The impact of steroids given with macrolide therapy on experimental Mycoplasma pneumoniae respiratory infection.
BACKGROUND
Systemic steroids have been advocated in addition to antimicrobial therapy for severe Mycoplasma pneumoniae pneumonia. We evaluated the efficacy of clarithromycin, dexamethasone, and combination therapy for M. pneumoniae respiratory infection.


METHODS
Mice infected with M. pneumoniae were treated with clarithromycin, dexamethasone, combined clarithromycin/dexamethasone, or placebo daily; mice were evaluated at baseline and after 1, 3, and 6 days of therapy. Outcome variables included M. pneumoniae culture, lung histopathologic score (HPS), and bronchoalveolar lavage cytokine, chemokine, and growth factor concentrations.


RESULTS
Clarithromycin monotherapy resulted in the greatest reductions in M. pneumoniae concentrations. After 3 days of treatment, combination therapy significantly reduced lung HPS compared with placebo, clarithromycin, and dexamethasone alone, whereas, after 6 days of therapy, clarithromycin alone and combination therapy significantly reduced lung HPS compared with placebo. Concentrations of interleukin (IL)-12 p40, RANTES, macrophage chemotactic protein-1, and cytokine-induced neutrophil chemoattractant were significantly lower in mice treated with clarithromycin alone and/or combination therapy compared with dexamethasone alone and/or placebo; combination therapy resulted in a significantly greater reduction than clarithromycin alone for IL-12 p40 and RANTES.


CONCLUSIONS
Although monotherapy with clarithromycin had the greatest effect on reducing concentrations of M. pneumoniae, combination therapy had the greatest effect on decreasing levels of cytokines and chemokines as well as pulmonary histologic inflammation.
Tagliabue
C
C
Institute of Pediatrics, University of Milan Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Maggiore Policlinico, Milan, Italy.
Salvatore
C M
CM
Techasaensiri
C
C
Mejias
A
A
Torres
J P
JP
Katz
K
K
Gomez
A M
AM
Esposito
S
S
Principi
N
N
Hardy
R D
RD
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D017291:Clarithromycin / Q000008:administration & dosage / Q000627:therapeutic use; D003470:Culture Media; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009177:Mycoplasma pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D011019:Pneumonia, Mycoplasma / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D003470:Culture Media; D003907:Dexamethasone; D017291:Clarithromycin