Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea.
Translation Research Center, Inha University School of Medicine, Incheon, Korea.
J Korean Med Sci. 2014 Feb;29(2):183-9. doi: 10.3346/jkms.2014.29.2.183. Epub 2014 Jan 28.
We performed an in vitro cell culture experiment to ascertain whether rifampin exhibits bactericidal effects against Orientia tsutsugamushi, the causative agent of scrub typhus. ECV304 cells were infected with the Boryong or AFSC-4 strain of O. tsutsugamushi and then, the cultures were maintained in media with increasing concentrations of rifampin, azithromycin, doxycycline, or chloramphenicol for 4 days. On day 5, the media were replaced with fresh antibiotic-free medium and the cultures were maintained until day 28. On days 5, 13, and 28, immunofluorescence (IF) staining of O. tsutsugamushi was performed. IF staining on days 13 and 28 revealed increasing numbers of IF-positive foci in all cultures, even in cultures initially exposed to the highest concentration of rifampin (80 µg/mL), azithromycin (80 µg/mL), doxycycline (20 µg/mL), or chloramphenicol (100 µg/mL). The present study reveals that rifampin has no bactericidal effect against O. tsutsugamushi as observed for azithromycin, doxycycline, and chloramphenicol. A subpopulation of the bacteria that are not killed by high concentrations of the antibiotics may explain the persistence of O. tsutsugamushi in humans even after complete recovery from scrub typhus with antibiotic therapy.
我们进行了一项体外细胞培养实验，以确定利福平是否对恙虫病东方体（导致恙虫病的病原体）具有杀菌作用。将 ECV304 细胞感染 Boryong 或 AFSC-4 株恙虫病东方体，然后在含有不同浓度利福平、阿奇霉素、强力霉素或氯霉素的培养基中培养 4 天。第 5 天，更换新鲜无抗生素的培养基，并培养至第 28 天。在第 5、13 和 28 天，进行恙虫病东方体的免疫荧光（IF）染色。第 13 和 28 天的 IF 染色显示，即使在最初暴露于最高浓度利福平（80µg/mL）、阿奇霉素（80µg/mL）、强力霉素（20µg/mL）或氯霉素（100µg/mL）的所有培养物中，IF 阳性焦点的数量也在不断增加。本研究表明，利福平对恙虫病东方体没有杀菌作用，与阿奇霉素、强力霉素和氯霉素的结果一致。可能是由于抗生素高浓度下未被杀死的细菌亚群，解释了即使在恙虫病患者经抗生素治疗完全康复后，恙虫病东方体仍在体内持续存在的现象。
