Activity in vitro of CGP 31608, a new penem antibacterial agent.

D S Reeves, M J Bywater, H A Holt

Department of Medical Microbiology, Southmead Hospital, Bristol, UK.

The Journal of antimicrobial chemotherapy 1987 Aug

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The in-vitro activity of CGP 31608 (hereinafter termed CGP), a new penem, was tested by an agar dilution technique in comparison with imipenem, Sch 34343, cefotaxime, ceftazidime, aztreonam, ampicillin, gentamicin and ciprofloxacin. 480 clinical isolated were tested, some of which were selected because of their multiple resistance. CGP showed consistent activity against a wide range of species, having MIC90 values of 2-8 mg/l for almost all Enterobacteriaceae, Pseudomonas spp., Haemophilus spp., Corynebacterium spp. and Bacteroides spp. It was the most active agent tested against staphylococci having an MIC90 of 0.25 mg/l, showing no reduction in activity against methicillin-resistant strains. Lesser activity was observed against some streptococci, Proteus spp. and clostridia. Tests carried out in broth demonstrated that CGP activity was constant over a pH range of 6-8 and was unaffected by the presence of 50% serum or 50% urine. The rate of killing of CGP, gentamicin, cefotaxime and ciprofloxacin was investigated in broth against log and stationary-phase cultures of Staphylococcus aureus and Escherichia coli. The most rapid rate of kill was seen with ciprofloxacin, while CGP exhibited a more rapid bactericidal effect than cefotaxime against Staph. aureus. The stability of CGP was studied at two concentrations in serum, broth and phosphate buffer at 4 degrees C, room temperature and 37 degrees C. In serum the half-life was 112 h at 4 degrees C, 35 h at room temperature and 11.4 h at 37 degrees C. Protein binding tested at concentrations of 5-100 mg/l was 2-6.3%.

Citation

D S Reeves, M J Bywater, H A Holt. Activity in vitro of CGP 31608, a new penem antibacterial agent. The Journal of antimicrobial chemotherapy. 1987 Aug;20(2):165-78