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INFECTIOUS DISEASES

Once-Daily Cefazolin and Probenecid for Skin and Soft Tissue Infections

at time of writing, PharmD Student, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada; now, Clinical Pharmacy Specialist, Emergency Medicine/Drug Information, Lions Gate Hospital, North Vancouver, British Columbia

Peter J Zed, PharmD

Pharmacotherapeutic Specialist—Emergency Medicine, Clinical Services Unit Pharmaceutical Sciences, Vancouver General Hospital; Clinical Assistant Professor, Faculty of Pharmaceutical Sciences & Associate Member, Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver

Reprints: Peter J Zed PharmD, CSU Pharmaceutical Sciences, Vancouver General Hospital, 855 W. 12th Ave., Vancouver, British Columbia V5Z 1M9, Canada, fax 604/875-5267, zed{at}interchange.ubc.ca

OBJECTIVE: To review the pharmacokinetic and clinical evidence for the use of once-daily cefazolin and probenecid in the treatment of skin and soft tissue infections (SSTI).

DATA SOURCES: MEDLINE (1966-July 2003), EMBASE (1980-July 2003), and PubMed (1966-July 2003) databases for English language, human reports were searched. Search terms included cefazolin, probenecid, cellulitis, and soft tissue infections.

STUDY SELECTION AND DATA EXTRACTION: Studies that described pharmacokinetic and clinical outcomes that evaluated the use of cefazolin in conjunction with probenecid for SSTI were included. All studies were evaluated independently by both authors. For pharmacokinetic studies, the effect of probenecid on the pharmacokinetics of cefazolin was evaluated. For clinical trials, efficacy and safety endpoints were evaluated. For efficacy endpoints, definition of cure was used as defined by each trial.

DATA SYNTHESIS: In all 3 pharmacokinetic studies identified, the addition of probenecid to cefazolin therapy prolonged the half-life and increased serum concentrations of cefazolin. This process allowed serum concentrations to be above the minimal inhibitory concentrations (MIC) for the most likely skin pathogens (Staphylococcus aureus, ß-hemolytic streptococci) at the end of the dosing interval. In the first of 2 clinical trials, 7 (7%) of 96 patients receiving intravenous ceftriaxone 2 g and oral probenecid 1 g daily were reported to fail therapy compared with 8 (8%) of 98 patients receiving intravenous cefazolin 2 g and oral probenecid 1 g daily. In the second clinical trial, clinical success was reported in 51 (86%) of 59 patients receiving the same doses of cefazolin and probenecid as above compared with 55 (96%) of 57 patients receiving intravenous ceftriaxone 1 g and oral placebo daily.

CONCLUSIONS: Limited pharmacokinetic and clinical data suggest that intravenous cefazolin 2 g and oral probenecid 1 g daily is an effective regimen in the treatment of SSTI.

Key Words: cefazolin, cellulitis, probenecid, skin and soft tissue infections

Published Online, January 23, 2004. www.theannals.com, DOI 10.1345/aph.1D251