Sloan Derek J, Dedicoat Martin J, Lalloo David G
School of Clinical Sciences, University Clinical Departments, University of Liverpool, Liverpool, UK.
Curr Opin Infect Dis. 2009 Oct;22(5):455-63. doi: 10.1097/QCO.0b013e32832fa214.
Cryptococcal meningitis most commonly occurs in advanced HIV. Although diminishing in the developed world with antiretroviral therapy (ART), it remains a major problem in resource-limited settings. ART rollout will improve long-term HIV survival if opportunistic infections are effectively treated. Considering cryptococcal meningitis in that context, this review addresses excess morbidity and mortality in developing countries, treatment in areas of limited drug availability and challenges posed by combined anticryptococcal and HIV therapy.
From Early Fungicidal Activity (EFA) studies, amphotericin B-flucytosine is best induction therapy but often unavailable; high dose amphotericin B monotherapy may be feasible in some settings. Where fluconazole is the only option, higher doses are more fungicidal. Serum cryptococcal antigen testing may identify patients at highest disease risk and primary prophylaxis is effective; the clinical role of such interventions needs to be established. Timing of ART introduction remains controversial; early initiation risks Immune Reconstitution Disease (IRD) delays may increase mortality.
Amphotericin B based treatment is appropriate where possible. More studies are needed to optimize fluconazole monotherapy doses. Other research priorities include management of raised intracranial pressure, appropriate ART initiation and IRD treatment. Studies should focus on developing countries where problems are greatest.
隐球菌性脑膜炎最常发生于晚期艾滋病患者。尽管在发达国家，随着抗逆转录病毒疗法（ART）的应用，其发病率有所下降，但在资源有限的地区，它仍然是一个主要问题。如果机会性感染得到有效治疗，ART的推广将提高艾滋病患者的长期生存率。在这种背景下，考虑到隐球菌性脑膜炎，本综述探讨了发展中国家的额外发病率和死亡率、药物供应有限地区的治疗方法以及抗隐球菌治疗与抗艾滋病治疗联合带来的挑战。
从早期杀菌活性（EFA）研究来看，两性霉素B-氟胞嘧啶是最佳诱导治疗药物，但通常难以获得；高剂量两性霉素B单药治疗在某些情况下可能可行。在氟康唑是唯一选择的地方，更高剂量更具杀菌性。血清隐球菌抗原检测可识别疾病风险最高的患者，一级预防是有效的；此类干预措施的临床作用有待确定。开始ART的时机仍存在争议；早期开始有免疫重建疾病（IRD）风险，延迟可能增加死亡率。
尽可能采用基于两性霉素B的治疗方法。需要更多研究来优化氟康唑单药治疗剂量。其他研究重点包括颅内压升高的管理、适当开始ART以及IRD的治疗。研究应聚焦于问题最严重的发展中国家。
