PHARMACODYNAMIC ACTIVITY OF 5 ORAL CEPHALOSPORINS AGAINST HAEMOPHILUS-INFLUENZAE

Study Objectives. To determine the time above minimum inhibitory conce ntration (T > MIC) and serum bactericidal activity of five oral cephal osporins against two strains of Haemophilus influenzae. Design. Random ized, crossover study. Setting. University-associated research center. Subjects. Ten healthy volunteers. Interventions. Each subject receive d a single dose of cefpodoxime 200 mg, cefuroxime 500 mg, cefaclor 500 mg, cefprozil 500 mg, or loracarbef 400 mg each week for 5 weeks. Blo od for serum levels was obtained at time zero and 1, 2, 3, 4, 6, 8, an d 12 hours after each dose. Measurements and Main Results. Cefopodoxim e produced serum concentrations above the MIC for more than 90% of the time for both beta-lactamase-negative and -positive strains of H. inf luenzae. Moreover, it had serum bactericidal activity for 12 hours aga inst both isolates. Cefuroxime was the second most active cephalospori n, with serum concentrations above the MIC of both isolates for 60% of the time. Cefuroxime provided serum bactericidal activity for 12 hour s against the beta-lactamase-negative strain and 6 hours against the b eta-lactamase-positive strain of H. influenzae. Even though the T > MI C was less than 50% of the study period for the other cephalosporins, all but cefaclor provided serum bactericidal activity for 12 hours aga inst the beta-lactamase-negative isolate. Cefaclor provided measurable serum bactericidal activity for only 3 hours. The duration of serum b actericidal activity of cefprozil, loracarbef, and cefaclor against th e beta-lactamase-positive isolate was 4, 2, and 0 hours, respectively. Conclusion. Cefpodoxime was the most active cephalosporin studied bas ed on T > MIC and serum bactericidal activity against isolates of H. i nfluenzae.