Cefdinir pharmacokinetics and tolerability in children receiving 25 mg/kg once daily

Background: Of several oral cephalosporins, cefdinir is recommended as an alternative therapy for children with acute otitis media who have type I hypersensitivity to beta-lactams. Because the current cefdinir dosage of 14 mg/kg/d is approved for treatment of acute otitis media caused by penicillin-susceptible Streptococcus pneumoniae, we hypothesized that a 25-mg/kg dose given daily would be more effective for nonsusceptible S. pneumoniae. Methods: We performed pharmacokinetic analyses on 37 infants and children who were given cefdinir in dosages of 14 or 25 mg/kg once daily for 10 days, for the treatment of respiratory and skin or skin structure infections. Cefdinir plasma concentrations were determined with validated liquid chromatology, and pharmacokinetics and pharmacodynamics were determined in relation to the minimum inhibitory concentration values of S. pneumoniae. Results: The maximal plasma concentrations and area-under-the-curve values were significantly higher after the 25-mg/kg in relation to the minimum inhibitory concentration values for S. pneumoniae strains. The pharmacodynamics measure of bacteriologic effectiveness was < 40% of the dosing interval (ie, 24 hours), indicating that many of the penicillin-nonsusceptible S. pneumoniae causing acute otitis media would not be effectively treated. Diarrhea occurred in 20% of the 39 subjects that received the larger dosage of cefdinir. Conclusion: A cefdinir dosage of 25 mg/kg daily would be ineffective for treatment of acute otitis media caused by penicillin-nonsusceptible S. pneumoniae strain.