This Article
Right arrow Full Text
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 Edelstein, P. H.
Right arrow Articles by Edelstein, M. A. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Edelstein, P. H.
Right arrow Articles by Edelstein, M. A. C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 1999, p. 90-95, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

In Vitro Activity of the Ketolide HMR 3647 (RU 6647) for Legionella spp., Its Pharmacokinetics in Guinea Pigs, and Use of the Drug To Treat Guinea Pigs with Legionella pneumophila Pneumonia

Paul H. Edelstein1,2,* and Martha A. C. Edelstein1

Departments of Pathology and Laboratory Medicine1 and Medicine,2 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283

Received 30 June 1998/Returned for modification 8 September 1998/Accepted 26 October 1998

The activities of HMR 3647, HMR 3004, erythromycin, clarithromycin, and levofloxacin for 97 Legionella spp. isolates were determined by microbroth dilution susceptibility testing. Growth inhibition of two Legionella pneumophila strains grown in guinea pig alveolar macrophages was also determined. The concentrations required to inhibit 50% of strains tested were 0.06, 0.02, 0.25, 0.03, and 0.02 µg/ml for HMR 3647, HMR 3004, erythromycin, clarithromycin, and levofloxacin, respectively. BYEalpha broth did not significantly inhibit the activities of the drugs tested, as judged by the susceptibility of the control Staphylococcus aureus strain; however, when Escherichia coli was used as the test strain, levofloxacin activity tested in BYEalpha broth was fourfold lower. HMR 3647, HMR 3004, erythromycin, and clarithromycin (0.25 and 1 µg/ml) reduced bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 0.5 to 1 log10, but regrowth occurred over a 2-day period. HMR 3647, erythromycin, and clarithromycin appeared to have equivalent intracellular activities which were solely static in nature. HMR 3004 was more active than all drugs tested except levofloxacin. In contrast, levofloxacin (1 µg/ml) was bactericidal against intracellular L. pneumophila and significantly more active than the other drugs tested. Therapy studies with HMR 3647 and erythromycin were performed in guinea pigs with L. pneumophila pneumonia. When HMR 3647 was given (10 mg/kg of body weight) by the intraperitoneal route to infected guinea pigs, mean peak plasma levels were 1.4 µg/ml at 0.5 h and 1.0 µg/ml at 1 h postinjection. The terminal half-life phase of elimination from plasma was 1.4 h. All 16 L. pneumophila-infected guinea pigs treated with HMR 3647 (10 mg/kg/dose given intraperitoneally once daily) for 5 days survived for 9 days after antimicrobial therapy, as did all 16 guinea pigs treated with the same dose of HMR 3647 given twice daily. Fourteen of 16 erythromycin-treated (30 mg/kg/dose given intraperitoneally twice daily) animals survived, whereas 0 of 12 animals treated with saline survived. HMR 3647 is effective against L. pneumophila in vitro, in infected macrophages, and in a guinea pig model of Legionnaires' disease. HMR 3647 given once daily should be evaluated as a treatment for Legionnaires' disease in humans.

* Corresponding author. Mailing address: Clinical Microbiology Laboratory, 4 Gates, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104-4283. Phone: (215) 662-6651. Fax: (215) 662-6655. E-mail: phe{at}mail.med.upenn.edu.

