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Antimicrobial Agents and Chemotherapy, January 2003, p. 43-47, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.43-47.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

In Vivo Antibacterial Activity of RWJ-54428, a New Cephalosporin with Activity against Gram-Positive Bacteria

David C. Griffith,* Laurie Harford, Robert Williams, Ving J. Lee, and Michael N. Dudley

Essential Therapeutics Inc., Mountain View, California 94043

Received 29 May 2002/ Returned for modification 1 August 2002/ Accepted 24 September 2002

RWJ-54428 (MC-02,479) is a new cephalosporin with activity against resistant gram-positive organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. The in vivo efficacy of RWJ-54428 was evaluated against gram-positive bacteria in four mouse models of infection. RWJ-54428 was effective in vivo against methicillin-susceptible and -resistant S. aureus in a mouse model of sepsis, with 50% effective doses being similar to those of vancomycin. In a single-dose neutropenic mouse thigh model of infection, RWJ-54428 at 30 mg/kg of body weight showed activity similar to that of vancomycin at 30 mg/kg against a strain of methicillin-resistant S. aureus. RWJ-54428 also showed a prolonged in vivo postantibiotic effect in this model. In a mouse model of pneumonia due to a penicillin-susceptible strain of Streptococcus pneumoniae, RWJ-54428 displayed efficacy and potency superior to those of penicillin G and cefotaxime. In a mouse model of pyelonephritis due to Enterococcus faecalis, RWJ-54428 had bactericidal effects similar to those of vancomycin and ampicillin, but at two- to threefold lower total daily doses. These studies show that RWJ-54428 is active in experimental mouse models of infection against gram-positive organisms, including strains resistant to earlier cephalosporins and penicillin G.

* Corresponding author. Mailing address: Essential Therapeutics Inc., 850 Maude Ave., Mountain View, CA 94043. Phone: (650) 428-3514. Fax: (650) 428-3550. E-mail: dgriffith{at}etrx.com.

Antimicrobial Agents and Chemotherapy, January 2003, p. 43-47, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.43-47.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Griffith, D. C., Rodriguez, D., Corcoran, E., Dudley, M. N. (2008). Pharmacodynamics of RWJ-54428 against Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis in a Neutropenic Mouse Thigh Infection Model. Antimicrob. Agents Chemother. 52: 244-247 [Abstract] [Full Text]  
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