TABLE 1

Treatment approaches to drug-susceptible (DS) and drug-resistant tuberculosis (TB): number and type of drugs, and treatment duration

ReferenceDS-/MDR-/XDR-TBMinimum number of drugs in the regimenDuration of the regimenDrugs in the regimenReason for changing (increasing or decreasing) the number of drugs in the regimenReason for changing (increasing or decreasing) the regimen duration
Fox et al. [3] (1999)
ATS [6] (1986)
DS-TB29 monthsH+R
Fox et al. [3] (1999)
ATS [6] (1986)
WHO [7] (1991)
DS-TB36 monthsH+R+Z or 2HRZ/4HRIncrease: adding Z to reduce duration of the treatment courseDecrease: two drugs with major sterilising activity
WHO [9] (2003)DS-TB46 months2HRZE/4HRIncrease: prevent failure in the era of increasing H resistanceDecrease: two drugs with major sterilising activity
Caminero et al. [4] (2018)DS-TB3/46 months2HRZE/4HR or 2HRZ/4HR if susceptibility is known before starting treatmentIncrease: prevent failure in the era of increasing H resistanceDecrease: two drugs with major sterilising activity
WHO [12] (1996)MDR-TB421 monthsAG, Eto, Z, OfxIncrease: quite a lot of drugs with very reduced efficacyIncrease: lack of drugs with strong sterilising activity
WHO [13] (2006)
WHO [14] (2008)
WHO [15] (2011)
MDR-/XDR-TBAt least 4–518–24 monthsFluoroquinolones (Ofx/Lfx, moderately sterilising)+othersIncrease: several drugs with limited efficacyIncrease: lack of drugs with strong sterilising activity
WHO [16] (2016)
Ahmad Khan et al. [18] (2017)
Nunn et al. [20] (2019)
MDR-TB79–11 monthsKm, Mfx, Pto, Cfz, Z, high-dose H, EIncrease: to assure bactericidal activity in the intensive phaseDecrease: two drugs with major sterilising activity plus the possible action of Z if susceptible
Ahmad et al. [21] (2018)MDR-TB519–22 monthsAll anti-TB drugs, excluding H and RIncrease: several drug with limited efficacyIncrease: lack of drugs with strong sterilising activity
WHO [1] (2019)MDR-TB4Two options: 18–20 months (including a 15 to 17-month continuation phase) or 9–11 monthsAt least four active drugs: always Lfx/Mfx, Bdq and Lzd+Cfz or cycloserine/terizidone (other group C drugs to be employed when first choices cannot be used)
Km, high-dose H, Pto, high-dose Mfx, Cfz, E, Z
Decrease: very active core drugs
Increase: to assure bactericidal activity in the intensive phase
Increase: not justified because four sterilising drugs are included
Decrease: two drugs with major sterilising activity, plus the possible action of Z if susceptible
Current paper 2019MDR-TB36Lfx/Mfx (Cfz), Bdq and LzdDecrease: very active drugs; unlikely resistance due to previous exposureDecrease: three drugs with major sterilising activity

ATS: American Thoracic Society; WHO: World Health Organization; MDR: multidrug resistant; XDR: extensively drug resistant; H: isoniazid; R: rifampicin; Z: pyrazinamide; E: ethambutol; AG: aminoglycoside; Eto: ethionamide; Ofx: ofloxacin; Lfx: levofloxacin; Km: kanamycin; Mfx: moxifloxacin; Pto: prothionamide; Cfz: clofazimine; Lzd: linezolid; Bdq: bedaquiline.