Invasive candidiasis in cancer patients: observations from a randomized clinical trial

BACKGROUND: Invasive candidiasis is a common and serious complication of cancer and its therapy. METHODS: We retrospectively identified patients with malignancies enrolled in a double-blind randomized trial of caspofungin (50 mg/day after a 70 mg loading dose) vs. conventional amphotericin B (0.6-1.0 mg/kg/day) as treatment of documented invasive candidiasis. A favorable response required complete resolution of signs and symptoms plus eradication of the Candida pathogen(s). The primary efficacy analysis used a modified intention-to-treat (MITT) approach that included all patients with a confirmed diagnosis of invasive candidiasis who received > or =1 dose of study medication. RESULTS: 74/224 (33%) patients in the MITT population had active malignancies. 25/30 (83%) hematological malignancies were acute or chronic leukaemias. 22/44 (50%) solid tumors were related to the gastrointestinal tract. Patients with hematological malignancies tended to be younger (median [range] age: 49 [19-74] vs. 59 [19-81] years) and have higher baseline acute physiology and chronic health evaluation (APACHE) II scores (mean [range]: 17 [0-28] vs. 15 [5-35]) than patients with solid tumors. Neutropenia [< or =500/microl] was present on entry in 23 (77%) patients with hematological malignancies and in one (3%) patient with a solid tumor. Candidemia was demonstrated in 56 (88%) cancer patients. C. albicans was the single most frequent isolate in cancer patients, although the majority of cases were caused by non-albicans species. Cancer patients in the caspofungin arm had more hematological malignancies (55 vs. 29%), higher baseline APACHE II scores (>20 in 36 vs. 15%), more frequent neutropenia (42 vs. 24%), and less C. albicans infections (27 vs. 49%) than the amphotericin B-treated cancer patients. Favorable response rates were 11/18 (61%) and 6/12 (50%) for patients with hematological malignancies treated with caspofungin or amphotericin B, respectively; the corresponding outcomes in patients with solid tumors were 12/15 (80%) and 17/29 (59%) for the 2 treatment arms. 7/14 (50%) caspofungin- and 4/10 (40%) amphotericin B-treated patients who were neutropenic on entry responded favorably. All-cause mortality rates during the study for caspofungin recipients were 11/18 (61%) with hematological malignancies and 6/15 (40%) with solid tumors, and for amphotericin recipients were 4/12 (33%) with hematological malignancies and 6/29 (21%) with solid tumors. CONCLUSIONS: Underlying cancers, most commonly leukaemias and gastrointestinal tumors, were present in one-third of patients enrolled in this study of invasive candidiasis. Overall, 70% of caspofungin-treated and 56% of amphotericin B-treated cancer patients responded favorably. Response rates were lower for neutropenic leukaemic patients than for non-neutropenic patients with solid tumors in both treatment groups.     

Successful control of exacerbation of Allergic Bronchopulmonary Aspergillosis due to Aspergillus terreus in a cystic fibrosis patient with short-term adjunctive therapy with voriconazole: A case report

A 12-year-old boy with cystic fibrosis (CF) and a history of glucocorticoid-dependent allergic bronchopulmonary aspergillosis (ABPA) was referred to our hospital. The ABPA was diagnosed when he was 8 years old and he had been treated with several course of oral glucocorticoids for recurrent exacerbations. He was readmitted when aged 12 with a history of worsening shortness of breath and chest tightness. A recurrence of ABPA was diagnosed based on eosinophilia and elevation of Aspergillusspecific IgE and IgG, and total IgE. Thoracic high-resolution computed tomography (HRCT) showed central bronchiectasis with parenchymal infiltrates. The treatment started with itraconazole and oral corticosteroid. After 2 months of treatment, he was re-admitted to the hospital due to a progressive worsening of respiratory symptoms. Chest HRCT revealed the a sub segmental atelectasis in the left lung. Microscopic examination of sputum and BAL samples demonstrated septate hyphae consistent with Aspergillus species. Sputum and BAL culture yielded Aspergillus ochraceus and Aspergillus terreus, which were both sensitive to itraconazole and voriconazole. The treatment was switched to voriconazole and the patient showed significant clinical, serological and mycological improvement after three months. This case shows that voriconazole may be used as an alternative for treatment of ABPA due to Aspergillus terreus.     

卡泊芬净经验性治疗白血病并发真菌感染的临床疗效分析与评价

目的 评估卡泊芬净经验性治疗白血病并发真菌感染的疗效分析及不良反应.方法 选择2009年1月-2011年10月医院白血病并发真菌感染的50例患者,分为卡泊芬净及伊曲康唑两组,每组25例,卡泊芬净组给予卡泊芬净经验性治疗,伊曲康唑组给予伊曲康唑抗真菌治疗,两组治疗时间均持续至体温恢复正常后5d或疗程达14 d或连续痰涂片阴性后3d;对两种药物的疗效和不良反应进行观察和评价.结果 卡泊芬净和伊曲康唑在治疗白血病并发真菌感染中,总有效率分别为88.0％和64.0％,差异有统计学意义(P＜0.05),两组比较后发现,卡泊芬净较伊曲康唑不良反应少,耐受性好.结论 在白血病并发真菌感染的治疗中,卡泊芬净较伊曲康唑疗效更好,不良反应更少,患者耐受性更好,是治疗白血病并发真菌感染安全有效的药物.     

