Non-tuberculous mycobacterial disease (NTM disease), caused by infection with non-tuberculous mycobacteria (NTM), is a chronic disease. Unlike the downward trend in the number of tuberculosis cases, NTM cases have been increasing in recent years. With the increase of NTM disease, the harm of NTM to human has also attracted more and more attention. Now we will introduce the challenges encountered in the diagnosis and treatment of NTM disease.
01 NTM disease has a higher mortality rate than tuberculosis?
A 15-year follow-up study abroad showed that the overall 5-year, 10-year, and 15-year cumulative mortality rates of patients with nontuberculous mycobacterial lung disease were 12%, 24%, and 36%, respectively. [1]
FIG 1. Cumulative survival rate of patients with different NTM infections
Moreover, another study showed that the mortality rate of NTM disease was significantly higher than that of the tuberculosis group ![2]
FIG 2 Cumulative survival probability of patients with tuberculosis and NTM disease
02 What are the difficulties in the treatment of NTM disease?
First, the clinical symptoms of NTM lung disease and tuberculosis are very similar, and in the absence of bacterial species identification results, it can be misdiagnosed as tuberculosis for a long time [3]. However, NTM and Mycobacterium tuberculosis have different susceptibility to drugs. Most NTMs are naturally insensitive to anti-tuberculosis drugs [4], and the susceptibility of different NTMs to drugs is also different. Compared with the treatment of tuberculosis, the treatment of NTM disease more complex and longer duration of treatment [5]. Moreover, NTM disease often requires the application of macrolides and aminoglycosides, which have large toxic and side effects, and poor patient compliance, making treatment difficult [5]. In addition, the emergence of mixed infection of NTM and MTB complicates treatment and leads to increased mortality. [2]
Because the treatment of NTM disease is difficult, patients need more precise treatment to improve the cure rate. Regarding the treatment of NTM, the “Guidelines for the Diagnosis and Treatment of Nontuberculous Mycobacteriosis (2020 Edition)” provides detailed reference for treatment principles, treatment drugs, and cure criteria.
03 What is the treatment principle of NTM disease?
Clinicians should weigh the pros and cons and make a comprehensive judgment when deciding whether to treat NTM disease. Consensus [6], combined with domestic and foreign guidelines and literature, recommends the following principles for the treatment of NTM disease:
✔ Anti-mycobacterial therapy is required for confirmed NTM disease, especially NTM lung disease with positive acid-fast sputum and/or cavitation on imaging.
✔ Mycobacterial species identification and drug susceptibility test results before treatment are important.
✔ For NTMs whose drug susceptibility test results have a clear correlation with clinical efficacy, drug susceptibility testing should be carried out before formulating a chemotherapy regimen for NTM disease.
✔ The type and course of medication for different NTM diseases are different.
✔ Trial treatments for suspected NTM disease are not recommended.
✔ Surgery should be used with caution in patients with NTM lung disease.
✔ It is necessary to actively carry out drug safety monitoring and management for all patients included in NTM disease treatment, and timely detect and deal with adverse reactions of anti-NTM drugs.
04 What are the common NTM treatment drugs?
Different from anti-tuberculosis treatment, standard treatment is not recommended for the treatment of NTM disease. The formulation of the treatment plan should consider the NTM species, clinical factors and the patient’s condition, and explain the potential side effects of the drug and the uncertainty of the treatment effect to the patient. and the possibility of recurrence, carry out individualized treatment. [7-9]
Table 1 Antibacterial status of different drugs [6]
Table 2 Reference treatment plan for common NTM infections[6]
05 What are the cure criteria for NTM disease?
Complete the course of anti-NTM therapy and meet the criteria for bacteriological cure and clinical cure at the same time [6].
Bacteriological cure: Bacteriologically negative (3 consecutive negative NTM tests, at least 1 month apart).
Clinical cure: Clinical symptoms improved during anti-mycobacterial therapy and continued until the end of treatment.
06 What are the prerequisites for effective treatment?
Because different NTMs have different sensitivities to drugs, and the drug regimens and courses of treatment are also different, the expert consensus does not recommend experimental treatment for suspected NTM disease. Therefore, only through rapid identification of mycobacteria species can accurate diagnosis and effective treatment. How to achieve rapid identification of mycobacterial species? We will solve the mystery for you in the next article, so stay tuned!
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Reference:
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[2]Lee H, Myung W, Lee EM, Kim H, Jhun BW. Mortality and Prognostic Factors of Nontuberculous Mycobacterial Infection in Korea: A Population-based Comparative Study. Clin Infect Dis. 2021 May 18;72(10):e610-e619. doi: 10.1093/cid/ciaa1381. PMID: 32926135.
[3]姚岚，郝晓晖，唐神结，等．非结核分枝杆菌肺病144例的影像学特点分析[J]．中华结核和呼吸杂志，2012，35(8)：615—616．
[4]GRIFFITH D E, AKSAMIT T, BROWN-ELLIOTT B A, et al. An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases [J]. American Journal of Respiratory and Critical Care Medicine, 2007, 175(4): 367-416.
[5]Gopalaswamy R, Shanmugam S, Mondal R, Subbian S. Of tuberculosis and non-tuberculous mycobacterial infections – a comparative analysis of epidemiology, diagnosis and treatment. J Biomed Sci. 2020 Jun 17;27(1):74. doi: 10.1186/s12929-020-00667-6. PMID: 32552732; PMCID: PMC7297667.
[6]中华医学会结核病学分会. 非结核分枝杆菌病诊断与治疗指南(2020年版)[J]. 中华结核和呼吸杂志 2020年43卷11期, 918-946页, MEDLINE ISTIC PKU CSCD, 2021.
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[9]Wallace RJ Jr., Zhang Y, Brown-Elliott BA, et al. Repeat positive cultures in Mycobacterium intracellulare lung disease after macrolide therapy represent new infections in patients with nodular bronchiectasis. J Infect Dis 2002; 186(2): 266–73.