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Antimicrobial Agents and Chemotherapy, July 2000, p. 1980-1982, Vol. 44, No. 7
Laboratoire de Bactériologie,
Université Victor Segalen Bordeaux 2, 33076 Bordeaux
Cedex,1 and Hoechst Marion Roussel,
93235 Romainville Cedex,2 France
Received 8 December 1999/Returned for modification 25 March
2000/Accepted 11 April 2000
The activities of telithromycin and levofloxacin against 99 mycoplasma strains were compared to those of several macrolides, ofloxacin, and doxycycline. Telithromycin MICs of Only a few classes of antimicrobial
agents are available for the treatment of mycoplasmal infections in
humans. They are mainly the tetracyclines, macrolides, and
fluoroquinolones (15). Resistance to tetracyclines by the
acquisition of the tetM gene has been frequently described
for urogenital mycoplasmas (12, 13). Concerning macrolides,
Mycoplasma hominis and Mycoplasma fermentans are
innately resistant to erythromycin but not to josamycin, while Mycoplasma pneumoniae and Mycoplasma genitalium
are very susceptible to all these antibiotics. The newest macrolides
are semisynthetic compounds known as ketolides (6). They
have improved activity against microorganisms resistant to macrolides,
especially gram-positive bacteria (8). One of them is
telithromycin (HMR 3647), an erythromycin A derivative. Newer
fluoroquinolones with enhanced activity against gram-positive bacteria
and intracellular organisms have been developed (9).
Levofloxacin, the l-isomer of ofloxacin, is one of these (10, 14).
In this study, we compared the in vitro activity of telithromycin to
those of several macrolides, including erythromycin A, roxithromycin,
dirithromycin, clarithromycin, azithromycin, josamycin, and spiramycin,
and the in vitro activity of levofloxacin to that of ofloxacin against
clinical and reference strains of different human mycoplasma species.
Doxycycline was used as a reference compound. Each of the following
antimicrobial agents was provided by the manufacturer: telithromycin,
levofloxacin, erythromycin A, roxithromycin, and ofloxacin (Hoechst
Marion Roussel, Romainville, France); azithromycin and doxycycline
(Pfizer, Orsay, France); clarithromycin (Abbott, Rungis, France);
dirithromycin (Lilly France, Saint Cloud, France); and josamycin and
spiramycin (Rhône-Poulenc-Rorer, Vitry-sur-Seine, France).
Ninety-nine strains, including 25 strains of M. pneumoniae
(24 clinical respiratory isolates and 1 reference strain [FH]), 5 strains of M. genitalium (4 clinical isolates and 1 reference strain [G37]), 32 strains of M. hominis (29 josamycin-susceptible clinical isolates, 2 josamycin-resistant clinical
isolates, and 1 reference strain [PG21]), 5 strains of M. fermentans (4 clinical isolates and 1 reference strain [PG18]),
2 strains of Mycoplasma penetrans (1 urethral isolate and 1 reference strain [GTU-54]), 15 Ureaplasma urealyticum
doxycycline-susceptible strains (14 clinical isolates and 1 reference
strain, serotype 8), and 15 U. urealyticum
doxycycline-resistant strains (14 clinical isolates and 1 reference
strain, serotype 9), were studied.
Susceptibility testing was carried out as previously described
(1) by an agar dilution method with Hayflick modified agar for mycoplasmal strains and by a broth dilution method with Shepard medium for ureaplasmal strains. Minimal bactericidal concentrations (MBCs) of the different compounds were determined as previously reported (3) for a reference strain of each species.
The in vitro activities of telithromycin, levofloxacin, and other
antimicrobial agents are shown in Table
1.
Telithromycin inhibited all mycoplasmal
and ureaplasmal strains, except for M. hominis, at
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Copyright © 2000, American Society for Microbiology. All rights reserved.
Comparative Activities of Telithromycin (HMR 3647), Levofloxacin,
and Other Antimicrobial Agents against Human Mycoplasmas
ABSTRACT
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0.25 µg/ml were
found for all isolates, except for Mycoplasma hominis,
while levofloxacin was active at concentrations of 1 µg/ml against all species studied.
TEXT
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0.25
µg/ml. Telithromycin shared the best activity (MIC at which 90% of
strains were inhibited [MIC90] or MIC range, 0.015
µg/ml) with erythromycin A, roxithromycin, clarithromycin, and
azithromycin against M. pneumoniae isolates and with
erythromycin A and roxithromycin against M. genitalium
isolates. Telithromycin had the lowest MIC range, from 0.06 to 0.25 µg/ml, against both M. fermentans and M. penetrans. Against M. hominis isolates for which
josamycin was the only active macrolide, telithromycin had a high
MIC90 (16 µg/ml), but this MIC90 was fourfold
lower than those of the macrolides, except for josamycin. However, the
two josamycin-resistant clinical isolates of M. hominis
previously described (5) were found to be as resistant to
telithromycin as to the macrolides (MIC, >128 µg/ml).
