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2022•Emerging infectious diseasesOpen access

Revised Definitions of Tuberculosis Resistance and Treatment Outcomes, France, 2006–2019

Yousra Kherabi, Mathilde Fréchet-Jachym, Christophe Rioux, Yazdan Yazdanpanah, F. Méchaï, Valérie Pourcher, J. Robert, Lorenzo Guglielmetti, for the MDR-TB Management Group

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Abstract

R ifampin-resistant tuberculosis (RR TB) and multidrug-resistant tuberculosis (MDR TB), defined as TB resistant to both rifampin and isoniazid, are a global public health threat.In 2019, there were 465,000 incident cases of RR TB, among which 78% were MDR TB (1).In France, the yearly incidence of MDR TB cases was stable at ≈50 cases during 2006-2010, dramatically increased in the next 4 years (2) to >100 cases in 2014 (3), and slightly decreased afterwards to 75 cases in 2019 (4).RR/MDR TB cases are difficult to treat, and patients need prolonged treatment courses, which are burdened by frequent drug-related adverse events.Global treatment success for RR/MDR TB was 59% in 2018 (1).At that time, fluoroquinolones were considered the cornerstone of RR/MDR TB treatment.In 2018, the World Health Organization (WHO) published new treatment guidelines, relying on a largescale meta-analysis (5), which revolutionized the traditional hierarchy of anti-TB drugs (6).In those guidelines, newer and repurposed drugs, such as bedaquiline and linezolid, were recommended for all MDR TB patients in addition to fluoroquinolones; second-line injectables would be reserved for cases where no other options are available.Globally, 16.2% of RR/MDR TB isolates have acquired resistance to fluoroquinolones (1), indicating the need for an update in resistance definitions.Thus, in January 2021, WHO defined pre-extensively drug-resistant TB (pre-XDR TB) as MDR TB with additional resistance to fluoroquinolones, and XDR TB as pre-XDR TB with additional resistance to >1 additional group A drug (bedaquiline and linezolid as of July 2022) (7).Resistance to fluoroquinolones is classically considered a risk factor for treatment failure (5,8,9).However, recent studies from countries with both low (10) and high (11) TB prevalence did not confirm this finding in high-income settings in which diagnostics and group A drugs are widely available.Furthermore, Revised Definitions of Tuberculosis

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R ifampin-resistant tuberculosis (RR TB) and multidrug-resistant tuberculosis (MDR TB), defined as TB resistant to both rifampin and isoniazid, are a global public health threat.In 2019, there were 465,000 incident cases of RR TB, among which 78% were MDR TB (1).In France, the yearly incidence of MDR TB cases was stable at ≈50 cases during 2006-2010, dramatically increased in the next 4 years (2) to >100 cases in 2014 (3), and slightly decreased afterwards to 75 cases in 2019 (4).RR/MDR TB cases are difficult to treat, and patients need prolonged treatment courses, which are burdened by frequent drug-related adverse events.Global treatment success for RR/MDR TB was 59% in 2018 (1).At that time, fluoroquinolones were considered the cornerstone of RR/MDR TB treatment.In 2018, the World Health Organization (WHO) published new treatment guidelines, relying on a largescale meta-analysis (5), which revolutionized the traditional hierarchy of anti-TB drugs (6).In those guidelines, newer and repurposed drugs, such as bedaquiline and linezolid, were recommended for all MDR TB patients in addition to fluoroquinolones; second-line injectables would be reserved for cases where no other options are available.Globally, 16.2% of RR/MDR TB isolates have acquired resistance to fluoroquinolones (1), indicating the need for an update in resistance definitions.Thus, in January 2021, WHO defined pre-extensively drug-resistant TB (pre-XDR TB) as MDR TB with additional resistance to fluoroquinolones, and XDR TB as pre-XDR TB with additional resistance to >1 additional group A drug (bedaquiline and linezolid as of July 2022) (7).Resistance to fluoroquinolones is classically considered a risk factor for treatment failure (5,8,9).However, recent studies from countries with both low (10) and high (11) TB prevalence did not confirm this finding in high-income settings in which diagnostics and group A drugs are widely available.Furthermore, Revised Definitions of Tuberculosis

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Available abstract

R ifampin-resistant tuberculosis (RR TB) and multidrug-resistant tuberculosis (MDR TB), defined as TB resistant to both rifampin and isoniazid, are a global public health threat.In 2019, there were 465,000 incident cases of RR TB, among which 78% were MDR TB (1).In France, the yearly incidence of MDR TB cases was stable at ≈50 cases during 2006-2010, dramatically increased in the next 4 years (2) to >100 cases in 2014 (3), and slightly decreased afterwards to 75 cases in 2019 (4).RR/MDR TB cases are difficult to treat, and patients need prolonged treatment courses, which are burdened by frequent drug-related adverse events.Global treatment success for RR/MDR TB was 59% in 2018 (1).At that time, fluoroquinolones were considered the cornerstone of RR/MDR TB treatment.In 2018, the World Health Organization (WHO) published new treatment guidelines, relying on a largescale meta-analysis (5), which revolutionized the traditional hierarchy of anti-TB drugs (6).In those guidelines, newer and repurposed drugs, such as bedaquiline and linezolid, were recommended for all MDR TB patients in addition to fluoroquinolones; second-line injectables would be reserved for cases where no other options are available.Globally, 16.2% of RR/MDR TB isolates have acquired resistance to fluoroquinolones (1), indicating the need for an update in resistance definitions.Thus, in January 2021, WHO defined pre-extensively drug-resistant TB (pre-XDR TB) as MDR TB with additional resistance to fluoroquinolones, and XDR TB as pre-XDR TB with additional resistance to >1 additional group A drug (bedaquiline and linezolid as of July 2022) (7).Resistance to fluoroquinolones is classically considered a risk factor for treatment failure (5,8,9).However, recent studies from countries with both low (10) and high (11) TB prevalence did not confirm this finding in high-income settings in which diagnostics and group A drugs are widely available.Furthermore, Revised Definitions of Tuberculosis

Key concepts: Bedaquiline, Medicine, Extensively drug-resistant tuberculosis, Tuberculosis, Linezolid, Internal medicine, Drug resistance, Multiple drug resistance

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