Mvelase Nomonde R, Cele Lindiwe P, Singh Ravesh, Naidoo Yeshnee, Giandhari Jennifer, Wilkinson Eduan, de Oliveira Tulio, Swe-Han Khine Swe, Mlisana Koleka P
Department of Medical Microbiology, KwaZulu-Natal Academic Complex, National Health Laboratory Service, Durban, South Africa.
School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Afr J Lab Med. 2023 Feb 6;12(1):1975. doi: 10.4102/ajlm.v12i1.1975. eCollection 2023.
Rifampicin resistance missed by commercial rapid molecular assays but detected by phenotypic assays may lead to discordant susceptibility results and affect patient management.
This study was conducted to evaluate the causes of rifampicin resistance missed by the GenoType MTBDR and its impact on the programmatic management of tuberculosis in KwaZulu-Natal, South Africa.
We analysed routine tuberculosis programme data from January 2014 to December 2014 on isolates showing rifampicin susceptibility on the GenoType MTBDR assay but resistance on the phenotypic agar proportion method. Whole-genome sequencing was performed on a subset of these isolates.
Out of 505 patients with isoniazid mono-resistant tuberculosis on the MTBDR, 145 (28.7%) isolates showed both isoniazid and rifampicin resistance on the phenotypic assay. The mean time from MTBDR results to initiation of drug-resistant tuberculosis therapy was 93.7 days. 65.7% of the patients had received previous tuberculosis treatment. The most common mutations detected in the 36 sequenced isolates were I491F (16; 44.4%) and L452P (12; 33.3%). Among the 36 isolates, resistance to other anti-tuberculosis drugs was 69.4% for pyrazinamide, 83.3% for ethambutol, 69.4% for streptomycin, and 50% for ethionamide.
Missed rifampicin resistance was mostly due to the I491F mutation located outside the MTBDR detection area and the L452P mutation, which was not included in the initial version 2 of the MTBDR. This led to substantial delays in the initiation of appropriate therapy. The previous tuberculosis treatment history and the high level of resistance to other anti-tuberculosis drugs suggest an accumulation of resistance.
商业快速分子检测未检出但表型检测可检测到的利福平耐药性可能导致药敏结果不一致，并影响患者管理。
本研究旨在评估Genotype MTBDR漏检利福平耐药性的原因及其对南非夸祖鲁-纳塔尔省结核病规划管理的影响。
我们分析了2014年1月至2014年12月结核病常规规划数据，这些数据来自在Genotype MTBDR检测中显示利福平敏感但在表型琼脂比例法中显示耐药的分离株。对这些分离株的一个子集进行了全基因组测序。
在MTBDR检测为异烟肼单耐药结核病的505例患者中，145例（28.7%）分离株在表型检测中显示异烟肼和利福平均耐药。从MTBDR结果到开始耐多药结核病治疗的平均时间为93.7天。65.7%的患者曾接受过结核病治疗。在36株测序分离株中检测到的最常见突变是I491F（16株；44.4%）和L452P（12株；33.3%）。在这36株分离株中，对其他抗结核药物的耐药率分别为：吡嗪酰胺69.4%，乙胺丁醇83.3%，链霉素69.4%，乙硫异烟胺50%。
漏检的利福平耐药性主要归因于位于MTBDR检测区域之外的I491F突变以及MTBDR初始版本2中未包含的L452P突变。这导致了适当治疗开始的实质性延迟。既往结核病治疗史以及对其他抗结核药物的高耐药率表明存在耐药性积累。
