Cockeran, RianaSteel, Helen CarolynWolter, NicoleDe Gouveia, L.Von Gottberg, AnneKlugman, Keith P.Leanord, A.T.Inverarity, D.J.Mitchell, Timothy J.Feldman, CharlesAnderson, Ronald2012-06-192012-06-192012-02Cockeran, R, Steel, HC, Wolter, N, De Gouveia, L, Von Gottberg, A, Klugman, KP, Leanord, AT, Inverarity, DJ, Mitchell, TJ, Feldman, C & Anderson, R 2012, 'Effects of clarithromycin at sub-minimum inhibitory concentrations on early ermB gene expression, metabolic activity and growth of an erm(B)-expressing macrolide-resistant strain of Streptococcus pneumoniae', Open Journal of Respiratory Diseases, vol. 2, no. 1, pp. 1-8.2163-940X (print)2163-9418 (online)10.4236/ojrd.2012.21001http://hdl.handle.net/2263/19209AIM: To investigate the effects of exposure of a macrolide-resistant [erm(B)-expressing] strain of Streptococcus pneumo- niae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initiation of culture on early gene expression, energy metabolism, and growth. METHODS: Bacterial growth was determined by turbidometric and colony counting procedures, energy metabolism by measurement of ATP, while analysis of gene expression was per- formed using reverse transcription-PCR and sequencing. RESULTS: Addition of clarithromycin, at either concentration, at the outset of culture, caused transient suppression of growth of 10 - 12 hours duration, while delayed addition of antibi-otic (during the logarithmic phase) resulted in an abrupt halt in growth followed by recovery. These inhibitory effects of clarithromycin on bacterial growth were associated with up-regulation of expression of erm(B), decreased ATP and protein synthesis, and were unaffected by inclusion of either catalase (500 and 1000 kunits/L), or compe- tence-stimulating peptide (CSP-1, 0.5 mg/L). The inhibitory effects could, however, be overcome by pre-exposure of the bacteria to the antibiotic. Moreover, clarithromycin appeared to potentiate the antimicrobial actions of ceftriaxone, at sub-MIC concentrations, for strain 2507. CONCLUSIONS: Unlike several other common bacterial pathogens, the full expression of erm(B)-mediated macrolide resistance by the pneumococcus has a slow onset, which is associated with transient susceptibility to macrolides and inhibition of growth.enCopyright © 2012 SciRes.ClarithromycinPneumococcusMacrolide-resistancePneumonia -- TreatmentArticle