Department of Pathology and Microbiology, The Aga Khan University, Stadium Road, PO Box 3500, Karachi 74800, Pakistan.
Antimicrob Agents Chemother. 2011 Dec;55(12):5654-9. doi: 10.1128/AAC.05101-11. Epub 2011 Sep 12.
The increasing incidence of extensively drug-resistant (XDR) Mycobacterium tuberculosis in high-tuberculosis-burden countries further highlights the need for improved rapid diagnostic assays. An increasing incidence of XDR M. tuberculosis strains in Pakistan has been reported, but drug resistance-associated mutations in these strains have not been evaluated previously. We sequenced the "hot-spot" regions of rpoB, katG, inhA, ahpC, gyrA, gyrB, and rrs genes in 50 XDR M. tuberculosis strains. It was observed that 2% of rifampin, 6% of isoniazid, 24% of fluoroquinolone, and 32% of aminoglycoside/capreomycin resistance in XDR M. tuberculosis strains would be undetected if only these common hot-spot regions were tested. The frequencies of resistance-conferring mutations were found to be comparable among all XDR M. tuberculosis strain families present, including the Central Asian Strain, Beijing, and East African Indian genogroups and the Unique isolates. Additional genetic loci need to be tested for detection of mutations conferring fluoroquinolone, aminoglycoside, and capreomycin resistance in order to improve molecular diagnosis of regional XDR M. tuberculosis strains.
在结核病负担较高的国家，广泛耐药（XDR）结核分枝杆菌的发病率不断上升，这进一步凸显了改进快速诊断检测方法的必要性。据报道，巴基斯坦的 XDR 结核分枝杆菌菌株的发病率不断上升，但这些菌株中的耐药相关突变此前尚未得到评估。我们对 50 株 XDR 结核分枝杆菌菌株的 rpoB、katG、inhA、ahpC、gyrA、gyrB 和 rrs 基因的“热点”区域进行了测序。结果表明，如果仅检测这些常见的热点区域，XDR 结核分枝杆菌菌株中 2%的利福平、6%的异烟肼、24%的氟喹诺酮和 32%的氨基糖苷类/卷曲霉素耐药性将无法被检测到。在所有存在的 XDR 结核分枝杆菌菌株家族中，包括中亚株、北京株和东非印度基因型以及独特分离株，发现耐药相关突变的频率相当。为了提高对区域性 XDR 结核分枝杆菌菌株的分子诊断，需要进一步检测其他遗传基因座，以检测与氟喹诺酮、氨基糖苷类和卷曲霉素耐药相关的突变。
