Effectiveness and safety of fully oral modified shorter treatment regimen for multidrug-resistant tuberculosis in Georgia, 2019-2020

Abstract

Tuberculosis treatment is challenging, especially among people with drug-resistant forms of tuberculosis. The introduction of fully oral modified short treatment regimen has a great potential to shorten duration of treatment, improve safety and ultimately increase treatment success rate. In 2019 Georgia has piloted the modified fully oral shorter treatment regimen in a routine programmatic condition. Our study aimed to evaluate effectiveness and safety of the modified shorter treatment regimen in Georgia among the first 25 consecutively enrolled patients with rifampicin-resistant tuberculosis with proven sensitivity to fluoroquinolone and without prior exposure to second-line tuberculosis drugs. Regimen consisted of 9-month daily administration of bedaquilline, linezolid, levofloxacin, clofazimine and cycloserine. Study patients were enrolled between March-August 2019. We used a national electronic surveillance system, medical records and active TB drug-safety monitoring and management database to extract study related data. The mean age of the study participants was 48 years, 68% were male, 8% were HIV positive, 16% had diabetes and 12% tested positive for hepatitis C infection. The median time to culture conversion among 16 patients who were culture positive at treatment initiation was 1.0 (95% CI: 1.0-2.0) month. Of those, by the end of treatment 15 patients converted to negative. Out of the 25 patients in the study cohort 22 (88%) had successful treatment outcome, one patient (4%) died and two (8%) were lost to follow up. The regimen was largely well tolerated. Three patients (12%) experienced serious adverse events, of which in two cases were possibly related to TB drugs in the regimen. Seven patients developed adverse events of interest in eight instances, including musculoskeletal (twice), psychiatric, gastrointestinal disorders, hepatotoxicity, peripheral neuropathy, cardiotoxicity and myelosuppression (once each). In four patients (16%) the duration of the treatment was extended beyond nine months due to insufficient radiological improvements. Our findings demonstrate that good treatment outcomes are achievable in people with fluoroquinolone-sensitive tuberculosis within routine programmatic conditions using fully oral modified short treatment regimen. The extensive use of fully oral modified shorter treatment regimen in Georgia and other high priority countries in the World Health Organization European Region is warranted.

Effectiveness and safety of a modified short-term regimen of antimycobacterial therapy to treat rifampicin-resistant tuberculosis in elderly patients with concomitant diabetes (a clinical case)

“…The presented case demonstrates the high safety and efficacy of all oral mSTR, including Lfx-Bdq-Lzd-Cfz-Cs, in the elderly person with RR-TB and concomitant decompensated T2DM. These results are in agreement with those of M. B. Souleymane et al [13], T. Avaliani et al [4] and V. Schwbel et al [11].…”

Six Months of Bedaquiline-Pretomanid-Linezolid (BPaL) Regimen in Patients with Drug-Resistant Tuberculosis: A Narrative Review

“…[22] Furthermore, a study by Avaliani et al demonstrated that in MDR-TB patients in Georgia receiving five drugs of STR (bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine), the treatment success was 22/25 (88%). [23] Treatment success of more than 90% in Bedaquiline, Pretomanid, and Linezolid ( BPaL) regimen was higher compared to the study by Soeroto et al, who reported that 64.5% of successful treatment in Indonesian MDR/RR-TB patients treated with the second line injectablecontaining 7-drug STR [3].…”

Effectiveness and safety of bedaquiline-based, modified all-oral 9–11-month treatment regimen for rifampicin-resistant tuberculosis in Vietnam

“…Treatment success of our simplified mSTR was comparable with those obtained for other mSTR cohorts, also using BDQ and FQ as core drugs, and LZD and CFZ as companion drugs, but with CS instead of PZA. In Georgia's cohort of 25 patients: 88% success was achieved, and in Belarus, 90% success was achieved among 222 patients ( Avaliani et al. , 2021 ).…”

“…No safety data were published for the Belarus cohort, while in a small cohort of 25 patients in Georgia, three SAEs were reported ( Yatskevich et al. , 2021 ; Avaliani et al. , 2021 ).…”

“…In Belarus and Georgia, compared to the WHO STR, LZD, and cycloserin (CS) replaced ethambutol, isoniazid, prothionamide and PZA. However, in Georgia, the cohort consisted only of 25 patients ( Avaliani et al. , 2021 ).…”