When to use oral cephalosporins and which one

Oral SECOND-generation agents, such as cefprozil (Cefzil, etc) cover Strep pneumoniae and H. influenzae. Suggest saving them for specific situations..
Abdelwahab Ward, BS Pharm, PharmD
2 minute read

When to use oral cephalosporins and which one?! - As a pharmacist, you should know that cephalosporins are NOT first-line for many OUTpatient infections anymore.

Oral FIRST-generation agents, such as cephalexin (Keflex, Ceporex, etc) are known for their gram-positive coverage, but have little gram-negative coverage.

  • Recommend cephalexin (Ceporex) for outpatient skin infections IF MRSA isn't suspected. For possible MRSA, recommend TMP/SMX (Septrin DS) or doxycycline.

Oral SECOND-generation agents, such as cefprozil (Cefzil, etc) cover Strep pneumoniae and H. influenzae. Suggest saving them for specific situations due to resistance concerns.

  • For example, consider suggesting them for bacterial upper respiratory tract infection (otitis media, bronchitis and sinusitis) in patients allergic to penicillins.
  • Discourage using cefaclor (Ceclor), it doesn't cover common pathogens.

NPS-adv

Oral THIRD-generation agents, such as cefpodoxime (Podacef, etc) add even more gram-negative activity, but they don't reliably cover INpatient gram-negatives such as Enterobacter or Pseudomonas aeruginosa. There's overlap between 2nd- and 3rd-generation agents for respiratory tract infections. Explain that cefpodoxime (Podacef) or cefdinir (Omnicef, Cefdin) can be used for the same infections as cefprozil.

  • Recommend cefixime (Suprax, Ximacef) only for gonorrhea, and only when an oral medication is necessary (can be combined with azithromycin).
  • It has other indications, but is NOT the best choice.

Don't automatically avoid cephalosporins in penicillin-allergic patients. Cross-reactivity between penicillins and cephalosporins is less than 1% instead of 10% as previously thought. And it's less likely with 2nd- and 3rd-generation cephalosporins than 1st-generation. Caution about using cephalosporins if the reaction to penicillin is severe (angioedema, bronchospasm, urticaria, anaphylaxis).

References

  1. Pichichero ME. A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics. 2005 Apr;115(4):1048-57.
  2. Holten, K.B. and Onusko, E.M. (2013). Appropriate Prescribing of Oral Beta-Lactam Antibiotics. American Family Physician, [online] 62(3), pp.611–620.
  3. Pichichero ME. Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift. Diagn Microbiol Infect Dis. 2007 Mar;57(3 Suppl):13S-18S.

This note has been edited and reviewed by the pharmacy doctors on NPS team.

  • Published on December 17, 2021
  • This note last updated in March 05, 2025
Abdelwahab Ward, BS Pharm, PharmD