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BackgroundPatients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.Patients and methodsPatients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients).ResultsA total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality.ConclusionsClinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies.Clinical trial identifierNCT04354701.

Background: Coccidioidomycosis is a fungal infection that poses a serious risk when transmitted through organ transplantation. We analyzed cases reported to the Organ Procurement and Transplantation Network ad hoc Disease Transmission Advisory Committee from 2013 to 2022., Methods: Donors and/or recipients who had positive Coccidioides immitis/posadasii serology, pathology, and/or culture were included in this study. Cases adjudicated as 'proven' or 'probable' were analyzed for donor infection risk factors, the timing of infection, transmission by organ type, clinical manifestations, and recipient outcomes. Patient and facility identifiers were removed prior to review., Results: During this time period, 73 potential instances of Coccidioides donor disease transmission events were reported. Among them, infection was transmitted from seven deceased donors to eight recipients. All seven deceased donors had prior infection or exposure to regions where coccidioidomycosis is endemic. Of 20 individuals receiving organs from these donors, eight developed infection, resulting in a 40% transmission rate. The median time to diagnosis post-transplant was 39 days. Disseminated disease occurred in six recipients, five of whom died from the infection. Notably, none of the recipients who received prophylactic antifungal treatment died from the infection., Conclusion: Despite its rarity, donor-derived Coccidioides infection is a serious concern, particularly due to the high mortality rate in the early post-transplant period. To mitigate these risks, a thorough assessment of donor exposure history, coupled with donor serology and bronchoalveolar lavage cultures, can effectively guide post-transplant antifungal prophylaxis. Prompt reporting is crucial to prevent Coccidioides infections among other recipients., (© 2024 Wiley Periodicals LLC.)

Frailty is a syndrome that can inform clinical treatments and interventions for older adults. Although implementation of frailty across medical subspecialties has the potential to improve care for the aging population, its uptake has been heterogenous. While frailty assessment is highly integrated into certain medical subspecialties, other subspecialties have only recently begun to consider frailty in the context of patient care. In order to advance the field of frailty-informed care, we aim to detail what is known about frailty within the subspecialties of internal medicine. In doing so, we highlight cross-disciplinary approaches that can enhance our understanding of frailty, focusing on ways to improve the implementation of frailty measures, as well as develop potential interventional strategies to mitigate frailty within these subspecialties. This has important implications for the clinical care of the aging population and can help guide future research., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation., Aim: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy., Methods: The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted., Results: From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV-) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV- livers as well as non-liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41-1117) days post-transplant in the setting of missing, inadequate, or truncated prophylaxis., Conclusion: HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non-transplant population, possibly due to the common use of HBV prophylaxis in the at-risk transplant population., (© 2024 The Author(s). Transplant Infectious Disease published by Wiley Periodicals LLC.)

Importance: Cytomegalovirus (CMV) is associated with significant morbidity and mortality in solid organ transplant (SOT) recipients. The risk factors for CMV seropositivity in SOT recipients, including area-level social deprivation in the US, have not been fully characterized., Objective: To (1) evaluate CMV seroprevalence, (2) assess the recipient characteristics associated with CMV seropositivity, and (3) assess the association of area-level social deprivation index (SDI) scores with pretransplant CMV serostatus., Design, Setting, and Participants: This retrospective cross-sectional analysis of the Scientific Registry of Transplant Recipients database included all adult (aged ≥18 years) SOT recipients from January 1, 2008, to May 31, 2022. Data were analyzed from April 10 to October 25, 2023., Exposure: Recipient characteristics and area-level SDI., Main Outcomes and Measures: Multivariable generalized linear models were used to evaluate the association between (1) patient characteristics and CMV and (2) social deprivation (measured by SDI scores, which were assessed in quintiles, from lowest to highest) and CMV seropositivity. In addition, differences based on patient demographics and the transplanted organ(s) were evaluated., Results: Among the 389 288 SOT recipients included in the analysis, mean (SD) age was 53.3 (13.0) years; 63.0% were male, 21.4% were Black, 15.2% were Hispanic White, 56.2% were non-Hispanic White, and 62.7% were CMV seropositive. The mean (SD) age was higher among CMV seropositive (54.0 [12.7] years) compared with CMV seronegative (52.0 [13.5] years) patients. Seropositivity for CMV was higher among women (69.9%) than men (58.5%) and among Black (74.8%) and Hispanic White (80.2%) patients compared with non-Hispanic White patients (50.4%). Seropositivity for CMV was highest among kidney (64.5%), liver (63.6%), and kidney and liver (66.2%) recipients. Greater SDI scores were associated with greater CMV seropositivity, ranging from 51.7% for the least deprived to 75.5% for the most deprived quintiles (P < .001), independent of age, sex, or race., Conclusions and Relevance: In this cross-sectional study, an association between SDI and CMV seropositivity was observed among SOT recipients, independent of age, sex, or race and ethnicity. To optimize posttransplant outcomes in CMV seropositive recipients, efforts targeting prevention of CMV reactivation need to be prioritized in these higher-risk populations.

