This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Malay, S.
Right arrow Articles by Hammerschlag, M. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malay, S.
Right arrow Articles by Hammerschlag, M. R.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, February 2002, p. 517-518, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.517-518.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Sheila Malay, Patricia M. Roblin, Tamara Reznik, Andrei Kutlin, and Margaret R. Hammerschlag*

Division of Infectious Diseases, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, New York 11203-2098

Received 21 August 2001/ Returned for modification 16 October 2001/ Accepted 2 November 2001


arrow
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 µg/ml (range, 0.015 to 0.03 µg/ml). BMS-284756 was the most active quinolone tested.


arrow
INTRODUCTION
 
Chlamydia pneumoniae is a frequent cause of community-acquired 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 L2434 (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 103 to 104 inclusion-forming units (IFU) per ml for a multiplicity of infection of 1:1, was centrifuged at 1,700 x g for 1 h, and was incubated at 35°C for 1 h. Wells were then aspirated and overlaid with 0.2 ml of medium (Iscove's modification of Dulbecco's modified Eagle's medium) containing 1 µg of cycloheximide per ml and serial twofold dilutions of the test drug. After incubation at 35°C for 72 h, the cultures in one plate were fixed and stained for inclusions with fluorescein-conjugated antibody to the lipopolysaccharide genus antigen (Pathfinder; Bio-Rad Labs, Hercules, Calif.). The MIC was the lowest antibiotic concentration at which no inclusions were seen. The minimal bactericidal concentration (MBC) was determined by aspirating the antibiotic-containing medium of the second plate, washing wells twice with phosphate-buffered saline, and adding antibiotic-free medium. Cultures were frozen at -70°C, thawed, passed onto fresh new cells, incubated for 72 h, and then fixed and stained as above. The MBC was the lowest antibiotic concentration that resulted in no inclusions after passage. Three replicates were conducted for each assay.

The MICs and MBCs for C. trachomatis are shown in Table 1. The MICs and MBCs for C. trachomatis were the following: BMS-284756, 0.015 µg/ml; levofloxacin, 0.5 µg/ml; moxifloxacin, 0.5 µg/ml; and clarithromycin, 0.03 µg/ml. The MIC and MBCs for C. pneumoniae are shown in Table 2. The MICs at which 90% of the isolates tested are inhibited and the MBCs at which 90% of the strains tested are killed for C. pneumoniae were the following: BMS-284756, 0.015 µg/ml; levofloxacin, 0.5 and 1.0 µg/ml; moxifloxacin, 0.5 and 1.0 µg/ml; and clarithromycin, 0.03 and 0.06 µg/ml. The MICs obtained for BMS-284756 against C. trachomatis and C. pneumoniae in the present study were very consistent, especially in view of the wide geographic distribution of the isolates tested.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Activities of BMS-28476 and other antibiotics against 5 strains of C. trachomatis


View this table:
[in this window]
[in a new window]
  		TABLE 2. Activities of BMS-28476 and other antibiotics against 20 isolates of C. pneumoniae

Fung-Tomc et al. (3) reported that BMS-284756 was the most active quinolone tested against a wide range of bacteria. They tested 10 isolates of C. trachomatis, and the MICs were <=0.004 to 0.016 µg/ml. Fung-Tomc et al. (3) also tested 4 isolates of C. pneumoniae, and the MICs were <=0.004 to 0.008 µg/ml. The isolates tested were not specified, nor were the methods described, but their results were almost identical to ours.

The 1998 Centers for Disease Control Guidelines for the Treatment of Sexually Transmitted Diseases lists ofloxacin (300 mg orally twice a day for 7 days) as an alternative regimen for the treatment of uncomplicated genital C. trachomatis infection in adolescents and adults (2). Ofloxacin is similar in efficacy to doxycycline and azithromycin but is more expensive and offers no advantage with regard to dosing and the length of treatment (2). Based on its in vitro activity and pharmacokinetics (3), BMS-284756 should have equivalent if not better efficacy for treatment of C. trachomatis infections.

Data are limited on the efficacy of quinolones for treatment of C. pneumoniae infections. The majority of studies, especially for treatment of community-acquired pneumonia, have based the diagnosis of C. pneumoniae on serology; thus, microbiologic efficacy could not be assessed. However, results from two multicenter treatment studies of community-acquired pneumonia found that levofloxacin and moxifloxacin had 70 to 80% efficacy in the eradication of C. pneumoniae from the nasopharynx (6, 8). The MICs and MBCs for the C. pneumoniae isolates obtained from these patients after treatment were the same as those obtained before treatment, suggesting that persistence was not due to the development of resistance. These findings are similar to reported experiences with erythromycin, clarithromycin, and azithromycin (7, 10). BMS-284756 is the most active quinolone tested thus far and is more active than clarithromycin and azithromycin. Prospective studies of BMS-284756 for the treatment of genital chlamydia infections and community-acquired pneumonia utilizing culture of C. trachomatis and C. pneumoniae will determine the role of BMS-284756 in the treatment of these infections.


