Clarithromycin alone and in combination with ceftriaxone inhibits the production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of Streptococcus pneumoniae

Anderson, R., Steel, H.C., Cockeran, R., Smith, A.M., von Gottberg, A., de Gouveia, L., Brink, A., Klugman, K.P., Mitchell, T.J. and Feldman, C. (2007) Clarithromycin alone and in combination with ceftriaxone inhibits the production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of Streptococcus pneumoniae. Journal of Antimicrobial Chemotherapy, 59, pp. 224-229. (doi: 10.1093/jac/dkl479)

Abstract

Objectives 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. Methods The bacteria were cultured for 6 h at 37°C/5% CO2 in tryptone soy broth, washed, enumerated and resuspended to 0.5–3 × 108 cfu/mL in tissue culture medium, RPMI 1640. After 16 h of incubation at 37°C / 5% CO2, 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. Results 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. Conclusions 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mitchell, Professor Timothy
• Authors: Anderson, R., Steel, H.C., Cockeran, R., Smith, A.M., von Gottberg, A., de Gouveia, L., Brink, A., Klugman, K.P., Mitchell, T.J., and Feldman, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Antimicrobial Chemotherapy