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.

A QUALITATIVE STUDY OF KNOWLEDGE, ATTITUDE AND PRACTICE TOWARDS TB IN GEORGIA.

TB remains to be the major public health concern in Georgia. TB awareness and knowledge is usually low in the general population, which leads to delayed referral to a medical facility, which in turn hinders timely initiation of diagnostic and treatment interventions. Lack of knowledge also contributes much to the widespread stigma in the society. The aim of the study was to qualitatively explore TB knowledge, attitudes and practice, as well as related barriers and facilitators by conducting FGDs among representatives of general population as well as TB risk groups. The qualitative data was collected through FGDs among different target groups: (1) TB patients; (2) TB contacts; (3) Injecting drug users; (4) health care providers and (5) students. FGD recordings were transcribed using a predefined coding scheme and followed by contextual analysis. According to the study results, there is a good level of TB knowledge and awareness among current/former TB patients, their contacts, and health care providers, which is linked to their practice and experience. IDUs receive sufficient information on the disease within the educational component of the Needle and Syringe program. A significant lack of TB knowledge was revealed in a segment of the general population such as students. Lack of TB knowledge among general population is highly linked to the stigmatized attitude towards TB patients. Accurate TB knowledge is an important prerequisite determining positive attitude towards the disease and supporting stigma reduction. Correct information on TB should be disseminated through all possible channels and the process should have permanent nature.

Access to experimental medicines for TB: ethical and human rights considerations.

The revised edition of the WHO's Ethics Guidance for the Implementation of the TB Strategy has added a new chapter on compassionate use (CU) and expanded access (EA) to TB drugs. CU and EA programmes authorise access to drugs that have not yet received marketing approval outside of clinical trials. They are aimed at allowing researchers access to investigational drugs in the absence of complete evidence of efficacy and safety to patients with multidrug-resistant (MDR) or rifampicin-resistant TB (RR-TB) when no other treatment options are available. In doing so, the guidance acknowledged the urgent necessity to offer these patients all possible treatments in respect of considerations of justice, human rights, human dignity, autonomy of the individual and protection of the community. Regulators are in general willing to accept a higher level of uncertainty in the risk-benefit assessment of medicines for life-threatening diseases when there is an unmet medical need. This attests to a paradigm change, which this article argues should also apply to allow for effective access to experimental TB medicines. Furthermore, in this article, we analyse the challenges connected to the establishment of a secure and effective regime of access to experimental drugs in the context of MDR/RR-TB as well as the ethical principles and human rights arguments in favour of the development of such programmes.

Smoking behavior and beliefs about the impact of smoking on anti-tuberculosis treatment among health care workers.

SETTING: Tuberculosis (TB) health care facilities throughout Georgia. OBJECTIVE: To describe smoking behaviors among health care workers (HCWs) at TB facilities and determine HCWs' knowledge and beliefs regarding the impact of tobacco use on anti-tuberculosis treatment. DESIGN: Cross-sectional survey from May to December 2014 in Georgia. Adult HCWs (age 18 years) at TB facilities were eligible. We administered a 60-question anonymous survey about tobacco use and knowledge of the effect of smoking on anti-tuberculosis treatment. RESULTS: Of the 431 HCWs at TB facilities who participated, 377 (87.5%) were female; the median age was 50 years (range 20-77). Overall, 59 (13.7%) HCWs were current smokers and 35 (8.1%) were past smokers. Prevalence of current smoking was more common among physicians than among nurses (18.6% vs. 7.9%, P < 0.0001). Among HCWs, 115 (26.7%) believed smoking does not impact anti-tuberculosis treatment, and only 25.3% of physicians/nurses received formal training in smoking cessation approaches. Physicians who smoked were significantly more likely to believe that smoking does not impact anti-tuberculosis treatment than non-smoking physicians (aOR 5.11, 95%CI 1.46-17.90). CONCLUSION: Additional education about the effect of smoking on TB treatment outcomes is needed for staff of TB health care facilities in Georgia. Nurses and physicians need more training about smoking cessation approaches for patients with TB.

Geographical heterogeneity of multidrug-resistant tuberculosis in Georgia, January 2009 to June 2011.

In 2011, Georgia, in the Caucasus, reported that 11% of new and 32% of previously treated tuberculosis (TB) cases nationally had multidrug-resistant TB (MDR-TB). To help understand the mechanisms driving these high risks of drug-resistance and plan for targeted interventions, we identified geographical variability in the MDR-TB burden in Georgia and patient-level MDR-TB risk factors. We used routinely collected surveillance data on notified TB cases to estimate the MDR-TB incidence/100,000 people and the percentage of TB cases with MDR-TB for each of 65 districts and regression modelling to identify patient-level MDR-TB risk factors. 1,795 MDR-TB cases were reported (January 2009­June 2011); the nationwide notified MDR-TB incidence was 16.2/100,000 but far higher (837/100,000) in the penitentiary system. We found substantial geographical heterogeneity between districts in the average annual MDR-TB incidence/100,000 (range: 0.0­5.0 among new and 0.0­18.9 among previously treated TB cases) and the percentage of TB cases with MDR-TB (range: 0.0%­33.3% among new and 0.0%­75.0% among previously treated TB cases). Among treatment-naïve individuals, those in cities had greater MDR-TB risk than those in rural areas (increased odds: 43%; 95% confidence interval: 20%­72%). These results suggest that interventions for interrupting MDR-TB transmission are urgently needed in prisons and urban areas.