Purpose: Kidney transplantation has a survival benefit for people with human immunodeficiency virus (HIV) and end-stage kidney disease, however increased rates of rejection remain an issue. Questions remain regarding the impact of induction immunosuppression therapy and antiretroviral (ARV) choice on long-term outcomes., Methods: We performed a multicenter retrospective analysis of outcomes in recipients with HIV who received kidneys from donors without HIV transplanted between 2004 and 2019. The association between induction and ARV regimens and long-term outcomes including rejection, graft, and recipient survival over 5 years was investigated using Cox regression modeling., Results: Seventy-eight kidney transplants (KT) performed in 77 recipients at five US transplant centers were included, with median follow up of 7.1 (4.3-10.7) years. Overall recipient and graft survival were 83% and 67%, respectively. Rejection occurred in 37% (29/78). Recipients with rejection were more likely to be younger, recipients of deceased donor organs, and Black. Receipt of rabbit anti-thymocyte globulin (rATG) induction without protease-inhibitor (PI)-based ARVs was associated with 83% lower risk of rejection (adjusted hazard ratio (aHR) 0.17 (95% CI 0.05-0.63), p =.007) and a non-statistically significantly lower risk of graft failure (aHR 0.18 (0.03-1.16), p =.07) when compared to those who received other induction and ARV combinations., Conclusions: In this multicenter retrospective study, we found a trend toward lower rejection and improved graft survival among those who received both rATG for induction and PI-sparing ARVs., (© 2024 Takeda Development Center Americas, Inc. Transplant Infectious Disease published by Wiley Periodicals LLC.)

Background: Cytomegalovirus (CMV) seropositivity is associated with poor outcomes, including physical function impairment, in people without HIV. We examined associations between CMV IgG titer and physical function in virologically suppressed people with HIV (PWH)., Methods: REPRIEVE is a double-blind randomized trial evaluating pitavastatin for primary prevention of atherosclerotic cardiovascular disease in PWH. This analysis focused on participants enrolled in a substudy with additional biomarker testing, imaging [coronary CT angiography], and physical function measures at entry. CMV IgG was measured using quantitative enzyme immunoassay, physical function by Short Physical Performance Battery, and muscle density and area by CT. Associations between CMV IgG (risk factor) and outcomes were evaluated using the partial Spearman correlation and linear and log-binomial regression., Results: Among 717 participants, 82% male, the median CMV IgG was 2716 (Q1, Q3: 807, 6672) IU/mL, all above the limit of quantification. Among 631 participants with imaging, there was no association between CMV IgG and CT-based muscle density or area, controlling for age (r = -0.03 and r = -0.01, respectively; P ≥ 0.38). Among 161 participants with physical function data, higher CMV IgG was associated with poorer overall modified Short Physical Performance Battery score ( P = 0.02), adjusted for age, nadir CD4, and high-sensitivity C-reactive protein., Conclusions: Higher CMV IgG titer was associated with poorer physical function, not explained by previous immune compromise, inflammation, or muscle density or area. Further mechanistic studies are needed to understand this association and whether CMV-specific therapy can affect physical function in PWH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of overall patient and graft survival. Our primary objective was to describe the short- and long-term risks associated with high-risk CMV donor positive/recipient negative (D+/R-) mismatching among DDKT recipients with the explicit goal of deriving a mathematical mismatching penalty., Methods: We conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients (SRTR) database using donor-matched DDKT recipient pairs (N=105,608) transplanted between 2011-2022. All-cause mortality and graft failure hazard ratios were calculated from one year to ten years post-DDKT. All-cause graft failure included death events. Survival curves were calculated using the Kaplan-Meier estimation at 10 years post-DDKT and extrapolated to 20 years to provide the average graft days lost (aGDL) and average patient days lost (aPDL) due to CMV D+/R- serostatus mismatching. We also performed an age-based stratification analysis to compare the relative risk of CMV D+ mismatching by age., Results: Among 31,518 CMV D+/R- recipients, at 1 year post-DDKT, the relative risk of death increased by 29% (p<0.001), and graft failure increased by 17% (p<0.001) as compared to matched CMV D+/R+ group (N=31,518). Age stratification demonstrated a significant increase in the risk associated with CMV mismatching in patients 40 years of age and greater. The aGDL per patient due to mismatching was 125 days and the aPDL per patient was 100 days., Conclusion: The risks of CMV D+/R- mismatching are seen both at 1 year post-DDKT period and accumulated throughout the lifespan of the patient, with the average CMV D+/R- recipient losing more than three months of post-DDKT survival time. CMV D+/R- mismatching poses a more significant risk and a greater health burden than previously reported, thus obviating the need for better preventive strategies including CMV serodirected organ allocation to prolong lifespans and graft survival in high-risk patients., Competing Interests: MA was employed by Merck Corporation. KE was employed by Gilead Sciences, Merck Corporation, and ViiV HealthCare Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abidi, Schold, Kaplan, Weinberg, Erlandson and Malamon.)

