Sequence of Using Replacement Drugs to Modify the Longer Oral M/XDR-TB Regimen

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Table 1 shows the sequence of using replacement drugs to modify the longer oral multi (M)/extensively drug-resistant TB (XDR-TB) regimen. The physician at the nodal and district DR-TB centres (N/DDR-TBC) should use this table to replace the drugs to modify the regimen.

Sr. No	Drugs to be replaced	Number of drugs to include from	Final regimen after replacement
Group A (3 drugs)	Group B (2 drugs)	Group C (7 drugs)
1	None^$	3	2	-	6-8 Levofloxacin (Lfx), Bedaquiline (Bdq), Linezolid (Lzd), Clofazimine (Cfz), Cycloserine (Cs) / 12 Lfx, Lzd, Cfz, Cs
2	1 group A drug^@	2	2	1	No FQ, then 6-8 Bdq, Lzd, Cfz, Cs, Delamanid (Dlm) / 12 Lzd, Cfz, Cs No Bdq, then 6-8 Lfx, Lzd, Cfz, Cs, Dlm / 12 Lfx, Lzd, Cfz No Lzd, then 6-8 Lfx, Bdq, Cfz, Cs, Dlm / 12 Lfx Cfz, Cs
3	1 group B drug	3	1	1	No Cfz, then 6-8 Lfx* Bdq,Lzd, Cs, Dlm / 12 Lfx* Lzd, Cs No Cs, then 6-8 Lfx* Bdq, Lzd, Cfz, Dlm / 12 Lfx* Lzd, Cfz
4	1 group A drug^@and 1 group B drug	2	1	2	No Fluoroquinolone (FQ) and Cfz then 6-8 Bdq, Lzd, Cs, Dlm, Amikacin (Am)^# / 12 Lzd, Cs, Pyrazinamid (Z)^#, Ethionamide (Eto)^# No FQ & Cs then 6-8 Bdq, Lzd, Cfz, Dlm, Am^# / 12 Lzd, Cfz, Z^#, Eto^# No Bdq & Cfz then 6-8 Lfx* Lzd, Cs, Dlm, Am^# / 12 Lfx* Lzd, Cs No Bdq & Cs then 6-8 Lfx* Lzd, Cfz, Dlm, Am^# // 12 Lfx* Lzd, Cfz No Lzd & Cfz then 6-8 Lfx* Bdq, Cs, Dlm, Am^# // 12 Lfx, Cs, Z^#, Eto^# No Lzd & Cs then 6-8 Lfx Bdq, Cfz, Dlm, Am^# / / 12 Lfx*, Cfz, Z^#, Eto
5	2 group A drugs^@	1	2	2	No FQ & Bdq then 6-8 Lzd, Cfz, Cs, Dlm, Am^# / 12 Lzd, Cfz, Cs, Z^# No FQ & Lzd then 6-8 Bdq, Cfz, Cs, Dlm, Am^# / 12 Lfx, Cs, Z^#, Eto^# No Bdq & Lzd then 6-8 Lfx, Cfz, Cs, Dlm, Am^# /12 Lfx*, Cfz, Cs, Z^#
6	2 group B drugs	3	0	2	No Cfz & Cs then 6-8 Lfx* Bdq, Lzd, Dlm, Am^# / 12 Lfx*, Lzd, Z^#, Eto^#
$ No replacement required if any one drug is dropped in the last 12 months of treatment. @ FQs would be counted together as one drug of group A if neither Lfx nor Mfx(h) can be used. * if Lfx can’t be used, use Mfx(h) if second-line-line probe assay (SL-LPA) pattern suggests and continue if Mfx(1.0) sensitive on lab culture (LC) & Drug Susceptibility Test (DST). # if sensitive on LPA or LC&DST, inhA mutation would indicate Eto resistance. If resistance detected, then the drugs to be used in the order of Dlm, Am#, Z#, Eto#, PAS, E and as a final resort Imipenem / Cilastatin (Imp/Cls) or Meropenem (Mpm) in combination with Amoxiclav. Dlm & Am may not be introduced after initial 8 months of treatment and during this later phase the replacement sequence would be Z#, Eto#, p-aminosalicylic acid (PAS), Ethambutol (E).