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: Department of Pediatrics, Box 49, SUNY Downstate Medical Center, 450 Clarkson Ave., Brooklyn, NY 11203-2098. Phone: (718) 245-4075. Fax: (718) 245-2118. E-mail: mhammerschlag{at}pol.net. Back


arrow
REFERENCES
 
    1
  1. Barry, A. I., and P. C. Fuchs. 1997. Antibacterial activities of grepafloxacin, ciprofloxacin, ofloxacin and fleroxacin. J. Chemother. 9:9-16.[Medline]
    2. 2
  2. Centers for Disease Control and Prevention. 1998. 1998 Guidelines for the treatment of sexually transmitted diseases. Morb. Mortal. Wkly. Rep. 47(RR-1):53-60.
    3. 3
  3. Fung-Tomc, J. C., B. Minassian, B. Kolek, E. Huczko, L. Alekksuunes, T. Stickle, T. Washo, E. Gradelski, L. Valera, and D. Bonner. 2000. Antibacterial spectrum of a novel des-fluoro(6) quinolone, BMS-284756. Antimicrob. Agents Chemother. 40:3351-3356.
    4. 4
  4. Hammerschlag, M. R., C. L. Hyman, and P. M. Roblin. 1992. In vitro activities of five quinolones against Chlamydia pneumoniae. Antimicrob. Agents Chemother. 36:682-683.[Abstract/Free Full Text]
    5. 5
  5. Hammerschlag, M. R. 1994. Antimicrobial susceptibility and therapy of infections due to Chlamydia pneumoniae. Antimicrob. Agents Chemother. 38:1873-1878.[Free Full Text]
    6. 6
  6. Hammerschlag, M. R., and P. M. Roblin. 2000. Microbiological efficacy of moxifloxacin for treatment of community-acquired pneumonia due to Chlamydia pneumoniae. Int. J. Antimicrob. Agents 15:149-152.[CrossRef][Medline]
    7. 7
  7. Hammerschlag, M. R. 2000. Activity of gemifloxacin and other new quinolones against Chlamydia pneumoniae: a review. J. Antimicrob. Chemother. 45(Suppl. S1):35-39.[Abstract]
    8. 8
  8. Hammerschlag, M. R., and P. M. Roblin. 2000. Microbiological efficacy of levofloxacin for treatment of community-acquired pneumonia due to Chlamydia pneumoniae. Antimicrob. Agents Chemother. 44:409.
    9. 9
  9. Maskell, J. P., A. C. Whiley, and A. M. Sefton. 1998. In vitro activity of grepafloxacin against Haemophilus influenzae and Moraxella catarrhalis. Eur. J. Clin. Microbiol. Infect. Dis. 17:293-295.[Medline]
    10. 10
  10. Roblin, P. M., and M. R. Hammerschlag. 1998. Microbiologic efficacy of azithromycin and susceptibilities to azithromycin of isolates of Chlamydia pneumoniae from adults and children with community acquired pneumonia. Antimicrob. Agents Chemother. 42:194-196.[Abstract/Free Full Text]
    11. 11
  11. Takahata, M., M. Shimakura, R. Hori, K. Kizawa, Y. Todo, S. Minami, Y. Watanabe, and H. Naarita. 2001. In vitro and in vivo efficacies of T-3811ME (BMS-284756) against Mycoplasma pneumoniae. Antimicrob. Agents Chemother. 45:312-315.[Abstract/Free Full Text]

Antimicrobial Agents and Chemotherapy, February 2002, p. 517-518, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.517-518.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rupp, J., Gebert, A., Solbach, W., Maass, M. (2005). Serine-to-Asparagine Substitution in the GyrA Gene Leads to Quinolone Resistance in Moxifloxacin-Exposed Chlamydia pneumoniae. Antimicrob. Agents Chemother. 49: 406-407 [Abstract] [Full Text]  
  • Smith, R. P., Baltch, A. L., Ritz, W. J., Carpenter, A. N., Halse, T. A., Bopp, L. H. (2004). In Vitro Activities of Garenoxacin and Levofloxacin against Chlamydia pneumoniae Are Not Affected by Presence of Mycoplasma DNA. Antimicrob. Agents Chemother. 48: 2081-2084 [Abstract] [Full Text]  
  • Ameyama, S., Shinmura, Y., Takahata, M. (2003). Inhibitory Activities of Quinolones against DNA Gyrase of Chlamydia pneumoniae. Antimicrob. Agents Chemother. 47: 2327-2329 [Abstract] [Full Text]  
  • Roblin, P. M., Hammerschlag, M. R. (2003). In Vitro Activity of a New Antibiotic, NVP-PDF386 (VRC4887), against Chlamydia pneumoniae. Antimicrob. Agents Chemother. 47: 1447-1448 [Abstract] [Full Text]  
  • Andrews, J., Honeybourne, D., Jevons, G., Boyce, M., Wise, R., Bello, A., Gajjar, D. (2003). Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects. J Antimicrob Chemother 51: 727-730 [Abstract] [Full Text]  
  • Waites, K. B., Crabb, D. M., Bing, X., Duffy, L. B. (2003). In Vitro Susceptibilities to and Bactericidal Activities of Garenoxacin (BMS-284756) and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas. Antimicrob. Agents Chemother. 47: 161-165 [Abstract] [Full Text]  
  • Donati, M., Pollini, G. M., Sparacino, M., Fortugno, M. T., Laghi, E., Cevenini, R. (2002). Comparative in vitro activity of garenoxacin against Chlamydia spp.. J Antimicrob Chemother 50: 407-410 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Malay, S.
Right arrow Articles by Hammerschlag, M. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malay, S.
Right arrow Articles by Hammerschlag, M. R.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»