Razonable, Raymund R

ABSTRACT Background Cytomegalovirus (CMV) infection is among the most common infections after solid organ transplantation and leads to high rates of morbidity and mortality. With the proliferation of large, claims‐based datasets, there is a need to assess the validity of ICD‐10‐CM codes in identifying CMV infection. Methods We conducted a retrospective cohort study of solid organ transplant recipients (SOTRs) from a regional health system who underwent first transplantation between January 1, 2016, and June 30, 2025, had at least 30 days of post‐transplant follow‐up, and had known donor/recipient CMV serostatus. We performed cross‐sectional and time‐to‐event analyses comparing the test performance of B25 ICD‐10‐CM codes in identifying CMV infection, clinically significant CMV infection (csCMVi), CMV disease, and CMV DNA reaching various thresholds. Results Of 8169 SOTRs, 3084 (37.8%) had B25 coded during follow‐up. In addition, 4287 (52.5%) developed CMV infection, 2356 (28.8%) csCMVi, 297 (3.6%) CMV disease, and 1669 (20.4%) CMV DNA ≥ 1000 IU/mL. B25 codes were most specific to any CMV infection (88.5%), most sensitive to CMV DNA ≥ 100 000 IU/mL (98.2%), and csCMVi had the highest Youden's Index (0.651; sensitivity 84.1%, specificity 81.0%). Multivariable Cox regression provided similar results but with variations in effect measure between ICD‐10‐CM codes and clinical CMV definitions. Conclusions ICD‐10‐CM codes showed modest performance in identifying CMV infection, most closely resembling csCMVi. ICD‐10‐CM codes poorly reflect CMV severity, however, and may overestimate CMV infection by some clinical definitions. These limitations should be considered when using CMV diagnosis codes for claims‐based studies of SOTRs.

ABSTRACT Background Cytomegalovirus (CMV) infection remains one of the most prevalent and consequential post solid organ transplant (SOT) infections. Treatment is often challenging, especially when dealing with refractory and resistant CMV infections. Methods We performed a retrospective multicenter cohort study of SOT recipients with clinically significant CMV infection (csCMVi) during 2010–2016. The primary outcome was early refractory CMV infection and secondary outcomes were drug resistance, CMV recurrence, and mortality. Analysis was done with Kaplan‐Meier, univariable logistic regression analysis, and multivariable Cox regression. Results We included 145 SOT recipients with csCMVi, majority were liver transplant (49%). Most common induction was an anti‐IL‐2 antibody (43.9%). The majority ( n = 82; 56.5%) were CMV D+/R‐ mismatch and presented asymptomatic infection (50.3%). After the initial 3 weeks of antiviral therapy, 13 (8.9%) patients had probable refractory csCMVi; most of them (10 [76.9%]) were CMV D+/R‐ mismatch. Longer time after transplant had lower risk (OR 0.68; CI 0.48–0.95, p = 0.029) while lower absolute lymphocyte count (ALC) had a higher risk of early refractory csCMVi (OR 1.54; CI 1.01–2.44, p = 0.048). Drug‐resistant csCMVi occurred in 7 patients (4.8%); a high initial CMV DNA level was associated with resistant csCMVi (OR 2.00; CI 1.08–3.93, p = 0.031). 25 patients (17.2%) experienced recurrent csCMVi within 6 months. 30 patients (20.7%) died; refractory, resistant or recurrent CMV infections were not associated with mortality. Conclusion Refractory csCMVi is associated with a low ALC and an earlier onset after transplant. Resistant csCMVi is associated with high initial CMV DNA levels. Recurrence of csCMVi is common and potentially associated with low ALC at the end of antiviral treatment.

ABSTRACT Introduction Cytomegalovirus (CMV) causes substantial morbidity after solid organ transplantation. Valganciclovir (VGCV) remains a first‐line prophylactic agent, but it has significant myelosuppressive effect. Letermovir is approved for CMV prophylaxis in high‐risk kidney transplant recipients, but data on its use outside of that population are limited. We describe characteristics and outcomes of letermovir prophylaxis in non‐kidney transplant recipients. Methods We performed a retrospective, multi‐center study of all adult non‐kidney solid organ transplant recipients (SOTr) who received letermovir (March 2018–June 2024) for CMV prophylaxis. Outcomes included breakthrough and post‐prophylaxis delayed‐onset CMV infections, adverse events, and survival. Results A total of 64 patients were included in the final analysis. Of those, letermovir was used for primary prophylaxis in 56.2% of patients, while the remainder received it for secondary prophylaxis. The main rationale behind selecting letermovir was myelosuppression related to VGCV. During the median follow‐up of 361 days (IQR, 190–536), 40.6% remained on letermovir (median, 387 days); 25.0% completed prophylaxis (median, 116 days); and 34.3% discontinued prematurely (median, 49 days), mainly for cost barriers or adverse effects. Breakthrough infections occurred in 9 patients (14.1%), but only three (4.7%) were clinically significant. After stopping letermovir, 39.5% (15/38 among those who discontinued letermovir) developed post‐prophylaxis delayed‐onset CMV infection. Overall survival was 81.2%; there was one death attributed to CMV. Conclusion In this cohort of non‐kidney solid organ recipients, letermovir was well tolerated with low rates of clinically significant breakthrough infections. Early discontinuation was commonly cost‐driven. Post‐prophylaxis delayed‐onset CMV infections remain common. Large‐scale registry studies are needed to provide evidence for use of letermovir in non‐kidney transplant recipients.

