Cohen Y, Perronne C, Truffot-Pernot C, Grosset J, Vilde J L, Pocidalo J J
Institut National de la Santé et de la Recherche Médicale Unité 13, Hôpital Bichat-Claude Bernard, Paris, France.
Antimicrob Agents Chemother. 1992 Oct;36(10):2104-7. doi: 10.1128/AAC.36.10.2104.
The activities of the fluoroquinolone WIN-57273, 14-OH clarithromycin (a human metabolite of clarithromycin), and minocycline against two virulent strains of Mycobacterium avium complex were evaluated in a model of intracellular infection and compared with that of clarithromycin. Human monocyte-derived macrophages were infected at day 6 of culture. Intracellular CFU at 60 min and intracellular and supernatant CFU on days 4 and 7 were counted after inoculation. The concentrations used, which were equal to peak levels in serum, were 3 micrograms of WIN-57273 per ml (MICs for the two strains, 1 microgram/ml), 4 microgram of 14-OH clarithromycin per ml (MICs, 8 and 2 micrograms/ml, respectively, at pH 7.4), 4 micrograms of minocycline per ml (MICs, 64 and 32 micrograms/ml, respectively), and 4 micrograms of clarithromycin per ml (MICs, 2 and 0.5 micrograms/ml, respectively, at pH 7.4). On day 7, compared with controls, WIN-57273, minocycline (P less than 0.02), clarithromycin, or different combinations of clarithromycin and the other drugs (P less than 0.001) slowed the intracellular replication of strain MO-1. 14-OH clarithromycin (P less than 0.02), clarithromycin (P less than 0.02), 14-OH clarithromycin plus clarithromycin (P less than 0.01), clarithromycin plus minocycline, or clarithromycin plus minocycline plus 14-OH clarithromycin (P less than 0.001) slowed the intracellular replication of strain LV-2. WIN-57273 was less effective than clarithromycin against strain MO-1 (P less than 0.05). Clarithromycin plus 14-OH clarithromycin plus minocycline (P less than 0.02) was more effective than clarithromycin alone against strain LV-2. Thus, clarithromycin plus minocycline, which corresponds in humans to three active molecules, may exhibit a better efficacy than clarithromycin in this model.
在细胞内感染模型中评估了氟喹诺酮WIN - 57273、14 - 羟基克拉霉素（克拉霉素的一种人体代谢产物）和米诺环素对两株强毒鸟分枝杆菌复合群菌株的活性，并与克拉霉素进行了比较。在培养第6天用人单核细胞衍生的巨噬细胞进行感染。接种后计数60分钟时的细胞内菌落形成单位（CFU）以及第4天和第7天的细胞内和上清液中的CFU。所用浓度等于血清中的峰值水平，分别为每毫升3微克WIN - 57273（两株菌株的最低抑菌浓度[MIC]均为1微克/毫升）、每毫升4微克14 - 羟基克拉霉素（在pH 7.4时，MIC分别为8微克/毫升和2微克/毫升）、每毫升4微克米诺环素（MIC分别为64微克/毫升和32微克/毫升）以及每毫升4微克克拉霉素（在pH 7.4时，MIC分别为2微克/毫升和0.5微克/毫升）。在第7天，与对照组相比，WIN - 57273、米诺环素（P＜0.02）、克拉霉素或克拉霉素与其他药物的不同组合（P＜0.001）减缓了MO - 1菌株的细胞内复制。14 - 羟基克拉霉素（P＜0.02）、克拉霉素（P＜0.02）、14 - 羟基克拉霉素加克拉霉素（P＜0.01）、克拉霉素加米诺环素或克拉霉素加米诺环素加14 - 羟基克拉霉素（P＜0.001）减缓了LV - 2菌株的细胞内复制。WIN - 57273对MO - 1菌株的效果不如克拉霉素（P＜0.05）。克拉霉素加14 - 羟基克拉霉素加米诺环素（P＜0.02）对LV - 2菌株的效果比单独使用克拉霉素更好。因此，在人体中相当于三种活性分子的克拉霉素加米诺环素在该模型中可能比克拉霉素表现出更好的疗效。
