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Orientia tsutsugamushi 감염에서 doxycycline 용량과 투여 기간에 대한 실험

In vitro Study on the Dose and Duration of Doxycycline Treatment against Orientia tsutsugamushi

감염과화학요법 2008년 40권 5호 p.249 ~ 254
김은실, 강재승, 이진수, 정문현, 박재은, 김미경, 이혜명,
소속 상세정보
김은실 ( Kim Eun-Sil ) - 부천대성병원 내과
강재승 ( Kang Jae-Seung ) - 인하대학교 의과대학 미생물학교실
이진수 ( Lee Jin-Soo ) - 인하대학교 의과대학 내과학교실
정문현 ( Chung Moon-Hyun ) - 인하대학교 의과대학 내과학교실
박재은 ( Park Jae-Eun ) - 인하대학교 의과대학 내과학교실
김미경 ( Kim Mee-Kyung ) - 인하대학교 의과대학 임상의학연구실
이혜명 ( Lee Hye-Myung ) - 인하대학교 의과대학 임상의학연구실

Abstract


Background : Doxycycline, azithromycin, and chloramphenicol have been used for the treatment of scrub typhus; however, the duration of treatment for this disease is still controversial. Most clinical studies on the treatment of scrub typhus focus on the effectiveness of antibiotics; few studies have focused on the duration of the treatment. There has been no in vitro evaluation of the optimal duration of treatment of scrub typhus. We performed an experiment to evaluate the regrowth of Orientia tsutsugamushi after exposure to doxycycline of various concentration and exposure time. ]

Materials and Methods : O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were stained with FS15, a monoclonal antibody reacting against a linear epitope on the 56-kDa major outer membrane protein of O. tsutsugamushi; thereafter, the antimicrobial susceptibilities were measured by flow cytometry and expressed as a growth index (total mass of Orientia). Incubation in media containing 0.1 (the minimal inhibitory concentration of doxycycline against O. tsutsugamushi strain Boryong), 0.2, and 2 μg/mL doxycycline for 1, 3, 5, and 7 day was followed by incubation in antibiotic-free media for 5 day. Two inocula sizes were employed; low inoculum (45.18% of cells were infected) and high inoculum (87.21% of cells).

Results : The incubation with 0.1 μg/mL doxycycline resulted in O. tsutsugamushi regrowth irrespective of doxycycline treatment duration. When the concentration of doxycycline was increased to 0.2 or 2 μg/mL, regrowth was observed in short duration treatments (1-5 day at 0.2 μg/mL; 1 day at 2 μg/mL). Higher inoculum size of O. tsutsugamushi increased regrowth (1 day at the low inoculum; 1-5 day at the high inoculum).

Conclusions : The regrowth of O. tsutsugamushi after doxycycline treatment depends on the doxycycline dose; the higher the dose, the lower the relapse rate. If this result is extrapolated to humans, higher dose of doxycycline might be preferred to lower the relapse rate. The inoculum effect in O. tsutsugamushi infection needs further investigations.

키워드

Orientia tsutsugamushi;Scrub typhus;Doxycycline;Recurrence

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