Search

Background: human adenovirus (hAdV) infection constitutes an important cause of morbidity and mortality in transplant recipients, due to their immune status. Among drugs currently available, cidofovir (CDF) is the most prescribed. Methods: Retrospective study of hAdV infection in paediatric transplant recipients from a tertiary paediatric centre, describing characteristics, management, and outcomes, and focused on the role of CDF. Results: 49 episodes of infection by hAdV were detected during a four-year period: 38 episodes in patients that received allogeneic hematopoietic stem cell transplantation (77.6%) and 11 in solid organ transplant recipients (22.4%). Twenty-five patients (52.1%) were symptomatic, presenting mainly fever and/or diarrhoea. CDF was prescribed in 24 patients (49%), with modest results. CDF use was associated with the presence of symptoms resulting in lower lymphocyte count, paediatric intensive care unit admission, and high viral load. Other therapeutic measures included administration of intravenous immunoglobulin, reducing immunosuppression, and T-lymphocyte infusion. Despite treatment, 22.9% of patients did not resolve the infection and there were three deaths related to hAdV infection. All-cause mortality was 16.7% (8 episodes) by 30 days, and 32.7% (16 episodes) by 90 days, of which, 3 episodes (3/16, 18.8%) were attributed to hAdV directly. Conclusions: hAdV infection had high morbidity and mortality in our series. CDF use is controversial, and available therapeutic options are limited. Transplant patients with low lymphocyte count are at higher risk of persistent positive viremias, and short-term survival of these patients was influenced by the resolution of hAdV infection.

Diagnosis of invasive fungal disease remains an ongoing challenge for clinicians, while continuously evolving treatment regimens increase patient risk for invasive infection. This case highlights how molecular testing led to the diagnosis of co-infection with two fungal pathogens producing invasive disease in a hematopoietic stem cell transplant recipient with graft-versus-host disease (GVHD). Keywords: Invasive fungal infection, Molecular diagnostics, Ibrutinib, Aspergillus, Cunninghamella

Patients who undergo hematopoietic stem cell transplantation (HSCT) are at risk for developing bacterial, fungal, viral, and/or parasitic infections, resulting in high rates of morbidity and mortality. During the course of HSCT, infections are derived from the patient’s microbial flora, from a reactivation of a latent infection from either the recipient or donor, or from primary infection. Three periods of risk for infections in HSCT recipients include pre-engraftment, early postengraftment, and late postengraftment, during which patients are at a differing risk of developing specific infections. Measures to prevent infections during HSCT include determination of recipient risk, appropriate selection of donors, infection control measures, and targeted prophylactic and preemptive therapy. An overview of the infectious risks and prevention strategies are presented in this chapter.

BK polyomavirus (BKPyV) is an important pathogen in transplant recipients. We report four draft BKPyV genomes, three of BKPyV genotype I (subtype I-b2) (AUS-105, AUS-106, and AUS-108) and one of genotype II (AUS-107). These draft genomes were identified in longitudinal urine samples collected from a single hematopoietic stem cell transplant recipient.

