Bogdanovich Tatiana, Bozdogan Bülent, Appelbaum Peter C
Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, Pennsylvania 17033, USA.
Antimicrob Agents Chemother. 2006 Mar;50(3):893-8. doi: 10.1128/AAC.50.3.893-898.2006.
This study investigated the presence of telithromycin and azithromycin efflux in 58 clinical strains of Haemophilus influenzae with various susceptibilities to macrolides, azalides, and ketolides. Efflux pumps were studied by measuring accumulation of radioactive [3H]telithromycin and [N-methyl-3H]azithromycin in the presence and absence of carbonyl m-chlorophenylhydrazone (CCCP), a protonophore. In 17 strains for which the telithromycin MICs were 0.06 to 0.5 microg/ml (azithromycin MICs, < or = 0.06 to 0.125 microg/ml; clarithromycin MICs, < or = 0.06 to 2 microg/ml), telithromycin and azithromycin accumulations were high without CCCP and not affected by its addition, which indicates absence of efflux. In 22 strains for which the telithromycin MICs were 0.25 to 4 microg/ml (azithromycin MICs, 0.25 to 1 microg/ml; clarithromycin MICs, 1 to 8 microg/ml), initially low levels of telithromycin accumulation became higher after addition of CCCP, indicating a functioning efflux pump. Nineteen strains for which the telithromycin MICs were > or = 2 microg/ml had efflux as well as various mutations in ribosomal proteins L4, L22, and/or 23S rRNA (domains II and V). Of these 19 strains, the telithromycin MICs (> or = 8 microg/ml) for 17 of them were significantly raised (azithromycin, MICs 4 to >32 microg/ml; clarithromycin MICs, 8 to >32 microg/ml). From these results we conclude that telithromycin efflux with or without additional ribosomal alterations is present in all H. influenzae strains, except for those for which the telithromycin MICs were very low.
本研究调查了58株对大环内酯类、氮杂内酯类和酮内酯类具有不同敏感性的流感嗜血杆菌临床菌株中泰利霉素和阿奇霉素的外排情况。通过测量在存在和不存在羰基间氯苯腙（CCCP，一种质子载体）的情况下放射性[3H]泰利霉素和[N-甲基-3H]阿奇霉素的积累来研究外排泵。在17株泰利霉素MIC为0.06至0.5微克/毫升（阿奇霉素MIC，≤0.06至0.125微克/毫升；克拉霉素MIC，≤0.06至2微克/毫升）的菌株中，未添加CCCP时泰利霉素和阿奇霉素的积累量很高，且添加CCCP后不受影响，这表明不存在外排。在22株泰利霉素MIC为0.25至4微克/毫升（阿奇霉素MIC，0.25至1微克/毫升；克拉霉素MIC，1至8微克/毫升）的菌株中，添加CCCP后最初较低的泰利霉素积累水平升高，表明存在起作用的外排泵。19株泰利霉素MIC≥2微克/毫升的菌株存在外排以及核糖体蛋白L4、L22和/或23S rRNA（结构域II和V）的各种突变。在这19株菌株中，其中17株的泰利霉素MIC（≥8微克/毫升）显著升高（阿奇霉素MIC，4至>32微克/毫升；克拉霉素MIC，8至>32微克/毫升）。根据这些结果，我们得出结论，除了泰利霉素MIC非常低的菌株外，所有流感嗜血杆菌菌株均存在泰利霉素外排，无论是否有额外的核糖体改变。
