Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, May 2000, p. 1381-1382, Vol. 44, No. 5
Department of Laboratory
Medicine1 and the Second Department of
Internal Medicine,2 Nagasaki University
School of Medicine, Nagasaki 852-8501, Japan
Received 20 September 1999/Returned for modification 13 January
2000/Accepted 15 February 2000
The in vitro activity of telithromycin (HMR3647), a new ketolide,
against Mycoplasma pneumoniae was determined by the broth microdilution test using 41 clinical isolates obtained in Japan, as
compared with those of five macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin, and josamycin), minocycline, and levofloxacin. Telithromycin was less potent than azithromycin, but it
was more active than four other macrolides, minocycline, and
levofloxacin; its MICs at which 50 and 90% of the isolates tested were
inhibited were both 0.00097 µg/ml, justifying clinical studies to
determine its efficacy for treatment of M. pneumoniae.
Mycoplasma pneumoniae is
the common cause of community-acquired pneumonia; it was detected in
4.9% of patients with community-acquired pneumonia in a recent study
in Japan (7). Macrolides and minocycline, a tetracycline,
are the agents of first choice in the treatment of M. pneumoniae infections, but some strains are resistant to these
antibiotics (10). Levofloxacin, a quinolone, is also known to be active against the organism. Antibacterial studies conducted outside Japan have already revealed that telithromycin (HMR3647), a new
ketolide antibiotic, is highly effective against gram-positive organisms (e.g., Streptococcus pneumoniae), gram-negative
organisms (e.g., Haemophilus influenzae, Moraxella
catarrharis, and Legionella pneumophila), some enteric
pathogens, and anaerobic bacteria (1, 2, 4, 5, 11, 13).
Bacteria, especially their clinical isolates, are known to differ from
one country to another, but the efficacy of telithromycin against
Japanese clinical isolates of M. pneumoniae has not been examined yet. This study was conducted to determine the in vitro activity of the antibiotic against 41 strains of the organism isolated
in Japan, compared with those of five macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin, and josamycin),
minocycline, and levofloxacin.
Forty-one clinical isolates of M. pneumoniae were obtained
from Nagasaki University Hospital and its affiliated medical
facilities. Three standard strains used as controls were M. pneumoniae FH, Mac, and M129, which were kindly supplied by
M. F. Barile, Food and Drug Administration, Bethesda, Md.
In vitro antimycoplasmal susceptibility tests have not been
standardized; one was performed in this study by the broth
microdilution method, which has been recently applied for several
potent antibiotics for treatment of M. pneumoniae infections
(6, 8, 9, 12, 14, 15). M. pneumoniae isolates
were grown to a concentration of 108 CFU/ml in modified
Chanock broth medium (3) consisting of 7 parts
pleuropneumonia-like organism (PPLO) broth without crystal violet
(Difco Laboratories, Detroit, Mich.), 2 parts uninactivated horse
serum, and 1 part a mixture of 25% fresh yeast extract, 1% glucose,
and 0.002% phenol red adjusted to a pH of 7.8 with 1 N sodium
hydroxide. Drug concentrations were as follows: minocycline and
levofloxacin, 0.0078 to 8 µg/ml; erythromycin, clarithromycin, roxithromycin, and josamycin, 0.00024 to 0.25 µg/ml; and
azithromycin and telithromycin, 0.00003 to 0.031 µg/ml. The
isolates were inoculated in microtiter plates containing telithromycin
and reference antibiotics at a final concentration of 105
CFU/ml in the above broth medium. The inoculum numbers were confirmed by counting colonies grown on Chanock agar. The plates were sealed with
a plate sealer and incubated at 37°C under atmospheric conditions for
3 to 6 days. In each case, when the color of the medium of the
drug-free control changed from red to yellow, the minimal concentration
of drug preventing the color change was defined as the MIC
(6).
