Cefiderocol utilization in lung transplant recipients at a single center.

BACKGROUND: Multidrug-resistant organisms are increasing and are a significant cause of mortality among lung transplant recipients (LTRs). To assist with this issue, novel pharmacotherapies are being developed. This study describes the utilization of a novel antibiotic, cefiderocol (FDC), in LTRs where limited data exists in the current literature. We primarily assessed the clinical indications, duration of therapy, resistance, and adverse effects. METHODS: Conducted as a single-center retrospective review, this study included adult LTRs who received FDC for at least 24 h. Data, extracted from electronic medical records, encompassed patient demographics, transplant history, antimicrobial dosing, adverse effects, bacterial cultures, and outcomes. The research protocol received institutional review board approval. RESULTS: FDC exhibited effectiveness against multidrug-resistant Pseudomonas aeruginosa, with 26% 30-day mortality and microbiological clearance observed in nine out of 13 cases. Notably, FDC was used in diverse clinical settings, including for prophylaxis, empiric, and targeted treatment. CONCLUSION: Further studies are needed to evaluate optimal clinical indications for FDC use in LTRs.

The changing landscape of infections in the lung transplant recipient.

PURPOSE OF REVIEW: Infections in lung transplant recipients remain a major challenge and can affect lung allograft function and cause significant morbidity and mortality. New strategies for the prevention and treatment of infection in lung transplantation have emerged and are reviewed. RECENT FINDINGS: For important vaccine preventable infections (VPIs), guidance has been updated for at risk solid organ transplant (SOT) recipients. However, data on the efficacy of newer vaccines in lung transplant, including the respiratory syncytial virus (RSV) vaccine, are limited. Studies demonstrate improved vaccination rate with Infectious Diseases consultation during pretransplant evaluation. Two new antiviral agents for the treatment and prevention of cytomegalovirus (CMV) in SOT, letermovir and maribavir, are being incorporated into clinical care. CMV-specific cell-mediated immune function assays are more widely available. Antibiotics for the management of multidrug resistant pathogens and Burkholderia cepacia complex have been described in case series and case reports in lung transplant. SUMMARY: Although new vaccines and novel therapies for preventing and treating infections are available, larger studies evaluating efficacy in lung transplant recipients are needed.

Telehealth Access and Substitution in the VHA.

BACKGROUND: In response to COVID-19, the Veterans Health Administration (VHA) expanded telehealth availability, allowing veterans to receive care at home. We explore the extent of substitution of telehealth for in-person care among medical centers (facilities), providers, and patients. We explore the extent to which patient preferences drive telehealth utilization, and compare access to care (as measured by waiting times) for telehealth and in-person visits. METHODS: We use VHA electronic health records to identify scheduled outpatient mental health (MH) appointments from January 2019 through February 2023 focusing on care delivered by social workers, psychologists, and psychiatrists. For each quarter, we compute the proportion of completed appointments that were delivered via phone or video by each facility, provider, and patient and show the changes in these proportions before, during, and after the onset of COVID-19. To explore patient preferences, we match providers of patients with high rates of telehealth utilization and examine the extent to which those providers deliver in-person care. To examine access to care, we compute waiting times for in-person, video, and phone new patient appointments. We investigate differences between urban and rural patients, and patients of different ages. KEY RESULTS: Telehealth for MH grew dramatically in the VHA after the onset of COVID-19. While some facilities provided more telehealth than others, all facilities (as of early 2023) provided some telehealth MH services. Approximately 86% of individual providers provided telehealth, with 27% scheduling MH appointments almost exclusively as telehealth appointments and 59% providing a mix. Patients exhibited more polarization, with 36% scheduling only in-person visits for almost all their MH visits and 56% of them scheduling exclusively telehealth, and only 8% of them utilizing a mix of modalities. Of those who exclusively received telehealth care, a majority of them utilized video (80%) over phone (20%). Take-up of MH among younger patients was higher relative to older patients. Urban patients used telehealth more than rural patients. Patient preferences rather than provider preferences drove utilization of patients who almost exclusively utilized telehealth. Between April 2021 and February 2023, the average difference in waiting time for in-person and video appointments was less than 1 day, with comparable appointment volumes, suggesting that the supply of and demand for in-person and video were not different enough to merit waiting longer. Telehealth was chosen over in-person more among urban and younger patients, as older and rural patients exhibited higher willingness to wait for in-person over video appointments. By contrast, appointment volumes and waiting times for phone appointments were lower across all groups, suggesting that phone may not be as substitutable for in-person visits in MH. CONCLUSIONS: We find that the VHA has made telehealth widely available, providing access to many veterans. While telehealth utilization has increased, face-to-face care persists for MH services, suggesting that one modality may not serve all purposes and preferences for care. Patient preferences drive the modality decision among those who exclusively use MH care via telehealth. For those who persist in mostly utilizing in-person care, there may be various factors influencing those preferences such as issues with limited internet connectivity, language barriers, and digital literacy, especially for older and rural patients who utilize in-person care more than those who are younger and more urban. Further investigation is required to investigate the optimal mix of modalities which may allow for potential increases in patient satisfaction, quality of care, and clinic efficiency.

