تعليقInnovative rapid molecular tests to diagnose both pulmonary and extrapulmonary TB in all populations are strongly recommended over sputum smear microscopy and culture methods, because rapid tests can provide same day results (4). Some of the innovative tests also provide drug susceptibility results for rifampicin (R), isoniazid (H) and fluoroquinolones (FQ), allowing rapid confirmation of diagnosis, and timely and effective treatment allocation. Based on the data from global TB drugresistance surveillance, rifampicin-resistant TB (RR-TB) is rare when people are first diagnosed with TB, but it is reaching alarming proportions in some countries. Globally, the burden of multidrugresistant TB (MDR-TB) or RR-TB (MDR/RR-TB) is stable (5). For more than 10 years, the best estimate of the proportion of people diagnosed with TB for the first time who had MDR/RR-TB has remained at about 3–4%, and the best estimate among those previously treated for TB has remained at about 18–21% (4). The highest proportions (>50% in previously treated cases) are found in countries in Eastern Europe and Central Asia (5).
Resistance to fluoroquinolones in new TB patients without resistance to rifampicin is rare in most of the countries with available data (1.0–1.2%), although some countries show higher proportions (3.4–11.2%) (6-10). Isoniazid-resistant and rifampicin-susceptible TB is the most prevalent form of drug-resistance worldwide (besides streptomycin resistance), with estimates rising to 7% among those newly diagnosed and 8–11% among those previously treated (5, 11). Isoniazid-resistant TB is associated with a higher risk of acquiring further drug-resistance and evolving towards MDR-TB, which is defined by resistance to both isoniazid and rifampicin (12-14).
These data reiterate the importance of full transition from sputum smear microscopy to the widespread use of rapid diagnostic tests, especially in those with recurrent TB. Regular country reports to WHO and several surveys clearly demonstrate that the policy of using rapid molecular TB diagnostic tests has been widely adopted in countries with a significant burden of TB. However, the use of rapid TB testing has yet to surpass the use of smear microscopy (15-17).
With the range of available anti-TB medicines and treatment regimens, drug susceptibility testing (DST) for key drugs is crucial for the choice of an appropriate treatment strategy. For medicines with high potency against Mycobacterium tuberculosis – rifampicin, moxifloxacin (M) and isoniazid – rapid tests for drug susceptibility are now available and evidence-based recommendations for their use are given in relevant WHO documents (4, 18).
Resistance to rifampicin renders all of the available regimens for DS-TB ineffective; if rifampicin is used, it may cause both treatment failure and development of additional resistance to other drugs in the regimen. This finding means that the treatment strategy for DR-TB needs to be changed. Among new TB patients without resistance to rifampicin, resistance to fluoroquinolones is very low; this allows a general strategy of starting these patients on DS-TB regimens (including the 4-month regimen with moxifloxacin described in Section 4), without obligatory DST for fluoroquinolones. This general strategy should be regularly revisited and updated in response to the drug-surveillance data of the country or specific setting, to prevent potential misuse of moxifloxacin (an important medicine for treatment of DR-TB) and increased antimicrobial resistance. Resistance to isoniazid leads to decreased efficacy of the 6-month regimen (described in Section 3) and requires use of the specific regimens that include fluoroquinolones. The effect of isoniazid monoresistance on the efficacy of the 4-month regimen with rifapentine (P) and moxifloxacin has not been studied; however, the efficacy of the 4-month regimen for children (2HRZ(E)/2HR, described in Section 5) is expected to be affected.
In summary, in settings where rapid, molecular-based DST is available, the results should guide the choice of regimen. Although universal DST is the goal, priority should be given to testing patients undergoing re-treatment at, or before, the start of that re-treatment – at least for isoniazid and rifampicin resistance. Whenever rifampicin resistance is confirmed, testing for resistance to fluoroquinolones will be important in the design of an effective treatment regimen.
In settings where rapid DST results are not routinely available to guide the management of individual patients, the approach to treatment selection can be guided by clinical judgement and consideration of the epidemiology of TB and its drug-resistant forms in the specific setting. In TB patients whose treatment has failed or in other patient groups with a high likelihood of MDR/RR-TB, the clinician’s decision may lean towards an empirical MDR-TB regimen (18).