Article

Efficacy of clarithromycin against experimentally induced pneumonia caused by clarithromycin-resistant Haemophilus influenzae in mice.

Second Department of Internal Medicine, Nagasaki University Hospital, and Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan.
Antimicrobial Agents and Chemotherapy (impact factor: 4.84). 11/2009; 54(2):757-62. DOI:10.1128/AAC.00524-09 pp.757-62
Source: PubMed

ABSTRACT Clarithromycin is a 14-member lactone ring macrolide with potent activity against Haemophilus influenzae, including ampicillin-resistant strains. We evaluated the in vivo efficacy of clarithromycin at 40 mg/day and 100 mg/day for 3 days in the treatment of a murine model of pneumonia using a macrolide-resistant H. influenzae strain, which was also ampicillin resistant. The MIC of clarithromycin was 64 microg/ml. The viable bacterial counts in infected tissues after treatment with 100 mg clarithromycin/kg of body weight were lower than the counts obtained in control and 40-mg/kg clarithromycin-treated mice. The concentrations of macrophage inflammatory protein 2 (MIP-2) and interleukin 1beta (IL-1beta) in bronchoalveolar lavage fluid (BALF) samples from mice treated at both concentrations were lower than in the control group. Pathologically, following infection, clarithromycin-treated mice, particularly at a dose of 100 mg/kg, showed lower numbers of neutrophils in alveolar walls, and inflammatory changes had apparently improved, whereas large aggregates of inflammatory cells were observed within the alveoli of control mice. In addition, we demonstrated that clarithromycin has bacteriological effects against intracellular bacteria at levels below the MIC. Our results indicate that clarithromycin may be useful in vivo for macrolide-resistant H. influenzae, and this phenomenon may be related to the good penetration of clarithromycin into bronchoepithelial cells. We also believe that conventional drug susceptibility tests may not reflect the in vivo effects of clarithromycin.

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Keywords

100 mg clarithromycin/kg
 
14-member lactone ring macrolide
 
3 days
 
40-mg/kg clarithromycin-treated mice
 
body weight
 
bronchoalveolar lavage fluid
 
bronchoepithelial cells
 
Clarithromycin
 
clarithromycin-treated mice
 
control group
 
control mice
 
conventional drug susceptibility tests
 
good penetration
 
inflammatory cells
 
inflammatory changes
 
intracellular bacteria
 
macrophage inflammatory protein 2
 
viable bacterial counts
 
vivo effects
 
vivo efficacy
 

Shigeki Nakamura