Drug susceptibilities of Mycobacterium tuberculosis against injectable second-line drugs from Pakistan: Analysis of multidrug-resistant and non-multidrug-resistant tuberculosis strains

Pakistan is one of the high-tuberculosis (TB) burden countries (HBCs) with a considerable proportion of multidrug-resistant TB (MDR-TB) strains. Recently, high resistance to fluoroquinolone has been reported in both MDR and non-MDR-TB strains from Pakistan. This study aims to evaluate trends of resistance in Mycobacterium tuberculosis (MTB) against injectable second-line drugs (2010–July 2014) from Aga Khan University Laboratory, a technical partner of the Pakistan National TB Program and part of the WHO Supra-national Laboratory Network for TB based in Karachi, Pakistan. MTB strains were isolated using standard methods. Susceptibility testing was performed using the agar proportion method with drug concentrations as recommended by the Clinical Laboratory Institute Standards (CLSI). MTB H37Rv was used as a control with each batch of susceptibility testing. MDR-TB was defined as resistance to both isoniazid (0.2 μg/ml) and rifampicin (1.0 μg/ml). During the study period, 14,711 MTB strains were isolated. Of these, 43.5% were MDR and 56.5% were non-MDR. Resistance pattern to amikacin, kanamycin and capreomycin over the years is shown in the table below. Empty CellNumber of isolates per year (%)Empty Cell20102011201220132014 Jan–JulyTotalMTB3325312930003390186714711MDR-TB12661292134716808186403K resistance75 (5.9)65 (5)64 (2.1)79 (2.3)60 (7.3)343 (5.4)AK resistance59 (4.7)53 (4.1)54 (1.8)70 (2.1)48 (5.7)284 (4.4)CAP resistance66 (5.2)44 (3.4)58 (1.9)81 (2.4)70 (8.5)319 (5)Non-MDR TB205918371653171010498308K resistance1976225 (0.3)AK resistance0754117 (0.2)CAP resistance17151118NT61 (0.8) MTB: M. tuberculosis; MDR-TB: multidrug-resistant tuberculosis; AK: amikacin; K: kanamycin; CAP: capreomycin; NT: not tested. Rising resistance to injectable anti-tuberculous agents in MDR-TB isolates possibly reflects their increasing use in patient management. Presence of capreomycin resistance even amongst non-MDR strains is alarming for a country where fluoroquinolone resistance is also high and patient follow-up and drug compliance is a challenge.