ElMaraachli W, Slater M, Berrada Z L, Lin S-Y G, Catanzaro A, Desmond E, Rodrigues C, Victor T C, Crudu V, Gler M T, Rodwell T C
Department of Medicine, University of California San Diego, San Diego, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, USA.
Int J Tuberc Lung Dis. 2015 Oct;19(10):1222-6. doi: 10.5588/ijtld.14.0936.
Rifampin (RMP) resistant Mycobacterium tuberculosis is usually assumed to be resistant to all rifamycins. Increasing evidence indicates, however, that some rpoB mutations, detectable by rapid molecular diagnostics, confer resistance to RMP but not to rifabutin (RBT), suggesting that RBT may be effective for the treatment of M. tuberculosis with these mutations.
To determine if specific rpoB mutations reliably predict differential phenotypic resistance to RMP and RBT.
We selected 60 clinical M. tuberculosis isolates from a repository of multinational multidrug-resistant tuberculosis isolates and stratified them into two groups: 1) those with rpoB mutations suspected to confer differential resistance to RMP and RBT, and 2) those expected to be cross-resistant to RMP and RBT. These assumptions were tested by comparing the phenotypic susceptibilities of RMP/RBT with those predicted by mutations in the rpoB gene.
Of 20 suspected RMP-resistant/RBT-susceptible isolates, 15 were RMP-resistant but RBT-susceptible, 3 were RMP- and RBT-susceptible, and 2 were cross-resistant to both RMP and RBT. In comparison, 40 of 40 suspected cross-resistant isolates were both RMP- and RBT-resistant.
Our data support the association between specific rpoB mutations and differential resistance of M. tuberculosis to RMP and RBT. Clinical studies are required to investigate the efficacy of RBT in the treatment of M. tuberculosis harboring these mutations.
通常认为对利福平（RMP）耐药的结核分枝杆菌对所有利福霉素均耐药。然而，越来越多的证据表明，一些可通过快速分子诊断检测到的rpoB基因突变会导致对RMP耐药，但对利福布汀（RBT）不耐药，这表明RBT可能对治疗具有这些突变的结核分枝杆菌有效。
确定特定的rpoB基因突变是否能可靠地预测结核分枝杆菌对RMP和RBT的不同表型耐药性。
我们从一个跨国耐多药结核分枝杆菌菌株库中选择了60株临床结核分枝杆菌分离株，并将它们分为两组：1）那些rpoB基因突变疑似导致对RMP和RBT产生不同耐药性的菌株，以及2）那些预期对RMP和RBT交叉耐药的菌株。通过比较RMP/RBT的表型敏感性与rpoB基因突变预测的敏感性来检验这些假设。
在20株疑似对RMP耐药/对RBT敏感的分离株中，15株对RMP耐药但对RBT敏感，3株对RMP和RBT均敏感，2株对RMP和RBT均交叉耐药。相比之下，40株疑似交叉耐药的分离株中有40株对RMP和RBT均耐药。
我们的数据支持特定的rpoB基因突变与结核分枝杆菌对RMP和RBT的不同耐药性之间的关联。需要进行临床研究来调查RBT治疗携带这些突变的结核分枝杆菌的疗效。
