Impact of Prior Tuberculosis Treatment With New/Companion Drugs on Clinical Outcomes in Patients Receiving Concomitant Bedaquiline and Delamanid for Multidrug- and Rifampicin-Resistant Tuberculosis.

BACKGROUND: There are scarce data on the clinical outcomes of persons retreated with new/companion anti-tuberculosis (TB) drugs for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We sought to evaluate the efficacy and safety of bedaquiline and delamanid containing regimens among patients with and without prior exposure to the new/companion drugs (bedaquiline, delamanid, linezolid, clofazimine, and fluoroquinolones). METHODS: We conducted a retrospective cohort study among patients with pulmonary MDR/RR-TB in Georgia who received bedaquiline and delamanid combination as a part of a salvage regimen from November 2017 to December 2020 in a programmatic setting. RESULTS: Among 106 persons with a median age of 39.5 years, 44 (41.5%) were previously treated with new/companion TB drugs. Patients with prior exposure to new/companion drugs had higher rates of baseline resistance compared to those without exposure to new/companion TB drugs (bedaquiline 15.2% vs 1.8%, linezolid 22.2% vs 16.7%). Sputum culture conversion rates among patients exposed and not exposed to new/companion drugs were 65.9% vs 98.0%, respectively (P < .001). Among patients with and without prior new/companion TB drug use, favorable outcome rates were 41.0% and 82.3%, respectively (P < .001). Treatment adherence in 32 (30.2%) patients was ≤80%. Five of 21 patients (23.8%) who had a baseline and repeat susceptibility test had acquired bedaquiline resistance. QTC/F prolongation (>500 ms) was rare (2.8%). CONCLUSIONS: Prior exposure to new/companion TB drugs was associated with poor clinical outcomes and acquired drug resistance. Tailoring the TB regimen to each patient's drug susceptibility test results and burden of disease and enhancing adherence support may improve outcomes.

Low BMI increases all-cause mortality rates in patients with drug-resistant TB.

BACKGROUND: Loss to follow-up (LTFU) is common among patients with drug-resistant TB (DR-TB) receiving second-line TB treatment; however, little is known about outcomes after LTFU, including mortality.OBJECTIVE: To determine rates of and factors associated with all-cause mortality among patients with DR-TB who were LTFU.METHODS: Retrospective cohort study of adult patients with DR-TB in Georgia who initiated second-line TB treatment during 2011-2014 and were LTFU. Survival analyses were used to estimate all-cause mortality rates and adjusted hazard ratios (aHR).RESULTS: During 2011-2014, 2,437 second-line treatment episodes occurred and 695 patients were LTFU. Among 695 LTFU patients, 143 (21%) died during 2,686 person-years (PY) post-LTFU (all-cause mortality rate 5.1%, 95% CI 4.3-6.0 per 100 PY). In multivariable analysis, low weight (BMI < 18.5 kg/m²) at treatment initiation (aHR 3.2, 95% CI 2.2-4.7), return to treatment after LTFU (aHR 3.1, 95% CI 2.2-4.4), <12 months of treatment (aHR 2.4, 95% CI 1.4-4.1) and a pre-LTFU positive culture (aHR 3.3, 95% CI 2.2-4.9) were associated with all-cause mortality.CONCLUSION: High all-cause mortality occurred among patients with DR-TB after LTFU despite a low HIV prevalence. Providing additional assistance for patients during DR-TB treatment to prevent LTFU and use of new and shorter treatment regimens may reduce mortality among LTFU.

Setting up pharmacovigilance based on available endTB Project data for bedaquiline.

