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Background: Understanding of TAC pharmacokinetics is required to avoid both overdosing and underdosing. VRCZ is known to increase the TAC blood concentration by inhibiting CYP3A4; however, detailed, practical information on pediatric cases is still scarce. Herein, we investigated the association between the TAC blood concentration and dosage focusing on the administration route and concomitant use of VRCZ in children., Methods: In total, 38 children who received TAC during stem cell transplantation at our hospital between January 2013 and April 2018 were included. The ratio of the TAC blood concentration (ng/mL) to dosage (mg/kg/day) (C/D) was calculated at the last continuous intravenous infusion (C/Div) and after switching to oral administration (C/Dpo)., Results: Patients with VRCZ (n = 14) showed a higher C/D regardless of administration route (median C/Div: with VRCZ/without VRCZ = 832/643, median C/Dpo: with VRCZ/without VRCZ = 339/45). Additionally, the (C/Div)/(C/Dpo) was about one-fourth in cases with VRCZ; the median (C/Div)/(C/Dpo) was 3.3 for cases with VRCZ and 13.5 for cases without VRCZ. Interestingly, the increase in the TAC blood concentration due to VRCZ was higher when TAC was administered orally, especially in adolescent patients., Conclusions: To obtain an optimal TAC blood concentration, dose adjustment based on multiple factors, such as administration route, concomitant use of VRCZ, and age, is required., (© 2019 Wiley Periodicals, Inc.)

Background: Delays in diagnosing pulmonary invasive aspergillosis (IA), a significant cause of morbidity and mortality among heart transplant recipients (HTRs), may impact on successful treatment. The appropriate screening strategy for IA in these patients remains undefined, particularly in the setting of nosocomial outbreaks. We describe our experience employing chest computed tomography (CT) scans as a screening method for IA. In addition, we comment on antimicrobial prophylaxis in HTRs in the setting of an outbreak., Methods: Screening CT scans of the chest and serum galactomannan (GM) were performed in HTRs during an outbreak that followed the index case of IA. Abnormal CT findings prompted a diagnostic workup. Antimicrobial prophylaxis for new transplants recipients included intravenous micafungin while hospitalized, followed by outpatient inhaled amphotericin B for up to 3 months., Results: During a 10-month period, five cases of IA were identified among HTRs. Two additional asymptomatic patients were diagnosed with IA among 15 asymptomatic HTRs who underwent screening chest CT scans. Among the five cases of IA in HTRs, two of five (40%) had a partial response and the other three failed voriconazole therapy. Complete response to voriconazole therapy assessed at 12 weeks was achieved in these two asymptomatic HTRs diagnosed via screening CTs. Serum GM was positive only in one of the symptomatic cases. The negative predictive value of CT scans was 100% (95% confidence interval, 71.5%-100%)., Conclusions: In an outbreak setting, screening CT scans of the chest may aid in early detection of asymptomatic HTRs with IA and improve outcome., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Non-Candida opportunistic yeasts are emerging causes of bloodstream infection (BSI) in immunocompromised hosts. However, their clinical presentation, management, and outcomes in stem cell transplant (SCT) recipients are not well described. We report the first case to our knowledge of Pseudozyma BSI in a SCT recipient. He had evidence of cutaneous involvement, which has not been previously described in the literature. He became infected while neutropenic and receiving empiric micafungin, which is notable because Pseudozyma is reported to be resistant to echinocandins. He was successfully treated with the sequential use of liposomal amphotericin B and voriconazole. A review of the literature revealed nine reported instances of Pseudozyma fungemia. We performed a retrospective review of 3557 SCT recipients at our institution from January 2000 to June 2015 and identified four additional cases of non-Candida yeast BSIs. These include two with Cryptococcus, one with Trichosporon, and one with Saccharomyces. Pseudozyma and other non-Candida yeasts are emerging pathogens that can cause severe and disseminated infections in SCT recipients and other immunocompromised hosts. Clinicians should have a high degree of suspicion for echinocandin-resistant yeasts, if patients develop breakthrough yeast BSIs while receiving echinocandin therapy., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report the recent isolation of Cryptococcus laurentii from the feces of a patient with Hodgkin's lymphoma who underwent autologous hematopoietic stem cell transplant (HSCT). The organism was identified using microscopic morphology, cultural characteristics, and biochemical tests including sugar assimilation. Minimum inhibitory concentration of various antifungals was determined by microbroth dilution method. The recovery of pure culture of C. laurentii from stool culture, and the patient's response to treatment with voriconazole support its potential etiological role. To the best of our knowledge, we report the first case of diarrhea caused by C. laurentii in an HSCT recipient., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Trichosporon is an ubiquitous yeast that has emerged as an opportunistic pathogen in the immunocompromised host. We describe a case of invasive trichosporonosis in an allogeneic hematopoietic stem cell transplant (allo-HSCT) recipient while on caspofungin antifungal prophylaxis. She developed disseminated trichosporonosis in the pre-engraftment period and was successfully treated with voriconazole. She later developed 2 further episodes of invasive trichosporonosis involving the central nervous system. This case highlights the challenges of managing