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

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 methiciilin-resistant Staphylococcus aureus (MRSA), RWJ-54428 was as active as vancomycin, with an MIC at which 90% of isolates are inhibited (MIC90) of 2 mug/ml. For coagulase-negative staphylococci, RWJ-54428 was 32 times more active than imipenem, with an MIG,, of 2 mug/ml. RWJ-54428 was active against S, aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus isolates with reduced susceptibility to glycopeptides (RWJ-54428 MIC range, less than or equal to0.0625 to 1 mug/ml). RWJ-54428 was eight times more potent than methicillin and cefotaxime against methicillin-susceptible S, aureus (MIC,, 0.5 mug/ml), For ampicillin-susceptible Enterococcus faecalis (including vancomycin-resistant and high-level aminoglycoside-resistant strains), RWJ-54428 had an MIG(90) of 0.125 mug/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 less than or equal to0.0625 and 1 mug/ml for ampicillin-susceptible strains and 0.125 and 8 mug/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 less than or equal to0.0625 mug/ml, respectively). RWJ54428 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 mug/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,