Shio Yen Tio, Chin Fen Neoh, David Ritchie, Lynette Chee, David C M Kong, Leon J Worth, Michelle K Yong, Monica A Slavin
{"title":"The Changing Epidemiology of Breakthrough Invasive Fungal Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients in the Era of Modified-Release Posaconazole Prophylaxis.","authors":"Shio Yen Tio, Chin Fen Neoh, David Ritchie, Lynette Chee, David C M Kong, Leon J Worth, Michelle K Yong, Monica A Slavin","doi":"10.1111/tid.70104","DOIUrl":"https://doi.org/10.1111/tid.70104","url":null,"abstract":"<p><strong>Background: </strong>Allogeneic hemopoietic stem cell transplant (aHSCT) recipients are at high-risk for invasive fungal disease (IFD), even with mould-active antifungal prophylaxis (AFP).</p><p><strong>Methods: </strong>This was a retrospective, observational, single-center cohort study involving 300 adult aHSCT recipients transplanted from January 2017-May 2020. Patient demographics, underlying hematological malignancy (HM), transplant characteristics and AFP were described. The primary objectives were rate and characteristics of breakthrough IFD (bIFD) within 1-year post-transplant.</p><p><strong>Results: </strong>Of 300 aHSCT recipients, 195 (65%) were males; median age at transplantation was 54 years (IQR 43-62). Acute leukemia was the most common underlying HM (50%), and modified-release posaconazole was the main primary AFP (88%). B-IFD occurred in 26 patients (9%): 14 breakthrough invasive mould diseases (bIMD), which Aspergillus species predominated (56%), followed by Lomentospora prolificans (31%); and 12 breakthrough invasive yeast infections, with Nakaseomyces glabratus most frequently isolated. Neither Aspergillus fumigatus complex nor Candida albicans was cultured as breakthrough organisms. bIMD occurred late post aHSCT at median of 167 days, whereas breakthrough invasive yeast infection occurred at median of 21 days. Twelve patients (46%) had therapeutic-drug-monitoring at time of bIFD-all were within therapeutic range. All-cause mortality at 12-weeks from bIMD and breakthrough invasive yeast infection infections were 50% and 58%, respectively.</p><p><strong>Conclusion: </strong>Although bIFD rate was consistent with other reports, mortality after bIFD remained significant. Use of mould-active AFP likely explained the changing epidemiology of fungal isolates. Resistant breakthrough fungal organisms, especially L. prolificans, reflected local epidemiology. Ongoing surveillance of IFD including resistant organisms is warranted to optimize treatment and patient outcome.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e70104"},"PeriodicalIF":2.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cowdry A Bodies of Varicella Zoster Virus in a Renal Transplant Recipient.","authors":"Kiran Gajurel, Gautam M Phadke, Muammar Arida","doi":"10.1111/tid.70111","DOIUrl":"https://doi.org/10.1111/tid.70111","url":null,"abstract":"","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e70111"},"PeriodicalIF":2.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NUDT15 Genetic Polymorphism as a Risk Factor for Early Neutropenia During Valganciclovir Prophylaxis in Lung Transplant Patients.","authors":"Yurie Katsube, Keisuke Umemura, Yuzuki Urabe, Miori Ono, Yoshiki Katada, Daiki Hira, Akihiro Ohsumi, Daisuke Nakajima, Masahiro Tsuda, Shunsaku Nakagawa, Tomoyuki Mizuno, Miki Nagao, Hiroshi Date, Tomohiro Terada","doi":"10.1111/tid.70108","DOIUrl":"https://doi.org/10.1111/tid.70108","url":null,"abstract":"<p><strong>Background: </strong>Valganciclovir (VGCV) prophylaxis effectively prevents cytomegalovirus infection in lung transplant patients. However, VGCV-induced neutropenia causes early cessation. Nucleoside diphosphate-linked moiety X-type motif (NUDT) 15 degrades the ganciclovir (GCV) triphosphate, an active metabolite. We assessed the effects of NUDT15 variants on neutropenia and VGCV cessation in recipients of lung transplants.</p><p><strong>Methods: </strong>We recruited 28 patients who had received lung transplants and VGCV prophylaxis and genotyped NUDT15 exons 1-3 using Sanger sequencing. Neutrophil counts were monitored from 1 month to 1 year in the wild-type and NUDT15 reduced-function variant groups. Cumulative incidences of neutropenia (< 1500/mm<sup>3</sup>) and neutropenia-related cessation within 1 year, including late-onset neutropenia, were assessed using Kaplan-Meier analysis. A subgroup analysis was conducted focusing on patients with stable renal function, the primary route of excretion for GCV.</p><p><strong>Results: </strong>Of the 28 patients, nine carried NUDT15 variants (Arg139Cys, Val18Ile, Val18_Val19insGlyVal, Arg139Cys/Val18Ile). The neutrophil count nadir within 1 month of treatment was lower in the NUDT15-variant group than in the wild-type group. A higher incidence of neutropenia and VGCV cessation was observed in the NUDT15-variant group, but without statistical significance. Among 13 patients with stable renal function, all four in the NUDT15-variant group developed neutropenia and cessation within 60 days, compared with two of nine in the wild-type group. Covariance analysis showed that NUDT15 variants were associated with decreased neutrophil counts, independent of GCV trough concentration.</p><p><strong>Conclusion: </strong>NUDT15 variants increase the risk of early neutropenia during VGCV prophylaxis in lung transplant recipients.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e70108"},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adam G Stewart, Felicity Edwards, Kevin B Laupland
