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Protective effects of sparfloxacin in experimental pneumonia caused by Chlamydia pneumoniae in leukopenic mice
K Nakata1, Y Okazaki, H Hattori
1Bioscience Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Abstract:
The in vivo antichlamydial activities of sparfloxacin and reference drugs were examined in a experimental model of pneumonia caused by Chlamydia pneumoniae in leukopenic mice; their in vitro activities were also examined. The most potent agents in vitro were sparfloxacin (MICs for C. pneumoniae Kajaani and IOL 207, (0.031 and 0.031 micrograms/ml, respectively), clarithromycin (0.031 and 0.031 micrograms/ml, respectively), and minocycline (0.031 and 0.031 micrograms/ml, respectively); these were followed by tosufloxacin (0.063 and 0.125 micrograms/ml, respectively) and ofloxacin (0.5 and 0.5 micrograms/ml, respectively). The MBCs of sparfloxacin, tosufloxacin, ofloxacin, clarithromycin, and minocycline for these two strains were 0.063 and 0.063 micrograms/ml, 0.125 and 0.25 micrograms/ml, 1.0 and 1.0 micrograms/ml, 0.125 and 0.125 micrograms/ml, and 0.25 and 0.25 micrograms/ml, respectively. Fatal pneumonia was induced by intranasal inoculation of cyclophosphamide-treated leukopenic mice with C. pneumoniae IOL 207; infiltration of neutrophils and lymphocytes was observed in the lungs of these mice by histopathological examination. The 50% effective dose of sparfloxacin (oral dose of 0.97 mg/kg of body weight) against the pneumonia was the lowest among the drugs tested; this was followed by those of minocycline (2.22 mg/kg), tosufloxacin (3.47 mg/kg), clarithromycin (4.66 mg/kg), and ofloxacin (16.6 mg/kg). The results indicate that it may be worthwhile to use sparfloxacin against C. pneumoniae infections in humans.
Insights
Sparfloxacin demonstrated potent in vitro and in vivo antichlamydial activity against Chlamydia pneumoniae pneumonia in mice. It exhibited the lowest effective dose, suggesting potential for treating human C. pneumoniae infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Chlamydia pneumoniae is a significant cause of respiratory infections.
- Antibiotic resistance necessitates the evaluation of novel therapeutic agents.
- Leukopenic mouse models are utilized to study C. pneumoniae pneumonia.
Purpose of the Study:
- To evaluate the in vitro and in vivo antichlamydial activities of sparfloxacin.
- To compare sparfloxacin's efficacy against C. pneumoniae with established reference drugs.
- To assess the therapeutic potential of sparfloxacin for C. pneumoniae infections.
Main Methods:
- In vitro susceptibility testing (MIC and MBC) of sparfloxacin and reference drugs against C. pneumoniae strains.
- Induction of experimental pneumonia in leukopenic mice using C. pneumoniae.
- Histopathological examination of lung tissues to assess inflammatory responses.
- Determination of the 50% effective dose (ED50) for oral administration of sparfloxacin and reference drugs.
Main Results:
- Sparfloxacin exhibited potent in vitro activity with minimum inhibitory concentrations (MICs) of 0.031 µg/ml for both C. pneumoniae strains.
- In vivo, sparfloxacin demonstrated the lowest 50% effective dose (ED50) of 0.97 mg/kg for treating C. pneumoniae-induced pneumonia in mice.
- Histopathological analysis confirmed inflammatory infiltration in the lungs of infected mice, which was ameliorated by drug treatment.
Conclusions:
- Sparfloxacin possesses significant in vitro and in vivo antichlamydial activity.
- Sparfloxacin is more potent than minocycline, tosufloxacin, clarithromycin, and ofloxacin in this experimental model.
- Sparfloxacin warrants further investigation for its clinical utility in treating human Chlamydia pneumoniae infections.