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Background Outcomes of retreatment for rifampicin-resistant tuberculosis (RR-TB) are rarely reported. We report 'definitive outcomes' after a cascade approach to RR-TB treatment. After a bacteriologically adverse outcome for the 9-months fluoroquinolone-based Short Treatment Regimen (STR), patients were retreated with a bedaquiline-based regimen (BDQ-regimen). Methods A Retrospective cohort study of RR-TB patients treated with the STR during 2012–2019 and retreated with a BDQ-regimen in case of failure or relapse was conducted. Definitive relapse-free cure took into account BDQ-regimen outcomes. Results Of 367 patients treated with the STR, 20 (5.4%) experienced failure or relapse. Out of these 20 patients, 14 started a BDQ-regimen, of whom none experienced failure or relapse. Definitive end of treatment outcomes of STR after revising with third-line BDQ-regimen outcomes, 84.7% (311/367) were cured relapse-free, 10.6% (39/367) died during treatment and 3.0% (11/367) were lost to follow-up during treatment with either the STR or BDQ-regimen. Six patients (1.6%; 6/367) with STR failure/relapse died before starting a BDQ-regimen. No patient had definitive treatment failure or relapse and remained without treatment. Conclusions If fluoroquinolone resistance is excluded or rare, it is beneficial to use fluoroquinolone as the core drug for a first RR-TB treatment regimen and to safeguard bedaquiline for those in need of retreatment. [ABSTRACT FROM AUTHOR]

In its 2020 guidelines for the treatment of rifampicin-resistant TB (RR-TB), the WHO recommends all-oral fluoroquinolone-based regimens, with bedaquiline replacing the second-line injectable drugs (SLIDs). SLIDs were used for their strong acquired resistance-preventing activity. Data from three cohorts showed acquired bedaquiline resistance ranging between 2.5% and 30.8%, with no protection from a SLID in most cases. If bedaquiline resistance is that easily acquired, it will fail to protect fluoroquinolones and other drugs from acquiring resistance. Until evidence on resistance-preventing activity shows that SLIDs can safely be replaced, we call for more prudent use of the few potent second-line TB drugs available. Studies on new treatment regimens need to prioritize the prevention of acquired resistance along with treatment success. Meanwhile, reducing the dosing of SLIDs to thrice weekly from Day 1, and their replacement for any degree of audiometry abnormalities before or during treatment will largely avoid serious ototoxicity. [ABSTRACT FROM AUTHOR]

We report 2 cases for whom Xpert MTB/RIF falsely signaled rifampicin-resistant tuberculosis, based on unusually low cycle threshold and 3 of 5 probes missing. Other mycobacterial tests were negative. Further optimization of the Xpert MTB/RIF algorithm is warranted. [ABSTRACT FROM AUTHOR]

Background: A drug resistance survey is an essential public health management tool for evaluating and improving the performance of National Tuberculosis control programmes. The current manuscript describes the implementation of the first national drug resistance survey in Tanzania. Methods: Description of the implementation process of a national anti-tuberculosis drug resistance survey in Tanzania, in relation to the study protocol and Standard Operating Procedures. Results: Factors contributing positively to the implementation of the survey were a continuous commitment of the key stakeholders, the existence of a well organized National Tuberculosis Programme, and a detailed design of cluster-specific arrangements for rapid sputum transportation. Factors contributing negatively to the implementation were a long delay between training and actual survey activities, limited monitoring of activities, and an unclear design of the data capture forms leading to difficulties in form-filling. Conclusion: Careful preparation of the survey, timing of planned activities, a strong emphasis on data capture tools and data management, and timely supervision are essential for a proper implementation of a national drug resistance survey. [ABSTRACT FROM AUTHOR]

Objective To determine the relative frequencies of reinfection vs. reactivation or treatment failure in patients from a high tuberculosis incidence setting with a low prevalence of HIV infection. Method We performed DNA fingerprinting on serial isolates from one and multiple TB episodes from 97 retreatment patients; 35 patients had been previously cured, whereas 62 had not. Results DNA fingerprinting patterns of recurrence Mycobacterium tuberculosis isolates of 5 of the 35 previously cured patients did not match with those of the corresponding initial isolates, indicating reinfection. We did not document reinfection during treatment. Isolates from each of the remaining 30 previously cured patients had identical DNA fingerprinting results, indicating reactivation. DNA fingerprinting patterns of isolates from the 62 patients with persistently positive sputum smears were identical, suggesting treatment failure. Conclusion These findings suggest that reinfection is not a common cause of relapse and treatment failure in this rural predominantly HIV-free population despite the high incidence of TB. [ABSTRACT FROM AUTHOR]

Extensive drug resistance in TB is not a new phenomenon. It is created when patients with multidrug-resistant TB (MDR-TB) are treated with second-line anti-TB drugs but fail to be cured. The first principle in managing the risk of extensively drug-resistant TB (XDR-TB) is 'do not generate XDR-TB'. Once it is created, every effort must be made to prevent it from spreading. Health workers and care givers in long-term care facilities and prisons may have a considerable risk of exposure to TB, including XDR-TB. The principles in the control of TB transmission in healthcare settings, long-term care facilities and prisons include early identification and isolation of infectious TB patients, effective treatment of TB as soon as possible, environmental control with proper ventilation and personal protection of healthcare workers and others. Patients with the highest risk of developing XDR-TB are those MDR-TB patients who failed treatment using a second-line regimen and TB patients who have a history of contact with XDR-TB patients. The core principles in managing the risk of XDR-TB for health workers and care givers are reducing the risks of exposure to XDR-TB, becoming infected and developing XDR-TB. If TB has developed, the principles include promptly diagnosing XDR-TB and starting proper treatment.