JAC Advance Access published online on January 11, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl479
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Clarithromycin alone and in combination with ceftriaxone inhibits the production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of Streptococcus pneumoniae
1 Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa 2 MRC/NICD/WITS Respiratory and Meningeal Pathogens Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa 3 Ampath Laboratories, Johannesburg, South Africa 4 Hubert Department of Global Health, Rollins School of Public Health, and Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA, USA 5 Division of Infection and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, Scotland 6 Division of Pulmonology, Department of Medicine, Johannesburg Hospital and University of the Witwatersrand, Johannesburg, South Africa
Received 13 September 2006; returned 4 October 2006; revised 1 November 2006; accepted 2 November 2006
* Corresponding author. Tel: +27-12-319-2425; Fax: +27-12-323-0732; E-mail: randerso{at}medic.up.ac.za
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 0.5–3x108 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.
Key Words: ß-lactam antibiotics , community-acquired pneumonia , macrolide resistance , Streptococcus pneumoniae
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