To the Editors:
In a retrospective study, Migliori et al. 1 have elegantly shown that linezolid 600 mg daily or twice daily added to an individualised multidrug regimen was efficacious in treating multidrug-resistant tuberculosis (MDR-TB). Once-daily dosing was associated with less major adverse effects than twice-daily dosing, corroborating the results of an earlier study in South Korea 2. As a result of the potentially serious side-effects, Migliori et al. 1 have appropriately recommended reserving linezolid treatment for the most complicated cases of MDR-TB. We concur with these views and would like to share our experience regarding the use of linezolid 800 mg once daily in the treatment of extensively drug-resistant tuberculosis (XDR-TB) and fluoroquinolone-resistant MDR-TB.
Table 1⇓ shows the clinical profiles of two patients. The first is a 41-yr-old male smoker with smear-positive XDR-TB following a long history of treatment for chronic tuberculosis overseas. His chest radiograph initially showed an extremely large cavity involving the right upper lobe and the apical segment of the right lower lobe. Despite apparent sputum culture conversion after treatment for 12 weeks, drug susceptibility testing (DST) revealed an increase in the minimum inhibitory concentration of linezolid against Mycobacterium tuberculosis from 0.5 mg·L−1 to 4 mg·L−1 for the last positive-culture isolate after 2 months of therapy. Besides reflecting the activity of the oxazolidinones against M. tuberculosis, this phenomenon might represent transitional bacillary resistance prior to bacteriological conversion from positivity to negativity. The second patient is a 60-yr-old diabetic male with smear-positive fluoroquinolone-resistant MDR-TB and a high possibility of sequestered lung disease due to a thick-walled cavity in the left upper lobe. He has received two main periods of linezolid administration of varying dosages; the second period is still ongoing. Compared to the experience with linezolid 600 mg twice-daily dosing, his tolerance was better with 800 mg once daily. In addition, to date, there is no evidence of bacillary resistance to linezolid from serial DST. Both patients have apparently achieved lowering of bacillary load after administration of linezolid, together with shrinkage of cavities even when the dose of linezolid was 800 mg once daily. Surgery after achieving sputum culture conversion was contemplated in both cases, but the thought was abandoned by patients and surgeons in view of the high risk of post-operative morbidity and mortality. However, without surgery, reversion of bacteriological status to positivity would be very likely.
Clinical profile of two patients
Our data corroborate previous findings of good diffusion of linezolid into tuberculosis cavities 3. An in vitro pharmacodynamic model in Bacillus anthracis has suggested that an optimised once-daily dose of linezolid might prevent emergence of drug resistance, in addition to conferring antibacterial efficacy 4. Linezolid has a reasonably low mutant prevention concentration that would theoretically help to restrict the development of mycobacterial resistance 5. Thus, more exploration is required to delineate an optimal dose of linezolid in the treatment of “complicated” or “difficult” MDR-TB.
Statement of interest
None declared.
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