{"title":"Bloodstream Infection and Risk for Plasma Cell Neoplasms: A Population-Based Cohort Study.","authors":"Adam G Stewart, Felicity Edwards, Kevin B Laupland","doi":"10.1111/tid.70110","DOIUrl":"https://doi.org/10.1111/tid.70110","url":null,"abstract":"<p><strong>Background: </strong>Invasive infection may be the first prompt to investigate the occult presence of a plasma cell neoplasm. The objective of this study was to quantify the risk for subsequent diagnosis of a plasma cell neoplasm following bloodstream infection (BSI).</p><p><strong>Methods: </strong>Statewide population-based surveillance was conducted from January 1 2000 - December 31 2019. Statewide databases were used to identify patients with incident plasma cell neoplasms diagnosed within 1-year following a BSI diagnosis.</p><p><strong>Results: </strong>A cohort of 90 individuals who had BSI within the year preceding diagnosis of plasma cell neoplasm and 95 753 patients with BSI without this malignancy were included. The time to diagnose a plasma cell neoplasm was a median 123 (31-221) days after index BSI. The overall incidence of plasma cell neoplasms among those with incident BSI was 93.9 per 100 000 population annually. Among the study population, development of a BSI was associated with a 13-fold increased risk for diagnosis of plasma cell neoplasm (IRR; 12.9; 95% CI, 10.3-15.8; p < 0.001). The increased risk following BSI was elevated for both sexes, with a magnitude of risk higher for females (IRR; 14.0; 95% CI, 9.8-19.4). Streptococcus pneumoniae BSI was associated with the highest risk for subsequent diagnosis of a plasma cell neoplasm (IRR 46.9; 95% CI; 26.2-77.4).</p><p><strong>Conclusions: </strong>The presence of a BSI, particularly with S. pneumoniae, is a marker for occult plasma cell neoplasms in a small but significant number of patients. Further studies are warranted to identify occult neoplastic disease investigation strategies for patients with incident BSIs.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e70110"},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tamara Krekel, Jennifer Miller, Alan Catalano, Anupam Pande, Jeff Klaus
{"title":"Evaluation of Therapeutic Target Attainment With Various Posaconazole Formulations.","authors":"Tamara Krekel, Jennifer Miller, Alan Catalano, Anupam Pande, Jeff Klaus","doi":"10.1111/tid.70105","DOIUrl":"https://doi.org/10.1111/tid.70105","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring (TDM) is recommended for posaconazole oral immediate release suspension due to saturable absorption and variable bioavailability; however, it has been suggested that TDM may not be necessary for the delayed-release tablet or intravenous formulations. Our study evaluated target trough attainment with the delayed-release tablet and intravenous solution.</p><p><strong>Methods: </strong>This retrospective, single-center study included adult patients who received posaconazole at a dose of 300 mg every 24 h with at least one steady-state (SS) trough while on the delayed-release tablet or intravenous solution exclusively. Outcomes included the percentage of patients who achieved an initial SS trough ≥ 1300, ≥ 1000, or ≥ 700 ng/mL, in addition to a risk factor analysis.</p><p><strong>Results: </strong>Among the 142 patients included, 74 (52.1%), 102 (71.8%), and 122 (86%) patients had an initial SS trough ≥ 1300, ≥ 1000, and ≥ 700 ng/mL, respectively. More patients achieved an initial SS trough ≥ 1300 ng/mL under the following conditions: total body weight < 90 kg, body mass index < 30 kg/m<sup>2</sup>, or no receipt of acid suppressive therapy. No significant differences were found for median initial SS troughs or percentage of patients with an initial SS trough ≥ 1000 or ≥ 700 ng/mL.</p><p><strong>Conclusion: </strong>With 47.9% of initial SS troughs < 1300 ng/mL and 28.8% < 1000 ng/mL, we recommend TDM for all patients receiving posaconazole for treatment, irrespective of formulation. Initial doses higher than 300 mg q24h should be considered for all patients and strongly considered for patients with risk factors for subtherapeutic troughs.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e70105"},"PeriodicalIF":2.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth Yasmine Wardoyo, Sanja Behera, Harmandeep Singh
