Effect of Mixed Infections with Mycobacterium tuberculosis and Nontuberculous Mycobacteria on Diagnosis of Multidrug-Resistant Tuberculosis: A Retrospective Multicentre Study in China

Abstract

Background

Correct species identification is essential before initiation of TB treatment, due to substantial drug susceptibility profile differences among mycobacterial species. Given that nontuberculous mycobacteria (NTM) are frequently resistant to first-line anti-tuberculosis drugs, cases with mixed infections with Mycobacterium tuberculosis (MTB) and NTM tend to be diagnosed as multidrug-resistant tuberculosis (MDR-TB) cases. Here we report results of a retrospective multicentre study that was conducted to determine the prevalence of TB-NTM infections in previously diagnosed laboratory-confirmed multidrug-resistant tuberculosis (MDR-TB) patients using phenotypic drug susceptibility testing. The results were then used to identify risk factors associated with susceptibility to mixed infections.

Methods

From January 2019 through December 2019, we retrospectively collected MDR-TB isolates from three TB specialised hospitals. Species identifications of isolates were performed using the MeltPro Myco assay.

Results

A total of 837 MDR-TB isolates were analysed, of which 22 isolates (2.6%) were found to contain a mixture of NTM and MTB organisms. Significant differences in prevalence rates of mixed infections across regions were observed, with prevalence rates ranging from 0.0% (0/213) in Beijing to 3.4% (12/353) in Fuzhou to 3.7% (10/271) in Guangzhou. Among the 22 patients with NTM-TB mixed infections, a total of five different mycobacterial species were identified, of which the most prevalent species was Mycobacterium intracellulare. Notably, a history of previous TB episodes correlated with higher mixed infection risk.

Conclusion

The results reported here demonstrated that mixed infections with MTB and NTM occurred in approximately 3% of suspected MDR-TB patients in China. These findings raise concerns about the accuracy of molecular diagnostics-based species identification tests and draw attention to the possibility that NTM-MTB mixed infections will be misdiagnosed as MDR-TB in high TB burden settings.

Keywords:

• tuberculosis
• nontuberculous mycobacteria
• multidrug-resistant
• China

Abbreviations

TB, tuberculosis; MDR-TB, multidrug-resistant tuberculosis; INH, isoniazid; RIF, rifampicin; WHO, World Health Organization; DST, drug susceptibility testing; MTB, Mycobacterium tuberculosis; NTM, nontuberculous mycobacteria; L-J, Löwenstein-Jensen; OR, odds ratio; CI, confidence interval.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of Beijing Chest Hospital, Capital Medical University (2020KY030). The adults or the parents/legal guardians of patients under 18 years of age signed a written informed consent to agree with the anonymous use of clinical data.

Acknowledgments

We thank all the pilots that participated in this study.

Author Contributions

All authors have made a significant contribution to this study, all the way through the conception, study design, execution, acquisition of data, data analysis and interpretation to drafting, revising or critically reviewing stages of the article. The authors also gave final approval of the version to be published, agreed on the journal to which the article has been submitted, and agreed to be accountable for all aspects of the work.

Disclosure

The authors declare no competing interests.

Additional information

Funding

The study was supported by the Beijing Hospitals Authority’ Ascent Plan (DFL20191601), the Beijing Hospitals Authority Clinical Medicine Development of Special Funding (ZYLX202122), Fuzhou Science and Technology Project (2019-SZ-59). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.