Catheter-related candidemia caused by Candida haemulonii in a patient in long-term hospital care

Candida haemulonii, one of the non-albicans Candida species, is an emerging yeast pathogen that is known to be resistant to amphotericin B and other antifungal agents such as azoles. These anti-fungal agents have often been associated with clinical treatment failure, so no treatment regimen has been clearly established for invasive C. haemulonii infections. We investigated a catheter-related infection of C. haemulonii candidemia in an adult patient in long-term hospital care. In the early stages, the candidemia remained persistent despite treatment with fluconazole. However, after changing the antifungal agent to caspofungin, the candidemia was resolved. Fluconazole and amphotericin B are not reliable empirical antifungal agents for invasive C. haemulonii infections, as shown in previous case reports. An echinocandin such as caspofungin may be an appropriate empirical choice of antifungal agent for an invasive C. haemulonii infection.     

卡泊芬净治疗癌症患者侵袭性真菌感染疗效分析

目的观察卡泊芬净治疗癌症患者合并侵袭性真菌感染（IFI）的疗效和安全性。方法选择经氟康唑治疗无效和不能耐受两性霉素B的54例侵袭性真菌感染的癌症患者,其中氟康唑治疗无效的30例为A组,不能耐受两性霉素B治疗的24例为B组,两组都给予卡泊芬净治疗,治疗时间均持续至体温正常后5d或连续痰涂片阴性后3d,或者疗程达14d,观察并评价卡泊芬净的疗效和毒副作用。结果卡泊芬净治疗癌症患者合并侵袭性真菌感染患者的总有效率为72.2%,其中A组30例,有效率66.7%;B组24例,有效率79.2%。毒副作用少,发生不良反应者占20.4%,包括电解质紊乱、静脉炎、胃肠道反应、转氨酶异常等,但以上反应均不严重,经对症处理后缓解。结论卡泊芬净治疗癌症患者合并侵袭性真菌感染有效,且安全,可在临床推广应用。     

卡泊芬净和伊曲康唑治疗侵袭性肺部真菌感染的回顾性分析

目的：比较卡泊芬净和伊曲康唑治疗侵袭性肺部真菌感染（IPFI）的有效性和安全性。方法：回顾性分析本院2010年9月-2011年8月入住呼吸科并诊断为IPFI的患者病例,记录患者一般情况、身体体征和临床表现的变化过程及不良反应,比较临床疗效和不良反应的发生情况,并进行统计分析。结果：卡泊芬净组36例,有效率为58_3％,伊曲康唑组31例,有效率为38．7％,两组有效率比较差异有统计学意义（P〈0．05）;卡泊芬净组和伊曲康唑组不良反应发生率分别为22．2％和54．8％;卡泊芬净组和伊曲康唑组因毒性反应停药的病例数分剐为0例和4例,差异存在统计学意义（P〈0．05）。结论：治疗侵袭性肺部真菌感染时,卡泊芬净比伊曲康唑具有更好的疗效且副作用小,需合理使用以减少耐药菌株的产生。     

卡泊芬净治疗儿童血液病合并肺孢子菌肺炎的疗效评价

目的评价卡泊芬净治疗儿童肺孢子菌肺炎(PCP)临床疗效。方法回顾性分析我科在2008年3月至2011年6月间,6例不能耐受复方磺胺甲基异恶唑(SMZCO)治疗的PCP患儿应用卡泊芬净治疗的临床资料。结果应用卡泊芬净治疗的6例患儿疗效显著,与SMZCO相比疗效无差异性。结论对于不能耐受SMZCO治疗的PCP患儿,应用卡泊芬净替代治疗疗效显著,为PCP的临床治疗提供更多的治疗方法。     

抗真菌新药卡泊芬净在血液病患者经验性抗真菌治疗中的疗效观察

目的 探讨卡泊芬净在血液病患者经验性抗真菌治疗中的疗效.方法 将2008年10月至2010年10月收治的40例抗生素治疗无效且怀疑真菌感染的血液病患者随机分为两组,各20例,A组给予卡泊芬净治疗,第1天70 mg静脉滴注,第2天起50 mg静脉滴注;B组患者给予脂质体两性霉素B治疗,3 mg/(kg·d)静脉滴注.两组均治疗10 d,观察两组患者的疗效和不良反应.结果两组总有效率比较(66.7% vs.61.1%),差异无统计学意义(χ2=1.17,P>0.05),但A组肾毒性、输液反应发生率明显低于B组(χ2=4.37,4.37,P<0.05).结论 卡泊芬净用于血液病患者经验性抗真菌治疗,效果较好,患者耐受性较好,是侵袭性真菌感染的一个较好选择.