Introduction: Cytomegalovirus (CMV) can cause significant morbidity and mortality in cord blood transplant (CBT) recipients. Development of CMV-specific cell-mediated immunity (CMV-CMI) has been associated with protection against CMV clinically significant reactivation (CsCMV). In this study, we evaluated CMV-CMI reconstitution during letermovir prophylactic therapy, which prevents CsCMV without complete suppression of CMV reactivation., Methods: We measured CMV-CMI in CMV-seropositive CBT recipients pre-transplant after Day+90 of letermovir prophylaxis and at Days +180, and +360- post-transplant using a dual color CMV-specific IFNγ/IL2 FLUOROSpot. CsCMV and nonCsCMV reactivations were abstracted from medical records. CsCMV was defined as CMV viral load ≥5,000 IU/ml using a whole blood assay., Results: Among 70 CBT recipients, 31 developed CMV-CMI by Day+90 and an additional eight and five participants by Days +180 and +360, respectively. Thirty-eight participants developed CMV reactivation, including nine with CsCMV. Most reactivations (33 of 38) occurred before Day+180. Early CMV-CMI was present in six out of nine participants with CsCMV, indicating a lack of protection against CsCMV. Moreover, the magnitude of CMV-CMI at Day+90 did not differ between participants with CsCMV and nonCsCMV., Conclusion: Approximately 50% of CBT recipients reconstituted CMV-CMI during letermovir prophylactic therapy. However, CMV-CMI did not reach levels protective against CsCMV. Extension of CMV prophylaxis beyond Day+90 may be considered in CMV-seropositive CBT recipients., (© 2023 Wiley Periodicals LLC.)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disproportionately affects immunocompromised and elderly patients. Not only are hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR) T-cell recipients at greater risk for severe COVID-19 and COVID-19-related complications, but they also may experience suboptimal immune responses to currently available COVID-19 vaccines. Optimizing the use, timing, and number of doses of the COVID-19 vaccines in these patients may provide better protection against SARS-CoV-2 infection and better outcomes after infection. To this end, current guidelines for COVID-19 vaccination in HCT and CAR T-cell recipients from the American Society of Transplantation and Cellular Therapy Transplant Infectious Disease Special Interest Group and the American Society of Hematology are provided in a frequently asked questions format., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

