Simple, direct drug susceptibility testing technique for diagnosis of drug-resistant tuberculosis in resource-poor settings

Abstract

The Korean Institute of Tuberculosis, Seoul, Republic of Korea. To develop a simple, direct drug susceptibility testing (DST) technique using Kudoh-modified Ogawa (KMO) medium. The critical concentrations of isoniazid (INH), rifampicin (RMP), kanamycin (KM) and ofloxacin (OFX) for KMO medium were calibrated by comparing the minimal inhibitory concentrations (MICs) against clinical isolates of Mycobacterium tuberculosis on KMO with those on Löwenstein-Jensen (LJ). The performance of the direct KMO DST technique was evaluated on 186 smear-positive sputum specimens and compared with indirect LJ DST. Agreement of MICs on direct vs. indirect DST was high for INH, RMP and OFX. KM MICs on KMO were ∼10 g/ml higher than those on LJ. The critical concentrations of INH, RMP, OFX and KM for KMO were therefore set at 0.2, 40.0, 2.0, and 40.0 g/ml. The evaluation of direct DST of smear-positive sputum specimens showed 100% agreement with indirect LJ DST for INH and RMP. However, the respective susceptible and resistant predictive values were 98.8% and 100% for OFX, and 100% and 80% for KM. Direct DST using KMO is useful, with clear advantages of a shorter turnaround time, procedural simplicity and low cost compared to indirect DST. It may be most indicated in resource-poor settings for programmatic management of drug-resistant tuberculosis.