BOX 5.4EXAMPLE OF AN XDR-TB REGIMEN DESIGN
EXAMPLE 1. A patient failed the standardized regimen of Z-Km-Lfx-Eto-Cs and remained sputum smear-positive after eight months of treatment. The DST from a specimen taken four months ago revealed resistance to HRZE-S-Km-Cm-Lfx and susceptibility to Eto. What treatment regimen is recommended?
Answer: The patient may now have developed resistance to Eto as the patient was on only one or two effective drugs since the specimen collection and has remained smear-positive. Cs, while not tested for DST in this example, is also likely not effective with the strain being resistant. Furthermore, the DST is not reproducible or reliable enough for Eto, E or Z and we should depend on history more than DST – all of which are likely compromised. The later-generation fluoroquinolone Mfx may have some effect, even though Lfx is testing resistant. Options are limited and there is no expert consensus on a specific regimen that would be best for this patient. See Annex 4 for more information on the use of Bdq. Following the recommendations below would be considered acceptable (these are based on and Box 5.3).
Z-Mpm (plus Clv)-Mfx-PAS-Lzd-Cfz
Z-Mpm (plus CLV)-Bdq-PAS-Lzd-Cfz
Z-Mfx-PAS-Amx (plus CLV)-Cfz-Lzd.
Notes
Other possibilities exist apart from the above three regimens.
The injectable drugs in the regimen are generally used for eight months but in cases where there is confidence in very few drugs and high confidence in the injectable agent, it can be used for a longer period.
For dosing of drugs see
Part 3 – Individual Drug Sheets.
High-dose isoniazid can be added to any regimen if low-level resistance or absence of the katG gene is documented.
If Bdq is added to the regimen, currently its maximum recommended duration of use is first six months of any treatment regimen (see
Annex 4).