This document is intended as a guide for diagnosis and management of Coronavirus Disease 2019 (COVID-19), caused by the virus SARS-CoV-2, in adult and pediatric HCT and cellular therapy patients. This document was prepared using available data and with expert opinion provided by members of the (ASTCT) Infectious Diseases Special Interest Group (ID-SIG) and is an update of pervious publication. Since our original publication in 2020, the NIH and IDSA have published extensive guidelines for management of COVID-19 which are readily accessible ( NIH Guidelines , IDSA Guidelines ). This update focuses primarily on issues pertaining specifically to HCT/cellular therapy recipients. Information provided in this manuscript may change as new information becomes available., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Younger kidney transplant (KT) candidates and recipients may have cognitive impairment due to chronic diseases and reliance on dialysis., Methods: To quantify cognitive impairment burden by age across the KT care continuum, we leveraged a two-center cohort study of 3854 KT candidates at evaluation, 1114 recipients at admission, and 405 recipients at 1-year post-KT with measured global cognitive performance (3MS) or executive function (Trail Making Test). We also estimated burden of severe cognitive impairment that affects functional dependence (activities of daily living [ADL] < 6 or instrumental activities of daily living [IADL] < 8)., Results: Among KT candidates, global cognitive impairment (18-34 years: 11.1%; 35-49 years: 14.0%; 50-64 years: 19.5%; ≥65 years: 22.0%) and severe cognitive impairment burden (18-34 years: 1.1%; 35-49 years: 3.0%; 50-64 years: 6.2%; ≥65 years: 7.7%) increased linearly with age. Among KT recipients at admission, global cognitive impairment (18-34 years: 9.1%; 35-49 years: 6.1%; 50-64 years: 9.3%; ≥65 years: 15.7%) and severe cognitive impairment burden (18-34 years: 1.4%; 35-49 years: 1.4%; 50-64 years: 2.2%; ≥65 years: 4.6%) was lower. Despite lowest burden of cognitive impairment among KT recipients at 1-year post-KT across all ages (18-34 years: 1.7%; 35-49 years: 3.4%; 50-64 years: 4.3%; ≥65 years: 6.5%), many still exhibited severe cognitive impairment (18-34 years: .0%; 35-49 years: 1.9%; 50-64 years: 2.4%; ≥65 years: 3.5%)., Conclusion: Findings were consistent for executive function impairment. While cognitive impairment increases with age, younger KT candidates have a high burden comparable to community-dwelling older adults, with some potentially suffering from severe forms. Transplant centers should consider routinely screening patients during clinical care encounters regardless of age., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Invasive candidiasis (IC) is a substantial cause of morbidity and mortality among lung transplant recipients (LTRs). Postoperative factors include prolonged hospital stay, central lines, delayed chest closure, and dehiscence increase IC risk. Correspondingly, current guidelines propose targeted IC coverage early posttransplant with fluconazole or an echinocandin., Methods: This retrospective analysis was performed on LTRs from January 2016 to January 2020 and evaluated effectiveness of a recent protocol utilizing perioperative anidulafungin for early IC prevention in addition to long-term triazole antifungal prophylaxis. Prior to this protocol, patients were primarily established on itraconazole prophylaxis alone. The primary endpoint was proven or probable IC within 90 days after transplant. Multivariable logistic regression modeling was used to assess risk factors for invasive fungal infection (IFI)., Results: Among 144 LTRs, there was a numerically lower incidence of IC in the protocol group, although not statistically significant (6% vs. 13%, p = 0.16). Incidence of proven or probable IFI was 7.5% in the protocol cohort and 19.5% in the pre-protocol cohort (p = 0.038). In multivariable analysis, when controlling for lung allocation score (OR 1.04, 95% CI 1.01-1.08), donor perioperative culture with fungal growth (OR 2.92, 95% CI 1.02-8.92), and dehiscence (OR 3.54, 95% CI 1.14-10.85), protocol cohort was not significantly associated with IFI (OR 0.41, 95% CI 0.12-1.23)., Conclusions: To our knowledge, this is the first study investigating combination triazole/echinocandin use in the early post-lung transplant period. These findings demonstrate that in-hospital anidulafungin offers unclear benefit for early IC prevention when used in combination with triazole prophylaxis., (© 2021 Wiley Periodicals LLC.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

