Abstract:
Background: World Health Organization (WHO) recommended both genotypic and
phenotypic methods for M. tuberculosis (MTB) drug susceptibility testing (DST).
Discordance between genotypic and phenotypic methods for the detection of rifampicin (RIF)
and isoniazid (INH) resistant MTB is poorly documented in Southwestern Oromia, Jimma,
Ethiopia. This study aimed to determine discordance between genotypic and phenotypic
method for the detection of RIF and INH resistant MTB and its effect on patient treatment
outcomes in Southwestern Oromia, Jimma, Ethiopia.
Methods: A cross-sectional study was conducted on 57 sputum Xpert MTB/RIF assay
(Xpert) positive MTB isolates (45 RIF resistant from new and retreatment TB patients, and
12 RIF susceptible from retreatment TB patients) stored at Jimma University
Mycobacteriology Research Center (JUMRC) laboratory. All isolates were sub-cultured on
Lowenstein–Jensen (LJ) medium. DNA was extracted from LJ culture positive isolates for
the detection of RIF and INH resistance by line probe assay (LPA). In parallel, phenotypic
DST for RIF, INH, streptomycin (STR), and ethambutol (EMB) was performed by MGIT
960. Socio-demographic and clinical data were extracted from JUMRC laboratory
registration book. Treatment outcomes data were extracted from patient medical records.
Online GraphPad prism software was used to analyze the discordance between the 2 DST
methods.
Results: Overal1, 6 (10.5%) isolates had discordant results between genotypic and
phenotypic DST method for RIF and or INH (3 for RIF, 1 for INH, and 2 for both RIF and
INH). There was higher agreement between LPA and phenotypic DST for both RIF and INH
(kappa=0.86), but lower between Xpert and phenotypic DST (kappa=0.76). Four Xpert RIF
resistant isolates were RIF susceptible by phenotypic DST. Two RIF resistant isolates on
LPA were RIF susceptible by phenotypic DST. For INH, 3 INH susceptible isolates on LPA
were INH resistant by phenotypic DST. A total of 11 (19.3%) patients had unfavorable
outcome: 3 (5.3%) were loss to follow up, 5 (8.7%) died, and 3 (5.3%) failed treatment. Out
of these, 3 (27.3%) had discordant results for RIF and or INH, and all of them were died.
Conclusion: Presence of discordance between genotypic and phenotypic DST for RIF and
INH has clinical impact on patient treatment outcome. Thus, parallel use of rapid molecular
assay with phenotypic DST would help to improve patient outcome.
