a Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux cedex; b GlaxoWellcome, 100 Route de Versailles, 78163 Marly le Roi, France
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Abstract |
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Introduction |
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Materials and methods |
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Each of the following antimicrobial agents was provided by the manufacturer: grepafloxacin (GlaxoWellcome, Marly le Roi, France); sparfloxacin (Rhône-Poulenc-Rorer, Vitry-sur-Seine, France); ofloxacin and erythromycin (Roussel-Uclaf, Paris, France); ciprofloxacin (Bayer-Pharma, Puteaux, France) and doxycycline (Pfizer, Orsay, France).
Susceptibility testing
MICs were determined as previously described, using an agar dilution method with Hayflick modified agar for mycoplasma strains, and a broth dilution method with Shepard medium for ureaplasma strains. 5 The final concentrations of antibiotics tested were 0.015- 32 mg/L. Minimal bactericidal concentrations (MBCs) of grepafloxacin and of the comparative compounds were determined as previously reported, for a reference strain of each species in test tubes, containing Shepard broth medium for Ureaplasma urealyticum and Hayflick modified broth medium for the other mycoplasma species. 6 The MBC was the lowest antibiotic concentration inhibiting a colour change in the broth culture, within 4-10 days (according to the species).
Strains
A total of 106 strains, including 32 strains of Mycoplasma pneumoniae (31 clinical respiratory isolates and one reference strain, FH), six strains of Mycoplasma genitalium (five clinical isolates and one reference strain, G37), nine strains of Mycoplasma fermentans (six clinical strains and three reference strains, PG18, K7 and incognitus), two strains of Mycoplasma penetrans (one urethral isolate and one reference strain, GTU-54), 16 strains of Mycoplasma hominis (15 clinical isolates and one reference strain, PG21), 21 U. urealyticum doxycycline-susceptible strains (20 clinical isolates and one reference strain, serotype 8), and 21 U. urealyticum doxycycline-resistant strains (20 clinical isolates and one reference strain, serotype 9) were studied. An additional group of eight fluoroquinolone-resistant mutants obtained from the reference strain M. hominis PG21 by stepwise selection on increasing concentrations of various fluoroquinolones was studied. 7
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Results and discussion |
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As noted previously, 8 U. urealyticum was slightly less susceptible to grepafloxacin than it was to sparfloxacin, but overall grepafloxacin was four-fold more active than ofloxacin and ciprofloxacin. Doxycycline-resistant strains were as susceptible to grepafloxacin and sparfloxacin as doxycycline-susceptible strains (as previously described for other fluoroquinolones). 6,8
For all Mycoplasma spp. (Table), the MBCs of grepafloxacin were two- to 16-fold higher than the MICs. MBCs of sparfloxacin were lower by one dilution, except for M. genitalium. Ofloxacin and ciprofloxacin exhibited higher MBCs for mycoplasma strains than grepafloxacin or sparfloxacin. It should be noted that sparfloxacin MBCs were two-fold lower than those of grepafloxacin for all mycoplasma strains except M. genitalium. For the doxycycline-susceptible and -resistant strains of U. urealyticum, MBCs of grepafloxacin and sparfloxacin were bactericidal at only one dilution lower than MIC. These results indicate that grepafloxacin, like sparfloxacin, is bactericidal in vitro for all mycoplasmas and ureaplasmas.
In summary, grepafloxacin, like sparfloxacin 9 and BAY-128039, 6 can be ranked among the most active fluoroquinolones tested against Mycoplasma and Ureaplasma spp.; this study extends significantly the results of previous studies. 3,8 Its reportedly high distribution in lung tissue 4 and demonstrated clinical efficacy in M. pneumoniae pneumonia 10 may ensure an important role for grepafloxacin in the treatment of respiratory infections caused by mycoplasma species.
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Acknowledgments |
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Notes |
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References |
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Received 4 September 1998; returned 23 November 1998; revised 21 December 1998; accepted 22 January 1999