LAUSR

We read with great interest the recent article by Upadhyay et al. on drug sensitivity patterns in Xpert-positive spinal tuberculosis published in this journal [1]. We congratulate the authors for addressing this important topic—drug-resistant tuberculosis (TB) is indeed a bane of our times; these cases require individualized treatment which depends upon multiple factors with drug sensitivity arguably being the most important amongst them. However, we wish to bring a few points which we think are extremely relevant to the notice of this journal’s readership which would send out the message expounded in this study with more clarity. Firstly, the authors have highlighted some very important factors contributing to emergence of drug resistance. In our experience, underdosing of antitubercular drugs is also quite prevalent in developing countries—more so, when these drugs are procured loosely rather than in the form of fixed drug combinations (FDC), standardized to various weight bands [2]. It is important to emphasize the need for prescribing and ensuring patients take these drugs in weight-adjusted dosage, failure of which would contribute to drug resistance. Secondly, the authors have mentioned that rifampicin and isoniazid are the only bactericidal first line drugs—we wish to highlight that even pyrazinamide (Z) has been labelled as a ‘weakly bactericidal’ drug in the most recent WHO guidelines [2]. As a sterilizing drug, pyrazinamide is almost as effective as rifampicin—it works best in the inflammation-induced acidic micro-environment under closed anoxic conditions which are typically seen in spinal TB lesions—and is an essential part of the intensive phase of antitubercular therapy [3]. Thirdly, although Xpert test is used for detecting rifampicin resistance, due to close linkage of the isoniazid resistance gene, a positive Xpert test is also considered as a surrogate marker for isoniazid resistance. Although authors have shown that not all patients showing rifampicin resistance were found to have isoniazid resistance on drug sensitivity testing (DST), it is still wise to consider them as multi-drug-resistant TB (MDR-TB) in view of the possibility of different strain being present in two different samples or parts of single sample used for different tests. In their most recent guidelines, WHO has also suggested that MDR-TB and rifampicin-resistant tuberculosis (RR-TB) should be grouped together in the recently published guidelines for drug-resistant TB [4]. Lastly, the article seems to be sending out a message that is discordant with the most recently published WHO guidelines for drug-resistant TB in 2019 [4]. These guidelines have recently been extensively revised—an all-oral regimen is now recommended to improve treatment compliance and reduce adverse drug reactions. The second-line drugs for TB are divided into 3 groups: Group A = levofloxacin/ moxifloxacin, bedaquiline, linezolid; Group B = clofazimine, cycloserine/terizidone; and Group C = ethambutol, delamanid, pyrazinamide, imipenem–cilastatin, meropenem, amikacin (streptomycin), ethionamide/prothionamide, p-aminosalicylic acid. WHO recommends the inclusion of all three Group A drugs with at least one Group B drug as empirical treatment of MDR-TB. If the regimen cannot be composed with agents from Groups A and B alone, Group C agents are added to complete it. Kanamycin and capreomycin are no longer recommended for inclusion in MDR-TB treatment regimes. We believe that this should be * Nishank Mehta [email protected]