TABLE 1.
Comparative in vitro activities of telithromycin,
levofloxacin, and other antimicrobial agents against human mycoplasmas
Against U. urealyticum strains, telithromycin was found to be as active as clarithromycin, the most active macrolide tested, with an MIC90 of 0.03 µg/ml. Furthermore, ketolide activity was the same whatever the doxycycline susceptibility profile of the ureaplasmal isolates. Our study on telithromycin globally confirms our results previously reported for other ketolides, such as RU 004, RU 306, RU 469, and RU 399, for mycoplasmas, with MICs ranking in similar ranges (2).
The MBCs of telithromycin were found to be close to the MICs for
M. pneumoniae and M. genitalium (MBCs, 0.12
µg/ml), as were the MBCs of the macrolides tested. Against M. fermentans and M. penetrans, the telithromycin MBCs
were found to be 2 and 1 µg/ml, respectively, much lower than those
of the macrolides, especially for M. fermentans (MBCs of
comparative macrolides, 16 to >128 µg/ml). Against M. hominis, the telithromycin MBC (16 µg/ml) was comparable to that
of josamycin, the only macrolide that had low MICs against this
species. Against U. urealyticum, despite a very low
MIC90, telithromycin did not have good bactericidal
activity, with an MBC of 
32 µg/ml. Only two macrolides,
clarithromycin and azithromycin, had lower MBCs, between 1 and 8 µg/ml. In summary, except against M. hominis and U. urealyticum, telithromycin was bactericidal against mycoplasmal isolates.
Comparative results for levofloxacin are also shown in Table 1. All the mycoplasma strains studied were inhibited by 1 µg of levofloxacin per ml. Against the five mycoplasma species studied, levofloxacin had activity similar to that of ofloxacin, with equal MICs for M. pneumoniae and M. genitalium (MIC range, 0.5 to 1 µg/ml) or an MIC twofold lower for M. hominis, M. fermentans, and M. penetrans. Against U. urealyticum, levofloxacin was two- to fourfold more active than ofloxacin (MIC90, 0.5 to 1 µg/ml), with similar activity against doxycycline-susceptible or -resistant strains. In a previous study, Ullmann et al. (16) obtained results within the same range as ours for levofloxacin against U. urealyticum but not against M. hominis, for which they found an MIC90 fourfold higher. Waites et al. (17) found the same MIC90 of levofloxacin as we did against M. hominis by the E test method (17). It should be noted that levofloxacin showed only slightly enhanced activity against mycoplasmas in comparison to ofloxacin, with MICs only one dilution higher. In terms of in vitro activity, levofloxacin does not seem to be significantly more active than its l-isomer, ofloxacin, against mycoplasmas.
For all mycoplasmal and ureaplasmal strains, MBCs of levofloxacin were
equal to or twofold lower than those of ofloxacin, ranging from 0.12 µg/ml against M. penetrans to 4 µg/ml against M. genitalium and M. hominis. For M. pneumoniae, M. genitalium, M. penetrans, and
U. urealyticum, MBCs were only 2- to 4-fold higher than
MICs, while they were 8- to 16-fold higher than MICs for M. hominis and M. fermentans. However, levofloxacin seemed to be bactericidal in vitro against mycoplasmas, with MBCs of 4
µg/ml.
As a reference compound, doxycycline showed good activity, ranging between those of telithromycin and levofloxacin, against mycoplasmas and U. urealyticum doxycycline-susceptible strains (MICs, 0.03 to 0.25 µg/ml), except for M. hominis strains, some of which were doxycycline resistant.
In conclusion, our data suggest that levofloxacin, like other new fluoroquinolones (3, 4, 7, 11, 16), may be interesting for the treatment of respiratory and urogenital mycoplasma infections. Telithromycin, belonging to the new class, ketolides, seems to be very effective against mycoplasmas, except for M. hominis, and could have useful clinical activity against these microorganisms.
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ACKNOWLEDGMENTS |
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This study was supported in part by a grant from Hoechst Marion Roussel (Romainville, France).
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FOOTNOTES |
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* Corresponding author. Mailing address: Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France. Phone: (33) 5.57.57.16.25. Fax: (33) 5.56.93.29.40. E-mail: cecile.bebear{at}u-bordeaux2.fr.
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Antimicrobial Agents and Chemotherapy, July 2000, p. 1980-1982, Vol. 44, No. 7
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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