excess deaths) and from explained versus unexplained causes, reported for the season overall and for time periods defined a priori: pandemic awareness (19 January through 28 March); initial pandemic peak (29 March through 30 May) and pandemic post-peak (31 May through 26 September). RESULTS: Depending on seasonal benchmark, 287 957-306 267 excess deaths occurred through September 2020: 179 903 (58.7%-62.5%) attributed to COVID-19; 44 022-49 311 (15.2%-16.1%) to other reported causes; 64 032-77 054 (22.2%-25.2%) unexplained (unspecified or unreported cause). Unexplained deaths constituted 65.2%-72.5% of excess deaths from 19 January to 28 March and 14.1%-16.1% from 29 March through 30 May. CONCLUSIONS: Unexplained mortality contributed substantially to US pandemic period excess deaths. Onset of unexplained mortality in February 2020 coincided with previously reported increases in psychotropic use, suggesting possible psychiatric or injurious causes. Because underlying causes of unexplained deaths may vary by group or region, results suggest excess death calculations provide limited actionable information, supporting previous calls for improved cause-of-death data to support evidence-based policy.

Impact of the FilmArray meningitis/encephalitis panel on antimicrobial duration among patients with suspected central nervous system infection.

Ten controlled studies evaluated antimicrobial use following implementation of the FilmArray meningitis and encephalitis panel versus usual care. Only one-half of studies identified significant reductions in antibiotic duration, with 8/10 reporting modest reductions for acyclovir. Coupling the FilmArray meningitis and encephalitis panel with interventions by antimicrobial stewardship programs may help enhance its clinical impact.

Nocardia prophylaxis, treatment, and outcomes of infection in lung transplant recipients: A matched case-control study.

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.

Patient perspectives of pharmacists prescribing HIV pre-exposure prophylaxis: A survey of patients receiving antiretroviral therapy.

BACKGROUND: Groundbreaking new laws granting community pharmacists the authority to prescribe human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) medications have the potential to substantially expand PrEP access in high-risk communities. However, whether patients will be accepting of pharmacists as PrEP providers is underexplored within the literature. OBJECTIVES: To assess patient perspectives of pharmacist PrEP prescribing and identify potential barriers to acceptance of pharmacist-prescribed PrEP. METHODS: Adult patients currently receiving antiretroviral therapy for HIV prophylaxis or treatment at a specialty pharmacy were surveyed telephonically from January 2020-April 2020. A 4-point Likert scale was used to measure perceptions in addition to open-ended questions. RESULTS: The participation rate was 87.5%. Of the 49 included patients, 100% agreed/strongly agreed that pharmacists were knowledgeable about medications, but they were less likely to strongly agree that pharmacists were knowledgeable about HIV drugs (14.3% vs. 75.5% for other drugs, P < 0.001). Most (93.9%) of the patients agreed/strongly agreed that they would feel comfortable seeking a pharmacist for PrEP information or HIV testing. With respect to PrEP prescribing, 16.3% disagreed that they would feel comfortable having a pharmacist prescribe their first fill of PrEP, preferring to speak to their physician or expressing concerns that pharmacists have inadequate training. All patients expressed a desire for additional HIV/PrEP training requirements for pharmacists before allowing them to prescribe PrEP. A portion of the respondents (18.4%) expressed concerns that the increased availability of PrEP would lead to persons becoming lax about barrier protection. However, 100% of the patients agreed/strongly agreed that having pharmacist-prescribed PrEP would benefit their community. CONCLUSION: Patients receiving antiretroviral therapy reported overall favorable perceptions of pharmacist PrEP prescribing; however, some concerns relating to pharmacists' level of training in HIV exist. This may be ameliorated through increased pharmacist education, including how to counsel patients seeking PrEP on behavioral risk reduction.

COVID-19 in a lung transplant recipient: Exploring the diagnostic role of circulating exosomes and the clinical impact of advanced immunosuppression.

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.