Breakthrough trichosporonosis in patients receiving echinocandins: case report and literature review

Trichosporon species now ranks as the second most common cause of disseminated yeast infections with a high mortality rate. Breakthrough trichosporonosis in patients receiving echinocandins therapy is being recognized recently. We present a case of breakthrough trichosporonosis with acute viral myocarditis while receiving caspofungin therapy. Trichosporon infection should be considered in patients, who have risk factors for invasive fungal infection and develop unexplained clinical manifestations of infection despite treatment with echinocandins.

     

The clinical and pharmacoeconomic analysis of invasive aspergillosis in adult patients with haematological diseases

Invasive pulmonary aspergillosis (IPA) poses major management problems for clinicians caring for patients with haematological diseases. The clinical courses of patients with IPA who had been hospitalised in Hematology Unit, Bone Marrow Transplantation Unit and Infectious Diseases and Clinical Microbiology Unit between 1998 and 2005, the efficacy and adverse effects and costs of antifungal drugs (conventional amphotericin B deoxycholate, liposomal amphotericin B, amphotericin B lipid complex and caspofungin) used in the therapy of these patients were analysed in this study. Ninety-three patients with IPA were reviewed retrospectively. Mean age of the patients was 40.4 ± 15.1 years (range 14–70 years). Fifty-eight male patients and 35 female patients were included in the study. Manageable hypopotassemia, nausea/vomiting and headache were the most commonly observed side-effects during antifungal (AF) therapy. While it was not found to be statistically significant with regard to the mean time to resolution of fever ( P  = 0.8), it was found to be statistically significant with regard to radiological regression at 30th day, and mean duration of therapy between patients who were dead or alive ( P  < 0.05, P  < 0.001). Total cost of AF therapy for 93 patients was found to be US$4 461 824 (minimum US$387-maximum US$279 023). Of this amount, US$4 272 845 represents the payment for AF drugs, US$188 979 the payment for other expenditures. Mean cost of therapy for a patient with IPA was found to be US$49 336. Although it seemed to be difficult, investigations should primarily focus on providing standardisation of parameters relating to the duration of AF therapy. Despite the less-than-optimal safety profile of CAB, it often remains to be the preferred first line option for the treatment of fungal infections because of its broad spectrum, activity and low acquisition cost.     

卡泊芬净在移植患者中应用的安全性评价

 目的拟对卡泊芬净在器官移植术后患者深部真菌感染治疗过程中的安全性进行评价。方法采用病例对照研究方法,以应用氟康唑或两性霉素B治疗的患者为对照组,数据采用SPSS14.0处理。结果试验组和对照2组患者治疗前后ALT,对照2组患者治疗前后血BUN治疗前后的差异有统计学意义(P<0.05)。试验组和对照2组用药后血浆电解质水平有所变化(P<0.05)。对照1组用药前后他克莫司血药浓度有统计学意义。3组不良反应发生率分别为5.6%,5.6%和14.3%。结论卡泊芬净用于治疗移植术后患者深部真菌感染有较好的安全性。     

Clinical Efficacy and Tolerability of Caspofungin in a Renal Transplant Patient with Aspergillus flavus Lung Infection: Case Report

Abstract

Organ transplant recipients are at increased risk for severe invasive aspergillosis, and amphotericin deoxycholate has been the standard treatment for many years. Currently, however, lipid formulations are preferred due to their few side effects. Also, a number of new antifungal drugs have been developed including new azoles and echinocandins. Caspofungin is the first of the echinocandin derivatives patented to treat patients with invasive aspergillosis who are refractory or intolerant to other therapies.

A renal transplant patient on immunosuppressive treatment with chronic hepatitis B virus infection was admitted with fever, hemophthisis and lung consolidation, diagnosed to be probably caused by Aspergillus flavus. The patient developed cholestatic hepatitis most likely related to itraconazole. Clinical failure and in vitro itraconazole resistance of the isolate was also documented while the patient was receiving itraconazole at a reduced dosage. Caspofungin was administered once a day as ambulatory treatment and was well tolerated. Clinical improvement was observed after 6 weeks of treatment and no hepatic toxicity was documented.

Caspofungin seems to be a potentially useful antifungal agent in renal transplant patients with invasive aspergillosis. Further evaluation of the efficacy of caspofungin is needed.     