{"title":"Disseminated Cryptococcosis With Multifocal Osteomyelitis Presenting as a Non-Healing Ulcer in a Kidney Transplant Recipient.","authors":"Elizabeth Yasmine Wardoyo, Sanja Behera, Harmandeep Singh","doi":"10.1111/tid.70103","DOIUrl":"https://doi.org/10.1111/tid.70103","url":null,"abstract":"","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e70103"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Henna Butt, Neal Jeffries, Triscia Martin, Valeria De Giorgi, Alison Zamora, John F Tisdale, Matthew M Hsieh
{"title":"Revaccination Response and Lack of Hepatitis B Reactivation After HCT for Sickle Cell Disease.","authors":"Henna Butt, Neal Jeffries, Triscia Martin, Valeria De Giorgi, Alison Zamora, John F Tisdale, Matthew M Hsieh","doi":"10.1111/tid.70097","DOIUrl":"https://doi.org/10.1111/tid.70097","url":null,"abstract":"<p><strong>Background: </strong>Sickle cell disease (SCD) can be cured by hematopoietic cell transplantation (HCT), but patients face increased risk of hepatitis B virus (HBV) reactivation due to immunosuppression. Understanding hepatitis B surface antibody (anti-HBs) kinetics is essential for optimizing HBV revaccination and posttransplant care.</p><p><strong>Methods: </strong>This post hoc analysis examined HBV immunity, reactivation, and revaccination response in 71 SCD patients who underwent HCT at the National Heart, Lung, and Blood Institute (2008-2021) using alemtuzumab and low-dose total body irradiation.</p><p><strong>Results: </strong>At baseline, 55% showed HBV immunity (anti-HBs ≥ 12 mIU/mL). Most patients responded to revaccination regardless of baseline immunity. Post-HCT revaccination was given to 93%, with 89% completing full series (Heplisav-B or Engerix-B). Vaccinated patients had a 67.5% chance of increased anti-HBs titers between Years 1 and 2, though no significant difference was seen compared to unvaccinated patients (p = 0.12). No HBV reactivation occurred; two patients with baseline HBcAb and HBsAg positivity showed decreasing HBV DNA levels.</p><p><strong>Conclusions: </strong>Results indicate that HBV immunity can decline post-HCT, but most patients remain immune, and revaccination is effective. However, some non-responders-especially those treated with IVIG, rituximab, or prolonged immunosuppression-need further study. Prospective research is needed to optimize revaccination timing and immune monitoring in this high-risk group.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e70097"},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
José Luis Piñana, Clara Martínez-López, Pedro Chorão, Ariadna Pérez, Dolores Gómez, Jaime Sanz, Carlos Solano de la Asunción, Juan Carlos Hernández-Boluda, David Navarro, Juan Montoro, Carlos Solano
{"title":"Characterizing Respiratory Virus Infections during the Peri-engraftment Period of Allogeneic Hematopoietic Cell Transplant.","authors":"José Luis Piñana, Clara Martínez-López, Pedro Chorão, Ariadna Pérez, Dolores Gómez, Jaime Sanz, Carlos Solano de la Asunción, Juan Carlos Hernández-Boluda, David Navarro, Juan Montoro, Carlos Solano","doi":"10.1111/tid.70101","DOIUrl":"https://doi.org/10.1111/tid.70101","url":null,"abstract":"<p><strong>Background: </strong>Community-acquired respiratory virus (CARV) infections are frequent and potentially severe in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. However, their impact during the peri-engraftment period remains underexplored.</p><p><strong>Methods: </strong>In this retrospective multicenter study, we assessed the characteristics, effects on neutrophil engraftment, and risk factors for lower respiratory tract disease (LRTD) progression and 100-day mortality of symptomatic peri-engraftment CARV infections [from Day -8 until Day +36 after stem cell infusion]. A total of 112 allo-HCT recipients and 114 CARV episodes were included. Univariable and multivariable Cox regression analyses and cumulative incidence estimates were used.</p><p><strong>Results: </strong>The median patient age was 51 years. Rhinovirus (47%) and respiratory syncytial virus (23%) were the most common pathogens. Half of the infections occurred before neutrophil engraftment (median day +18), and 50% progressed to LRTD. The 100-day mortality rate was 17%, increasing to 27% in those with LRTD. CARV infection prior to engraftment was associated with delayed neutrophil recovery (Day +18 vs. +16; p = 0.04) in multivariable cause-specific Cox regression analysis (HR 0.42, p < 0.001). Multivariable analysis identified lymphocyte count <0.2×10⁹/L (HR 3.1, p = 0.004) and active graft-versus-host disease (HR 2.36, p = 0.004) as independent predictors of LRTD. Risk factors for 100-day mortality included LRTD (HR 3.34, p = 0.04), use of anti-thymocyte globulin (HR 3.48, p = 0.019), and bacterial coinfection (HR 4.48, p = 0.006).</p><p><strong>Conclusion: </strong>CARV infections during the peri-engraftment allo-HCT phase carry a high risk for delayed engraftment and LRTD in case of profound lymphopenia and GvHD. LRTD, ATG use, and bacterial coinfections contributed significantly to mortality.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e70101"},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}