In vitro and in vivo antibacterial activities of GV129606, a new broad-spectrum trinem

GV129606 is a new parenteral trinem antibiotic belonging to the beta-lactam class, It combines broad-spectrum activity (against gram-negative and -positive bacteria, aerobes and anaerobes), with high potency and resistance to beta-lactamases. Comparative in vitro and in vivo antibacterial activities were determined for GV129606 against more than 400 recent clinical isolates (aerobes, including beta-lactamase producers, and anaerobes), using representative antibacterial agents (meropenem, piperacillin, ceftazidime, cefpirome, ciprofloxacin, and gentamicin for aerobes and metronidazole, cefoxitin, piperacillin, and clindamycin for anaerobes). Against methicillin-susceptible staphylococci and streptococci, GV129606 and meropenem were the most active of the drugs tested. GV129606 showed an MIC for 90% of strains tested (MIC90) ranging from less than or equal to 0.015 to 0.06 mu g/ml against methicillin-susceptible staphylococci and Streptococcus sanguis, Streptococcus pyogenes, and Streptococcus agalactiae. Against penicillin-susceptible and -resistant Streptococcus pneumoniae isolates, GV129606, meropenem, and cefpirome showed MIC(90)s of less than or equal to 0.015 and 1 mu g/ml, respectively. Meropenem was the most active compound against members of the family Enterobacteriaceae with MIC(90)s of less than or equal to 0.5 mu g/ml. Against these species, GV129606 possessed activity superior to those of piperacillin, ceftazidime, cefpirome, and gentamicin, with MIC(90)s of less than or equal to 8 mu g/ml, but its activity was two- to sixfold less than that of ciprofloxacin (with the exception of Proteus rettgeri and Providencia stuartii). Haemophilus spp., Moraxella catarrhalis, Neisseria gonorrhoeae, and Pseudomonas aeruginosa were also included in the spectrum of GV129606. GV129606 showed good antianaerobe activity, similar to metronidazole. It was stable against all clinically relevant p-lactamases (similar to meropenem). The in vitro activity was confirmed in vivo against septicemia infections Induced in mice by selected gram-positive and -negative bacteria with 50% effective doses (ED(50)s) of less than or equal to 0.05 and less than or equal to 0.5 mg/kg of body weight/dose, respectively. GV129606 was as effective as meropenem against septicemia in mice caused by ceftazidime-resistant Pseudomonas aeruginosa, exhibiting an ED50 of 0.33 mg/kg/dose.