Clinical effectiveness and cost-impact after 2 years of a ketogenic diet and virtual coaching intervention for patients with diabetes.

AIM: We previously evaluated the impacts at 5 months of a digitally delivered coaching intervention in which participants are instructed to adhere to a very low carbohydrate, ketogenic diet. With extended follow-up (24 months), we assessed the longer-term effects of this intervention on changes in clinical outcomes, health care utilization and costs associated with outpatient, inpatient and emergency department use in the Veterans Health Administration. MATERIALS AND METHODS: We employed a difference-in-differences model with a waiting list control group to estimate the 24-month change in glycated haemoglobin, body mass index, blood pressure, prescription medication use, health care utilization rates and associated costs. The analysis included 550 people with type 2 diabetes who were overweight or obese and enrolled in the Veterans Health Administration for health care. Data were obtained from electronic health records from 2018 to 2021. RESULTS: The virtual coaching and ketogenic diet intervention was associated with significant reductions in body mass index [-1.56 (SE 0.390)] and total monthly diabetes medication usage [-0.35 (SE 0.054)]. No statistically significant differences in glycated haemoglobin, blood pressure, outpatient visits, inpatient visits, or emergency department visits were observed. The intervention was associated with reductions in per-patient, per-month outpatient spending [-USD286.80 (SE 97.175)] and prescription drug costs (-USD105.40 (SE 30.332)]. CONCLUSIONS: A virtual coaching intervention with a ketogenic diet component offered modest effects on clinical and cost parameters in people with type 2 diabetes and with obesity or overweight. Health care systems should develop methods to assess participant progress and engagement over time if they adopt such interventions, to ensure continued patient engagement and goal achievement.

Effect of Mycetoma in Lung Transplant Patients - a Single Center Experience.

BACKGROUND: Mycetomas are uncommon in lung transplant recipients. Prior studies have shown increased mortality associated with mycetoma in lung transplant recipients (LTR). We reviewed our center's experience in outcome of LTRs with pre -or post-transplant mycetoma. METHODS: We retrospectively reviewed electronic health records of LTRs performed at our institute between January 1, 2013 to December 31, 2020. RESULTS: Mycetoma was present in less than 1 percent of LTR patients (7/1086). Mean age at the time of the transplant was 65 years. Idiopathic pulmonary fibrosis (5/7), interstitial lung disease (1/7), and sarcoidosis (1/7) were underlying pulmonary diagnoses. Seventy-one percent (5/7) received single lung transplant and 29% received double lung transplant. Seventy-one percent had negative serum galactomannan vs 29% (2/7) of patients who had positive serum galactomannan (one post and one pre). Fifty-seven percent had positive bronchoalveolar aspergillus galactomannan (23% had negative). A total of 42% (3/7) were found to have mycetoma before transplant and 58% (4/7) had mycetoma post transplant. Chest computed tomography findings in all patients were consistent with mycetoma. CONCLUSIONS: In our cohort of patients, mycetoma was not found to be the primary cause of death if diagnosed pre transplant. Transplant recipients with mycetoma pre transplant did not develop invasive fungal infection or mycetoma post transplant. Careful evaluation of lung transplant candidates with mycetoma is critical. Further studies are needed to determine optimal duration of antifungal therapy and to determine if surgical resection may be needed to manage post-lung transplant mycetoma.

