Diagnosis of Nontuberculous Mycobacterial Infections

Jakko van Ingen, MD, PhD


Semin Respir Crit Care Med. 2013;34(1):103-109. 

In This Article


Despite tremendous advances in clinical and laboratory diagnosis of the different NTM diseases, diagnosing NTM diseases remains complicated. It is, of course, key to think of NTM as possible causative agents of disease. Then, because of limited sensitivity and specificity of symptoms, radiology, and direct microscopy of clinical samples, culture remains the gold standard. Yet culture is time consuming and demands the use of multiple media types and incubation temperatures to optimize the yield. Outside of reference centers, such elaborate culture algorithms are scarce.

Determining the clinical relevance of isolated NTM presents its own challenges. Three particular issues merit specific attention and should be subjects of future studies. First, it is now generally accepted that NTM species differ in their clinical relevance;[6] yet a single species may also differ in clinical relevance in different regions or settings, which adds another layer of complexity.[53] To prevent unwarranted diagnoses and treatment of NTM disease as well as unnecessary diagnostic delay, it could be helpful to use separate, more stringent criteria for species of low, and less stringent criteria for species considered to be of high clinical relevance in the local setting. This stepped approach requires complete and up to date insight in locally prevalent NTM and their clinical relevance. In the absence of obligatory reporting for NTM, this too is an area where continuous contact between clinicians and microbiologists is important.

Virulence factors are a second understudied field in NTM. Yet detecting these may aid in determining the clinical relevance of isolated NTM. Here the species M. kansasii is the best example. In a previous case series, M. kansasii subtype 1 was most strongly associated with clinical disease, whereas subtypes 3 through 5 seemed nonpathogenic.[54] A recent study of the ESX-1 virulence factor of M. tuberculosis also evaluated M. kansasii and found that M. kansasii subtype 1 had an active ESX-1 system, whereas this system was inactive in M. kansasii type 5.[55] Assessing such virulence factors could be a valuable addition to species identification.

The third key issue in diagnosing NTM infections is the recognition of patients at increased risk for these diseases. Even though some predisposing conditions are very clear(e.g., HIV, immunosuppressive drug use) many others remain poorly understood. Even though preexistent lung diseases, including chronic obstructive pulmonary disease and CF, are clear risk factors, it remains impossible to predict which individual patient will develop NTM disease, even though we are all exposed to NTM on a daily basis.[56] This also should be an area of future studies.