Razonable, Raymund R.

ABSTRACT Cytomegalovirus (CMV) is a significant cause of morbidity and mortality among immunocompromised hosts, including transplant recipients. Antiviral prophylaxis or treatment is used to reduce the incidence of CMV disease in this patient population; however, there is concern about increasing antiviral resistance. Detection of antiviral resistance in CMV was traditionally accomplished using Sanger sequencing of UL54 and UL97 genes, in which specific mutations may result in reduced antiviral activity. In this study, a novel next-generation sequencing (NGS) method was developed and validated to detect mutations in UL54 / UL97 associated with antiviral resistance. Plasma samples ( n = 27) submitted for antiviral resistance testing by Sanger sequencing were also analyzed using the NGS method. When compared to Sanger sequencing, the NGS assay demonstrated 100% (27/27) overall agreement for determining antiviral resistance/susceptibility and 88% (22/25) agreement at the level of resistance-associated mutations. The limit of detection of the NGS method was determined to be 500 IU/mL, and the lower threshold for detecting mutations associated with resistance was established at 15%. The NGS assay represents a novel laboratory tool that assists healthcare providers in treating patients who are infected with CMV harboring resistance-associated mutations and who may benefit from tailored antiviral therapy.

AbstractBackgroundEndemic mycoses after hematopoietic stem cell transplantation (HSCT) are rarely reported. We aimed to comprehensively review the clinical presentation and outcomes of endemic mycoses in this immunocompromised population.MethodsMultiple databases were reviewed from inception through May 31, 2023 using endemic fungi as keywords (e.g., coccidioides, histoplasma, blastomyces, talaromyces, and paracoccidioides). Only hematopoietic transplants were included.ResultsThere were 16 publications on endemic mycoses after HSCT that reported nine unique cases of histoplasmosis, seven coccidioidomycosis, and two talaromycosis. No cases of paracoccidioides and blastomycoses were identified. Fifteen cases were allogeneic hematopoietic transplant recipients and three were autologous. Many were male (14/18, 77.8%) and overall median age was 50 (range 21–75) years. Among the 16 patients with coccidiodomycosis or histoplasmosis, fever, cytopenias and disseminated disease were the most common clinical presentations, with median onset of 8 or 12 months after HSCT, respectively. Likewise, the two HSCT patients with talaromycosis presented with disseminated disease at 12 and 48 months after transplantation. The vast majority were not on effective azole prophylaxis at the time of presentation, and many had recent intensification of immunosuppression. Nine of 18 patients died (50%), and all deaths occurred among patients with disseminated endemic mycoses.ConclusionEndemic mycoses among HSCT are uncommon. Onset was late, after discontinuation of azole prophylaxis, or was associated with intensification of immunosuppression. Disseminated disease was a common presentation, manifested by fever and cytopenias. Attributable mortality was high, and emphasizes the need for a high index of clinical suspicion so that prompt diagnosis and treatment is provided. image

Abstract Background: A multitude of factors are considered in an infectious diseases (ID) training program’s meticulous selection process of ID fellows but their correlation to pre and in-fellowship academic success as well as post-fellowship academic success and short-term outcomes is poorly understood. Our goal was to investigate factors associated with subsequent academic success in fellowship as well as post-fellowship short-term outcomes. Methods: In 2022, we retrospectively analyzed deidentified academic records from 39 graduates of the Mayo Clinic Rochester ID Fellowship Program (July 1, 2013- June 30, 2022). Data abstracted included demographics, degrees, honor society membership, visa/citizenship status, medical school, residency training program, United States Medical Licensure Exam (USMLE) scores, letters of recommendation, in-training examination (ITE) scores, fellowship track, academic rank, career choice, number of honors, awards, and abstracts/publications prior to fellowship, during training, and within 2 years of graduation. Results: Younger fellows had higher USMLE step 1 scores, pre and in-fellowship scholarly productivity, and higher ITE performance. Female fellows had significantly higher USMLE step 3 scores. Prior research experience translated to greater in-fellowship scholarly productivity. Higher USMLE scores were associated with higher ID ITE performance during multiple years of fellowship, but USMLE step 2 clinical knowledge and 3 scores were associated with higher pre and in-fellowship scholarly productivity and receiving an award during fellowship. USMLE step 1 score did not correlate with fellowship performance beyond year 1 and 2 ITE scores. Conclusions: Multiple aspects of a prospective fellow’s application must be considered as part of a holistic reviewprocess for fellowship selection. USMLE step 2 CK and 3 scores may predict fellowship performance across multiple domains.

The literature regarding Clostridioides difficile infection (CDI) in left ventricular assist devices (LVADs) patients is limited. Therefore, we aimed to characterize the clinical course, risk factors, management, and outcomes of LVAD patients who developed CDI. Adult patients who underwent LVAD placement during 2010–2022 and developed CDI were included. To determine risk factors and outcomes, we matched CDI patients with LVAD patients who did not develop CDI. Each CDI case was matched with up to two control subjects by age, sex, and time from LVAD implantation. Forty-seven of 393 LVAD patients (12.0%) developed CDI. The median time from LVAD implantation to CDI was 147 days (interquartile range 22.5–647.0). The most common CDI treatment was oral vancomycin (n = 26, 55.3%). Thirteen patients (27.7%) required treatment extension because of a lack of clinical response. Three patients (6.4%) developed recurrent CDI. When 42 cases were matched to 79 control subjects, antibiotic exposure within 90 days was significantly associated with CDI (adjusted odds ratio 5.77; 95% confidence interval, 1.87–17.74; p = 0.002). Moreover, CDI was associated with 1 year mortality (adjusted hazard ratio 2.62; 95% confidence interval, 1.18–5.82; p = 0.018). This infection occurs most often within the first year after LVAD implantation and was associated with 1 year mortality. Antibiotic exposure is an important risk for CDI.

