8.5 Cross resistance


There is well-known cross-resistance between some of the antibacterial drugs used in treatment of TB. Resistance mutations to one anti-TB drug may confer resistance to some or all of the members of the drug family, and less commonly, to members of other families. For example, among aminoglycosides, resistance to kanamycin is associated with near complete cross-resistance to amikacin. In contrast, cross-resistance between kanamycin and streptomycin is generally low. Moreover, TB isolates that are resistant to kanamycin at high doses may be resistant to capreomycin (a polypeptide).

Table 8.3 - Summary on cross-resistance between anti-TB agents3

Drugs class

Cross-resistance

Rifamycins

R and Rfb have high levels of cross-resistance.

Isoniazid

Eto/Pto can have cross-resistance to H if the inhA mutation is present.

Aminoglycosides
and polypeptides

Amk and Km have very high cross-resistance.
Km (or Amk) and Cm have low to moderate cross-resistance.
S has low cross resistance with Amk and Km.

Fluoroquinolones

FQs are believed to have variable cross-resistance between each other. Some in vitro data show that strains can be susceptible to some later-generation FQs when resistant to earlier-generation FQs (Ofx). In these cases, it is unknown if the later-generation FQs remain clinically effective.

Thioamides

Eto and Pto have 100% cross-resistance.

Thioacetazone

Thz cross-resistance to H, Eto/Pto, and PAS has been reported, but is generally considered low.