All plates were examined for prevention of the color change by each
antibiotic once daily during the incubation. MIC50 and MIC90 were defined as the drug concentrations required to
inhibit the growth of 50 and 90% of the total number of isolates
tested, respectively (6, 8, 9, 12, 14, 15). As a control for
potential interactions between antibiotics, medium components, and pH,
which could potentially affect the observed MICs, the American Type
Culture Collection bacterial reference strain Staphylococcus aureus ATCC 29213 was inoculated into microtiter plates containing Chanock broth.
The MIC range, MIC50, and MIC90 of each
antibiotic against M. pneumoniae isolates are shown in Table
1. Telithromycin was less potent than
azithromycin, but it was more active than four other macrolides,
minocycline, and levofloxacin; its MIC50 and MIC90 were both 0.00097 µg/ml.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
In Vitro Activity of Telithromycin (HMR3647), a New
Ketolide, against Clinical Isolates of Mycoplasma pneumoniae
in Japan
ABSTRACT
Top
Abstract
Text
References
TEXT
Top
Abstract
Text
References
TABLE 1.
MICs of antimycoplasmal agents
The excellent in vitro activity of telithromycin against clinical isolates of M. pneumoniae justifies further studies to determine its clinical efficacy for treatment of community-acquired infections due to this organism.
| |
FOOTNOTES |
|---|
* Corresponding author. Mailing address: Department of Laboratory Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Phone: 81 (95)-849-7420. Fax: 81 (95)-849-7422. E-mail: toshi-ngs{at}umin.ac.jp.
| |
REFERENCES |
|---|
|
Top
Abstract
Text
References
|
|---|
| 1. |
Barry, A. L.,
P. C. Fuchs, and S. D. Brown.
1998.
Antipneumococcal activities of a ketolide (HMR 3647), a streptogramin (quinupristin-dalfopristin), a macrolide (erythromycin), and a lincosamide (clindamycin).
Antimicrob. Agents Chemother.
42:945-946 |
| 2. |
Barry, A. L.,
P. C. Fuchs, and S. D. Brown.
1998.
In vitro activities of the ketolide HMR 3647 against recent gram-positive clinical isolates and Haemophilus influenzae.
Antimicrob. Agents Chemother.
42:2138-2140 |
| 3. |
Chanock, R. M.,
L. Hayflick, and M. F. Barile.
1962.
Growth on artificial medium of an agent associated with atypical pneumonia and its identification as PPLO.
Proc. Natl. Acad. Sci. USA
48:41-49 |
| 4. |
Edelstein, P. H., and M. A. Edelstein.
1999.
In vitro activity of the ketolide HMR 3647 (RU 6647) for Legionella spp., its pharmacokinetics in guinea pigs, and use of the drug to treat guinea pigs with Legionella pneumophila pneumonia.
Antimicrob. Agents Chemother.
43:90-95 |
| 5. |
Hamilton-Miller, J. M., and S. Shah.
1998.
Comparative in-vitro activity of ketolide HMR 3647 and four macrolides against gram-positive cocci of known erythromycin susceptibility status.
J. Antimicrob. Chemother.
41:649-653 |
| 6. | Ishida, K., M. Kaku, K. Irifune, R. Mizukane, H. Takemura, R. Yoshida, H. Tanaka, T. Usui, N. Suyama, K. Tomono, H. Koga, S. Kohno, K. Izumikawa, and K. Hara. 1994. In vitro and in vivo activities of macrolides against Mycoplasma pneumoniae. Antimicrob. Agents Chemother. 4:790-798. |
| 7. |
Ishida, T.,
T. Hashimoto,
M. Arita,
I. Ito, and M. Osawa.
1998.
Etiology of community-acquired pneumonia in hospitalized patients: a 3-year prospective study in Japan.
Chest
114:1588-1593 |
| 8. |
Izumikawa, K.,
Y. Hirakata,
T. Yamaguchi,
R. Yoshida,
H. Tanaka,
H. Takemura,
S. Maesaki,
K. Tomono,
M. Kaku,
K. I. Izumikawa,
S. Kamihira, and S. Kohno.
1998.
