Major role for amphotericin B-flucytosine combination in severe cryptococcosis.
Major role for amphotericin B-flucytosine combination in severe cryptococcosis.
复制标题
DOI：
10.1371/journal.pone.0002870
复制
发表时间：
2008-08-06
期刊：
影响因子：
3.7
通讯作者：
French Cryptococcosis Study Group
中科院分区：
文献类型：
--
作者：
Dromer F;Bernede-Bauduin C;Guillemot D;Lortholary O;French Cryptococcosis Study Group
美国传染病学会于2000年发布了管理隐球菌病的实用指南。然而，由于治疗试验期间的排除标准，治疗策略尚未在各种临床环境中得到充分验证。在这里，我们在分析了大学或三级保健医院隐球菌病的常规临床护理后，使用观察性前瞻性CryptoA/D研究评估了严重隐球菌病的最佳治疗策略。如果至少有一种培养结果对新生隐球菌呈阳性，则患者入选。在抗真菌治疗开始后2周(WK2)和3个月(M03)进行灭菌控制。对208例HIV阳性或阴性成人患者进行分析。WK2和M03的治疗失败(死亡或真菌学失败)是测量的主要结果。两性霉素B+氟胞嘧啶(AMB+5FC)是治疗脑膜脑炎、真菌负荷高及神经学异常的最佳诱导治疗方案。在这些患者中，AMB+5FC组在WK2的治疗失败率为26%，而任何其他治疗组的失败率为56%(p<；0.001)。在接受AMB+5FC治疗的患者中，与WK2真菌学失败独立相关的因素是基线时血清抗原滴度高(OR[95%CI] = 4.43[1.21~16.23]，p = 0.025)和脑显像异常(OR = 3.89[1.23~12.31]，p = 0.021)。恶性血液病(OR = 4.02[1.32-12.25]，p = 0.015)、基线神经学异常(OR = 2.71[1.10-6.69]，p = 0.030)和服用5FC少于14天(OR = 3.30[1.12-9.70]，p = 0.030)是治疗失败的独立危险因素。我们的结果支持这样的结论，在所有基线真菌负荷高的患者中，应至少使用AMB+5FC进行至少14天的诱导治疗，而不是任何其他诱导治疗，无论他们的HIV血清状态如何，以及是否存在证实的脑膜脑炎。
The Infectious Diseases Society of America published in 2000 practical guidelines for the management of cryptococcosis. However, treatment strategies have not been fully validated in the various clinical settings due to exclusion criteria during therapeutic trials. We assessed here the optimal therapeutic strategies for severe cryptococcosis using the observational prospective CryptoA/D study after analyzing routine clinical care of cryptococcosis in university or tertiary care hospitals. Patients were enrolled if at least one culture grew positive with Cryptococcus neoformans. Control of sterilization was warranted 2 weeks (Wk2) and 3 months (Mo3) after antifungal therapy onset. 208 HIV-positive or -negative adult patients were analyzed. Treatment failure (death or mycological failure) at Wk2 and Mo3 was the main outcome measured. Combination of amphotericin B+flucytosine (AMB+5FC) was the best regimen for induction therapy in patients with meningoencephalitis and in all patients with high fungal burden and abnormal neurology. In those patients, treatment failure at Wk2 was 26% in the AMB+5FC group vs. 56% with any other treatments (p<0.001). In patients treated with AMB+5FC, factors independently associated with Wk2 mycological failure were high serum antigen titer (OR [95%CI] = 4.43[1.21–16.23], p = 0.025) and abnormal brain imaging (OR = 3.89[1.23–12.31], p = 0.021) at baseline. Haematological malignancy (OR = 4.02[1.32–12.25], p = 0.015), abnormal neurology at baseline (OR = 2.71[1.10–6.69], p = 0.030) and prescription of 5FC for less than 14 days (OR = 3.30[1.12–9.70], p = 0.030) were independently associated with treatment failure at Mo3. Our results support the conclusion that induction therapy with AMB+5FC for at least 14 days should be prescribed rather than any other induction treatments in all patients with high fungal burden at baseline regardless of their HIV serostatus and of the presence of proven meningoencephalitis.
登录
查看更多内容
影响因子：
168.9
作者：
Brouwer, AE;Rajanuwong, A;Harrison, TS
通讯作者：
Harrison, TS
影响因子：
6.4
作者：
Pappas, PG;Bustamante, B;Hsu, HH
通讯作者：
Hsu, HH
影响因子：
11.8
作者：
Graybill, JR;Sobel, J;Dismukes, W
通讯作者：
Dismukes, W
影响因子：
4.9
作者：
Dannaoui, E;Abdul, M;Drorner, F
通讯作者：
Drorner, F
影响因子：
11.8
作者：
Mirza, SA;Phelan, M;Hajjeh, RA
通讯作者：
Hajjeh, RA