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

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

Mi Zhou  1   2 , Shan Liu  3 , Qingfeng Li  2 , Qiming Wang  2 , Ma Zhu  2 , Ling Cao  2 , Dongmei Wang  2 , Yuanhong Xu  2 , Tianli Zheng  1 , Qian Ye  4 , Xiuying Hu  5 , Haojiang Zuo  1   5 , Xiaofang Pei  1
Affiliations
Clinical Trial

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

Mi Zhou et al. PLoS One. .

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow diagram of participant enrollment.
DST, drug sensitivity testing; NTM, nontuberculous mycobacteria.
Fig 2
Fig 2. AFB smear positivity rates for the TB-HIV group and TBw/oHIV group.
Fig 3
Fig 3. ATD profiles of patients with different treatment histories.
3A: ATD profiles of TB-HIV groups with different treatment histories. 3B: ATD profiles of TBw/oHIV groups with different treatment histories.
Fig 4
Fig 4. ATD profiles of all TB patients of different ages.
Fig 5
Fig 5. ATD profiles in different years.
5A: ATD profiles of TB-HIV groups in different years. 5B: ATD profiles of TBw/oHIV groups in different years.
See this image and copyright information in PMC

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