Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama 701-0192, Japan
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The antimicrobial agents tested were telithromycin and roxithromycin (Hoechst-Marion-Roussel Ltd, Tokyo, Japan), erythromycin A (Shionogi Co., Osaka, Japan), clarithromycin (Taisho Pharmaceutical Co., Osaka, Japan) and azithromycin (Pfizer Pharmaceutical Co., Tokyo, Japan). Solutions of the agents were prepared following the manufacturer's instructions.
Chlamydial strains
Twenty C. pneumoniae strains 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 strains (designated KKpn-115), which were isolated from nasopharyngeal swab specimens collected from patients with acute respiratory tract infections at Kawasaki Medical School Hospital, Japan, were also tested. The clinical isolates 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 USA.3,4
Measurement of MICs and minimal chlamydiacidal concentrations (MCCs)
One millilitre of culture medium [Eagle's 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/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/mL of each chlamydial strain were inoculated into each well. Then plates were centrifuged at 900g for 60 min, and 1 mL of each preparation of the culture medium containing 1 mg/L of cycloheximide (Nakarai Tesque Inc., Tokyo, Japan) and one concentration (final concentrations range from 0.008 to 2 mg/L) of the test antibiotic was 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 to 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 which resulted in no inclusions after passage. All tests were run in triplicate.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In our study, telithromycin showed good in vitro anti- C. pneumoniae activity higher than that of roxithromycin, azithromycin and erythromycin A. Roblin & Hammerschlag6 found the MIC50 and MIC90 of telithromycin against 19 isolates of C. pneumoniae, including a reference strain, TW-183, to be 0.0625 and 0.25 mg/L, respectively. Subsequently, the same group reported the same results in a different study.7 Our results were almost consistent with former reports,68 although the type of C. pneumoniae isolates differed. Our MCC results were consistent with those of Roblin et al.,6,7 but not with those of Gustafsson et al.,8 who found MCC values to be almost 100 times higher than the MIC values. This may be because of a difference in the technique used for passage (not freezing) and a pre-incubation time of 2 h in their study. This technique may reflect a situation more similar to what occurs in vivo. Based on the above and previous reports of the potent and broad antibacterial activity of telithromycin, we can conclude that telithromycin could be a useful oral agent for the acute treatment of respiratory tract infections. Prospective studies of telithromycin for the treatment of community-acquired pneumonia should be able to determine the role of this drug in the treatment of such infections.
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 . Boswell, F. J., Andrews, J. M., Ashby, J. P., Fogarty, C., Brenwald, N. P. & Wise, R. (1998). In vitro activity of HMR 3647, a new ketolide antimicrobial agent. Journal of Antimicrobial Chemotherapy 42, 7039.[Abstract]
3 . Kuo, C. C., Jackson, L. A., Campbell, L. A. & Grayston, J. T. (1995). Chlamydia pneumoniae (TWAR). Clinical Microbiology Review 8, 45161.[ISI]
4 . Miyashita, N., Niki, Y., Kishimoto, T., Nakajima, M. & Matsushima, T. (1997). In vitro and in vivo activities of AM-1155, a new fluoroquinolone, against Chlamydia spp. Antimicrobial Agents and Chemotherapy 41, 13314.[Abstract]
5 . Niki, Y., Kimura, M., Miyashita, N. & Soejima, R. (1994). In vitro and in vivo activities of azithromycin, a new azalide antibiotic, against Chlamydia. Antimicrobial Agents and Chemotherapy 38, 22969.[Abstract]
6
.
Roblin, P. M. & Hammerschlag, M. R. (1998). In vitro activity of a new ketolide antibiotic, HMR 3647, against Chlamydia pneumoniae. Antimicrobial Agents and Chemotherapy 42, 15156.
7
.
Strigl, S., Roblin, P. M., Reznik, T. & Hammerschlag, M. R. (2000). In vitro activity of ABT 773, a new ketolide antibiotic, against Chlamydia pneumoniae. Antimicrobial Agents and Chemotherapy 44, 11123.
8
.
Gustafsson, I., Hjelm, E. & Cars, O. (2000). In vitro pharmacodynamics of the new ketolides HMR 3004 and HMR 3647 (telithromycin) against Chlamydia pneumoniae. Antimicrobial Agents and Chemotherapy 44, 18469.
9 . Block, S., Hedrick, J., Hammerschlag, M. R., Cassell, G. H. & Craft, J. C. (1995). Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric community-acquired pneumonia: comparative efficacy and safety of clarithromycin vs. erythromycin ethylsuccinate. Pediatric Infectious Disease Journal 14, 4717.[ISI][Medline]
10 . Soejima, R., Kimura, M., Kubota, Y., Kishimoto, T., Niki, Y. & the Japan Roxithromycin Respiratory Chlamydial Infection Study Group. (1994). Laboratory and clinical studies on roxithromycin in the treatment of chlamydial respiratory infections. Japanese Journal of Chemotherapy (Tokyo) 42, 87789.
Received 18 December 2000; returned 21 March 2001; revised 18 April 2001; accepted 11 June 2001