title: Clarithromycin alone and in combination with ceftriaxone inhibits the production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of Streptococcus pneumoniae.
abstract: OBJECTIVE
  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 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.
  
  
  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.
authors.affiliation: 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. randerso@medic.up.ac.za
authors.forename: R
authors.initials: R
authors.lastname: Anderson
authors.forename: H C
authors.initials: HC
authors.lastname: Steel
authors.forename: R
authors.initials: R
authors.lastname: Cockeran
authors.forename: A M
authors.initials: AM
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: von Gottberg
authors.forename: L
authors.initials: L
authors.lastname: de Gouveia
authors.forename: A
authors.initials: A
authors.lastname: Brink
authors.forename: K P
authors.initials: KP
authors.lastname: Klugman
authors.forename: T J
authors.initials: TJ
authors.lastname: Mitchell
authors.forename: C
authors.initials: C
authors.lastname: Feldman
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D002443:Ceftriaxone / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000378:metabolism; D013301:Streptolysins / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D002443:Ceftriaxone; D017291:Clarithromycin