Gaskell Katherine M, Rothe Camilla, Gnanadurai Roshina, Goodson Patrick, Jassi Chikondi, Heyderman Robert S, Allain Theresa J, Harrison Thomas S, Lalloo David G, Sloan Derek J, Feasey Nicholas A
Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Department of Medicine, University of Malawi, College of Medicine, Blantyre, Malawi; Queen Elizabeth Central Hospital, Ministry of Health, Blantyre, Malawi.
PLoS One. 2014 Nov 6;9(11):e110285. doi: 10.1371/journal.pone.0110285. eCollection 2014.
We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes.
This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day.
47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, p = 0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055]).
There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis.
我们之前曾报道，马拉维成年隐球菌性脑膜炎患者在采用800毫克口服氟康唑进行诱导治疗后，十周死亡率较高（57%[33/58]）。马拉维和其他非洲国家的国家指南现在提倡将诱导剂量增加至1200毫克。我们评估了这是否改善了治疗结果。
这是一项对经诊断性腰椎穿刺确诊为隐球菌性脑膜炎的HIV感染成年患者进行的前瞻性观察性研究。治疗方法为每天服用1200毫克氟康唑，持续两周，然后每天服用400毫克，持续八周。前十周内的死亡率是研究终点，并将当前结果与我们之前以每天800毫克氟康唑开始治疗的患者队列数据进行了比较。
47名参与者接受了氟康唑单药治疗。尽管诱导治疗剂量为1200毫克，但十周死亡率仍为55%（26/47）。这并不比我们之前的研究更好（1200毫克与800毫克氟康唑的死亡风险比[HR]：1.29（95%CI：0.77 - 2.16，p = 0.332））。有证据表明，在早期治疗期间进行重复腰椎穿刺以降低颅内压的患者生存率有所提高（HR：0.27[95%CI：0.07 - 1.03，p = 0.055]）。
对于隐球菌性脑膜炎，迫切需要确定更有效、可负担且可实施的治疗方案。
