Abstract:
Mutations causing mono and cross-resistance among amikacin, kanamycin and capreomycin of second-line injectable
drugs (SLIDs) namely are not well understood.We investigated 124 isolates of Mycobacterium tuberculosis
for mutations within rrs, eis, tlyA and efflux pump (Rv1258c and Rv0194) genes involved in resistance
towards SLIDs. The distribution of mutations across these genes were significantly different in strains with
mono-resistance or cross-resistance. A new mutation G878A was found in rrs gene, among strains with
capreomycin mono-resistant, or in strains with cross-resistance of capreomycin, kanamycin and amikacin. This
mutation was associated with the Euro-American X3 lineage (P b 0.0001). Mutations in the two efflux genes
Rv1258c and Rv0194 were confined to strains with only capreomycin/amikacin/kanamycin cross-resistance.
Wefurther investigated the minimuminhibitory concentration of capreomycin on isolateswith newG878Amutation
ranging from 8 μg/mL to 64 μg/mL. Inclusion of G878A on new molecular assays could increase the sensitivity
of capreomycin resistance detection.
