IN-VITRO EFFECTIVENESS OF AZITHROMYCIN AGAINST DOXYCYCLINE-RESISTANT AND DOXYCYCLINE-SUSCEPTIBLE STRAINS OF RICKETTSIA-TSUTSUGAMUSHI, ETIOLOGIC AGENT OF SCRUB TYPHUS
IN-VITRO EFFECTIVENESS OF AZITHROMYCIN AGAINST DOXYCYCLINE-RESISTANT AND DOXYCYCLINE-SUSCEPTIBLE STRAINS OF RICKETTSIA-TSUTSUGAMUSHI, ETIOLOGIC AGENT OF SCRUB TYPHUS
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DOI：
10.1128/aac.39.11.2406
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发表时间：
1995-11-01
影响因子：
4.9
通讯作者：
KUSCHNER, R
中科院分区：
文献类型：
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作者：
STRICKMAN, D;SHEER, T;KUSCHNER, R
为了寻找治疗恙虫病的潜在替代疗法，我们评估了标准药物多西环素和新的大环内酯阿奇霉素对恙虫病立克次体多西环素敏感株（Karp）和多西环素耐药株（AFSC-4）的有效性，在体外试验系统中测试抗生素，其中感染的小鼠成纤维细胞（L929）在不同浓度的药物中孵育3天。通过Giemsasted细胞中立克次体的直接目视计数或通过流式细胞术评价立克次体的生长。在被认为是敏感性上限的每种抗生素的浓度（强力霉素为16 μ g/ml，阿奇霉素为8 μ g/ml）下进行初始试验。Karp和AFSC-4的生长均被两种抗生素强烈抑制，如通过视觉计数所测量的，尽管在多西环素存在下AFSC-3感染的细胞百分比比Karp感染的细胞百分比大三倍，但仅为在阿奇霉素存在下Karp感染的细胞百分比的60%，流式细胞术证实，立克次体的生长发生在没有抗生素的情况下，但它未能检测到它在存在高浓度的药物，在较低浓度的抗生素（0.25至0.0078 μ g/ml）下，立克次体生长的目视计数显示Karp菌株对强力霉素的敏感性是AFSC-4菌株的16倍。阿奇霉素对AFSC-4比多西环素有效得多，在0.0156 μ g/ml时抑制立克次体生长的水平低于0.25 μ g/ml多西环素所达到的水平。阿奇霉素对Karp菌株也比多西环素有效，在较低浓度时引起每个细胞立克次体数量的更大减少。如果体内试验证实了阿奇霉素的体外有效性，它可能被证明是治疗儿童和孕妇的恙虫病的首选药物，这些人不应该服用强力霉素，以及来自强力霉素耐药菌株的地区的难治性疾病患者。在体外试验系统中，阿奇霉素对多西环素敏感和耐药的恙虫病立克次体菌株的作用优于多西环素。恙虫病。
In an effort to find a potential alternative treatment for scrub typhus, we evaluated the effectiveness of the standard drug doxycycline and the new macrolide azithromycin against a doxycycline-susceptible strain (Karp) and a doxycycline-resistant strain (AFSC-4) of Rickettsia tsutsugamushi, The antibiotics were tested in an in vitro assay system in which infected mouse fibroblast cells (L929) were incubated for 3 days in various concentrations of the drugs. Rickettsial growth was evaluated by direct visual counts of rickettsiae in Giemsastained cells or by flow cytometry, Initial tests were conducted at the concentration of each antibiotic considered to be the upper breakpoint for susceptibility (16 mu g/ml for doxycycline and 8 mu g/ml for azithromycin). Growth of both Karp and AFSC-4 was strongly inhibited with both antibiotics, as measured by visual counts, although the percentage of cells infected with AFSC-3 in the presence of doxycycline was three times greater than the percentage of cells infected with Karp but was only 60% as great as the percentage of cells infected with Karp in the presence of azithromycin, Flow cytometry confirmed that rickettsial growth occurred in the absence of antibiotics, but it failed to detect it in the presence of high concentrations of either drug, Visual counts of rickettsial growth at lower concentrations of the antibiotics (0.25 to 0.0078 mu g/ml) showed that the Karp strain was 16 times more susceptible that the AFSC-4 strain to doxycycline. Azithromycin was much more effective than doxycycline against AFSC-4, inhibiting rickettsial growth at 0.0156 mu g/ml to levels below that achieved by 0.25 mu g of doxycycline per mi, Azithromycin was also more effective than doxycycline against the Karp strain, causing greater reductions in the number of rickettsiae per cell at lower concentrations. If in vivo testing confirms the in vitro effectiveness of azithromycin, it may prove to be the drug of choice for the treatment of scrub typhus in children and pregnant women, who should not take doxycycline, and in patients with refractory disease from locations where doxycycline-resistant strains of R. tsutsugamushi have been found, When tested in an in vitro assay system, azithromycin was more effective than doxycycline against doxycycline-susceptible and -resistant strains of R. tsutsugamushi.