Best Evidence Topics
  • Send this BET as an Email
  • Make a Comment on this BET

Is once-daily cefazolin plus probenecid similar to twice-daily cefazolin in the treatment of cellulitis?

Three Part Question

In [patients with moderate to severe soft tissue infection], is [daily cefazolin plus oral probenecid] compared to [two or three times a day intravenous cefazolin alone] associated with [success in therapy] ?

Clinical Scenario

A 43 years old man presents to the emergency department with a moderate cellulitis with lymphangitis of the forearm following a trivial skin trauma in the previous days. The patient is not known for any health problem nor does he have any risk factor for CA-MRSA. You wonder if daily intravenous cefazolin following oral probenecid is as effective as two or three times a day intravenous cefazolin treatment.

Search Strategy

The search was performed on January 8th, 2013.
MEDLINE (through PubMED)
EMBASE 1966 to 01/2013
MEDLINE: skin diseases, infectious[MeSH Terms] AND probenecid[MeSH Terms] AND cefazolin[MeSH Terms]

EMBASE: \"skin infection\" and \"cefazolin\" and \"probenecid\"

Search Outcome

32 papers were screened for relevance. Of those, one was found relevant to the question.


Once-daily cefazolin plus probenecid is a commonly prescribed antibiotic regimen in uncomplicated cellulitis. However, data supporting this practice is limited. Most studies have focused on pharmacokinetic evidence (2) or comparison with another broad-spectrum agent (3). Despite a lack of similar control group in the only clinical study addressing the question, this treatment appears to be safe in selected population. 2) Cox VC, Zed PJ, “Once-daily cefazolin and probenecid for skin and soft tissue infections”, Annals of Pharmacotherapy, 2004, 38(3):458-63. 3) Brown G, et al., “Ceftriaxone versus cefazolin with probenecid for severe skin and soft tissue infections”, Journal of Emergency Medicine, 1996; 14:547-51.

Clinical Bottom Line

In young (≤ 75) and healthy patients, once-daily cefazolin plus probenecid appears to be safe regarding TTPN and treatment failure in uncomplicated cellulitis, although one might expect more treatment related side-effects. However, no conclusion can be drawn about the relative efficacy compared to twice-daily regimen. Better-designed studies are needed to precisely answer this question.