Linezolid safety, tolerability and efficacy to treat multidrug- and extensively drug-resistant tuberculosis

Abstract

To the Editors: Treatment of multidrug-resistant (MDR) tuberculosis (TB) (defined as in vitro resistance to at least isoniazid and rifampicin, the two most potent first-line drugs for TB treatment) and extensively drug-resistant (XDR)-TB (defined as in vitro resistance to isoniazid and rifampicin plus any fluoroquinolone and at least one of the injectable drugs: amikacin, capreomycin or kanamycin) is still a major problem from both a clinical and a public health perspective [1–5]. Treatment outcomes for complicated MDR-TB cases (those with additional resistance beyond isoniazid and rifampicin) and XDR-TB cases being still poor, the need for information on the safety, tolerability and efficacy of other antibiotics that are potentially useful in their treatment is urgent [6–9]. In vitro and pharmacological data suggest that linezolid, an oxazolidinone antibiotic, could be useful in treating mycobacterial infections, including MDR-TB [9–11]. However, clinical experience with the off-label use of linezolid is still limited to case reports and small case series involving nontuberculous mycobacterial diseases [12] and TB, the four largest cohorts including 10 [13], 12 [14], 30 [15] and 85 cases (but only 45 with information on efficacy) [9], respectively. The aim of this study was to evaluate the safety, tolerability and efficacy of linezolid in a cohort of patients with MDR/XDR-TB from Portugal. Clinical information necessary to study safety, tolerability and efficacy was prospectively collected on all MDR-TB cases treated with linezolid in Portugal between 2004 and 2009, with the exception of one case who started the treatment in 2003 (whose information was …