There are currently limited data on the epidemiology, clinical manifestations, and optimal management of Coronavirus Disease 2019 (COVID-19) in hematopoietic cell transplantation and cellular therapy recipients. Given the experience with other respiratory viruses, we anticipate that patients may develop severe clinical disease and thus provide the following general principles for cancer centers across the nation. These guidelines were developed by members of the American Society for Transplantation and Cellular Therapy Infectious Diseases Special Interest Group. Specific practices may vary depending on local epidemiology and testing capacity, and the guidance provided in this document may change as new information becomes available., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Cytomegalovirus (CMV) is a DNA virus of the Herpesviridae family and is estimated to affect 15%-30% of high-risk solid organ transplant recipients. Typical manifestations of CMV end-organ disease in this population include colitis, esophagitis, and pneumonitis, and myocarditis is a rarely reported manifestation. We describe two cases of CMV myocarditis in solid organ transplant recipients and review the literature regarding previously published cases of CMV myocarditis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We compared CMV outcomes of three prophylactic approaches used for CBT and haploidentical cord transplants from December 2009 through 2018: letermovir (n = 32) through day 100 post transplant, "valacyclovir day 100" (valacyclovir 2 g orally three times daily through day 100) (n = 60), and "valacyclovir hospital discharge" (valacyclovir 2 g orally three times daily through hospital discharge then acyclovir 800 mg twice daily) (n = 41). Through day 100, none in the letermovir group, six (10%) in the "valacyclovir day 100," and nine (22%) in the "valacyclovir hospital discharge" group required CMV directed treatment (p = 0.005 and 0.06 comparing letermovir to "valacyclovir hospital discharge" and "valacyclovir day 100"). Fewer patients in the letermovir group (n = 7, 22%) had any CMV reactivation versus the "valacyclovir day 100" group (n = 20, 33%) versus the "valacyclovir hospital discharge" group (n = 23, 57%) (p = 0.003 and 0.21 comparing letermovir to "valacyclovir hospital discharge" and "valacyclovir day 100"). Among patients not reactivating CMV before 100 days, reactivation rates between day 100 and 180 were higher in the letermovir and "valacyclovir day 100" groups than the "valacyclovir hospital discharge" group. Letermovir is safe and effective compared with alternative prophylaxis approaches following CBT through day 100. Reactivation and monitoring after day 100 remain potential concerns.

The risk of toxoplasmosis in high-risk cardiac transplant recipients is well recognized prompting universal donor and candidate screening with administration of targeted post-transplant chemoprophylaxis in high-risk (D+/R-) cardiac transplant patients. In contrast, until recently, there have been neither well-defined recommendations nor consensus regarding toxoplasmosis preventive strategies among non-cardiac solid organ transplant recipients. We report 3 cases of post-transplant toxoplasmosis in non-cardiac transplant recipients (one lung and two liver); all 3 infections presumed to be donor-derived. Not surprisingly, pre-transplant Toxoplasma serology was negative in all the patients. None of the patients were on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis of toxoplasmosis. The median time from transplant to onset of infection was 90 days (range: 30-120 days). Clinical presentations included cerebral (n = 1) and disseminated infections (n = 2). Two of the 3 patients, both with disseminated infection died (mortality ~ 67%)., (© 2019 Wiley Periodicals, Inc.)

