重庆地区儿童耐药结核病患者耐药情况及临床特征分析
收稿日期: 2024-07-31
网络出版日期: 2024-10-08
基金资助
重庆市科卫联合医学科研项目面上项目(2023MSXM051);重庆市自然科学基金面上项目(CSTB2024NSCQ-MSX1048);国家儿童健康与疾病临床医学中心临床医学研究项目(NCRCCH-2020-GP-06);重庆医科大学附属儿童医院杰出青年人才基金项目(RC02017);儿童新发重大传染病病原体实时动态监测机制建立(2022YFC2704904)
Analysis of drug resistance and clinical characteristics of children with drug-resistant tuberculosis in Chongqing
Received date: 2024-07-31
Online published: 2024-10-08
目的 本研究旨在分析重庆地区耐药结核病(DR-TB)患儿的耐药谱、耐药位点及临床特征。方法 以2014年1月至2022年12月重庆医科大学附属儿童医院收集的296株结核分枝杆菌(MTB) 菌株及其对应患儿为研究对象。采用比例法药物敏感性试验(DST)检测耐药性,用全基因组测序(WGS) 检测耐药位点。回顾性分析DR-TB患儿的临床特征。结果 经比例法DST检测,17.2%(51/296)菌株为DR-TB,WGS未发现新的耐药位点。敏感组240例,耐药组51例。耐药组女性、复治、重症结核病、肺结核合并肺外结核、使用二线药物、治疗失败或死亡比例均高于敏感组,但卡介苗接种率低于敏感组,差异均有统计学意义(P<0.05)。共288例患儿完成胸部CT检查,与敏感组相比,耐药组累及双侧肺部比例更高,累及肺叶数量也更多,更容易累及右下叶,坏死比例也更高,差异均有统计学意义(P<0.05)。与敏感组相比,耐药组患儿抗酸染色涂片≥1次阳性的比例更高,T-SPOT.TB阳性率更低,差异有统计学意义(P<0.05)。结论 重庆地区儿童DR-TB比例较高,耐药位点与成人相近。女性、复治、未接种卡介苗可能与DR-TB相关,DR-TB患儿肺野受累更广,更易出现肺坏死、扩散至肺外器官并进展为重症,且治疗失败或死亡比例较高。DR-TB患儿整体病原检测阳性率更高,但免疫学检查阳性率偏低,可能存在免疫功能抑制。
龙晓茹 , 杨汝铃 , 张祯祯 , 许红梅 , 赵瑞秋 , 郑改焕 . 重庆地区儿童耐药结核病患者耐药情况及临床特征分析[J]. 临床儿科杂志, 2024 , 42(10) : 868 -875 . DOI: 10.12372/jcp.2024.24e0778
Objective Our study was to analyze the drug resistance spectrum, drug resistance sites, and clinical characteristics of children with drug-resistant tuberculosis (DR-TB) in Chongqing. Methods A total of 296 Mycobacterium tuberculosis (MTB) strains were isolated from pediatric patients of Children's Hospital of Chongqing Medical University from January 2014 to December 2022. These isolates were tested for anti-TB drugs with phenotypic drug susceptibility test (DST), and their potential genotypic resistance mutations were identified with whole genome sequencing (WGS). The clinical characteristics of DR-TB patients were analyzed retrospectively. Results According to phenotypic DST, 17.2% (51/296) of the strains were DR-TB, and no new gene mutations associated with drug resistance were detected by WGS. There were 240 patients in the drug-sensitive group and 51 in the drug-resistant group. Compared with the drug-sensitive group, the proportion of female, retreatment, severe tuberculosis, pulmonary tuberculosis combined with extrapulmonary tuberculosis, second-line drug use, treatment failure or death was higher, but the BCG vaccination rate was lower in the drug-resistant group, and the differences were statistically significant (P<0.05). A total of 288 children completed chest CT examination. Compared with the drug-sensitive group, the drug-resistant group involved a higher proportion of both lungs, involved more lobes, more likely to involve the lower right lobe, and had a higher percentage of necrosis, and the differences were all statistically significant (P<0.05). Compared with the drug-sensitive group, the proportion of positive acid-fast staining smear ≥1 times was higher, and the positive rate of T-SPOT.TB was lower in the drug-resistant group, with statistical significance (P<0.05). Conclusions The proportion of DR-TB in children in Chongqing is relatively high, and the gene mutations associated with drug resistance are similar to those in adults. Female, retreatment, and no BCG vaccination may be associated with DR-TB. Children with DR-TB have a wider range of lung involvement, are more likely to experience lung necrosis, and have a higher risk of lung lesions spreading to extra-pulmonary organs and progressing to severe disease, with higher rates of treatment failure or death. The overall positive rate of pathogen detection was higher in DR-TB children, but the positive rate of immunological examination was lower, suggesting that the children may have immune suppression.
Key words: tuberculosis; drug-resistant; clinical feature; child
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