Mallick Jahan Saeed, Nair Parvati, Abbew Elizabeth Tabitha, Van Deun Armand, Decroo Tom
Institute of Tropical Medicine Antwerp, Department of Clinical Sciences, Kronenburgstraat 43, 2000 Antwerpen, Belgium.
Cape Coast Teaching Hospital, Interberton Road, Cape Coast, Ghana.
JAC Antimicrob Resist. 2022 Mar 29;4(2):dlac029. doi: 10.1093/jacamr/dlac029. eCollection 2022 Apr.
Drug-resistant tuberculosis (DR-TB) is considered to be a public health threat and is difficult to cure, requiring a lengthy treatment with potent, potentially toxic drugs. The novel antimicrobial agent bedaquiline has shown promising results for patients with DR-TB, improving the rate of culture conversion and reducing TB-related mortality. However, increasing numbers of cases with acquired bedaquiline resistance (ABR) have been reported in recent years.
This systematic review aimed to assess the frequency of ABR and characteristics of patients acquiring it. Studies showing data on sequential bedaquiline drug-susceptibility testing in patients treated with a bedaquiline-containing regimen were included. The databases CENTRAL, PubMed and Embase were manually searched, and 866 unique records identified, eventually leading to the inclusion of 13 studies. Phenotypic ABR was assessed based on predefined MIC thresholds and genotypic ABR based on the emergence of resistance-associated variants.
The median (IQR) frequency of phenotypic ABR was 2.2% (1.1%-4.6%) and 4.4% (1.8%-5.8%) for genotypic ABR. Among the studies reporting individual data of patients with ABR, the median number of likely effective drugs in a treatment regimen was five, in accordance with WHO recommendations. In regard to the utilization of important companion drugs with high and early bactericidal activity, linezolid was included in the regimen of most ABR patients, whereas the usage of other group A (fluoroquinolones) and former group B drugs (second-line injectable drugs) was rare.
Our findings suggest a relevant frequency of ABR, urging for a better protection against it. Therefore, treatment regimens should include drugs with high resistance-preventing capacity through high and early bactericidal activity.
耐多药结核病（DR-TB）被视为一种公共卫生威胁，且难以治愈，需要使用强效、可能有毒性的药物进行长期治疗。新型抗菌药物贝达喹啉已在耐多药结核病患者中显示出有前景的结果，提高了痰菌阴转率并降低了结核病相关死亡率。然而，近年来报告的获得性贝达喹啉耐药（ABR）病例数量不断增加。
本系统评价旨在评估ABR的发生率及获得ABR患者的特征。纳入了显示接受含贝达喹啉方案治疗患者序贯贝达喹啉药敏试验数据的研究。对CENTRAL、PubMed和Embase数据库进行了手工检索，共识别出866条独特记录，最终纳入13项研究。基于预定义的最低抑菌浓度（MIC）阈值评估表型ABR，基于耐药相关变异的出现评估基因型ABR。
表型ABR的中位（四分位间距）发生率为2.2%（1.1%-4.6%），基因型ABR为4.4%（1.8%-5.8%）。在报告ABR患者个体数据的研究中，治疗方案中可能有效的药物中位数为5种，符合世界卫生组织的建议。关于具有高早期杀菌活性的重要辅助药物的使用，大多数ABR患者的治疗方案中包含利奈唑胺，而其他A组药物（氟喹诺酮类）和原B组药物（二线注射用药物）的使用较少。
我们的研究结果表明ABR发生率较高，迫切需要更好地预防。因此，治疗方案应包括通过高早期杀菌活性具有高耐药预防能力的药物。
