title: Efficacy of increasing dosages of clarithromycin for treatment of experimental Mycoplasma pneumoniae pneumonia.
abstract: OBJECTIVE
  Mycoplasma pneumoniae respiratory infection is a common cause of acute respiratory infection in children and adults. We evaluated the efficacy of increasing dosages of clarithromycin for the optimized therapy of M. pneumoniae respiratory infection in a mouse model.
  
  
  METHODS
  BALB/c mice were intranasally inoculated once with M. pneumoniae or SP4 broth (control). Groups of mice were treated with increasing dosages of clarithromycin (10, 25 or 75 mg/kg/day) or placebo subcutaneously daily. Groups of mice were evaluated after 1, 2, 3, 6 and 12 days of therapy. Outcome variables included quantitative M. pneumoniae culture, histopathological score of the lungs, bronchoalveolar lavage (BAL) cytokine/chemokine/growth factor concentrations and plethysmography after aerosolized methacholine to assess airway hyperresponsiveness.
  
  
  RESULTS
  Elevated dosages of clarithromycin resulted in greater antimicrobial efficacy with significantly reduced M. pneumoniae quantitative cultures (P < 0.05), as well as greater improvement in markers of disease severity with significantly reduced lung histopathology scores, BAL cytokine concentrations and airway hyperresponsiveness (P < 0.05).
  
  
  CONCLUSIONS
  Escalated dosing of clarithromycin resulted in significantly greater therapeutic efficacy in the treatment of experimental M. pneumoniae respiratory infection.
authors.affiliation: Department of Maternal and Pediatric Sciences, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tagliabue
authors.forename: C
authors.initials: C
authors.lastname: Techasaensiri
authors.forename: J P
authors.initials: JP
authors.lastname: Torres
authors.forename: K
authors.initials: K
authors.lastname: Katz
authors.forename: C
authors.initials: C
authors.lastname: Meek
authors.forename: T R
authors.initials: TR
authors.lastname: Kannan
authors.forename: J J
authors.initials: JJ
authors.lastname: Coalson
authors.forename: S
authors.initials: S
authors.lastname: Esposito
authors.forename: N
authors.initials: N
authors.lastname: Principi
authors.forename: R
authors.initials: R
authors.lastname: Leff
authors.forename: J B
authors.initials: JB
authors.lastname: Baseman
authors.forename: R D
authors.initials: RD
authors.lastname: Hardy
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D018925:Chemokines / Q000032:analysis; D017291:Clarithromycin / Q000008:administration & dosage* / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009177:Mycoplasma pneumoniae / Q000187:drug effects*; D011019:Pneumonia, Mycoplasma / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D017291:Clarithromycin