The postantibiotic effect of cefcanel on beta-hemolytic streptococci group A in vitro and in vivo

The postantibiotic effect (PAE) of cefcanel, a new oral cephalosporin with high in vitro activity against Gram-positive bacteria, was investigated. Ten clinical isolates of Streptococcus pyogenes group A and one reference strain (M12, P1800) were exposed to 5 X MIC of cefcanel for 2 h in vitro. The PAE was found to be 2.3 (range 1.7-3.2) h. To investigate the PAE in vivo, a newly developed animal model with implanted tissue cages in rabbits was used. The rabbits received different doses of cefcanel i.v. and unbound concentrations in the tissue cage fluid (TCF) were measured. The protein binding of cefcanel in TCF was approximately 98%. Above a certain dose level, unexpectedly high TCF concentrations were found, indicating that the albumin binding capacity for the drug was surpassed. A PAE in vivo of 0.9-2.6 h was confirmed for cefcanel when the free drug concentration in TCF exceeded 3 X MIC.