Background Invasive mold infections (IMIs) remain a significant cause of morbidity and mortality in patients with acute leukemia (AL) and those undergoing hematopoietic stem cell transplantation (HSCT). We describe the epidemiology of IMIs, the incidence of IMI in patients with acute myelogenous Leukemia (AML) post HSCT, and risk factors for mortality. Methods Patients were identified using ICD9 and ICD10 codes using a University of Kansas internal database from 2009-2019, microbiology records, and an AML HSCT database and were followed through May 1st, 2020. Patients’ electronic medical records were reviewed for inclusion. IMI was defined as proven or probable using the 2009 National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) guidelines. Incidence was calculated as IMI cases/100-person-years. Risk factors for overall mortality were evaluated using a Cox regression model. Results We included 138 patients: 79 developed IMI after HSCT (8 autologous, 71 allogeneic) and 59 developed IMI after AL diagnosis. Seventeen of the AL patients underwent HSCT after IMI diagnosis (12 within 100 days of IMI). Proven IMI occurred in 45 (32.6%) and probable IMI occurred in 93 (67.4%) patients. The most common prophylactic agent prior to IMI diagnosis was fluconazole (31.2%), with 21.0% receiving none. Aspergillus was the most commonly identified mold with 91 (65.9%) cases. The average treatment duration was 101 (range 0 - 799) days. The incidence of IMI in patients with AML who underwent HSCT was 2.35 cases/100 person-years. All-cause mortality among patients with AL or HSCT who developed IMI was 23.1% at 6 weeks, 34.1% at 12 weeks, and 61.2% at 1 year. On univariate Cox model, Karnofsky performance status > 70 was associated with lower mortality (hazard ratio (HR) 0.317, 95% confidence interval (CI) [0.110, 0.914]) among HSCT recipients. ICU admission within 7 days prior to IMI diagnosis (HR 6.469, 95% CI [1.779, 23.530]) and each one point increase in BMI (HR 1.051, CI [1.001, 1.103]) were associated with increased mortality in the AL group. Figure 1 - Invasive mold infections by pathogen in HSCT-recipients and acute leukemia patients from 2009-2019. Figure 2 - Antifungal prophylactic agents prescribed for at least one week at time of IMI diagnosis Table 1 - Univariate survival analysis calculated using a Cox proportional-hazards regression model among patients who developed IMI after HSCT and patients who developed IMI after acute leukemia diagnosis Conclusion IMIs are associated with significant mortality in HSCT recipients and AL patients; patients at higher risk for mortality include those with lower baseline Karnofsky scores, recent ICU admissions, and higher BMI at time of IMI diagnosis. Disclosures Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)

Toxic epidermal necrolysis (TEN) and cutaneous Graft-Versus-Host Disease (GVHD) are rare, life-threatening skin eruptions that can occur after a hematopoietic stem cell transplant (HSCT). Because t...

Human adenovirus infection is rare in adult population, except for in immunocompromised individuals. Recipients of allogenic haploidentical hematopoietic stem cell transplantation are reported at high risk for human adenovirus, which is often lethal when it evolves into the disseminated form. Despite existent guidelines, prevention, early diagnosis, and therapeutics remain challenging. Here, we report the case of a fatal evolution of human adenovirus respiratory infection and discuss the actual recommendations to prevent recurrence of this major issue.

Oral mucormycosis is a rare and high risk of infection in patients following hematopoietic cell transplantation few cases in the literature. We review the literature and present an additional case to emphasize the subtle changes that resulted in positive outcome when diagnosed and managed in a comprehensive transplant team.A patient was diagnosed with gingival mucormycosis on day +25 following a hematopoietic stem cell transplant for lymphoblastic transformation of chronic myeloid leukemia. The patient was diagnosed with minor and nonspecific symptoms and was successfully treated with local dental extraction, a short course of liposomal amphotericin B and 4 months of oral posaconazole.The good outcome of this case highlights the subtle clinical changes that present early in mucormycosis and the importance of early detection and treatment of post-transplant oral infections by an experienced multidisciplinary team.

Vancomycin-resistantenterococcus(VRE) is now one of the leading causes of nosocomial infections in the United States. Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of VRE colonization and infection. VRE has emerged as a major cause of bacteremia in this population, raising important clinical questions regarding the role and impact of VRE colonization and infection in HSCT outcomes as well as the optimal means of prevention and treatment. We review here the published literature and scientific advances addressing these thorny issues and provide a rational framework for their approach.

Pediatric hematopoietic stem cell transplant recipients are at risk for acquiring a variety of lower respiratory tract infections (LRTI), which result in frequent pediatric intensive care unit admission with high mortality. Recent advances in conditioning regimens, opportunistic infection prophylaxis, diagnostic tools, and treatment modalities have broadly impacted our understanding of LRTI among these vulnerable patients. In this review, the most common bacteria, viruses, and fungi causing LRTI in pediatric hematopoietic stem cell transplant patients are discussed.

Hepatitis C virus (HCV) is the most common chronic bloodborne infection in the United States. According to the Centers for Disease Control, approximately 2.7 million people in the United States hav...

A 58-year-old man had a history of chronic lymphocytic leukemia. Seven weeks after an allogeneic hematopoietic stem cell transplant, he presented with loss of vision in his left eye, impaired depth perception, and gait imbalance. Before the transplant, he had developed mild impairment of visual acuity.

