Therapeutic efficacy of J-111,225, a novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenem, against experimental murine systemic infections.

In a murine model of systemic infection with methicillin-resistant Staphylococcus aureus (MRSA), J-111,225 showed an ED(50) value of 5. 83 mg/kg, which was comparable to vancomycin (ED(50) 4.84 mg/kg), whereas imipenem failed to cure infected mice (ED(50) >100 mg/kg). Against a mixed infection caused by MRSA and Pseudomonas aeruginosa, monotherapy with J-111,225 showed an ED(50) value of 7.23 mg/kg, whereas combined treatment with vancomycin plus imipenem (1:1) had an ED(50) of 20.86 mg/kg. J-111,225 showed good therapeutic efficacy against methicillin-susceptible S. aureus, penicillin-resistant Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae and P. aeruginosa. The unusually broad spectrum suggests that monotherapy with this novel carbapenem may be suitable for polymicrobial infections associated with MRSA.