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 Original Articles |
| In Vitro Antibiotic Susceptibility of Orientia tsutsugamushi strain Boryong Measured by Flow Cytometry |
| Eun Sil Kim1, Mee Kyung Kim2, Hye Myung Lee2, Moon-Hyun Chung3, Jin-Soo Lee3, Jae Eun Park3, and Jae-Seung Kang4 |
| 1Department of Internal Medicine, DaeSung General Hospital, Buchon, 2Clinical Research Center, 3Department of Internal Medicine, 4Department of Microbiology, Inha University College of Medicine, Inchon, Korea |
Vol.40 Num.4 (p212~217)
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Background:Scrub typhus, an infectious disease caused by Orientia tsutsugamushi, is endemic in Korea. With the introduction of tetracycline and chloramphenicol in clinical practice, the mortality due to scrub typhus has markedly decreased. In 1995, scrub typhus poorly responsive to doxycycline was reported in Thailand; the need for safe antibiotics for the treatment of scrub typhus acquired during pregnancy or for children is emerging; also, broader spectrum antibiotics having anti-Orientia activity may be preferred for empirical therapy of enteric fever syndrome and for complicated scrub typhus. The anti-Orientia activities of various antibiotics, including recently licensed antibiotics, were investigated by flow cytometry.
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 56-kDa major outer membrane protein of O. tsutsugamushi. Then the antimicrobial susceptibilities were measured by flow cytometry and expressed as a growth index (total mass of Orientia). A concentration at which no further decrease in growth index occurred was defined as the minimal inhibitory concentration (MIC). Microbial susceptibilities to the following antibiotics were measured: quinupristin-dalfopristin (Synercid), levofloxacin, ciprofloxacin, moxifloxacin, metronidazole, linezolid, clindamycin, chloramphenicol, doxycycline, azithromycin, and rifampin.
Results:Considering the usual serum concentrations of rifampin (MIC=0.025-0.05 µg/mL), azithromycin (MIC=0.05-0.5 µg/mL) and doxycycline (MIC=0.05-0.1 µg/mL), these antibiotics exhibited very low MICs. Synercid (MIC=0.2-1.0 µg/mL), clindamycin (MIC=1.0 µg/mL) and chloramphenicol (MIC=1-2 µg/mL) exhibited moderately low MICs; moxifloxacin (MIC=8 µg/mL), ciprofloxacin (MIC=25.6 µg/mL or more) and levofloxacin (MIC=30 µg/mL) exhibited relatively high MICs; and cefotaxime (MIC＞50 µg/mL), metronidazole (MIC＞30 µg/mL) and linezolid (＞30 µg/mL) exhibited high MICs.
Conclusions:Among the new antibiotics, none was superior to doxycycline, azithromycin or rifampin with respect to anti-Orientia activity. Synercid, clindamycin, and moxifloxacin may show moderate therapeutic efficacies in human.
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Keywords : Orientia tsutsugamushi, Scrub typhus, Antimicrobial susceptibility, Flow cytometry |
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