Is once-daily cefazolin plus probenecid similar to twice-daily cefazolin in the treatment of cellulitis?
Date First Published:
March 12, 2013
Last Updated:
March 12, 2013
Report by:
Francis Fournier, Resident Physician (Laval University)
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 (through PubMED)
EMBASE 1966 to 01/2013
Search Details:
MEDLINE: skin diseases, infectious[MeSH Terms] AND probenecid[MeSH Terms] AND cefazolin[MeSH Terms]
EMBASE: \"skin infection\" and \"cefazolin\" and \"probenecid\"
EMBASE: \"skin infection\" and \"cefazolin\" and \"probenecid\"
Outcome:
32 papers were screened for relevance. Of those, one was found relevant to the question.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Once or twice-daily, algorithm-based intravenous cephazolin for home-based cellulitis treatment Garrett T, Harbort Y, Trebble M, et al. 2012 Australia | Patients > 18 years old referred to a hospital-in-the-home service for treatment of uncomplicated cellulitis. Exclusion criteria: pregnancy or breast-feeding, allergy to cefazolin or probenecid, ALT, AST or AP level > twice upper reference limit, CrCl < 40 ml/min, C-I to cefazolin or probenecid | Prospective observational cohort | Time until non-progression (TTPN) | TTPN was similar in each group: 2.11 (1.98-2.23) and 2.13 (1.81-2.45) for once and twice daily regimen, respectively. | 1)tNo randomization, no blinding to treatment groups 2)tTwo different groups compared: patients in the twice-daily regimen were older and had more comorbidities 3)tNo intention-to-treat analysis: Only patients completing prescribed therapy are included in the analysis 4)tMean duration of cellulitis before initiation of i.v. treatment of 3 days in once-daily treatment compared with 6 days in twice-daily treatment 5)tFew follow-up data available |
| Length of stay (LOS) | Mean LOS of 6.55 (5.96-7.15) in once-daily regimen and 7.67 (6.69-8.65) in twice-daily regimen. | ||||
| Treatment failure | Treatment failure in 7 patients in once-daily (3%) and 10 patients (9%). | ||||
| Treatment related side-effects | Treatment side effects in 15.5% (33/213) of once-daily regimen and in 9.1% (8/88) of twice-daily regimen, including mostly nausea, drowsiness and diarrhea. |
Author Commentary:
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)tCox VC, Zed PJ, “Once-daily cefazolin and probenecid for skin and soft tissue infections”, Annals of Pharmacotherapy, 2004, 38(3):458-63.
3)tBrown G, et al., “Ceftriaxone versus cefazolin with probenecid for severe skin and soft tissue infections”, Journal of Emergency Medicine, 1996; 14:547-51.
2)tCox VC, Zed PJ, “Once-daily cefazolin and probenecid for skin and soft tissue infections”, Annals of Pharmacotherapy, 2004, 38(3):458-63.
3)tBrown G, et al., “Ceftriaxone versus cefazolin with probenecid for severe skin and soft tissue infections”, Journal of Emergency Medicine, 1996; 14:547-51.
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.
References:
- Garrett T, Harbort Y, Trebble M, et al.. Once or twice-daily, algorithm-based intravenous cephazolin for home-based cellulitis treatment