trichosporonosis in allo-HSCT recipients and suggests the need for lifelong therapy in some patients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lasiodiplodia species are environmental fungi that have been reported as a cause of infection in both immunocompetent and immunocompromised patients. We present a case of fungal osteomyelitis caused by Lasiodiplodia species in a patient with multiple myeloma after autologous stem cell transplant. The patient was successfully treated with a combination of surgery and oral voriconzole. To the best of our knowledge, this is the first reported case of fungal osteomyelitis caused by Lasiodiplodia species., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aspergillus infection localized to the renal allograft is a rare and potentially life-threatening infection and typically requires a combination of operative and medical management. We report the case of a renal allograft aspergilloma in a renal transplant patient presenting 2 years post transplant, successfully managed non-surgically. To our knowledge, this is the first report of a patient presenting with an allograft aspergilloma so long after transplantation and being successfully managed with antifungal therapy alone., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Penicillium marneffei is a thermally dimorphic fungus that can cause severe opportunistic infections in endemic regions of Southeast Asia, particularly in individuals infected with human immunodeficiency virus-1, but has rarely been reported in solid organ transplant recipients. Herein, we report the first case, to our knowledge, of P. marneffei infection in a lung transplant recipient, occurring in a 41-year-old woman 28 months post lung transplantation, after recent travel to Vietnam. We have reviewed the literature to derive some management principles for this rare infection in this clinical context. The number of P. marneffei infections in transplant recipients may increase, as a result of increasing rates of transplantation and travel to endemic areas., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Fungal infections are common after lung transplantation. However, disseminated fusariosis is rare and we report the first case of airway complications associated with this infectious process. A 77-year-old Caucasian woman, who was status post left single-lung transplant for emphysema, presented to clinic 8 months after lung transplantation with pleurisy, shortness of breath, and declining lung function. Bronchoscopy showed narrowing of the left anastomotic site with dynamic compression during exhalation. An AERO stent was deployed successfully, but 3 weeks later, her symptoms recurred. Bronchoscopy showed total stent occlusion with thick tenacious mucus. Fusarium solani was isolated from cultures, and a new 1.5 cm skin nodule was found on the anteromedial midportion of the patient's left lower leg. Voriconazole and anidulafungin were started. No evidence of mucus accumulation was seen during a follow-up bronchoscopy. It is likely that Fusarium infection contributed to the initial anastomotic complication as well as to obstruction of the stent. Furthermore, the stent may have contributed to establishment and development of disseminated fusariosis. With antifungal therapy, stent patency was maintained and the patient improved clinically., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report the first case, to our knowledge, of Candida arteritis in a liver transplant recipient. The patient presented with hemorrhagic shock requiring emergency arterial repair. As Candida albicans, Candida tropicalis, and Candida glabrata were growing in the arterial tissue, the patient received antifungal therapy for 5 months, but died because of chronic graft dysfunction. No evidence of fungal infection was found in the tissue on postmortem examination., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pituitary aspergillosis is a very rare disease, documented in only 12 cases. Although seen in both immunocompetent and immunocompromised patients, serious invasive sequelae, such as meningoencephalitis and death, have been noted in immunocompromised patients. Immunocompromised patients are susceptible and require complex multidisciplinary care to contain the spread of infection and maximize outcomes. This is the first case report, to our knowledge, of pituitary aspergillosis in the setting of an organ transplant. A 68-year-old woman presented with cephalgia, left temporal hemianopsia, and ptosis. Non-contrast magnetic resonance imaging of the head revealed a sellar mass, which was believed to be a benign pituitary adenoma. She underwent trans-sphenoidal resection, and subsequent histopathologic examination showed aspergillosis. She was subsequently started on voriconazole. On postoperative day 3, she developed a left anterior cerebral artery ischemic stroke, likely from Aspergillus angioinvasion and occlusion. Her mental status declined further and she died when care was withdrawn., (© 2013 John Wiley & Sons A/S.)

Common variable immunodeficiency (CVID) is the most common primary immune defect, resulting in hypogammaglobulinemia as well as deficits in cell-mediated immunity. Although it mainly manifests in immunodeficiency and related infection, CVID can also be associated with autoimmune phenomena such as immune thrombocytopenic purpura, hemolytic anemia, rheumatoid arthritis, lupus, primary biliary cirrhosis, and autoimmune hepatitis (AIH). AIH is a less common but serious complication of CVID, which can result in early cirrhosis, ascites, and even hepatocellular carcinoma. Here, we discuss a recent case of transplantation for cirrhosis secondary to AIH in the context of CVID. Although the patient's surgery occurred without complication, he rapidly developed fulminant alveolar hemorrhage and seizures, and died secondary to disseminated neuroaspergillosis., (© 2013 John Wiley & Sons A/S.)