Buyukdogan, Murat/0000-0001-7948-0235; Aki, Sahika Zeynep/0000-0002-3068-5085; acar, muradiye/0000-0003-4357-5229; hancer, veysel sabri/0000-0003-2994-1077 WOS:000416975700007 Therapeutic management of cytomegalovirus (CMV) disease in hematopoietic stem cell transplantation patients can become a challenge because of the emergence of anti-CMV drug resistance. This case report presents a patient with clinical ganciclovir resistance due to a new mutation: histidine-to-asparagine change at residue 393 of UL97. This mutation, which is located in the nonfunctional region of the UL97 gene, is very unusual. Having more information about the mutations leading to drug resistance in CMV is important for both improved clinical management and development of new diagnostic tests and drugs.

Summary What is known and objective Invasive fungal infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). This provides a clear rationale for antifungal prophylaxis in this population. A concern is the potential for drug interactions, given that most of antifungals are metabolized through the P450 cytochrome system. Case summary We present a case of a 33-year-old woman, with a past history of high-risk epilepsy, who underwent allogeneic HSCT for a myelodysplastic syndrome. Anidulafungin was successfully used as antifungal prophylaxis to minimize drug interactions with her antiepileptic treatment. What is new and conclusion This is the first reported case of antifungal prophylaxis with this echinocandin in HSCT. Anidulafungin may be an option in transplant recipients with multiple risk factors for drug interactions.

Despite a dramatic increase in the number of commercially available agents to treat invasive fungal infections, they remain a common and devastating problem in a variety of patients. The impact of these infections has furthered interest in optimizing antifungal therapy. Therapeutic drug monitoring has emerged as a potentially important area allowing the efficacy of select antifungals to be optimized. This article reviews emerging data examining the utility and rationale for voriconazole and posaconazole therapeutic drug monitoring.

Recent evidence shows that many hospital-acquired infections, including most device-associated infections, involve the persistence of sessile organisms in the form of biofilms that are attached to a device surface and encased in an extracellular matrix. The cells in this environment exhibit an altered phenotype with respect to antimicrobial resistance and thus are extraordinarily difficult to eradicate without device removal. Although a number of implantable and topical devices are at risk for Candida biofilm formation, this review focuses on the diagnosis of the most common of these infections, biofilm growth on the surface of central venous catheters and urinary catheters.

Oral acute graft-versus-host disease (aGVHD) is a significant sequelae of allogeneic hematopoietic stem cell transplantation (HSCT). Presently, transplant physicians have to diagnose GVHD based on clinical judgment by interpreting available clinical and relevant laboratory findings. As such, characterization of diagnostic and distinctive clinical signs and symptoms of GVHD is essential for diagnosis and grading. The oral features of aGVHD have been reported infrequently and remain ill defined, unlike in oral chronic GVHD. The report describes an atypical and painful presentation of oral aGVHD in a 15-year-old boy, 16 days after haploidentical HSCT, who presented with swollen lips, herpetiform ulcerations, and erythematous fungiform papilla.

We describe the first reported pediatric patient to our knowledge with a spindle cell pseudotumor caused by Mycobacterium genavense in a hematopoietic stem cell transplant recipient, and review the literature of such an entity in the transplant population.

The (1, 3)-β-D-glucan (β-D-glucan) is one of the polysaccharides composing the fungal cell wall, and assays to detect serum β-D-glucan through specific enzyme activity have been widely used as a tool for the diagnosis and monitoring of invasive fungal infection.1 However, the usefulness of this assay is partly limited by its poor specificity owing to various factors.1,2 We experienced a patient showing a marked elevation of serum β-D-glucan after allogeneic hematopoietic stem cell transplantation, which was found to be caused by daily oral intake of kelp, a widely consumed seaweed. This article is protected by copyright. All rights reserved.

There is variability in critical care outcome of the HSCT recipient. One potential reason may be due to the inconsistent ventilation approaches. To quantitate this variability, we conducted a survey to assess self-reported use of ventilation and adjunctive strategies for the HSCT recipient. Electronic survey, open from June 2012 through January 201, distributed through the Pediatric Acute Lung Injury and Sepsis Investigators network electronic mailing list. Ninety-four individual responses were from 36 different institutions. The majority indicated that HSCT recipients requiring critical care were admitted to the general PICU. The vast majority (89%) endorsed routine practice of low-tidal-volume ventilation strategies. More than half stated that pressure-regulated volume control is the starting mode of choice. Eighty-three percent felt their group practiced early initiation of lung protective strategies. Eleven percent encouraged "early transition" to HFOV. Inhaled nitric oxide and milrinone were reported at the highest frequencies, but the majority used these empirically. Opinions regarding variables that affect outcomes of the HSCT were diverse. The estimated mortality of HSCT patients with respiratory was highly variable. Strategies for ventilation and oxygenation, use of HFOV, and adjunctive therapies are variable among pediatric intensivists.

