Pham Ngoc Thach Tuberculosis and Lung Disease Hospital, Ho Chi Minh City, Vietnam.
Clin Infect Dis. 2010 Oct 15;51(8):879-86. doi: 10.1086/656410.
Studies have suggested that the Mycobacterium tuberculosis Beijing genotype causes more severe clinical disease and higher treatment failure rates with standard regimens, possibly in association with an increased risk of acquiring drug resistance. We studied the effect of genotype on treatment failure in a rural area in Vietnam where multidrug resistance is strongly associated with the Beijing genotype.
In a population-based prospective cohort study, patients with smear-positive tuberculosis were tested before and after treatment by spoligotyping and drug susceptibility analysis. Reinfections were excluded by DNA fingerprinting. The outcome was treatment failure based on culture.
Of 1106 patients eligible for analysis, 33 experienced treatment failure (3.0%; 95% confidence interval [CI], 2.1%-4.1%). The proportion of failure was 5.3% (95% CI, 0.3%-7.9%) among 380 patients with Beijing genotype infections. Multidrug-resistant tuberculosis strongly predicted failure (odds ratio [OR], 114; 95% CI, 30-430). After adjusting for multidrug-resistant tuberculosis, treatment failure was not associated with the Beijing genotype (adjusted OR, 0.7; 95% CI, 0.3-2.0). Amplification of drug resistance occurred in 3 patients (0.3%; 95% CI, 0.1%-0.7%) and was associated with multidrug resistance at baseline (P = .004) but not with the Beijing genotype. No multidrug resistance was created.
The Beijing genotype was not associated with treatment failure in Vietnam; apparent associations were explained by the strong association of this genotype with multidrug resistance. Amplification of resistance in this patient population was rare.
研究表明,结核分枝杆菌北京基因型可能与耐药风险增加有关,导致更严重的临床疾病和更高的标准治疗方案失败率。我们在越南一个农村地区进行了一项研究,该地区的耐多药结核病与北京基因型密切相关,研究了基因型对治疗失败的影响。
在一项基于人群的前瞻性队列研究中,对涂片阳性肺结核患者进行治疗前和治疗后的 spoligotyping 和药敏分析检测。通过 DNA 指纹分析排除再感染。根据培养结果判断治疗失败。
在 1106 名符合分析条件的患者中,有 33 名(3.0%;95%置信区间[CI],2.1%-4.1%)发生治疗失败。380 名北京基因型感染者中,失败率为 5.3%(95%CI,0.3%-7.9%)。耐多药结核病强烈预测失败(比值比[OR],114;95%CI,30-430)。在调整耐多药结核病后,北京基因型与治疗失败无关(调整 OR,0.7;95%CI,0.3-2.0)。3 名患者(0.3%;95%CI,0.1%-0.7%)发生耐药扩增,与基线时的耐多药相关(P=0.004),但与北京基因型无关。没有产生新的耐药性。
在北京基因型与越南的治疗失败无关;这种基因型与耐多药的强烈关联解释了明显的关联。在该患者人群中,耐药性扩增很少见。