AbstractBackgroundManagement of multidrug‐resistant (MDR) and rifampin‐resistant (RR) tuberculosis is challenging. Data on transplant recipients is limited. We reviewed published literature to examine treatment choices, outcomes, and adverse effects from MDR‐TB/RR‐TB treatment in transplant recipients.MethodsMultiple databases from inception to 12/2022 were reviewed using the keywords “drug‐resistant TB” or “drug‐resistant tuberculosis” or “multidrug‐resistant TB” or “multidrug‐resistant tuberculosis”. MDR‐TB was defined as resistance to isoniazid (H) and rifampin (R), and RR if resistant to rifampin alone. Cases without patient‐level data and reports which did not describe treatment and/or outcomes for MDR‐TB were excluded.ResultsA total of 12 patients (10 solid organ transplants and two hematopoietic cell transplants) were included. Of these, 11 were MDR‐TB and one was RR‐TB. Seven recipients were male. The median age was 41.5 (range 16–60) years. Pre‐transplant evaluation for the majority (8/12, 66.7%) did not reveal a prior history of TB or TB treatment, but 9/12 were from TB intermediate or high‐burden countries. Seven patients were initially treated with the quadruple first‐line anti‐TB regimen. Those who had early RR confirmation (5/12) via Xpert MTB/RIF assay were initiated on alternative therapies. Final regimens were individualized based on susceptibility profiles and tolerability. Adverse events were reported in seven recipients, including acute kidney injury (n = 3), cytopenias (n = 3), and jaundice (n = 2). Four recipients died, with two deaths attributable to TB. The remaining eight patients who survived had functioning allografts at the last follow‐up.ConclusionsMDR‐TB treatment in transplant recipients is associated with many complications. Xpert MTB/RIF detected RR early and guided early empiric therapy. image

AbstractNeutralizing antispike monoclonal antibody (mAb) therapies were highly efficacious in preventing coronavirus disease 2019 (COVID‐19) hospitalization. While severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants may harbor spike protein mutations conferring reduced in vitro susceptibility to these antibodies, the effect of these mutations on clinical outcomes is not well characterized. We conducted a case–control study of solid organ transplant recipients who received an antispike mAb for treatment of mild‐to‐moderate COVID‐19 and had an available sample from initial COVID‐19 diagnosis for genotypic sequencing. Patients whose SARS‐CoV‐2 isolate had at least one spike codon mutation conferring at least fivefold decreased in vitro susceptibility were classified as resistant. Overall, 9 of 41 patients (22%) had at least one spike codon mutation that confers reduced susceptibility to the antispike mAb used for treatment. Specifically, 9 of 12 patients who received sotrovimab had S371L mutation that was predicted to confer a 9.7‐fold reduced susceptibility. However, among 22 patients who required hospitalization, 5 had virus with resistance mutation. In contrast, among 19 control patients who did not require hospitalization, 4 also had virus‐containing resistance mutations (p > 0.99). In conclusion, spike codon mutations were common, though mutations that conferred a 9.7‐fold reduced susceptibility did not predict subsequent hospitalization after treatment with antispike mAb.

Abstract The Infectious Diseases Society of America (IDSA) has set clear priorities in recent years to promote inclusion, diversity, access, and equity (IDA&E) in infectious disease (ID) clinical practice, medical education, and research. The IDSA IDA&E Task Force was launched in 2018 to ensure implementation of these principles. The IDSA Training Program Directors Committee met in 2021 and discussed IDA&E best practices as they pertain to the education of ID fellows. Committee members sought to develop specific goals and strategies related to recruitment, clinical training, didactics, and faculty development. This article represents a presentation of ideas brought forth at the meeting in those spheres and is meant to serve as a reference document for ID training program directors seeking guidance in this area.

Abstract Introduction During the early phase of the coronavirus disease 2019 (COVID‐19), remdesivir was only approved for hospitalized patients. Our institution developed hospital‐based, outpatient infusion centers for selected hospitalized patients with COVID‐19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods Retrospective study of all hospitalized adult patients with COVID‐19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals. Results Among 3029 hospitalized patients who received treatment with remdesivir for COVID‐19, the majority (89.5%) completed the recommended 5‐day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06–0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27–2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5‐day course of remdesivir (aOR 2.07, 95% CI 1.45–2.95, p < 0.001). Conclusions This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5‐day course of remdesivir.

Mechanical circulatory support is increasingly being used as bridge-to-transplant and destination therapy in patients with advanced heart failure. Technologic improvements have led to increased patient survival and quality of life, but infection remains one of the leading adverse events following ventricular assist device (VAD) implantation. Infections can be classified as VAD-specific, VAD-related, and non-VAD infections. Risk of VAD-specific infections, such as driveline, pump pocket, and pump infections, remains for the duration of implantation. While adverse events are typically most common early (within 90 days of implantation), device-specific infection (primarily driveline) is a notable exception. No diminishment over time is seen, with event rates of 0.16 events per patient-year in both the early and late periods postimplantation. Management of VAD-specific infections requires aggressive treatment and chronic suppressive antimicrobial therapy is indicated when there is concern for seeding of the device. While surgical intervention/hardware removal is often necessary in prosthesis-related infections, this is not so easily accomplished with VADs. This review outlines the current state of infections in patients supported with VAD therapy and discusses future directions, including possibilities with fully implantable devices and novel approaches to treatment.