Oxford University Clinical Research Unit Vietnam, Wellcome Trust Major Overseas Programme, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Antimicrob Agents Chemother. 2012 Jun;56(6):3074-9. doi: 10.1128/AAC.00319-12. Epub 2012 Apr 2.
HIV-associated tuberculous meningitis (TBM) has high mortality. Aside from the devastating impact of multidrug resistance (MDR) on survival, little is understood about the influence of other bacterial factors on outcome. This study examined the influence of Mycobacterium tuberculosis drug resistance, bacterial lineage, and host vaccination status on outcome in patients with HIV-associated TBM. Mycobacterium tuberculosis isolates from the cerebrospinal fluid of 186 patients enrolled in two studies of HIV-associated TBM in Ho Chi Minh City, Vietnam, were tested for resistance to first-line antituberculosis drugs. Lineage genotyping was available for 122 patients. The influence of antituberculosis drug resistance and M. tuberculosis lineage on 9-month mortality was analyzed using Kaplan-Meier survival analysis and Cox multiple regression models. Isoniazid (INH) resistance without rifampin resistance was associated with increased mortality (adjusted hazard ratio [HR], 1.78, 95% confidence interval [CI], 1.18 to 2.66; P = 0.005), and multidrug resistance was uniformly fatal (n = 8/8; adjusted HR, 5.21, 95% CI, 2.38 to 11.42; P < 0.0001). The hazard ratio for INH-resistant cases was greatest during the continuation phase of treatment (after 3 months; HR, 5.05 [95% CI, 2.23 to 11.44]; P = 0.0001). Among drug-susceptible cases, patients infected with the "modern" Beijing lineage strains had lower mortality than patients infected with the "ancient" Indo-Oceanic lineage (HR, 0.29 [95% CI, 0.14 to 0.61]; P = 0.001). Isoniazid resistance, multidrug resistance, and M. tuberculosis lineage are important determinants of mortality in patients with HIV-associated TBM. Interventions which target these factors may help reduce the unacceptably high mortality in patients with TBM.
HIV 相关结核性脑膜炎（TBM）死亡率高。除了耐多药（MDR）对生存的毁灭性影响外，人们对其他细菌因素对结果的影响知之甚少。本研究检查了结核分枝杆菌耐药性、细菌谱系和宿主疫苗接种状态对越南胡志明市两项 HIV 相关 TBM 研究中 186 名患者结局的影响。对来自 186 名患者脑脊液的结核分枝杆菌分离株进行了一线抗结核药物耐药性检测。对 122 名患者进行了谱系基因分型。使用 Kaplan-Meier 生存分析和 Cox 多因素回归模型分析了抗结核药物耐药性和 M. tuberculosis 谱系对 9 个月死亡率的影响。异烟肼（INH）耐药但无利福平耐药与死亡率增加相关（校正后的危险比 [HR]，1.78，95%置信区间 [CI]，1.18 至 2.66；P = 0.005），而耐多药则是致命的（n = 8/8；校正 HR，5.21，95%CI，2.38 至 11.42；P < 0.0001）。在治疗的延续阶段（3 个月后），INH 耐药病例的危险比最大（HR，5.05 [95%CI，2.23 至 11.44]；P = 0.0001）。在药物敏感病例中，感染“现代”北京谱系菌株的患者死亡率低于感染“古老”印度洋谱系的患者（HR，0.29 [95%CI，0.14 至 0.61]；P = 0.001）。INH 耐药、耐多药和 M. tuberculosis 谱系是 HIV 相关 TBM 患者死亡率的重要决定因素。针对这些因素的干预措施可能有助于降低 TBM 患者无法接受的高死亡率。