In vitro activities of quinupristin-dalfopristin and the streptogramin RPR 106972 against Mycoplasma pneumoniae.
Antimicrob. Agents Chemother.
42:698-699 |
| 9. | Kaku, M., K. Ishida, K. Irifune, R. Mizukane, H. Takemura, R. Yoshida, H. Tanaka, T. Usui, K. Tomono, N. Suyama, H. Koga, S. Kohno, and K. Hara. 1994. In vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae. Antimicrob. Agents Chemother. 4:738-741. |
| 10. | Lucier, T. S., K. Heitzman, S. K. Liu, and P. C. Hu. 1995. Transition mutations in the 23S rRNA of erythromycin-resistant isolates of Mycoplasma pneumoniae. Antimicrob. Agents Chemother. 12:2770-2773. |
| 11. |
Malathum, K.,
T. M. Coque,
K. V. Singh, and B. E. Murray.
1999.
In vitro activities of two ketolides, HMR 3647 and HMR 3004, against gram-positive bacteria.
Antimicrob. Agents Chemother.
43:930-936 |
| 12. |
Osada, Y., and H. Ogawa.
1983.
Antimycoplasmal activity of ofloxacin (DL-8280).
Antimicrob. Agents Chemother.
23:509-511 |
| 13. |
Piper, K. E.,
M. S. Rouse,
J. M. Steckelberg,
W. R. Wilson, and R. Patel.
1999.
Ketolide treatment of Haemophilus influenzae experimental pneumonia.
Antimicrob. Agents Chemother.
43:708-710 |
| 14. |
Waites, K. B.,
G. H. Cassel,
K. C. Canupp, and P. B. Fernandes.
1988.
In vitro susceptibilities of mycoplasmas and ureaplasmas to new macrolides and aryl-fluoroquinolones.
Antimicrob. Agents Chemother.
32:1500-1502 |
| 15. |
Waites, K. B.,
L. B. Duffy,
T. Schmid,
D. Crabb,
M. S. Pate, and G. H. Cassel.
1991.
In vitro susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to sparfloxacin and PD 127391.
Antimicrob. Agents Chemother.
35:1181-1185 |
Antimicrobial Agents and Chemotherapy, May 2000, p. 1381-1382, Vol. 44, No. 5
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Johnston, S. L., Blasi, F., Black, P. N., Martin, R. J., Farrell, D. J., Nieman, R. B., the TELICAST Investigators,
(2006). The Effect of Telithromycin in Acute Exacerbations of Asthma. NEJM
354: 1589-1600
[Abstract] [Full Text] -
Waites, K. B., Crabb, D. M., Duffy, L. B.
(2003). In Vitro Activities of ABT-773 and Other Antimicrobials against Human Mycoplasmas. Antimicrob. Agents Chemother.
47: 39-42
[Abstract] [Full Text] -
Maurin, M., Bryskier, A., Raoult, D.
(2002). Antibiotic Susceptibilities of Parachlamydia acanthamoeba in Amoebae. Antimicrob. Agents Chemother.
46: 3065-3067
[Abstract] [Full Text] -
Kenny, G. E., Cartwright, F. D.
(2001). Susceptibilities of Mycoplasma hominis, M. pneumoniae, and Ureaplasma urealyticum to GAR-936, Dalfopristin, Dirithromycin, Evernimicin, Gatifloxacin, Linezolid, Moxifloxacin, Quinupristin-Dalfopristin, and Telithromycin Compared to Their Susceptibilities to Reference Macrolides, Tetracyclines, and Quinolones. Antimicrob. Agents Chemother.
45: 2604-2608
[Abstract] [Full Text] -
Pereyre, S., de Barbeyrac, B., Renaudin, H., Poutiers, F., Bebear, C., Bebear, C. M.
(2001). In vitro activity of midecamycin diacetate against Mycoplasma pneumoniae and Chlamydia pneumoniae. J Antimicrob Chemother
47: 240-241
[Full Text]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»