First Case of Cupravidus paculus Infection in a Lung Transplant Recipient: A Case Report.

Cupravidus paculus is a rare Gram-negative bacterium that can cause a wide range of severe infections, largely in immunocompromised patients. It is a ubiquitous organism found in natural and man-made environments and in the hospital. Herein, we present the first case of C. paculus infection in a lung transplant recipient, which required prolonged antibiotic therapy to achieve complete clearance. Additionally, we review the existing literature on the clinical and microbiological profile of C. paculus, along with previously documented cases of clinical infections. Our case highlights the potential sources of C. paculus infections, the importance of appropriate disinfection protocols for medical devices, and the need for antibiotic sensitivities to guide treatment.

Effectiveness of a ketogenic diet and virtual coaching intervention for patients with diabetes: A difference-in-differences analysis.

AIM: To test the effectiveness of a ketogenic diet and virtual coaching intervention in controlling markers of diabetes care and healthcare utilization. MATERIALS AND METHODS: Using a difference-in-differences analysis with a waiting list control group-a quasi-experimental methodology-we estimated the 5-month change in HbA1c, body mass index, blood pressure, prescription medication use and costs, as well as healthcare utilization. The analysis included 590 patients with diabetes who were also overweight or obese, and who regularly utilize the Veterans Health Administration (VA) for healthcare. We used data from VA electronic health records from 2018 to 2020. RESULTS: The ketogenic diet and virtual coaching intervention was associated with significant reductions in HbA1c (-0.69 [95% CI -1.02, -0.36]), diabetes medication fills (-0.38, [-0.49, -0.26]), body mass index (-1.07, [-1.95, -0.19]), diastolic blood pressure levels (-1.43, [-2.72, -0.14]), outpatient visits (-0.36, [-0.70, -0.02]) and prescription drug costs (-34.54 [-48.56, -20.53]). We found no significant change in emergency department visits (-0.02 [-0.05, 0.01]) or inpatient admissions (-0.01 [-0.02, 0.01]). CONCLUSIONS: This real-world assessment of a virtual coaching and diet programme shows that such an intervention offers short-term benefits on markers of diabetes care and healthcare utilization in patients with diabetes.

Early post-transplant cutaneous bacillary angiomatosis in a kidney recipient: Case report and review of the literature.

Bacillary angiomatosis (BA) is an uncommon systemic disease caused by Bartonella henselae (BH) or Bartonella quintana (BQ) that occurs primarily in immunocompromised hosts. Few cases of BA recipients have been reported in adult solid transplant recipients over the years, with most cases presenting years after transplant. We describe a case of a kidney transplant recipient who developed cutaneous BA very early in the post-transplant period despite not having any exposures. Retrospective testing of donor and recipient's serum was performed and raised the concern for possible donor-derived infection. A literature review encompassing 1990 to present was also performed in order to better understand the clinical presentation, diagnostics and therapeutic approach of this unusual disease. Combined serology, histopathology and molecular testing (polymerase chain reaction [PCR]) were useful in diagnosing BA in our patient as serology alone might be unreliable. Macrolides or doxycycline for at least 3 months is the recommended therapeutic strategy; however, the optimal duration of treatment is not well established in transplant recipients. In our patient, we decided to use doxycycline for 1 year due to gradual resolution of lesions and ongoing immunosuppression. Patient responded successfully without any documented relapse.

