Cefdinir: Another Orally Administered Cephalosporin

Source: Hishida A, et al. Antimicrob Agents Chemother 1998; 42:1718-1721.

The most recent of the orally administered antibiotics to receive FDA approval is cefdinir. Approval was awarded in December 1997 for its use in the treatment of skin infections, as well as in upper and lower respiratory tract infections (i.e., acute sinusitis, otitis media, pharyngitis, acute exacerbations of chronic bronchitis, and community-acquired pneumonia.)

The bioavailability of cefdinir capsules is 20%, while that of the oral suspension is only slightly greater. The drug is excreted, unchanged, in the urine and has a half-life in plasma of approximately 1.7 hours. The recommended adult dose is 300-600 mg q12h; it may be taken without regard to feeding state. Preliminary data suggest that a dose of 100 mg daily may be sufficient in hemodialysis patients.

In terms of its antibacterial spectrum of activity, cefdinir most closely resembles, among the orally administered cephalosporins, cefpodoxime. It is active against Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, except for those isolates which are fully penicillin resistant. Methicillin-susceptible Staphylococcus aureus are susceptible, as are many Enterobacteriaceae, but not Pseudomonas aeruginosa. As with other cephalosporins, cefdinir is not active against "atypical pneumonia" pathogens, nor is it active against enterococci.

The following tentative interpretive criteria for determining the susceptibility of S. pneumoniae to cefdinir have been proposed: susceptible, MIC less than 0.5 mg/L or inhibition zone diameter greater than 23 mm; intermediate, MIC 1.0 mg/L or inhibition zone, 20-22 mm; resistant, MIC greater than 2.0 mg/L or inhibition zone diameter, less than 19 mm.1

Randomized Clinical Trials

Skin and Skin-Structure Infections. A randomized trial comparing cefdinir 300 mg bid to cephalexin given 500 mg qid, each for 10 days, in the treatment of 952 adults with mildly to moderately severe skin and skin-structure infections found no difference in outcome.2 A similar study in 394 children also found similar outcomes in comparing the results of treatment with these two drugs.3

Pharyngitis. Five days of cefdinir therapy appears to be at least as effective as 10 days of penicillin therapy in the treatment of acute pharyngitis due to S. pyogenes. A randomized trial involving 558 children found that bacterial eradication was achieved in 81.7% of the cefdinir recipients and in 88.2% of those treated with penicillin (P = 0.053).4

Acute Community-Acquired Paranasal Sinusitis. Two randomized studies, one involving 1229 patients, 698 of whom underwent antral puncture, and the other with 569 patients, all of whom underwent antral puncture, found similar outcomes between treatment with either cefdinir or amoxicillin-clavulanate.5

Acute Otitis Media. Response rates to cefdinir and to amoxicillin-clavulanate, in a randomized trial of 595 assessable children with acute otitis media, were similar.6

Community-Acquired Pneumonia. Six hundred ninety patients with community-acquired pneumonia were randomized to receive either cefdinir 300 mg bid or cefaclor 500 mg tid, each for 10 days.7 Bacteriological eradication rates were, respectively, 89% and 86%. Diarrhea occurred in 13.7% of those assigned cefdinir and 5.3% of those assigned cefaclor.

The wholesale cost of a 10-day course of cefdinir 300 mg twice daily is reported to be approximately $67. Cefdinir has been demonstrated to be an effective agent for the treatment of certain respiratory and skin structure infections. More data are required to determine its efficacy in the treatment of infections caused by pneumococci that are intermediately susceptible to penicillin. The increasing prevalence of high-level penicillin resistance among pneumococci may limit the usefulness of this and other available orally administered beta-lactam agents in the future.

References

1. Fuchs PC, et al. J Antimicrob Chemother 1995;36: 781-786.

2. Tack KJ, et al. Clin Ther 1998;20:244-256.

3. Tack KJ, et al. Antimicrob Agents Chemother 1997;41(4): 739-742.

4. Tack KJ, et al. Antimicrob Agents Chemother 1998; 42:1073-1075.

5. Gwaltney JM Jr, et al. Cefdinir Sinusitis Study Group.

6. Adler M, et al. Eur J Clin Microbiol Infect Dis 1997; 16:214-219.

7. Drehobl M, et al. Antimicrob Agents Chemother 1997;41:1579-1583.