Invasive aspergillosis in liver transplant recipients

Background

Liver transplantation is increasing worldwide with underlying pathologies dominated by metabolic and alcoholic diseases in developed countries.

Methods

We provide a narrative review of invasive aspergillosis (IA) in liver transplant (LT) recipients. We searched PubMed and Google Scholar for references without language and time restrictions.

Results

The incidence of IA in LT recipients is low (1.8%), while mortality is high (∼50%). It occurs mainly early (<3 months) after LT. Some risk factors have been identified before (corticosteroid, renal, and liver failure), during (massive transfusion and duration of surgical procedure), and after transplantation (intensive care unit stay, re-transplantation, re-operation). Diagnosis can be difficult and therefore requires full radiological and clinicobiological collaboration. Accurate identification of Aspergillus species is recommended due to the cryptic species, and susceptibility testing is crucial given the increasing resistance of Aspergillus fumigatus to azoles. It is recommended to reduce the dose of tacrolimus (50%) and to closely monitor the trough level when introducing voriconazole, isavuconazole, and posaconazole. Surgery should be discussed on a case-by-case basis. Antifungal prophylaxis is recommended in high-risk patients. Environmental preventative measures should be implemented to prevent outbreaks of nosocomial aspergillosis in LT recipient units.

Conclusion

IA remains a very serious disease in LT patients and should be promptly sought and, if possible, prevented by clinicians when risk factors are identified.

     

75例伏立康唑相关视觉损害的文献分析

目的 研究伏立康唑导致视觉损害的发生规律及特点。方法 收集PubMed、Embase、Web of Science、中国知网、万方、维普数据库纳入的伏立康唑导致视觉损害的病例。利用Excel软件进行统计分析患者的性别、年龄、用法用量、发生时间、临床表现、不良反应处理及转归等信息。结果 共纳入75例患者,其中男性53例(70.67%),女性22例(29.33%);年龄9~96岁,年龄≥60岁者48例,占比(64.00%)最大。视觉损害多发生在用药后第1~3天,共51例(68.92%)。持续时间集中在1~7d,共49例(72.06%)。视觉损害表现为幻视、畏光、视力模糊、色视、复视。结论 伏立康唑导致的视觉损害大部分患者预后良好,但发生时间及持续时间跨度较大,与药品说明书的描述有差异,建议用药期间应全程监护患者视力改变,尽可能完善眼科检查、伏立康唑谷浓度,有条件者可完善基因监测,指导临床用药,减少不良反应的发生。     

Characterization of Aspergillus spp. isolated from patients with coronavirus disease 2019

IntroductionInvasive pulmonary aspergillosis (IPA) is an important complication of coronavirus disease 2019 (COVID-19), and while there are case reports and epidemiological studies, few studies have isolated Aspergillus strains from patients. Therefore, we analyzed the strains, sensitivities, and genetic homology of Aspergillus spp. Isolated from patients with COVID-19.MethodsWe investigated the Aspergillus strains detected from patients with COVID-19 hospitalized in Osaka Metropolitan University Hospital from December 2020 to June 2021. A molecular epidemiological analysis of Aspergillus spp. was performed using drug susceptibility tests and TRESPERG typing, and data on patient characteristics were collected from electronic medical records.ResultsTwelve strains of Aspergillus were detected in 11 of the 122 patients (9%) with COVID-19. A. fumigatus was the most common species detected, followed by one strain each of Aspergillus aureolus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus. A. aureolus was resistant to voriconazole, and no resistance was found in other strains. All A. fumigatus strains were genetically distinct strains. Six of the 11 patients that harbored Aspergillus received antifungal drug treatment and tested positive for β-D-glucan and/or Aspergillus galactomannan antigen. The results indicated that Aspergillus infections were acquired from outside the hospital and not from nosocomial infections.ConclusionStrict surveillance of Aspergillus spp. is beneficial in patients at high-risk for IPA. When Aspergillus is detected, it is important to monitor the onset of IPA carefully and identify the strain, perform drug sensitivity tests, and facilitate early administration of therapeutic agents to patients with IPA.     

Positive correlation between voriconazole trough concentrations and C-reactive protein levels in patients with chronic pulmonary aspergillosis: A retrospective cohort study

BackgroundVoriconazole (VRCZ) is the first-line treatment for chronic pulmonary aspergillosis (CPA). VRCZ trough concentration monitoring is recommended for adequate therapy because VRCZ concentrations vary widely. However, factors associated with variations in VRCZ concentrations, especially in the same patient at different time points, have not been identified. The objective of this study was to identify factors influencing VRCZ trough concentrations.Patients and methodsThis single-center retrospective study conducted at our institute between April 2014 and August 2016 included patients with CPA who received VRCZ. Patient trough concentrations were measured more than twice while the patients received the same dose using the same administration route (defined as one series). A step-wise method and multiple regression analysis were used to test the effects of patient characteristics on VRCZ trough concentrations.ResultsSixty-nine series in 49 patients were analyzed. VRCZ was administered orally in 59 series, intravenously in 7 series, and by dry syrup in 3 series. The median VRCZ trough concentration and the median variation in VRCZ concentrations were 1.68 and 0.99 μg/ml, respectively. In the simple regression analysis, creatinine, alkaline phosphatase, C-reactive protein (CRP), and creatinine clearance significantly correlated with VRCZ concentrations. Multiple regression analysis demonstrated a significant positive correlation between CRP and VRCZ concentration (P < 0.0001).ConclusionIn patients with CPA, VRCZ concentration correlated with CRP levels in the same patients receiving the same dose of VRCZ at different time points.     

注射用伏立康唑细菌内毒素检查研究

目的:统一注射用伏立康唑细菌内毒素检查法质量标准，避免一药多项、一项多限的问题。方法:按照《中国药典》2020年版四部通则1143“细菌内毒素检查法”,确定细菌内毒素限值，进行干扰试验，并进行内毒素检查。结果:细菌内毒素限值定为“每1 mg伏立康唑中含内毒素的量应小于0.75 EU”,对两个公司生产的15批次样品进行细菌内毒素检查，结果均符合规定。结论:所建立的方法，可满足安全需要，且生产厂家的工艺水平也完全可以达到此要求，可用于注射用伏立康唑细菌内毒素检查。     

Pulmonary abscess caused by Cladosporium cladosporioides after receiving outpatient chemotherapy

Cladosporium cladosporioides is one of the most ubiquitous dematiaceous fungi that seldomly occur human infection. Here, we demonstrate a rare case of pulmonary phaeohyphomycosis with a distinctive pulmonary lesion during the nadir period of outpatient chemotherapy against endometrial cancer. In addition to severe neutropenia, excessive exposure to C. cladosporioides at patient's residence was considered as dominant causative factor. More caution is considered necessary for pulmonary phaeohyphomycosis in patients who receive outpatient chemotherapy and are homebound during neutropenic status.