Q fever in solid organ transplant (SOT) recipients is rarely described in the medical literature. We present a case of severe acute Q fever pneumonia that evolved into persistent localized Q fever endocarditis in a renal transplant recipient., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Clostridioides difficile infection (CDI) is a common complication in the hematopoietic stem cell transplantation (HSCT) and hematologic malignancy (HM) population. CDI is associated with increased hospital length of stay, health care and societal costs, morbidity, and mortality. Identifying strategies for secondary prevention of CDI is of extreme importance in the HSCT/HM population. In this study, our primary objective was to evaluate the effectiveness and safety of an oral vancomycin prophylaxis (OVP) protocol for secondary prevention of CDI in a retrospective cohort of adult autologous/allogeneic HSCT recipients and patients with HM who did not undergo HSCT with a first CDI episode treated with concomitant broad-spectrum antibiotics (BSA). Patients were diagnosed and treated for CDI as inpatients and/or outpatients and were divided into 2 groups based on a preprotocol versus postprotocol analysis: the OVP group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently received OVP posttreatment and a no OVP (NOVP) group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently did not receive OVP posttreatment. OVP was defined as vancomycin 125 mg every 12 hours for up to 7 days after BSA discontinuation. The primary endpoint was recurrent CDI (rCDI), defined as symptoms of loose stools/diarrhea with high clinical suspicion for CDI prompting empiric therapy within 60 days of completion of treatment/prophylaxis for the first CDI episode. The incidence of vancomycin-resistant enterococcal (VRE) infection and 60-day mortality were also compared between the 2 groups. Multivariate logistic regression was created from associated variables to identify independent associations with rCDI. A total of 50 patients were included, 21 in the OVP group (42%) and 29 in the NOVP group (58%). The mean patient age was 58 years, and the cohort was 60% male and 86% Caucasian. HSCT was performed in 60% of the patients, and 76% of CDI cases were diagnosed during hospitalization. The rate of rCDI was significantly lower in the OVP group compared with the NOVP group (5% [1 of 21] versus 35% [10 of 29]; P= .016), with no subsequent increase in VRE infection rate (14% [3 of 21] versus 10% [3 of 29]; P = .686). By multivariable logistic regression, rCDI was inversely associated with OVP (odds ratio [OR], .14; 95% confidence interval [CI], .007 to .994; P = .049) and directly associated with outpatient CDI diagnosis (OR, 8.72; 95% CI, 1.816 to 49.158; P = .007). No between-group differences were found in 60-day mortality (10% [2 of 21] for OVP versus 7% [2 of 29] for NOVP; P > 0.999). OVP appears to be safe and effective for secondary prevention of CDI in the HSCT/HM population. Prospective trials are needed to validate the effectiveness of OVP in this vulnerable population to prevent rCDI., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Limited data exist on characteristics of central nervous system viruses (CNS-V) in allogeneic hematopoietic stem cell transplant (HCT) recipients. Between 2007 and 2015, the Center for International Blood and Marrow Transplant Research (CIBMTR) received information on 27,532 patients undergoing HCT. Of these, centers reported 165 HCT recipients with CNS-V detected in cerebrospinal fluid within 6 months after HCT. CNS viruses predominantly included human herpes virus 6 (HHV-6) (73%), followed by Epstein-Barr Virus (10%), cytomegalovirus (3%), varicella zoster virus (3%), herpes simplex virus (3%) and Adenovirus (3%). Median time of viral detection in CNS was 31 days after HCT; and viral detection was earlier in patients with CNS HHV-6. Concurrent viremia occurred in 52% of patients. Cord blood transplant recipients (CBT) accounted for the majority (53%) of patients with CNS-V. Myeloablative conditioning (65%), use of fludarabine (63%), or use of anti-thymocyte globulin (61%) were also predominant. Overall survival from the time of detection of CNS-V was 50% at 6 months and 30% at 5 years. Infections were the leading cause of death (32%). In summary, CBT recipients predominated in the population with CNS-V. Outcomes after CNS-V were poor with significant mortality seen in the first 6 months.

Mycobacterium mucogenicum (MM) is a rapidly growing nontuberculous mycobacterium that may rarely cause bacteremia in immune-compromised hosts. All MM cases from 2008 to 2013 were analyzed across 4 risk groups: stem cell transplantation (SCT), hematologic malignancy, solid tumors, and others. Descriptive analysis was performed, as well as comparative analysis of neutropenic patients (absolute neutrophil count ≤1000/μL) with nonneutropenic patients. Of 39 MM cases, 27 patients had undergone SCT. Neutropenia was present in 12 patients. There was a significant difference in the presence of fever at the time of MM bacteremia between neutropenic and nonneutropenic groups (92% versus 42%; P=0.005). Central venous catheter (CVC) was present in 33 cases. All patients were treated with >1 antibiotic. Most frequently used combination antibiotic regimen involved clarithromycin and amikacin. Median duration of antibiotic treatment was 42days. Bacteremia resolved in all cases with CVC removal and combination antibiotic treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Rothia spp. are increasingly being recognized as emerging opportunistic pathogens associated with serious infections in immune-compromised hosts. Risk factors include neutropenia, hematologic malignancies, prosthetic devices, and intravascular catheters. We describe 29 patients at our institute from 2006 to 2014 with positive blood cultures for Rothia spp. Neutropenia was observed in 21/29 (72%) patients at the time of bacteremia, and 16/29 (61%) had leukemia. Neutropenic patients were less likely than nonneutropenic patients to have polymicrobial infection (24% versus 63%; P= 0.083) and were also more likely to have multiple positive blood cultures (76% versus 0%; P= 0.0003), indicating true infection. Sources of bacteremia included intravascular catheters, mucositis, and presumed gut translocation. A significant association was seen with steroid use (81% versus 13%; P= 0.0014) and fluoroquinolone use (86% versus 13%; P≤ 0.0001) preceding bacteremia in neutropenic patients. There was no difference between the 2 groups for admission to intensive care unit or mortality. One death was reported possibly due to Rothia infection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Parainfluenza virus (PIV) may cause life-threatening pneumonia in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Currently, there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, for treatment of PIV type 3 pneumonia in two allogeneic hematopoietic SCT recipients with respiratory failure.