ABSTRACT Purpose The purpose of this study was to evaluate the incidence and risk factors for developing recurrent clinically significant cytomegalovirus infections (csCMVi) in heart transplant recipients. Methods We conducted a retrospective cohort study involving adult heart transplant recipients at three large transplant centers in the United States between January 2011 and March 2019. All patients with a history of csCMVi, defined as CMV disease or CMV infection requiring preemptive therapy, were followed from the date of treatment completion for the primary csCMVi episode. Outcomes of interest were recurrent csCMVi and all‐cause mortality. Results Among 98 heart transplant recipients with csCMVi, 22 (22.4%) episodes of recurrent csCMVi occurred. Median time‐to‐recurrent csCMVi was 31.5 (IQR 21.3–59.8) days following treatment completion. A preceding episode of CMV disease (versus infection) was associated with a lower risk of recurrent csCMVi (HR 0.29, 95% CI 0.08–0.98; p = 0.047). Patients with lymphopenia had higher rates of recurrent csCMVi without statistical significance (HR 2.13, 95% CI 0.88–5.13; p = 0.093). Seroconversion by the end‐of‐therapy among CMV D+/R− mismatched patients was associated with a reduced risk of csCMVi recurrence (HR 0.07, 95% CI 0.02–0.30; p < 0.001). Overall, 17 (17.3%) patients died during follow‐up, which was not significantly higher among those with recurrent csCMVi (HR 2.13, 95% CI 0.78–5.79; p = 0.141). Conclusions About one in five heart recipients with csCMVi developed post‐treatment recurrence. A preceding episode of CMV disease and seroconversion was protective against recurrence. Lymphopenia may be a practical biomarker to stratify recurrence risk. Overall, recurrent csCMVi was not significantly associated with mortality.

ABSTRACT Background Multiple outpatient therapies have been developed for COVID‐19 in high‐risk individuals, but solid organ transplant (SOT) recipients were not well represented in controlled clinical trials. To date, few comparative studies have evaluated outcomes between outpatient therapies in this population. Methods We performed a retrospective cohort study using de‐identified administrative claims data from OptumLabs Data Warehouse. Patients were included if they were age ≥ 18 years, diagnosed with COVID‐19 between January 2022 and December 2023, and underwent SOT prior to COVID‐19. The primary outcome was 30‐day hospitalization. Stabilized inverse probability of treatment weighting was used to account for potential confounding variables. Results 4192 SOT recipients with COVID‐19 were identified. 1403 received an outpatient COVID‐19 therapy, including anti‐spike monoclonal antibodies ( N = 748, 53.3%), molnupiravir ( N = 327, 23.3%), ritonavir‐boosted nirmatrelvir ( N = 217, 15.5%), or remdesivir ( N = 141, 10.0%). In weighted analysis compared to no treatment, anti‐spike monoclonal antibodies (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.28–0.55; p < 0.001), molnupiravir (HR 0.56, 95% CI 0.36–0.89; p = 0.013), and nirmatrelvir (HR 0.47, 95% CI 0.25–0.89; p = 0.020) were associated with reduced hospitalization risk, while remdesivir (HR 1.00, 95% CI 0.50–1.98; p = 0.992) was not. Hospitalization rates were similar between the treatment agents, apart from remdesivir showing a higher risk compared to anti‐spike monoclonal antibodies. Conclusions Outpatient COVID‐19 therapies were largely associated with improved outcomes among SOT recipients. These treatment agents showed similar rates of 30‐day hospitalization, except for remdesivir. The choice of outpatient COVID‐19 therapy in SOT recipients should primarily account for patients’ individual circumstances and drug‐drug interactions rather than differential therapeutic efficacy. image

Abstract The field of infectious diseases (ID) offers a rewarding career path and is widely viewed as an essential subspecialty in medicine. However, in recent years, these positive aspects have been overshadowed by concerns surrounding low fellowship match rates, undercompensation, and burnout. The Infectious Diseases Society of America Fellowship Training Program Directors Committee met in 2023, discussed the future of ID as a specialty, and sought to develop strategies to highlight the value and opportunities of ID for future generations, as well as underscore the importance of and provide tools for positive messaging to trainees about the subspecialty. This paper presents ideas generated at this meeting and is meant to serve as a reference for ID training program directors, as well as the wider ID community, in uplifting and shaping the future of the field.

