An estimated 35% of MDR-TB is extensively drug-resistant or pre-XDR-TB

Among patients with multidrug-resistant tuberculosis (MDR-TB), it is likely that 26% have pre-extensively drug-resistant TB (pre-XDR-TB) and 9% have extensively drug-resistant TB (XDR-TB), suggesting a need to strengthening TB programs and drug resistance surveillance in countries with a high MDR-TB burden. These were among findings of a review and meta-analysis published in the International Journal of Infectious Diseases.

According to recently updated World Health Organization (WHO) guidelines, late-generation fluoroquinolones (FQs) — ie, levofloxacin and moxifloxacin — and WHO Group A drugs — ie, linezolid and bedaquiline — are recommended to treat MDR-TB. However, those with XDR-TB and pre-XDR-TB are resistant to some of these drugs: XDR-TB is defined as MDR-TB resistant to rifampin and isoniazid plus any FQ and at least 1 second-line injectable drug (ie, capreomycin, amikacin, or kanamycin); pre-XDR-TB is TB that is resistant to rifampin and isoniazid and either a second-line injectable or a FQ.

In the current review and meta-analysis, investigators sought to ascertain the pooled proportion of patients with XDR-TB and pre-XDR-TB in patients with MDR-TB. The researchers conducted a systematic review that included 64 observational studies on XDR-TB or pre-XDR-TB in patients with MDR-TB. The studies were identified from articles published in English retrieved in the Google Scholar, ScienceDirect, and PubMed databases and grey literature through July 2022. The pooled population of patients (n=12,711) included individuals from 22 countries across World Health Organization (WHO) regions (India, China, South-East Asia, Africa, Western Pacific, Europe, Americas, Eastern Mediterranean), treated from 2003 to 2020 (publication 2008-2021).

The meta-analysis found the overall estimated pooled proportion of XDR-TB in patients with MDR-TB was 9% (95% CI, 7%-11%; I²=95.98%). By countries, lowest proportion of XDR-TB was in Ethiopia (1%) and Cameroon (1%) and highest proportion in India (77%). By WHO regions, pooled proportion of XDR-TB was Eastern Mediterranean regions, 3%; African regions, 3%; Americas, 6%; South-East Asian regions, 10%; Western Pacific, 12%. The pooled proportion of XDR-TB among new MDR-TB patients was 3% and in previously treated cases was 6%.

The overall pooled proportion of pre-XDR-TB among MDR-TB cases was 26% (95% CI, 22%-31%; I²=97.31%). By countries, lowest proportion of pre-XDR-TB was in Ethiopia (3%) and highest proportion in China (66%). By WHO regions, pooled proportion of pre-XDR-TB was African regions, 12%; Americas, 14%; European regions, 22%; Eastern Mediterranean, 30%; South-East Asia, 32%; Western Pacific, 35%. The pooled proportion of pre-XDR-TB in new MDR-TB patients was 9% and in previously treated cases was 13%.

In evaluating the pooled proportion of patients with MDR-TB resistant to specific drug types, investigators found 11% were resistant second-line injectable-drugs (95% CI, 9%-13%; I²=91.31%; range 3% to 40%) and 27% were resistant to FQs (95% CI, 22%-33%; I²=97.53%; range, 4% to 77%). With respect to new drugs, the pooled proportion of patients showing resistance was 5% for bedaquiline (95% CI, 1%-8%), 4% for clofazimine (95% CI, 0%-10%), 5% for delamanid (95% CI, 2%-8%), and 4% for linezolid (95% CI, 2%-10%).

Review and meta-analysis limitations include use of studies published in English only and the use of a majority of studies reporting on the South-East Asian and Western Pacific regions of WHO.

“The current review study showed the presence of higher proportion of pre-XDR-TB and XDR-TB, than WHO estimates,” with the highest proportions of XDR-TB and pre-XDR-TB in the South-East Asian and Western Pacific regions, and a “[c]onsiderable proportion of resistance to new drugs was also observed,” said the study authors. “Countries should implement robust either passive or active surveillance of DR-TB to understand the current burden of resistance to second-line and newly introduced drugs,” the researchers concluded.

References:

Diriba G, Alemu A, Yenew B, et al. Epidemiology of extensively drug-resistant tuberculosis among multidrug resistant tuberculosis patients: a systematic review and meta-analysis. Int J Infect Dis. Published online April 16, 2023. doi:10.1016/j.ijid.2023.04.392

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