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Antimicrobial Agents and Chemotherapy, March 1998, p. 698-699, Vol. 42, No. 3
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
In Vitro Activities of Quinupristin-Dalfopristin and the
Streptogramin RPR 106972 against Mycoplasma pneumoniae
Koichi
Izumikawa,1,*
Yoichi
Hirakata,1
Toshiyuki
Yamaguchi,1
Ryoji
Yoshida,2
Hironori
Tanaka,2
Hiromu
Takemura,3
Shigefumi
Maesaki,2
Kazunori
Tomono,2
Mitsuo
Kaku,3
Kin-Ichi
Izumikawa,4
Shimeru
Kamihira,1 and
Shigeru
Kohno2
Department of Laboratory
Medicine1 and
Second Department of
Internal Medicine,2 Nagasaki University
School of Medicine, Nagasaki 852, Department of Microbiology,
St. Marianna University School of Medicine, Kawasaki
211,3 and
Izumikawa Hospital,
Nagasaki 859-15,4 Japan
Received 4 August 1997/Returned for modification 22 October
1997/Accepted 15 December 1997
 |
ABSTRACT |
The in vitro activities of quinupristin-dalfopristin and
streptogramin RPR 106972 were determined with 44 strains of
Mycoplasma pneumoniae and compared to those of macrolides,
minocycline, and quinolones. All isolates tested were highly
susceptible to macrolides and to quinupristin-dalfopristin (MIC at
which 90% of the isolates are inhibited [MIC90], 0.0625 µg/ml), followed by RPR 106972 (MIC90, 0.5 µg/ml),
quinolones, and minocycline.
| |
TEXT |
Mycoplasma pneumoniae is
recognized as a common pathogen in community-acquired pneumonia.
Macrolides and minocycline are agents of first choice in treatment of
M. pneumoniae infections, but some strains are
resistant to these agents (7). Quinupristin-dalfopristin and
RPR 106972 are injectable and oral streptogramins, respectively, composed of two synergistic components and developed for
multi-drug-resistant gram-positive bacteria (10). In this
study, we have investigated the in vitro activities of the
streptogramins against M. pneumoniae in comparison with
those of minocycline, macrolides, and quinolones.
A total of 41 clinical isolates of M. pneumoniae
obtained in Nagasaki University School of Medicine Hospital and
affiliated medical facilities and 3 standard strains (M. pneumoniae FH, Mac, and M129, which were kindly supplied by
M. F. Barile [Food and Drug Administration, Bethesda, Md.])
were used.
Antimycoplasmal susceptibility tests were performed by the broth
microdilution method (5, 6, 8, 13, 14). Briefly, M. pneumoniae isolates were grown to a concentration of
108 CFU/ml in modified Chanock broth medium (4)
consisting of 7 parts pleuropneumonialike organism broth without
crystal violet (Difco Laboratories, Detroit, Mich.), 2 parts
uninactivated horse serum, 1 part 25% fresh yeast extract, 1%
glucose, and 0.002% phenol red adjusted to pH 7.8 with 1 N sodium
hydroxide. Organisms were inoculated in microtiter plates containing
antimycoplasmal agents in the medium described above at a final
concentration of 105 CFU/ml. The plates were sealed with a
plate sealer and incubated at 37°C under atmospheric conditions.
All plates were examined once daily, and 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 (5, 6, 8, 13, 14). Staphylococcus aureus ATCC 29213 was used as a quality control for potential interactions between antibiotics, medium components, and pH.
MICs of potent antibiotics for M. pneumoniae,
including minocycline (Lederle, Ltd., Tokyo, Japan), erythromycin
(Dainippon, Ltd., Osaka, Japan), clarithromycin (Dynabot, Ltd.,
Tokyo, Japan), azithromycin (Pfizer, Ltd., Tokyo, Japan),
ofloxacin (Dai-ichi Pharmaceutical, Ltd., Tokyo, Japan), sparfloxacin
(Dainippon), quinupristin-dalfopristin (Rhone-Poulenc Rorer,
Ltd., Tokyo, Japan) and RPR 106972 (Rhone-Poulenc Rorer), were
determined.
The comparative MIC range, MIC at which 50% of the isolates are
inhibited (MIC50), and MIC90 are shown in Table
1. Macrolides, especially azithromycin,
were potent against M. pneumoniae isolates, followed by
quinupristin-dalfopristin, sparfloxacin, and RPR 106972. The in vitro
activities of streptogramins were lower than those of macrolides, but
higher than those of ofloxacin and minocycline. There was no
correlation between MICs of erythromycin and quinupristin-dalfopristin (r = 0.173) or between those of erythromycin and RPR
106972 (r = 0.013).
Streptogramin antibiotics have been developed for the treatment of
multi-drug-resistant gram-positive bacterial infections and consist of
two molecules which are group A streptogramins (macrolactones) and
group B streptogramins (cyclic hexadepsipeptides) (10). Both
group A and group B streptogramins are bacteriostatic alone, but
bactericidal in combination (12). They act synergistically against not only multi-drug-resistant gram-positive strains but also
other respiratory pathogens, including Moraxella
catarrhalis, Streptococcus pneumoniae, S. pyogenes, and Legionella pneumophila, and are somewhat
less active against Haemophilus influenzae (1-3, 9,
11). The most characteristic aspect of this class of drug is that
there is no cross-resistance with macrolides or lincosamides, although
these drugs also inhibit protein synthesis at the ribosomal level
(10).
In our study, there was no correlation between MICs of streptogramins
and erythromycin, although erythromycin-resistant strains have not yet
been tested. In conclusion, our results suggest that streptogramins
have the possibility of being used for community-acquired M. pneumoniae infections in addition to multi-drug-resistant
bacterial infections.
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FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Laboratory Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852, Japan. Phone: 81 (95)-849-7420. Fax: 81 (95)-849-7422. E-mail:
peaton-ngs{at}umin.u-tokyo.ac.jp.
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Antimicrobial Agents and Chemotherapy, March 1998, p. 698-699, Vol. 42, No. 3
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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