Smear Microscopy Complements Xpert MTB/RIF When Considering Nontuberculous Mycobacterial Infections.

To the Editor:

We read with great interest the article by Lee and colleagues on the use of the Xpert MTB/RIF assay as a substitute for smear microscopy in an intermediate-burden setting (1).

Although we agree with the authors’ conclusions regarding the diagnosis of tuberculosis, it must be remembered that smear microscopy also allows the diagnosis of nontuberculous mycobacterial (NTM) diseases. The main limitation of Xpert MTB/RIF as compared with microscopy is that it allows only the diagnosis of tuberculosis, whereas microscopy also diagnoses NTM infections.

In the author’s epidemiological setting, half of the positive cultures are a result of NTM and 45% of smear-positive cases are caused by NTM. Overall, the improvement in tuberculosis diagnosis (97 cases detected by Xpert among smear negative) was approximately equal to the number of missed NTM cases (82 smear positive).

Thus, relying solely on Xpert MTB/RIF improves the diagnosis of smear-negative tuberculosis but delays the diagnosis of the most severe NTM cases (the smear-positive ones). Whether the benefit in tuberculosis diagnosis is worth the disadvantage in NTM diagnosis remains to be studied before substituting smear microscopy with Xpert MTB/RIF. In epidemiological settings in which NTM diseases are more frequent than tuberculosis, the balance would be even more against replacing microscopy with Xpert MTB/RIF (2).

Moreover, although the lack of specificity of microscopy is well known (not all acid-fast bacilli are tuberculous bacilli; some are NTM), it must be underlined that Xpert MTB/RIF also lacks specificity. In the authors’ study, Xpert’s positive predictive value was 75%. In other words, a quarter of tuberculosis treatments started on the basis of Xpert MTB/RIF would have been done erroneously.

Overall, we believe that the Xpert MTB/RIF assay should be used as an identification test in patients who have undergone an initial screening: either positive-smear microscopy or, in case of a high clinical suspicion of tuberculosis, in case of negative-smear microscopy.