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Antimicrobial Agents and Chemotherapy, August 2002, p. 2595-2601, Vol. 46, No. 8
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.8.2595-2601.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Activities of Tigecycline (GAR-936), Daptomycin, and Comparative Antimicrobial Agents against Glycopeptide-Intermediate Staphylococcus aureus and Other Resistant Gram-Positive Pathogens

Peter J. Petersen,* Patricia A. Bradford, William J. Weiss, Timothy M. Murphy, P. E. Sum, and Steven J. Projan

Infectious Disease Research Section, Wyeth Research, Pearl River, New York 10965

Received 16 January 2002/ Returned for modification 28 February 2002/ Accepted 1 May 2002

Tigecycline (GAR-936) and daptomycin are potent antibacterial compounds in advanced stages of clinical trials. These novel agents target multiply resistant pathogenic bacteria. Daptomycin is principally active against gram-positive bacteria, while tigecycline has broad-spectrum activity. When tested by the standard protocols of the National Committee for Clinical Laboratory Standards in Mueller-Hinton broth II, tigecycline was more active than daptomycin (MICs at which 90% of isolates tested are inhibited, 0.12 to 1 and 0.5 to 16 µg/ml, respectively) against staphylococcal, enterococcal, and streptococcal pathogens. Daptomycin demonstrated a stepwise increase in activity corresponding to an increase in the supplemental concentration of calcium. When tested in base Mueller-Hinton broth supplemented with 50 mg of calcium per liter, daptomycin demonstrated improved activity (MIC90s, 0.015 to 4 µg/ml). The activity of daptomycin, however, equaled that of tigecycline against the glycopeptide-intermediate Staphylococcus aureus (GISA) strains only when the test medium was supplemented with excess calcium (75 mg/liter). Tigecycline and daptomycin demonstrated in vivo efficacies against GISA, methicillin-resistant S. aureus, and methicillin-susceptible S. aureus strains in an intraperitoneal systemic murine infection model. These data suggest that tigecycline and daptomycin may offer therapeutic options against clinically relevant resistant pathogens for which current alternatives for treatment are limited.

* Corresponding author. Mailing address: Infectious Disease Research, Wyeth Research, Bldg. 200/Rm. 3301, 401 N. Middletown Rd., Pearl River, NY 10965. Phone: (845) 602-3070. Fax: (845) 602-5671. E-mail: petersp{at}wyeth.com.

Antimicrobial Agents and Chemotherapy, August 2002, p. 2595-2601, Vol. 46, No. 8
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.8.2595-2601.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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