Pharmacodynamic activity of five oral cephalosporins against Haemophilus influenzae.
OBJECTIVE
To determine the time above minimum inhibitory concentration (T > MIC) and serum bactericidal activity of five oral cephalosporins against two strains of Haemophilus influenzae.


METHODS
Randomized, crossover study.


METHODS
University-associated research center.


METHODS
Ten healthy volunteers.


METHODS
Each subject received 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. Blood for serum levels was obtained at time zero and 1, 2, 3, 4, 6, 8, and 12 hours after each dose.


RESULTS
Cefpodoxime produced serum concentrations above the MIC for more than 90% of the time for both beta-lactamase-negative and -positive strains of H. influenzae. Moreover, it had serum bactericidal activity for 12 hours against both isolates. Cefuroxime was the second most active cephalosporin, with serum concentrations above the MIC of both isolates for 60% of the time. Cefuroxime provided serum bactericidal activity for 12 hours against the beta-lactamase-negative strain and 6 hours against the beta-lactamase-positive strain of H. influenzae. Even though the T > MIC was less than 50% of the study period for the other cephalosporins, all but cefaclor provided serum bactericidal activity for 12 hours against the beta-lactamase-negative isolate. Cefaclor provided measurable serum bactericidal activity for only 3 hours. The duration of serum bactericidal activity of cefprozil, loracarbef, and cefaclor against the beta-lactamase-positive isolate was 4, 2, and 0 hours, respectively.


CONCLUSIONS
Cefpodoxime was the most active cephalosporin studied based on T > MIC and serum bactericidal activity against isolates of H. influenzae.
Stein
G E
GE
Department of Medicine, College of Human Medicine, East Lansing, Michigan, USA.
Schooley
S
S
Walker
R D
RD
Strenkoski-Nix
L
L
D000328:Adult; D002433:Cefaclor / Q000494:pharmacology; D015296:Ceftizoxime / Q000031:analogs & derivatives / Q000494:pharmacology; D002444:Cefuroxime / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D018592:Cross-Over Studies; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D015610:Serum Bactericidal Test; D000097623:Cefpodoxime; D000097670:Cefprozil
D002433:Cefaclor; D015296:Ceftizoxime; D002444:Cefuroxime; D002511:Cephalosporins; D000097623:Cefpodoxime; D000097670:Cefprozil; C054920:loracarbef