Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama 701-0192, Japan
Received 14 February 2003; returned 15 April 2003; revised 13 June 2003; accepted 17 June 2003
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Abstract |
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Methods: The in vitro activity of cethromycin against 20 isolates of C. pneumoniae was compared with the activities of telithromycin, erythromycin A, azithromycin and clarithromycin against those isolates.
Results: The MIC at which 90% of the isolates were inhibited and the minimal chlamydiacidal concentration at which 90% of the isolates were killed by cethromycin were both 0.016 mg/L (range 0.0160.031 mg/L). Cethromycin was the most active antibiotic tested in this study.
Conclusions: Our results appear to indicate that cethromycin is an effective antibiotic that should play some role in the treatment of respiratory tract infections caused by C. pneumoniae.
Keywords: macrolides, telithromycin, community-acquired pneumonia
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Introduction |
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Materials and methods |
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The antimicrobial agents tested were erythromycin A (Shionogi Co., Osaka, Japan), clarithromycin (Taisho Pharmaceutical Co., Osaka, Japan), azithromycin (Pfizer Pharmaceutical Co., Tokyo, Japan), telithromycin (Aventis Pharma Co., Tokyo, Japan) and cethromycin (Dainabbott Laboratories, Osaka, Japan). Solutions of the agents were prepared following the manufacturers instructions.
Isolates
Twenty C. pneumoniae isolates were used in this study. TW-183, AR-39 and AR-388 were obtained from the Washington Research Foundation, Seattle, WA, USA. IOL-207 and Kajaani-6 were acquired from P. Saikku, National Public Health Institute, Oulu, Finland. Fifteen wild-type isolates (designated KKpn-1 to KKpn-15) were also tested, which were isolated from nasopharyngeal swab specimens collected from patients with acute respiratory tract infections at Kawasaki Medical School Hospital, Japan. The organisms from these clinical samples were positively stained with C. pneumoniae-specific monoclonal antibody. These clinical isolates were morphologically different from TWAR (TW-183, AR-39 and AR-388) strains from the United States (examples are given in Figure 1).3 KKpn-15 elementary bodies (EBs) have a narrow periplasmic space and are round in shape, whereas TW-183 EBs are enclosed by a wavy outer membrane and are pear-shaped in profile.
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One millilitre of culture medium [Eagles minimal essential medium (Nissui Pharmaceuticals Co., Tokyo, Japan) and 10% heat-inactivated fetal calf serum (GIBCO BRL Life Technologies Inc., Grand Island, NY, USA)] containing 105 HEp-2 cells per mL were dispensed into each well of plastic 24-well culture plates, which were then incubated in 5% CO2 at 35°C for 48 h. After confirming growth of a confluent monolayer, the culture fluid was removed from the wells by aspiration. Next, 104 inclusion-forming units per mL of each chlamydial strain were inoculated into each well. Then the plates were centrifuged at 900g for 60 min, and 1 mL of each preparation of the culture medium containing 1 mg/L cycloheximide (Nakarai Tesque Inc., Tokyo, Japan) and one concentration (final concentrations; range from 0.008 to 2 mg/L) of the test antibiotic were dispensed into each well. After incubation in 5% CO2 at 35°C for 72 h, the cultures were fixed and stained for inclusions with the fluorescein isothiocyanate-conjugated monoclonal antibody specific for the chlamydial genus-specific antigen (Chlamydia FA Seiken; Denka Seiken, Tokyo, Japan). The MIC was defined as the lowest concentration at which no inclusions were found. The MCCs were determined by aspirating the antibiotic-containing medium, washing the wells twice with phosphate-buffered saline, and adding antibiotic-free medium. The infected cells were frozen at 70°C, thawed, passed onto new cells, incubated for 72 h, and then fixed and stained as described above. The MCC was the lowest antibiotic concentration resulting in no inclusions after passage. All tests were run in triplicate. Antichlamydial activity was determined when the same results were observed in at least two out of three experiments.
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Results |
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Discussion |
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The available data on the activity of cethromycin against C. pneumoniae are limited. Strigl et al.4 found that both the MIC50 and MIC90 values of cethromycin against 20 isolates of C. pneumoniae including two reference strains, TW-183 and AR-39, were 0.015 mg/L.The MIC90 and MCC90 against 20 isolates of C. pneumoniae found in our study are also consistent with their report. Based on the above findings and previous reports of the potent and broad antibacterial activity of cethromycin, we can conclude that cethromycin, like telithromycin, could be a useful oral agent for the acute treatment of respiratory tract infections. Prospective studies of cethromycin for the treatment of CAP should be able to determine the role of this drug in the treatment of such infections.
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Acknowledgements |
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Footnotes |
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References |
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