Algorithm of use short 12 month regimens for the linezolid based for patients with multidrug-resistant tuberculosis: first encouraging results

Abstract

Objective — to formulate clear algorithms for use of short 12 month regimens based on linezolid, with differentiation indications depending on the resistance profile of the MBT (MDR, preXDR, risk MDR), develop clear inclusion/exclusion criteria and indications for their use in patients with MDR and XDR, based on the study of direct and longterm treatment outcomes.Materials and methods. Into the prospective «case—control» study, were enrolled 370 MDR patients (including preMDR) or risk MDR. For the treatment of patients in the main group (187 patients), 6 anti-TB drugs were administered before receiving the result of the DST: linezolid (Lzd), levofloxacine (Lfx), capreomycine (Cm), prothionamide (Pt), cycloserine (Cs), pyrazinamide (Z). In the case of MDR's DST, Cm was replaced with kanamycin (Km) and an intensive phase of antimycobacterial therapy lasted a total duration of 5 months, and then a continuation phase of chemoterapy of 7 months without Km. In the case of obtaining resistance to Ofloxacin (Ofx) or Km/Cm, replacing Lfx with moxifloxacin (Mfx), high dose isoniazid (H) was added, and continued with an intensive phase of 6 months, with a transition to a continuation phase with a duration of 6 months without Cm. In the absence of the result of DST in patients with risk of MDR, the shortened regimen were continued for 5 months, followed by a continuation phase of 7 months without Cm. Individualized chemotherapy regimens without linezolid with standard duration of 20 months were used in 183 control group patients (8 months — an itensive phase and 12 months of continuation phase).Results and discussion. In patients with MDR, who used 12 month regimens, an increase in effective treatment by 14.8 % was determined primarily by reducing «lost of follow-up». Relapse occurred only in 3.8 % of patients treated with standard regimen without linezolid. In patients with preMDR, who used 12 month regimens, an increase in effectivity of treatment by 41.6 % was found due to a reduction in not only the «lost of follow-up» but also the «treatment failure» and «die». Relapse occurred only in 1.8 % of patients treated with the standard regimen without linezolid. In patients with risk MDR, the use of both regimens without Lzd was found to be equally effective. There were no relapse during the observation period.Conclusions. The use of algorithms for the appointment and selection of shoirt 12 month regimens based on linzolid can improve the outcome of «effective treatment» in patients with MDR and risk MDR by 27.1 % due to a reduction in the number of «treatment failure» by 8.5 %, «lost of follow-up» on 16.8 % and avoid relapse of tuberculosis within 6—12 months after the end of treatment.