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.