Anderson R, Steel H C, Cockeran R, Smith A M, von Gottberg A, de Gouveia L, Brink A, Klugman K P, Mitchell T J, Feldman C
Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa.
J Antimicrob Chemother. 2007 Feb;59(2):224-9. doi: 10.1093/jac/dkl479. Epub 2007 Jan 11.
To investigate the effects of clarithromycin (0.01-0.5 mg/L) alone or in combination with ceftriaxone (0.1 and 0.25 mg/L) on pneumolysin production by both macrolide-susceptible and -resistant [2 erm(B) positive and 2 mef(A) positive] strains of Streptococcus pneumoniae.
The bacteria were cultured for 6 h at 37 degrees C/5% CO(2) in tryptone soy broth, washed, enumerated and resuspended to 0.5-3 x 10(8) cfu/mL in tissue culture medium, RPMI 1640. After 16 h of incubation at 37 degrees C / 5% CO(2), pneumolysin was assayed in the bacteria-free supernatants, as well as in lysates, using a functional assay based on the influx of calcium into human neutrophils.
Exposure of not only macrolide-susceptible strains, but also the macrolide-resistant strains, of S. pneumoniae to sub-MICs of clarithromycin resulted in dose-related inhibition of the pneumolysin production, whereas production of the toxin was unaffected by ceftriaxone.
These observations demonstrate that even in the setting of macrolide resistance the production of pneumolysin, a key virulence factor of the pneumococcus, is attenuated by exposure of this microbial pathogen to clarithromycin.
研究克拉霉素（0.01 - 0.5毫克/升）单独使用或与头孢曲松（0.1和0.25毫克/升）联合使用对大环内酯敏感和耐药的[2株erm(B)阳性和2株mef(A)阳性]肺炎链球菌菌株产生肺炎溶血素的影响。
将细菌在胰蛋白胨大豆肉汤中于37℃/5%二氧化碳条件下培养6小时，洗涤、计数并重悬于组织培养基RPMI 1640中，使其浓度达到0.5 - 3×10⁸ 菌落形成单位/毫升。在37℃/5%二氧化碳条件下孵育16小时后，使用基于钙离子流入人中性粒细胞的功能测定法，对无细菌的上清液以及裂解物中的肺炎溶血素进行检测。
肺炎链球菌的大环内酯敏感菌株和大环内酯耐药菌株暴露于克拉霉素的亚抑菌浓度下，均导致肺炎溶血素产生呈剂量相关的抑制，而毒素的产生不受头孢曲松的影响。
这些观察结果表明，即使在大环内酯耐药的情况下，这种微生物病原体暴露于克拉霉素也会减弱肺炎链球菌关键毒力因子肺炎溶血素的产生。