We present a case of foscarnet (FOS) resistance arising from a UL54 mutation after a short duration of FOS exposure, which has not been previously described in a stem cell transplant recipient, to our knowledge. We discuss the use of FOS to treat other viral infections and the implications this may have for the development of resistance mutations and treatment of cytomegalovirus disease.

Legionella londiniensis has been isolated from aqueous environments. However, to our knowledge, this organism has never been isolated from clinical specimens. A case of Legionnaires' disease in a hematopoietic stem cell transplant recipient caused by this organism is described, which confirms that L. londiniensis can be an opportunistic pathogen.

The major risk factor for posttransplant lymphoproliferative disorder (PTLD) is primary infection after transplantation The presenting signs and symptoms of PTLD are non-specific Epstein—Barr virus (EBV) serology is of limited value in the diagnosis of PTLD EBV load by itself has poor specificity for the diagnosis of PTLD Histopathologic examination of tissue is the gold standard for the diagnosis of PTLD

An estimated 50,000 to 60,000 patients undergo hematopoietic stem cell transplantation (HSCT) worldwide annually, of which 15.7% are admitted to the intensive care unit (ICU). The most common reason for ICU admission is respiratory failure and almost all develop single or multiorgan failure. Most HSCT recipients admitted to ICU receive invasive mechanical ventilation (MV). The overall short-term mortality rate of HSCT recipients admitted to ICU is 65%, and 86.4% for those receiving MV. Patient outcome has improved over time. Poor prognostic indicators include advanced age, poor functional status, active disease at transplant, allogeneic transplant, the severity of acute illness, and the development of multiorgan failure. ICU resource limitations often lead to triage decisions for admission. For HSCT recipients, the authors recommend (1) ICU admission for full support during their pre-engraftment period and when there is no evidence of disease recurrence; (2) no ICU admission for patients who refuse it and those who are bedridden with disease recurrence and without treatment options except palliation; (3) a trial ICU admission for patients with unknown status of disease recurrence with available treatment options.

Increasing numbers of cancer patients are being admitted to the intensive care unit (ICU), either for cancer-related complications or treatment-associated side effects, yet there are relatively few data concerning the epidemiology and prognosis of cancer patients admitted to general ICUs. The aim of this study was to assess the characteristics of critically ill cancer patients, and to evaluate their prognosis.This was a substudy of the Sepsis Occurrence in Acutely Ill Patients (SOAP) study, a cohort, multicentre, observational study that included data from all adult patients admitted to one of 198 participating ICUs from 24 European countries during the study period. Patients were followed up until death, hospital discharge or for 60 days.Of the 3147 patients enrolled in the SOAP study, 473 (15%) had a malignancy, 404 (85%) had solid tumours and 69 (15%) had haematological cancer. Patients with solid cancers had the same severity of illness as the non-cancer population, but were older, more likely to be a surgical admission and had a higher frequency of sepsis. Patients with haematological cancer were more severely ill and more commonly had sepsis, acute lung injury/acute respiratory distress syndrome, and renal failure than patients with other malignancies; these patients also had the highest hospital mortality rate (58%). The outcome of all cancer patients was comparable with that in the non-cancer population, with a 27% hospital mortality rate. However, in the subset of patients with more than three failing organs, more than 75% of patients with cancer died compared with about 50% of patients without cancer (p = 0.01).In this large European study, patients with cancer were more often admitted to the ICU for sepsis and respiratory complications than other ICU patients. Overall, the outcome of patients with solid cancer was similar to that of ICU patients without cancer, whereas patients with haematological cancer had a worse outcome.

Stevens-Johnson syndrome (SJS) is not typically reported following hematopoietic stem cell transplant (HSCT). The most severe form of SJS, which is toxic epidermal necrolysis (TEN) has been reported following HSCT, albeit very rarely. We describe a case of Mycoplasma-associated SJS following HSCT. While this association is commonly reported in previously healthy children, it has not been reported in patients following HSCT.