氨基丁酸联合卡泊芬净抗白色假丝酵母菌生物被膜协同作用研究

目的探讨氨基丁酸联合卡泊芬净抗白色假丝酵母菌生物被膜的协同作用。方法利用白色假丝酵母菌标准菌株SC5314,采用生物被膜形成实验,分为空白对照组、氨基丁酸单用组、卡泊芬净单用组、氨基丁酸联合卡泊芬净组,对比各组生物被膜形成情况。采用XTT还原法测定氨基丁酸、卡泊芬净单用以及氨基丁酸联合卡泊芬净对成熟生物被膜细胞代谢活性的抑制作用。采用YNB培养基菌丝形成实验,考察氨基丁酸与卡泊芬净合用是否具有协同抑制菌丝形成的作用。结果卡泊芬净0.1μg·mL-1联合氨基丁酸0.1μmol·L-1对白色假丝酵母菌SC5314生物被膜的形成具有显著的抑制作用。此外,XTT还原法测定氨基丁酸6.25μmol·L-1联合卡泊芬净0.1μg·mL-1时降低被膜细胞代谢活性的效率能够达到约15%。采用YNB培养基形成菌丝,氨基丁酸6.25μmol·L-1联合卡泊芬净0.1μg·mL-1对白色假丝酵母菌SC5314菌丝形成能力有显著的抑制作用。结论氨基丁酸联合卡泊芬净表现出显著的体外协同抗白色假丝酵母菌标准菌株SC5314生物被膜作用。     

High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia

A number of agents are now available for empirical antifungal treatment (EAFT) of patients with persistent fever and neutropenia. We carried out a study of efficacy of antifungal drugs to prevent breakthrough invasive aspergillosis by reviewing the medical records of all consecutive patients who received EAFT from November 2005 to February 2006. Patients’ characteristics and the type, dose and duration of antifungal therapy were recorded. Breakthrough invasive fungal infections were documented according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definition. Fifty-six episodes of persistent fever with neutropenia requiring EAFT were recorded among 49 patients. All patients received high-dose chemotherapy for acute myeloid leukaemia (51%), acute lymphoid leukaemia (12%), lymphoma (14%) or other haematologic conditions (22%). Fourteen (29%) and five (10%) patients were allogeneic and autologous haematopoietic stem cell transplant recipients, respectively. Caspofungin was prescribed initially in 40 episodes (71%), amphotericin B (AmB) desoxycholate and liposomal AmB being prescribed in six (10%) and ten (18%) episodes, respectively. Six patients were switched from liposomal AmB to caspofungin because of adverse events. The median duration of antifungal therapy was 9 days. During follow-up, six patients (12%) were diagnosed with invasive aspergillosis after a median of 8 days (range 3–16 days) of EAFT. Invasive aspergillosis breakthrough occurred in 6/46 (13%) caspofungin recipients and in 0/16 (0%) AmB recipients (OR 3.1, p 0.32). The observed high rate of invasive aspergillosis among caspofungin recipients requires further evaluation.     

新型抗真菌药物在眼科的研究进展

近年来,一些新的抗真菌药物相继问世,包括新三唑类（活力康唑、泊沙康唑等）和棘白菌素类（卡泊芬净、米卡芬净等）。这些药物具有更广的抗真菌谱,提供了更好的抗真菌活性。这些新的抗真菌药物在初步的眼科临床实践中已显示出良好的应用前景。兹就新型抗真菌药物在眼科临床研究的最新进展做一综述。     

Invasive infection with Trichosporon inkin in 2 siblings with chronic granulomatous disease

A 9-year-old girl with autosomal recessive chronic granulomatous disease (CGD) presented with asymptomatic bilateral pulmonary infiltrates on routine computed tomography. Fine-needle aspirate of the infiltrates was obtained and showed fungal cells resembling Trichosporon inkin . The specimen grew in culture, and testing by means of both API 20C and PCR amplification confirmed the diagnosis of T inkin . The infiltrates increased in size, despite sequential therapy with voriconazole, liposomal amphotericin B, caspofungin, and posaconazole. The patient required resection of the infected lung tissue, after which she recovered completely. While she was undergoing therapy, her 13-year-old brother, also with CGD, was given a diagnosis of bilateral T inkin -induced pulmonary infection. He also required bilateral pulmonary resection for cure. These cases demonstrate the predisposition of patients with CGD to have invasive infections with unusual fungal organisms, such as T inkin . They also illustrate the difficulty of treating invasive T inkin infections with antifungal agents alone. There are 9 previously reported cases of invasive infections caused by T inkin , 3 of which are in patients with CGD. All patients required removal of infected prosthetic devices or surgical resection of infected tissue for cure.     

Candida krusei– a serious complication in patients with hematological malignancies: successful treatment with caspofungin

Abstract: Candida krusei infections are serious complications in neutropenic patients with hematological malignancies. We report the successful treatment of C. krusei infection with caspofungin in 3 allogeneic hematopoietic stem cell transplant recipients and 1 patient with induction chemotherapy for acute myeloid leukemia.