Central nervous system infections after solid organ transplantation.

PURPOSE OF REVIEW: Significant advances to our understanding of several neuroinfectious complications after a solid organ transplant (SOT) have occurred in the last few years. Here, we review the central nervous system (CNS) infections that are relevant to SOT via a syndromic approach with a particular emphasis on recent updates in the field. RECENT FINDINGS: A few key studies have advanced our understanding of the epidemiology and clinical characteristics of several CNS infections in SOT recipients. Risk factors for poor prognosis and protective effects of standard posttransplant prophylactic strategies have been better elucidated. Newer diagnostic modalities which have broad clinical applications like metagenomic next-generation sequencing, as well as those that help us better understand esoteric concepts of disease pathogenesis have been studied. Finally, several studies have provided newer insights into the treatment of these diseases. SUMMARY: Recent findings reflect the steady progress in our understanding of CNS infections post SOT. They provide several avenues for improvement in the prevention, early recognition, and therapeutic outcomes of these diseases.

Mucormycosis in Hematopoietic Cell Transplant Recipients and in Patients With Hematological Malignancies in the Era of New Antifungal Agents.

BACKGROUND: The survival benefit of combination antifungal therapy for invasive mucormycosis (IM) in patients with hematologic malignancy (HM) and hematopoietic cell transplant (HCT) is not well defined. METHODS: This multicenter, retrospective study included HM and HCT recipients with proven or probable IM between January 1, 2007 and December 31, 2017 from 10 transplant centers across North America. RESULTS: Sixty-four patients with proven (n = 47) or probable (n = 17) IM defined by 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) consensus definitions were included. Thirty-nine (61%) were HCT recipients (95% allogeneic). Sites of infection included rhino-orbital-cerebral (33), pulmonary (30%), disseminated (19%), gastrointestinal (3%), and cutaneous (3%). Surgical debridement was performed in 66%. Initial antifungal treatment consisted of the following: lipid formulation of amphotericin B (AmB) alone (44%), AmB + posaconazole (25%), AmB + echinocandin (13%), AmB + isavuconazole (8%), posaconazole alone (5%), and isavuconazole alone (3%). All-cause mortality at 30 days and 1 year were 38% and 66%, respectively. Initial treatment with AmB plus posaconazole or isavuconazole (n = 28) was associated with a trend toward lower treatment failure compared with AmB (n = 21) (42% vs 64%, P = .136). CONCLUSIONS: Long-term survival with IM among HM and HCT populations remains poor. However, initial use of AmB + azole in conjunction with surgery may result in less treatment failure. More evidence from prospective controlled studies is needed to confirm this observation.

Vector-based kernel weighting: A simple estimator for improving precision and bias of average treatment effects in multiple treatment settings.

Treatment effect estimation must account for observed confounding, in which factors affect treatment assignment and outcomes simultaneously. Ignoring observed confounding risks concluding that a helpful treatment is not beneficial or that a treatment is safe when actually harmful. Propensity score matching or weighting adjusts for observed confounding, but the best way to use propensity scores for multiple treatments is unknown. It is unclear when choice of a different weighting or matching strategy leads to divergent inferences. We used Monte Carlo simulations (1000 replications) to examine sensitivity of multivalued treatment inferences to propensity score weighting or matching strategies. We consider five variants of propensity score adjustment: inverse probability of treatment weights, generalized propensity score matching, kernel weights (KW), vector matching, and a new hybrid that is easily implemented-vector-based kernel weighting (VBKW). VBKW matches observations with similar propensity score vectors, assigning greater KW to observations with similar probabilities within a given bandwidth. We varied degree of propensity score model misspecification, sample size, treatment effect heterogeneity, initial covariate imbalance, and sample distribution across treatment groups. We evaluated sensitivity of results to propensity score estimation technique (multinomial logit or multinomial probit). Across simulations, VBKW performed equally or better than the other methods in terms of bias, efficiency, and covariate balance measured via prognostic scores. Our simulations suggest that VBKW is amenable to full automation and is less sensitive to PS model misspecification than other methods used to account for observed confounding in multivalued treatment analyses.

