In Vitro Activities of BMS-284756 against Chlamydia trachomatis and Recent Clinical Isolates of Chlamydia pneumoniae

Abstract

The in vitro activities of BMS-284756 (a novel des-fluoroquinolone), levofloxacin, moxifloxacin, and clarithromycin were tested against 5 strains of Chlamydia trachomatis and 20 isolates of Chlamydia pneumoniae. The MIC at which 90% of the isolates were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed by BMS-284756 for all isolates of C. pneumoniae and C. trachomatis was 0.015 g/ml (range, 0.015 to 0.03 g/ml). BMS-284756 was the most active quinolone tested.Chlamydia pneumoniae is a frequent cause of communityacquired respiratory tract infection, including pneumonia and bronchitis, in adults and children. Quinolones have attracted interest as therapy for community-acquired respiratory tract infections because they are active against a wide range of pathogens responsible for these diseases, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Mycoplasma pneumoniae (1, 3, 9, 11). We previously reported that quinolones, including ofloxacin, levofloxacin, grepafloxacin, gatifloxacin, gemifloxacin, sparfloxacin, trovafloxacin, and moxifloxacin, have good activity against Chlamydia trachomatis and C. pneumoniae in vitro (4-8). BMS-284756 is a novel des-fluoro(6) quinolone, which differs from recently approved quinolones in that it lacks fluorine at the C-6 position. BMS-284756 has antibacterial activity similar to that of other fluorinated quinolones against most bacteria (3). We compared the in vitro activity of BMS-284756, levofloxacin, moxifloxacin, and clarithromycin against 5 strains of C. trachomatis and 20 recent clinical isolates of C. pneumoniae. Strains of C. trachomatis included E-BOUR (ATCC VR-384B), F-IC-CAL3 (ATCC VR-346), C-HAR32 (ATCC VR-572), J-UW-36 (ATCC VR-886), and L 2 434 (ATCC VR-902B).Isolates of C. pneumoniae tested included one reference isolate; TW183 (ATCC VR-2282; Washington Research Foundation, Seattle, Wash.); CM-1, a clinical isolate from the Centers for Disease Control and Prevention (ATCC VR-1360); and 18 recent clinical isolates from adults and children enrolled in multicenter community-acquired pneumonia treatment studies conducted in the United States: T2023 (ATCC VR-1356), 124, 453, 490, 493, 600, 08002, 08016, 21001, 21002, 2212, 24013, 25001, MC16005, MC01016, MT57001, PDS07015, and RR57002. BMS-284756 (Bristol-Myers Squibb, Wallingford, Conn.), levofloxacin (Ortho Pharmaceuticals, Raritan, N.J.), moxifloxacin (Bayer Pharmaceuticals, West Haven, Conn.), and clarithromycin (Abbott Laboratories, Abbott Park, Ill.) were supplied as powders and were solubilized according to the manufacturers' instructions. Susceptibility testing of C. trachomatis and C. pneumoniae was performed in cell culture with HEp-2 cells grown in 96-well microtiter plates as previously described (5). Each experiment was set up in duplicate plates. Each well was inoculated with 0.1 ml of the test organism diluted to yield 10 3 to 10 4 inclusion-forming units (IFU) per ml for a multiplicity of infection of 1:1, was centrifuged at ...

In Vitro Activities of Garenoxacin and Levofloxacin against Chlamydia pneumoniae Are Not Affected by Presence of Mycoplasma DNA

“…The susceptibilities of 20 isolates originating in Finland, Japan, and the United States were determined. The susceptibility testing method used in this study was that of Malay and colleagues (17), originally described by Hammerschlag (11). All but three isolates tested in our study were different from those tested previously (17).…”

“…The susceptibility testing method used in this study was that of Malay and colleagues (17), originally described by Hammerschlag (11). All but three isolates tested in our study were different from those tested previously (17). In the two studies the MIC at which 90% of isolates are inhibited (MIC 90 ) and the MBC at which 90% of isolates are killed (MBC 90 ) were the same, i.e., 0.06 g/ml for garenoxacin and 2.0 g/ml for levofloxacin.…”

“…Susceptibility testing was performed at the Infectious Disease Research Laboratory, Stratton Veterans Affairs Medical Center, as described previously (11,17). Briefly, HEp-2 cell monolayers in 96-well plates were inoculated with C. pneumoniae at a multiplicity of infection of 1 (10 3 inclusion-forming units/well), centrifuged at 1,700 ϫ g, and incubated for 1 h at 37°C.…”

Recombinant Human Peptidoglycan Recognition Proteins Reveal Antichlamydial Activity

“…The infection rate was determined as the ratio of the number of cells with antibody-labeled inclusions (FITC channel) to the total number of cells (ethidium bromide channel). MICs were determined as the lowest concentrations of PGLYRPs at which the infection rate was reduced to Ͼ90% of that in the control wells (18).…”

In Vitro Activity of a New Antibiotic, NVP-PDF386 (VRC4887), against Chlamydia pneumoniae

“…NVP-PDF386 (Novartis, Summit, N.J.), levofloxacin (Ortho Pharmaceuticals, Raritan, N.J.), and clarithromycin (Abbott Laboratories, Abbott Park, Ill.) were supplied as drug substances in powder form and were solubilized in accordance with the manufacturers' instructions. Susceptibility testing of C. pneumoniae was performed in cell culture by using HEp-2 cells grown in 96-well microtiter plates as previously described (1,2). Each experiment was set up in duplicate plates.…”