自1999年以来,多西环素和羟氯喹一直是慢性Q热的推荐治疗方法,由细菌病原体引起的威胁生命的疾病,伯内蒂柯西拉。尽管它的使用时间很长,由于治疗时间过长,治疗效果不理想,死亡率高,抗性菌株,以及禁忌使用的可能性。进行了文献检索以鉴定筛选针对C.burnetii的大量药物的研究,以鉴定具有针对C.burnetii的潜在功效的新靶标。选择了由美国食品和药物管理局批准用于人体的12种候选抗微生物剂,并确定了针对低毒力菌株9英里II期的最低抑制浓度(MIC)。利福布汀和利福昔明是表现最好的抗生素,MIC≤0.01µgmL-1。这些顶级候选药物的进一步筛选与来自同一类别的两种药物一起进行,利福平,特征良好,还有利福喷丁,以前没有针对C.Burnetii的报道。针对代表三种临床相关基因型的C.burnetii毒力菌株筛选这些菌株。利福喷丁在人单核细胞白血病细胞系中最有效,THP-1,MIC≤0.01µgmL-1。在人类肾脏上皮细胞系中,A-498利福喷丁的疗效,利福平,利福布汀在各菌株中变化,MIC在≤0.001和0.01µgmL-1之间。利福平,rifabutin,和利福喷丁对C.burnetii都是杀菌的;然而,利福布汀和利福喷丁表现出令人印象深刻的杀菌活性,低至0.1µgmL-1,鉴于其在体外的功效,应进一步探索作为替代Q发烧治疗方法。
目的:这项工作将帮助研究人员和医生了解针对Q热病原体的潜在替代抗菌疗法,伯内蒂柯西拉。慢性Q热难以治疗,和替代抗生素是必要的。本手稿探讨了利福霉素抗生素对代表三种临床相关基因型的体外C.burnetii毒株的功效。重要的是,这项研究确定了布氏杆菌对利福喷丁的易感性,以前没有报道过。对利福霉素的杀菌活性的评估表明,利福布丁和利福喷丁在低浓度下是杀菌的,这对对抗C.Burnetii的抗生素来说是不寻常的。
Since 1999, doxycycline and hydroxychloroquine have been the recommended treatment for chronic Q fever, a life-threatening disease caused by the bacterial pathogen, Coxiella burnetii. Despite the duration of its use, the treatment is not ideal due to the lengthy treatment time, high mortality rate, resistant strains, and the potential for contraindicated usage. A literature search was conducted to identify studies that screened large panels of drugs against C. burnetii to identify novel targets with potential efficacy against C. burnetii. Twelve candidate antimicrobials approved for use in humans by the US Food and Drug Administration were selected and minimum inhibitory concentrations (MICs) were determined against the low virulence strain Nine Mile phase II. Rifabutin and rifaximin were the best performing antibiotics tested with MICs of ≤0.01 µg mL-1. Further screening of these top candidates was conducted alongside two drugs from the same class, rifampin, well-characterized, and rifapentine, not previously reported against C. burnetii. These were screened against virulent strains of C. burnetii representing three clinically relevant genotypes. Rifapentine was the most effective in the human monocytic leukemia cell line, THP-1, with a MIC ≤0.01 µg mL-1. In the human kidney epithelial cell line, A-498, efficacy of rifapentine, rifampin, and rifabutin varied across C. burnetii strains with MICs between ≤0.001 and 0.01 µg mL-1. Rifampin, rifabutin, and rifapentine were all bactericidal against C. burnetii; however, rifabutin and rifapentine demonstrated impressive bactericidal activity as low as 0.1 µg mL-1 and should be further explored as alternative Q fever treatments given their efficacy in vitro.
OBJECTIVE: This work will help inform investigators and physicians about potential alternative antimicrobial therapies targeting the causative agent of Q fever, Coxiella burnetii. Chronic Q fever is difficult to treat, and alternative antimicrobials are needed. This manuscript explores the efficacy of rifamycin antibiotics against virulent strains of C. burnetii representing three clinically relevant genotypes in vitro. Importantly, this study determines the susceptibility of C. burnetii to rifapentine, which has not been previously reported. Evaluation of the bactericidal activity of the rifamycins reveals that rifabutin and rifapentine are bactericidal at low concentrations, which is unusual for antibiotics against C. burnetii.