Alternative pneumocystis prophylaxis in solid organ transplant recipients at two large transplant centers.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for Pneumocystis jirovecii pneumonia (PJP) prophylaxis and has activity against other opportunistic infections (OIs) after solid organ transplant (SOT). We aimed to describe the incidence, reasons for and outcomes of use of alternative prophylactic agents (APAs) across SOT programs in our high volume centers. METHODS: Solid organ transplant recipients (SOTRs) at our centers from 1/2015-12/2016 were identified. Pharmacy records identified APA (pentamidine, atovaquone, or dapsone) use within 1 year. Records were reviewed for allergies, laboratory values at APA initiation, diagnostic tests for TMP-SMX-preventable OIs, and APA side effects. RESULTS: An APA was initiated in 105/1173 (8.9%) SOTRs. Of these, 51 (48.6%) were because of sulfonamide allergy recorded pre-SOT, mostly rash/hives (58.8%). The remaining 54 (51.4%) had TMP-SMX discontinued post-SOT, mostly for neutropenia (48%) and renal effects (34%). Differences occurred across programs, with kidney transplant never stopping TMP-SMX for renal issues. Of those changed to APAs post-transplant, 19 (35%) were later successfully re-challenged with TMP-SMX. With thresholds in mind, 67 (64%) received an APA unnecessarily, accounting for up to $100 000/y excess cost. Potential TMP-SMX-preventable OIs occurred in 7 (5 Nocardia; 2 PJP). APA side effects occurred in 14/105 (13.3%). CONCLUSIONS: Use of APAs for PJP prophylaxis after SOT is less than previously reported but often unwarranted. Such decisions require scrutiny to avoid TMP-SMX-preventable OIs, cost and important APA side effects. Use of reasonable thresholds for cessation of TMP-SMX and data-driven approaches to re-challenge would substantially reduce APA use.

Miliary Histoplasmosis in a Patient with Rheumatoid Arthritis.

Miliary histoplasmosis is a rare presentation that may mimic miliary tuberculosis. We report a case of miliary histoplasmosis in a 52-year-old male who was being treated with hydroxychloroquine, methotrexate, and sulfasalazine for his rheumatoid arthritis and presented to the emergency department with shortness of breath and fevers. Computed tomography (CT) chest revealed miliary pulmonary nodules. Urine Histoplasma antigen and serum Histoplasma antigen were negative; however, Coccidioides immitis complement immunofixation assay and Coccidioides IgM were positive. The patient was initiated on treatment for pulmonary coccidioidomycosis and immunosuppression was held. However, a few days later, Histoplasma capsulatum was isolated from cultures from bronchoscopy. This case highlights the difficulty in diagnosing histoplasmosis in immunocompromised patients and the importance of having a broad differential diagnosis for miliary pulmonary nodules. Tissue culture and histopathology remain the gold standard for the diagnosis of histoplasmosis. Further research needs to be conducted to determine the optimal duration of histoplasmosis treatment in immunocompromised patients.

Vancomycin Taper and Pulse Regimen With Careful Follow-up for Patients With Recurrent Clostridium difficile Infection.

We retrospectively studied vancomycin taper and pulse treatment on 100 consecutive, evaluable patients with recurrent Clostridium difficile infection. Following taper to once-daily vancomycin dosing, 22 of 36 patients (61%) who received every-other-day dosing (QOD) and 50 of 64 (81%) who received QOD followed by every-third-day dosing were cured (P = .03).