Influence of Antituberculosis Drug Resistance and Mycobacterium tuberculosis Lineage on Outcome in HIV-Associated Tuberculous Meningitis
Influence of Antituberculosis Drug Resistance and Mycobacterium tuberculosis Lineage on Outcome in HIV-Associated Tuberculous Meningitis
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DOI：
10.1128/aac.00319-12
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发表时间：
2012-06-01
影响因子：
4.9
通讯作者：
Caws, Maxine
中科院分区：
文献类型：
--
作者：
Dau Quang Tho;Toeroek, M. Estee;Caws, Maxine
HIV相关结核性脑膜炎（TBM）死亡率高。除了多药耐药（MDR）对生存的破坏性影响外，对其他细菌因素对结果的影响知之甚少。本研究探讨了结核分枝杆菌耐药性、细菌谱系和宿主疫苗接种状态对HIV相关TBM患者预后的影响。在越南胡志明市进行的两项HIV相关TBM研究中，对186例患者脑脊液中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。谱系基因分型可用于122例患者。抗结核药物耐药性和M.采用Kaplan-Meier生存分析和考克斯多元回归模型分析结核谱系对9个月死亡率的影响。异烟肼（INH）耐药而利福平不耐药与死亡率增加相关（校正的风险比[HR]，1.78，95%可信区间[CI]，1.18 ~ 2.66; P = 0.005），多药耐药一致致死（n = 8/8;校正的HR，5.21，95%CI，2.38 ~ 11.42; P < 0.0001）。INN耐药病例的风险比在治疗的继续阶段最大（3个月后; HR，5.05 [95% CI，2.23 - 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的死亡率低于感染“古老”印度洋谱系菌株的患者（HR，0.29 [95%CI，0.14 - 0.61]; P = 0.001）。异烟肼耐药、多药耐药和M.结核谱系是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可能有助于降低TBM患者不可接受的高死亡率。
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 geno-typing 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 INN-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.