Affiliation:
1. Second Department of Internal Medicine
2. Department of Laboratory Medicine, Nagasaki University Hospital
3. Division of Molecular and Clinical Microbiology, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
Abstract
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 μg/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 1β (IL-1β) 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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
14 articles.
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