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Antimicrobial Agents and Chemotherapy, May 2001, p. 1422-1430, Vol. 45, No. 5
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.5.1422-1430.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

In Vitro Activities of RWJ-54428 (MC-02,479) against Multiresistant Gram-Positive Bacteria

Suzanne Chamberland,dagger Johanne Blais,* Monica Hoang, Cynthia Dinh, Dylan Cotter, Emmett Bond, Carla Gannon, Craig Park, Francois Malouin,dagger and Michael N. Dudley

Microcide Pharmaceuticals Inc, Mountain View, California 94043

Received 20 October 2000/Returned for modification 29 December 2000/Accepted 13 February 2001

RWJ-54428 (MC-02,479) is a new cephalosporin with a high level of activity against gram-positive bacteria. In a broth microdilution susceptibility test against methicillin-resistant Staphylococcus aureus (MRSA), RWJ-54428 was as active as vancomycin, with an MIC at which 90% of isolates are inhibited (MIC90) of 2 µg/ml. For coagulase-negative staphylococci, RWJ-54428 was 32 times more active than imipenem, with an MIC90 of 2 µg/ml. RWJ-54428 was active against S. aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus isolates with reduced susceptibility to glycopeptides (RWJ-54428 MIC range, <= 0.0625 to 1 µg/ml). RWJ-54428 was eight times more potent than methicillin and cefotaxime against methicillin-susceptible S. aureus (MIC90, 0.5 µg/ml). For ampicillin-susceptible Enterococcus faecalis (including vancomycin-resistant and high-level aminoglycoside-resistant strains), RWJ-54428 had an MIC90 of 0.125 µg/ml. RWJ-54428 was also active against Enterococcus faecium, including vancomycin-, gentamicin-, and ciprofloxacin-resistant strains. The potency against enterococci correlated with ampicillin susceptibility; RWJ-54428 MICs ranged between <= 0.0625 and 1 µg/ml for ampicillin-susceptible strains and 0.125 and 8 µg/ml for ampicillin-resistant strains. RWJ-54428 was more active than penicillin G and cefotaxime against penicillin-resistant, -intermediate, and -susceptible strains of Streptococcus pneumoniae (MIC90s, 0.25, 0.125, and <= 0.0625 µg/ml, respectively). RWJ-54428 was only marginally active against most gram-negative bacteria; however, significant activity was observed against Haemophilus influenzae and Moraxella catarrhalis (MIC90s, 0.25 and 0.5 µg/ml, respectively). This survey of the susceptibilities of more than 1,000 multidrug-resistant gram-positive isolates to RWJ-54428 indicates that this new cephalosporin has the potential to be useful in the treatment of infections due to gram-positive bacteria, including strains resistant to currently available antimicrobials.

* Corresponding author. Mailing address: Microcide Pharmaceuticals, Inc., 850 Maude Ave., Mountain View, CA 94043. Phone: (650) 428-3519. Fax: (650) 428-3550. E-mail: johanneb{at}microcide.com.

dagger Present address: Université de Sherbrooke, Sherbrooke, Québec, Canada J1K 2R1.

Antimicrobial Agents and Chemotherapy, May 2001, p. 1422-1430, Vol. 45, No. 5
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.5.1422-1430.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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