title: Experimental infection with Streptococcus pneumoniae in mice: correlation of in vitro activity and pharmacokinetic parameters with in vivo effect for 14 cephalosporins.
abstract: A mouse model using intraperitoneal inoculation of Streptococcus pneumoniae type 3 was used to compare in vitro and in vivo effects of 14 cephalosporins, selected to encompass a wide range of minimal inhibitory concentrations (MICs) against the organism. Antibiotics were subcutaneously administered as single doses 1 hr after inoculation of pneumococci, and the effect was measured as the 50% effective dose (ED50). The correlation between log ED50 and log MIC was highly significant (r = .87, P less than .001). Pharmacokinetic properties of the cephalosporins were estimated after a fixed dose of 5 mg per mouse (167 mg/kg) for all drugs. The only correlation that was significant was between log ED50 and the time the serum concentration remained above the MIC for each drug (r = -.90, P less than .001). Ceftriaxone was the most-effective cephalosporin in vivo because of a combination of high in vitro activity and prolonged serum elimination half-life.
mesh_terms: D000818:Animals; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006207:Half-Life; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D011008:Pneumococcal Infections / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D002511:Cephalosporins