In vitro activities of RWJ-54428 (MC-02,479) against multiresistant gram-positive bacteria.

Abstract

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 (MIC(90)) of 2 microg/ml. For coagulase-negative staphylococci, RWJ-54428 was 32 times more active than imipenem, with an MIC(90) of 2 microg/ml. RWJ-54428 was active against S. aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus isolates with reduced susceptibility to glycopeptides (RWJ-54428 MIC range, < or = 0.0625 to 1 microg/ml). RWJ-54428 was eight times more potent than methicillin and cefotaxime against methicillin-susceptible S. aureus (MIC(90), 0.5 microg/ml). For ampicillin-susceptible Enterococcus faecalis (including vancomycin-resistant and high-level aminoglycoside-resistant strains), RWJ-54428 had an MIC(90) of 0.125 microg/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 < or = 0.0625 and 1 microg/ml for ampicillin-susceptible strains and 0.125 and 8 microg/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 (MIC(90)s, 0.25, 0.125, and < or = 0.0625 microg/ml, respectively). RWJ-54428 was only marginally active against most gram-negative bacteria; however, significant activity was observed against Haemophilus influenzae and Moraxella catarrhalis (MIC(90)s, 0.25 and 0.5 microg/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.

• Authors: S Chamberland, J Blais, M Hoang, C Dinh, D Cotter, E Bond, C Gannon, C Park, F Malouin, M N Dudley
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 45 Issue 5 Pg. 1422-30 (May 2001) ISSN: 0066-4804 [Print] United States
• PMID: 11302805 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Cephalosporins
• Glycopeptides
• RWJ 54428

Topics

• Anti-Bacterial Agents (pharmacology)
• Cephalosporins (pharmacology)
• Drug Resistance, Multiple (physiology)
• Enterococcus (drug effects)
• Glycopeptides
• Gram-Positive Bacteria (drug effects)
• Haemophilus influenzae (drug effects)
• Humans
• Microbial Sensitivity Tests
• Moraxella catarrhalis (drug effects)
• Staphylococcus (drug effects)
• Streptococcus pneumoniae (drug effects)