OpiniãoThe regimens recommended for treatment of Hr-TB is not divided into an intensive and a continuation phase – this simplifies the delivery and monitoring of treatment. Treatment is given daily, and intermittent treatment should be avoided. Relevant measures to support adherence, social support and the use of digital technologies should be considered to ensure favourable treatment outcomes (19).
The cost of medicines to compose a full 6(H)RZE regimen with levofloxacin is slightly higher than the cost of a 2HRZE/4HR regimen used for DS-TB (122). Nonetheless, the 6(H)RZE regimen is an affordable and feasible intervention, even in low-income settings. Use of FDCs simplifies treatment and lowers costs, and the use of dispersible formulations of HRZ, ethambutol and levofloxacin is preferred in children. As with the treatment of other forms of TB, the expenses associated with the proper delivery of care (e.g. DST, adherence support and clinical monitoring) far exceed the cost of medicines.
A new diagnostic platform has been approved for the detection of Hr-TB – the new Xpert MTB/ XDR cartridge, which can detect isoniazid resistance in less than 90 minutes, matching the rapidity and convenience of Xpert MTB/RIF for rifampicin resistance. First-line LPA can also detect isoniazid resistance, and the infrastructure required is typically available in a provincial or central level facility. Typical processing time for an LPA specimen is about 2–3 days, owing to batching. DST based on liquid culture (or MGIT) could also detect Hr-TB at the level of a reference laboratory, but this means a processing delay of at least 10 days. Testing on solid media is also an option, but it takes several months to obtain results; hence, this approach is of limited use for baseline testing and monitoring of treatment response.
Current epidemiological data indicate that more than three quarters of the global burden of Hr-TB occurs among previously untreated (“new”) TB cases. Previous TB treatment is thus not a strong indicator of risk of Hr-TB – the correlation with previous TB treatment is weaker than it is with MDR-TB. Reserving isoniazid DST to such patients is therefore unlikely to yield many Hr-TB cases. There are various concerns about empirical Hr-TB treatment of previously treated TB cases, without prior DST. First, such treatment will lead to unnecessary overtreatment with fluoroquinolones and prolongation of pyrazinamide use in many patients. Most recurrent cases will not have Hr-TB and can be cured with a 2HRZE/4HR regimen. Second, unless rifampicin resistance is excluded at the baseline, patients with MDR/RR-TB would be exposed to an inadequate regimen, with the risk of acquiring additional resistance, including fluoroquinolones. Third, this policy would deflect the focus of the programme from testing new TB patients, who usually harbour the main burden of Hr-TB. Finally, this approach would risk creating once again a “re-treatment regimen”, similar to the situation that prevailed in many settings until recently with the indiscriminate use of the streptomycin-containing 8-month “Category 2” regimen in all previously treated TB patients.
In a situation where access to DST is good, a logical diagnostic algorithm would start with Xpert MTB/ RIF as the initial test for all patients evaluated for TB. Cases in whom TB is confirmed and rifampicin resistance is not detected would be further tested with Xpert MTB/XDR or LPA. Liquid culture may replace LPA, but the additional delay in obtaining results is a disadvantage.