AbstractBackgroundDevelopment of brain abscess following solid organ transplantation is associated with significant morbidity and mortality. We undertook a descriptive study to evaluate the etiology, clinical manifestations, diagnosis, management, and outcomes of brain abscess in solid organ transplant (SOT) recipients at three major transplant centers in the United States.MethodsThis is a retrospective study of adults with brain abscess following SOT between January 2000 and June 2021 at Mayo Clinic sites in Arizona, Minnesota, and Florida.ResultsA total of 39 patients were diagnosed with a brain abscess following SOT. The most common pathogens were Nocardia sp. (24 cases, 61.5% [Nocardia farcinica, 37.5%]), followed by fungi (12 cases, 30.7% [Aspergillus sp., 83.3%]). The majority were kidney transplant recipients (59%). Median time to brain abscess diagnosis was 1.3 years (range, 29 days–12 years) after SOT; 10 of 12 patients (83%) with fungal brain abscess were diagnosed within 1 year after SOT. Twelve patients underwent brain biopsy for diagnosis (25% Nocardia vs. 50% fungal), eight (20.5%) underwent surgical resection of the abscess, and 31 (79.5%) received antimicrobial therapy alone. Median time to brain abscess resolution was 166 days for Nocardia and 356 days for fungal pathogens. Eleven of 39 patients (28.2%) died as a result of their brain abscess, including four of 24 patients (16%) with Nocardia and six of 10 patients (60%) with Aspergillus brain abscess. All‐cause mortality was 43.6%.ConclusionBrain abscess remains an uncommon infectious complication following SOT. Nocardia and fungi accounted for 92% of pathogens in our cohort. Fungal brain abscess portends a poor prognosis. image

AbstractBackgroundCytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients (SOTRs). Secondary prophylaxis (SP) is not routinely recommended by guidelines on the management of CMV in SOTR but may be considered in certain higher‐risk situations.MethodsA comprehensive search of English language publications up to September 2023 was performed. The primary outcome was CMV relapse, defined as the recurrence of DNAemia or disease. Secondary outcomes included graft loss, mortality, and hematological toxicity. Meta‐analysis used the random‐effects model. The study protocol is registered in PROSPERO (no. CRD42022357028).ResultsSix retrospective comparative studies were included. A total of 520/727 (72%) of SOTR received SP with valganciclovir. The meta‐analysis did not demonstrate a significant difference in CMV relapse (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.79–2.63). Heterogeneity between the studies was low (I2 = 0%, p = 0.57). SP was significantly associated with a reduction in mortality (OR 0.2, 95% CI 0.07–0.54) but not graft loss (OR 0.67, 0.17–2.63). There was no significant difference in CMV relapse among kidney‐specific SOTR (OR 1.38, 95% CI 0.65–2.96).ConclusionEvidence from six nonrandomized studies is limited and cannot support a recommendation for or against routine SP in SOTR treated for CMV infection. Awaiting prospective‐controlled trials, the decision about SP should depend on individualized risk‐profile assessments by experienced clinicians. image

AbstractIntroductionCytomegalovirus (CMV) reactivation is one of the most common complications after allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir is approved for CMV prophylaxis among high‐risk recipients. However, delayed‐onset post‐prophylaxis clinically significant CMV infection (csCMVi) has been observed, suggesting the potential for extending letermovir prophylaxis beyond the first one hundred days post‐HSCT.MethodsRetrospective multicenter cohort study of allogeneic HSCT patients from August 2018 to March 2023. The primary aim of this study was to identify the risk factors at day 100 associated with delayed onset csCMVi, in patients who received letermovir prophylaxis up to day 100. Competing risk analysis was used to evaluate incidence with specific risk factors, using Gray's Test comparing groups for each event.ResultsAmong 166 eligible allogeneic HSCT recipients, the most common primary hematological diagnosis was acute myelogenous leukemia (AML) (42.2%). Twenty‐six (15.7%) developed a breakthrough csCMVi. Delayed‐onset csCMVi occurred in 23.5%, at a median time of 133 days after SCT. On multivariate analysis, having a matched unrelated donor (odds ratio [OR] 2.46) and a CMV donor negative/recipient positive status (OR 3.47) were associated with delayed onset csCMVi. In contrast, AML had a lower odd of having delayed‐onset csCMVi (OR 0.23).ConclusionsHaving a matched unrelated donor, a CMV donor negative/recipient positive status, and a non‐AML underlying disease were associated with delayed onset csCMVi. Prospective studies are needed to evaluate whether extended letermovir prophylaxis is beneficial for these patients. image