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2014 年至 2017 年中国四川结核分枝杆菌分离株的耐药特征:一项回顾性研究。

Drug resistance characteristics of Mycobacterium tuberculosis isolates between 2014 and 2017 in Sichuan, China: A retrospective study.

机构信息

Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu, Sichuan Province, China.

Department of Clinical Laboratory, Public Health Clinical Center of Chengdu, Chengdu, Sichuan Province, China.

出版信息

PLoS One. 2018 Dec 31;13(12):e0209902. doi: 10.1371/journal.pone.0209902. eCollection 2018.

Abstract

BACKGROUND

The prevalence of drug-resistant tuberculosis (DR-TB) has brought severe challenges to the prevention and control of tuberculosis. Studies have explored the status of antituberculosis drug (ATD) resistance in different regions of China. However, few studies have focused on DR-TB in Sichuan to date. Due to the large population in Sichuan, detailed investigations of the DR-TB burden in Sichuan are needed. The objective of this study was to investigate the drug resistance characteristics of TB isolates from tuberculosis patients with and without HIV (TB-HIV patients and TBw/oHIV patients) in Chengdu, Sichuan, China.

METHODS

Isolates from respiratory samples of TBw/oHIV patients and TB-HIV patients hospitalized between January 2014 and December 2017 were collected. Nontuberculosis mycobacteria (NTM) were excluded. Drug sensitivity testing (DST) was performed according to the dilution method in microplates with 4 first-line ATDs and 8 second-line ATDs. TB strains were separated according to patient treatment history, patient age, calendar year and GeneXpert MTB/RIF (GeneXpert) assay results for further analysis.

RESULTS

For the 7470 patients recruited, the multidrug-resistant tuberculosis (MDR-TB) rate was 2.1-fold (14.6% vs. 6.8%) higher than the national baseline level. The repeatedly admitted patients were more likely to have a resistance profile than the first-time-admitted cases in both the TB-only group (P<0.05) and the TB-HIV corresponding group (P<0.05). Among the 7273 TBw/oHIV cases and 197 TB-HIV cases, the positivity rates of acid-fast bacilli (AFB) in the TB-HIV group were significantly lower than those in the TBw/oHIV group (P<0.05). The repeatedly admitted TB-HIV patients had lower resistance rates to INH than the repeatedly admitted TBw/oHIV patients (24.4% vs. 41.5%, P<0.05). The Rifampicin-resistant TB strains in the TBw/oHIV group were more likely to be resistant to INH in the repeatedly admitted group than those in the first-time admitted patients (P<0.05). The proportions of XDR (3.6% vs. 1.3%, P<0.05) and XDR-TB/MDR-TB (7.3% vs. 2.2%, P<0.05) in all TB-HIV patients were significantly higher than those in all TBw/oHIV patients. The ratio of XDR-TB was significantly higher in the TB-HIV group than in the TBw/oHIV group (30.4% vs. 9.0%, P<0.05) and the all TB group (9.0% vs. 10.1%, P<0.05). Regarding age, the <25-year-old TB-HIV patients (9.1% vs. 0.7%, P<0.05) and 25~44-year-old TB-HIV patients (5.2% vs. 2.4%, P<0.05) were more likely to have a higher XDR proportion than their TBw/oHIV counterparts. The ATD-resistance profile in terms of different years from high to low was 2014>2015>2016≈2017 for TBw/oHIV patients. The same trend was also observed for TB-HIV patients: 2014>2015>2016≈2017. The GeneXpert TB-positive rate in the TBw/oHIV group was higher than that in the TB-HIV group [81%(639/792) vs. 65% (13/20), P<0.05]. In TBw/oHIV cases, the agreement was 92.3% and the Kappa value was 0.75. In TB-HIV cases, the agreement was 85.0% and the Kappa value was 0.32.

CONCLUSION

In Sichuan, ATD resistance has improved since 2014, but to date, it remains severe. The different resistance profiles of TBw/oHIV patients and TB-HIV patients indicates the need for personalized treatment plans. Specifically, the GeneXpert assay might be more suitable for TBw/oHIV patients than for TB-HIV patients.

摘要

背景

耐多药结核病(DR-TB)的流行给结核病的防控带来了严峻挑战。研究已经探索了中国不同地区抗结核药物(ATD)耐药的现状。然而,迄今为止,针对四川的 DR-TB 研究较少。由于四川人口众多,需要详细调查四川的 DR-TB 负担。本研究的目的是调查中国四川成都地区 HIV 阳性(TB-HIV)和 HIV 阴性(TBw/oHIV)结核病患者的结核分枝杆菌分离株的耐药特征。

方法

收集了 2014 年 1 月至 2017 年 12 月住院的 TBw/oHIV 患者和 TB-HIV 患者的呼吸道样本。排除非结核分枝杆菌(NTM)。根据微板稀释法进行药物敏感性试验(DST),共检测了 4 种一线 ATD 和 8 种二线 ATD。根据患者的治疗史、患者年龄、日历年份和 GeneXpert MTB/RIF(GeneXpert)检测结果对结核菌株进行分离,进一步进行分析。

结果

共纳入 7470 例患者,其中 MDR-TB 率较全国基线水平高 2.1 倍(14.6% vs. 6.8%)。TB 仅组(P<0.05)和 TB-HIV 对应组(P<0.05)中,重复入院患者的耐药谱比首次入院患者更常见。在 7273 例 TBw/oHIV 病例和 197 例 TB-HIV 病例中,TB-HIV 组的抗酸杆菌(AFB)阳性率明显低于 TBw/oHIV 组(P<0.05)。重复入院的 TB-HIV 患者对 INH 的耐药率低于重复入院的 TBw/oHIV 患者(24.4% vs. 41.5%,P<0.05)。TBw/oHIV 组中 Rifampicin 耐药的结核菌株在重复入院组中更有可能对 INH 耐药,而在首次入院患者中则不耐药(P<0.05)。所有 TB-HIV 患者中,XDR(3.6% vs. 1.3%,P<0.05)和 XDR-TB/MDR-TB(7.3% vs. 2.2%,P<0.05)的比例均明显高于所有 TBw/oHIV 患者。所有 TB-HIV 患者中,XDR-TB 的比例明显高于 TBw/oHIV 患者(30.4% vs. 9.0%,P<0.05)和所有 TB 患者(9.0% vs. 10.1%,P<0.05)。按年龄分层,<25 岁的 TB-HIV 患者(9.1% vs. 0.7%,P<0.05)和 25~44 岁的 TB-HIV 患者(5.2% vs. 2.4%,P<0.05)发生 XDR 的比例更高。TBw/oHIV 患者的 ATD 耐药谱从高到低分别为 2014 年>2015 年>2016 年≈2017 年。TB-HIV 患者也呈现出相同的趋势:2014 年>2015 年>2016 年≈2017 年。TBw/oHIV 组的 GeneXpert TB 阳性率高于 TB-HIV 组[81%(639/792)比 65%(13/20),P<0.05]。在 TBw/oHIV 病例中,一致性为 92.3%,Kappa 值为 0.75。在 TB-HIV 病例中,一致性为 85.0%,Kappa 值为 0.32。

结论

自 2014 年以来,四川的 ATD 耐药性有所改善,但迄今为止,耐药性仍然严重。TBw/oHIV 患者和 TB-HIV 患者的不同耐药谱表明需要制定个体化的治疗方案。具体来说,GeneXpert 检测可能更适合于 TBw/oHIV 患者,而不是 TB-HIV 患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a482/6312223/a3d24a743437/pone.0209902.g001.jpg

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