Ruxolitinib is widely in use for treatment of myeloproliferative disorders. It causes inhibition of the Janus kinase (JAK) signal transducer and activation of transcription (STAT) pathway, which plays a key role in the underlying pathophysiology of myeloproliferative diseases. We describe a case of reactivation pulmonary tuberculosis in a retired physician while on treatment with ruxolitinib. We also review the literature on opportunistic infections following use of ruxolitinib. Our case highlights the importance of screening for latent tuberculosis in patients from highly endemic areas prior to start of therapy with ruxolitinib.

We describe an immunosuppressed, 48-year-old male, allogeneic hematopoietic stem cell transplant recipient with severe graft-versus-host disease who developed invasive pulmonary Aspergillus fumigatus infection 6 months after transplant. His lack of response to voriconazole and undetectable serum trough levels of the drug led us to establish that he had the uncommon cytochrome P450, CYP2C19*17 allele, which leads to a rapid metabolism of voriconazole but not of the other azole antifungals. We discuss the particular challenges encountered in this case., (Copyright © 2015 Elsevier Inc. All rights reserved.)

As invasive mucormycosis (IM) numbers rise, clinicians suspect prior voriconazole worsens IM incidence and severity, and believe combination anti-fungal therapy improves IM survival. To compare the cumulative incidence (CI), severity and mortality of IM in eras immediately before and after the commercial availability of voriconazole all IM cases from 1995 to 2011 were analysed across four risk-groups (hematologic/oncologic malignancy (H/O), stem cell transplantation (SCT), solid organ transplantation (SOT) and other), and two eras, E1 (1995-2003) and E2, (2004-2011). Of 101 IM cases, (79 proven, 22 probable): 30 were in E1 (3.3/year) and 71 in E2 (8.9/year). Between eras, the proportion with H/O or SCT rose from 47% to 73%, while 'other' dropped from 33% to 11% (P = 0.036). Between eras, the CI of IM did not significantly increase in SCT (P = 0.27) or SOT (P = 0.30), and patterns of anatomic location (P = 0.122) and surgical debridement (P = 0.200) were similar. Significantly more patients received amphotericin-echinocandin combination therapy in E2 (31% vs. 5%, P = 0.01); however, 90-day survival did not improve (54% vs. 59%, P = 0.67). Since 2003, the rise of IM reflects increasing numbers at risk, not prior use of voriconazole. Frequent combination of anti-fungal therapy has not improved survival., (© 2014 Blackwell Verlag GmbH.)

Mucormycosis is a rare and often fatal invasive fungal infection mostly seen in immune-compromised individuals. A high index of clinical suspicion is necessary, so that effective preemptive therapy can be started, as timely intervention is crucial. In this series we present three cases of invasive mucormycosis in patients with underlying inflammatory bowel disease that had received therapy with immunomodulators prior to the infection. All three had varied clinical manifestations. We also review the literature of invasive mucormycosis in patients with inflammatory bowel disease.

A 57-year-old woman with common variable immune deficiency and liver failure of unknown etiology presented with recurrent fevers over a 5-month period. She was found to have Helicobacter canis bacteremia. Immunocompromised hosts with exposure to cats or dogs may be at risk for infection with this organism, which may be challenging to diagnose.