Comparative In Vitro Activities of the Investigational Fluoroquinolone DC-159a and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas

Abstract

The in vitro susceptibilities of 151 unique clinical isolates of Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma fermentans, Mycoplasma genitalium, and Ureaplasma species to DC-159a, an investigational fluoroquinolone, in comparison with those to other agents were determined. Macrolides were the most active agents against M. pneumoniae and M. genitalium, whereas clindamycin was most active against M. hominis. DC-159a MICs were <0.5 g/ml for all Mycoplasma species and <4 g/ml for ureaplasmas. DC-159a was the most active fluoroquinolone tested against M. pneumoniae and M. fermentans, and it was second to moxifloxacin against the other species. It was bactericidal against 10 M. pneumoniae isolates and demonstrated killing of >99.9% of the inoculum at 24 h for 2 isolates. The excellent in vitro activity of DC-159a demonstrates its potential for use in the treatment of infections due to mycoplasmas and ureaplasmas.Mycoplasmal species of human origin, including Mycoplasma pneumoniae, M. genitalium, M. hominis, M. fermentans, and Ureaplasma spp., can be responsible for infections in the respiratory and urogenital tracts. In some cases, these organisms can cause severe, systemic disease, especially in the setting of a debilitated or immunocompromised host (11). Current treatment alternatives are limited primarily to drugs in the macrolide, lincosamide, tetracycline, and fluoroquinolone classes, and various agents in these classes exhibit differential in vitro activities against these organisms.Fluoroquinolones are useful treatment options for mycoplasmal and ureaplasmal infections because they have the advantages of being well tolerated in oral formulations; they have long half-lives, allowing once-daily dosage; they possess bactericidal activity; they are not affected by resistance mechanisms that affect other drug classes, such as tetracyclines and macrolides; and documented in vitro resistance is uncommon (3,8,9,11). The broad spectrum of activity against many other microorganisms that may cause clinically similar illnesses makes fluoroquinolones attractive for empirical treatment since most mycoplasmal and ureaplasmal infections are rarely confirmed by microbiological testing.DC-159a is an investigational fluoroquinolone being developed by Daiichi Sankyo Pharmaceuticals Co., Ltd., Tokyo, Japan. This agent has been shown previously to have potent in vitro activity against other bacterial pathogens causing diseases in the respiratory tract, including Streptococcus pneumoniae, S. pyogenes, S. agalactiae, Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, and Bordetella pertussis (5, 6). The only susceptibility data available for DC-159a thus far are those in a report providing MICs for 10 strains of M. pneumoniae (4). The present study was undertaken to investigate the comparative in vitro inhibitory and bactericidal activities of DC-159a against a collection of mycoplasma and ureaplasma species that are known to cause disease in humans.(Results of this work were presented at the 47th Interscience ...

Efficacy of standard therapies againstUreaplasmaspecies and persistence among men with non-gonococcal urethritis enrolled in a randomised controlled trial

“…These high rates of persistent detection, even among men who denied unprotected sex between visits, contrast with the apparent in vitro susceptibility of UU-2 and UP isolates that we observed. Consistent with our findings, studies examining Ureaplasma susceptibility to azithromycin 19 and moxifloxacin 17 19-21 have generally observed isolates in the susceptible range and have not noted differences in susceptibility patterns by species. However, the universal in vitro susceptibility to doxycycline in this study is in contrast to studies conducted in Europe and West Africa, where 18-37% of Ureaplasma isolates demonstrated in vitro resistance to doxycycline.…”

Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance

“…There have been no reports of naturally occurring resistance to fluoroquinolones in M. pneumonia to date. In vitro activity against macrolide‐resistant M. pneumoniae isolates has been reported for a number of fluoroquinolones, with MIC 90 s being lower for moxifloxacin (≤0.0008–0.125 µg/mL), garenoxacin (0.016–0.0625 µg/mL) and gatifloxacin (0.016–0.064 µg/mL) than for levofloxacin (0.25–0.5 µg/mL), ciprofloxacin (0.5–4.0 µg/mL) and tosufloxacin (0.25–0.5 µg/mL) . Fluoroquinolones have also proved effective in the treatment of macrolide‐resistant M. pneumoniae infections.…”

Mycoplasma hominisnecrotizing pleuropneumonia in a previously healthy adolescent

“…Moreover, they are no longer a valid therapeutic option in some areas [ 5 , 7 ]. As no resistance to levofloxacin (or other newer fluoroquinolones) and clindamycin is yet identified, these drugs could be a suitable therapeutic alternative [ 5 , 7 , 20 , 22 , 23 ]. The increasing resistance of M. hominis strains to antibiotics makes guidance of therapy by in vitro susceptibility tests of paramount importance in invasive infections leading to life-threatening situations.…”