SETTING: Active pharmacovigilance (PV) is recommended for TB programmes, notably for multidrug-resistant TB (MDR-TB) patients treated with new drugs. Launched with the support of UNITAID in April 2015, endTB (Expand New Drug markets for TB) facilitated treatment with bedaquiline (BDQ) and/or delamanid of >2600 patients in 17 countries, and contributed to the creation of a central PV unit (PVU).OBJECTIVE: To explain the endTB PVU process by describing the serious adverse events (SAEs) experienced by patients who received BDQ-containing regimens.DESIGN: The overall PV strategy was in line with the 'advanced´ WHO active TB drug safety monitoring and management (aDSM) system. All adverse events (AEs) of clinical significance were followed up; the PVU focused on signal detection from SAEs.RESULTS and CONCLUSION: Between 1 April 2015 and 31 March 2019, the PVU received and assessed 626 SAEs experienced by 417 BDQ patients. A board of MDR-TB/PV experts reviewed unexpected and possibly drug-related SAEs to detect safety signals. The experts communicated on clusters of risks factors, notably polypharmacy and off-label drug use, encouraging a patient-centred approach of care. Organising advanced PV in routine care is possible but demanding. It is reasonable to expect local/national programmes to focus on clinical management, and to limit reporting to aDSM systems to key data, such as the SAEs.

Examples of bedaquiline introduction for the management of multidrug-resistant tuberculosis in five countries.

BACKGROUND: For the first time in almost 50 years, there are new drugs available for the treatment of tuberculosis (TB), including bedaquiline (BDQ) and delamanid (DLM). The rate of introduction, however, has not kept pace with patient needs. It is estimated that as many as 23% of multidrug-resistant TB (MDR-TB) patients have an indication for receiving BDQ. As this is the first time the MDR-TB community is introducing new medications, it is important to understand how implementation can be developed in a variety of settings. METHODS: A qualitative assessment of country TB programs in which more than 5% of MDR-TB patients were started on BDQ under program conditions. RESULTS: National TB programs in Belarus, France, Georgia, South Africa, and Swaziland all started sizeable cohorts of patients on BDQ in 2015. Common factors observed in these programs included experience with compassionate use/expanded access, support from implementing partners, and adequate national or donor-supported budgets. Barriers to introduction included restriction of BDQ to the in-patient setting, lack of access to companion drugs, and the development of systems for pharmacovigilance. CONCLUSION: The five countries in this paper are examples of the introduction of new therapeutic options for the treatment of TB.

Cancer screening program in Georgia (results of 2011).

This paper reviews and summarizes the results and epidemiological data of 2011 Cancer Screening Program in Georgia. The first paragraph of paper underlines main results of capacity building of the program and its implementation. The second paragraph is focused on activities conducted within the program on population behaviour change and communication campaign and the final paragraph analyses the data of epidemiological results collected during year 2011 of breast, cervical, prostate and colorectal cancer screening, reviews and summarizes. Implementation of cancer screening programs is of great medical and social importance. Cancer screening, using simple tests that can cover the general population, and also promotes the early diagnosis of cancer and its treatment in a timely manner, increasing life expectancy and reduce mortality.

Prevalence and risk factors for multidrug-resistant tuberculosis in the Republic of Georgia: a population-based study.

SETTING: Multidrug-resistant tuberculosis (MDR-TB, defined as resistance to at least isoniazid and rifampicin) has emerged as a serious global public health problem, especially in the former Soviet republics. The extent of the problem in Georgia has been incompletely defined. OBJECTIVE: To determine the prevalence and risk factors for MDR-TB in Georgia. DESIGN: A population-based study was carried out between July 2005 and May 2006. RESULTS: Of 1314 patients with acid-fast bacilli smear- and culture-positive pulmonary tuberculosis (TB), 799 (60.8%) were newly diagnosed patients and 515 (39.2%) had been treated previously. Overall, 733 (56%) patients had resistance to at least one anti-tuberculosis drug and 195 (15%) had MDR-TB. Patients who had been treated previously for TB were significantly more likely to have MDR-TB than newly diagnosed patients (141/515 [27.4%] vs. 54/794 [6.8%], OR 5.27, 95%CI 3.75-7.41). In multivariate analysis, previous TB treatment (aOR 5.47, 95%CI 3.87-7.74) and female sex (aOR1.58, 95%CI 1.02-2.32) were independent risk factors for the presence of MDR-TB. CONCLUSIONS: Drug-resistant TB, including MDR-TB, has emerged as a major public health problem in Georgia. Further TB control efforts need to be implemented to prevent the development of new cases of MDR-TB and to treat existing patients with MDR-TB.