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 < .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 < .001). Ceftriaxone was the most-effective cephalosporin in vivo because of a combination of high in vitro activity and prolonged serum elimination half-life.