Antimicrobial Agents and Chemotherapy, January 1999, p. 90-95, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Lee, J. H., Cho, Y. K., Jung, Y. S., Kim, Y. C., Lee, M. G. (2008). Effects of Escherichia coli Lipopolysaccharide on Telithromycin Pharmacokinetics in Rats: Inhibition of Metabolism via CYP3A. Antimicrob. Agents Chemother. 52: 1046-1051 [Abstract] [Full Text]  
  • Sabria, M., Pedro-Botet, M. L., Gomez, J., Roig, J., Vilaseca, B., Sopena, N., Banos, V., for the Legionnaires Disease Therapy Group, (2005). Fluoroquinolones vs Macrolides in the Treatment of Legionnaires Disease. Chest 128: 1401-1405 [Abstract] [Full Text]  
  • Lippert, C., Gbenado, S., Qiu, C., Lavin, B., Kovacs, S. J. (2005). The Bioequivalence of Telithromycin Administered Orally as Crushed Tablets Versus Tablets Swallowed Whole. J Clin Pharmacol 45: 1025-1031 [Abstract] [Full Text]  
  • Gattringer, R., Urbauer, E., Traunmuller, F., Zeitlinger, M., Dehghanyar, P., Zeleny, P., Graninger, W., Muller, M., Joukhadar, C. (2004). Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers. Antimicrob. Agents Chemother. 48: 4650-4653 [Abstract] [Full Text]  
  • Muller-Serieys, C., Andrews, J., Vacheron, F., Cantalloube, C. (2004). Tissue kinetics of telithromycin, the first ketolide antibacterial. J Antimicrob Chemother 53: 149-157 [Abstract] [Full Text]  
  • Roig, J., Rello, J. (2003). Legionnaires' disease: a rational approach to therapy. J Antimicrob Chemother 51: 1119-1129 [Abstract] [Full Text]  
  • Ackermann, G., Rodloff, A. C. (2003). Drugs of the 21st century: telithromycin (HMR 3647)--the first ketolide. J Antimicrob Chemother 51: 497-511 [Abstract] [Full Text]  
  • Edelstein, P. H., Weiss, W. J., Edelstein, M. A. C. (2003). Activities of Tigecycline (GAR-936) against Legionella pneumophila In Vitro and in Guinea Pigs with L. pneumophila Pneumonia. Antimicrob. Agents Chemother. 47: 533-540 [Abstract] [Full Text]  
  • Maurin, M., Bryskier, A., Raoult, D. (2002). Antibiotic Susceptibilities of Parachlamydia acanthamoeba in Amoebae. Antimicrob. Agents Chemother. 46: 3065-3067 [Abstract] [Full Text]  
  • Kadota, J.-I., Ishimatsu, Y., Iwashita, T., Matsubara, Y., Tomono, K., Tateno, M., Ishihara, R., Muller-Serieys, C., Kohno, S. (2002). Intrapulmonary Pharmacokinetics of Telithromycin, a New Ketolide, in Healthy Japanese Volunteers. Antimicrob. Agents Chemother. 46: 917-921 [Abstract] [Full Text]  
  • Edelstein, P. H., Shinzato, T., Edelstein, M. A. C. (2001). BMS-284756 (T-3811ME) a new fluoroquinolone: in vitro activity against Legionella, efficacy in a guinea pig model of L. pneumophila pneumonia and pharmacokinetics in guinea pigs. J Antimicrob Chemother 48: 667-675 [Abstract] [Full Text]  
  • Muller-Serieys, C., Soler, P., Cantalloube, C., Lemaitre, F., Gia, H. P., Brunner, F., Andremont, A. (2001). Bronchopulmonary Disposition of the Ketolide Telithromycin (HMR 3647). Antimicrob. Agents Chemother. 45: 3104-3108 [Abstract] [Full Text]  
  • Edelstein, P. H., Higa, F., Edelstein, M. A. C. (2001). In Vitro Activity of ABT-773 against Legionella pneumophila, Its Pharmacokinetics in Guinea Pigs, and Its Use to Treat Guinea Pigs with L. pneumophila Pneumonia. Antimicrob. Agents Chemother. 45: 2685-2690 [Abstract] [Full Text]  
  • Edelstein, P. H., Shinzato, T., Doyle, E., Edelstein, M. A. C. (2001). In Vitro Activity of Gemifloxacin (SB-265805, LB20304a) against Legionella pneumophila and Its Pharmacokinetics in Guinea Pigs with L. pneumophila Pneumonia. Antimicrob. Agents Chemother. 45: 2204-2209 [Abstract] [Full Text]  
  • Bermudez, L. E., Inderlied, C. B., Kolonoski, P., Wu, M., Aralar, P., Young, L. S. (2001). Telithromycin Is Active against Mycobacterium avium in Mice despite Lacking Significant Activity in Standard In Vitro and Macrophage Assays and Is Associated with Low Frequency of Resistance during Treatment. Antimicrob. Agents Chemother. 45: 2210-2214 [Abstract] [Full Text]  
  • Jonas, D., Engels, I., Friedhoff, C., Spitzmuller, B., Daschner, F. D., Frank, U. (2001). Efficacy of moxifloxacin, trovafloxacin, clinafloxacin and levofloxacin against intracellular Legionella pneumophila. J Antimicrob Chemother 47: 147-152 [Abstract] [Full Text]  
  • Namour, F., Wessels, D. H., Pascual, M. H., Reynolds, D., Sultan, E., Lenfant, B. (2001). Pharmacokinetics of the New Ketolide Telithromycin (HMR 3647) Administered in Ascending Single and Multiple Doses. Antimicrob. Agents Chemother. 45: 170-175 [Abstract] [Full Text]  
  • Maurin, M., Mersali, N. F., Raoult, D. (2000). Bactericidal Activities of Antibiotics against Intracellular Francisella tularensis. Antimicrob. Agents Chemother. 44: 3428-3431 [Abstract] [Full Text]  
  • Singh, K. V., Zscheck, K. K., Murray, B. E. (2000). Efficacy of Telithromycin (HMR 3647) against Enterococci in a Mouse Peritonitis Model. Antimicrob. Agents Chemother. 44: 3434-3437 [Abstract] [Full Text]  
  • Rastogi, N., Goh, K. S., Berchel, M., Bryskier, A. (2000). In Vitro Activities of the Ketolides Telithromycin (HMR 3647) and HMR 3004 Compared to Those of Clarithromycin against Slowly Growing Mycobacteria at pHs 6.8 and 7.4. Antimicrob. Agents Chemother. 44: 2848-2852 [Abstract] [Full Text]  
  • Yamaguchi, T., Hirakata, Y., Izumikawa, K., Miyazaki, Y., Maesaki, S., Tomono, K., Yamada, Y., Kamihira, S., Kohno, S. (2000). In Vitro Activity of Telithromycin (HMR3647), a New Ketolide, against Clinical Isolates of Mycoplasma pneumoniae in Japan. Antimicrob. Agents Chemother. 44: 1381-1382 [Abstract] [Full Text]  
  • Strigl, S., Roblin, P. M., Reznik, T., Hammerschlag, M. R. (2000). In Vitro Activity of ABT 773, a New Ketolide Antibiotic, against Chlamydia pneumoniae. Antimicrob. Agents Chemother. 44: 1112-1113 [Abstract] [Full Text]  
  • Dedicoat, M., Venkatesan, P. (1999). The treatment of Legionnaires' disease. J Antimicrob Chemother 43: 747-752 [Full Text]  


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