Q/A with Tony Friedman Volume 2.0 - Treatment of Cellulits in the ED

2. Treatment of cellulitis in the ED.

THE QUESTION:

There seems to be a lot of variation in the way we manage cellulitis in the department. Is there any evidence that a single dose of IV antibiotics before discharge is superior to immediate discharge on PO antibiotics? What are the options for outpatient IV antibiotics? And what about patients with chronic bilateral leg edema who come in with redness of both legs? Should I be treating that as cellulitis or is a different pathology present?


THE ANSWER:

While many reviews acknowledge the practice of administering a single dose of IV antibiotic before discharge, none of them cited any supporting data and I was unable to find any studies specifically addressing this question in a Medline search. Therefore, this practice cannot be assumed to have an advantage over immediate discharge with a prescription for oral antibiotics.
If you are not comfortable with discharge of the patient on oral antibiotics and ongoing observation of the patient in the ED is not an option, one alternative to admission is outpatient intravenous antibiotic therapy. As PICC line placement and home visits for antibiotic administration can rarely be arranged rapidly, the best option is likely for the patient to return to the ED or primary physician's office at intervals for administration of antibiotics. Practical considerations favor a once daily antibiotic over one that must be administered more frequently, such as cefazolin or oxacillin.
Ceftriaxone has been used for outpatient IV therapy of cellulitis for at least 20 years. Several studies indicate clinical cure rates of 75-80% and improvement rates of 15-20%, with only 5% treatment failure rates [1]. Daily dosage of ceftriaxone has also been shown to have equivalent clinical efficacy to cefazolin [2] and gentamicin/clindamycin [3] in clinical trials. However, a failure rate of 4/8 was reported in the subgroup of diabetic patients with foot infections in a small study [4].
An alternative to ceftriaxone is once daily dosage with IV cefazolin with a daily PO dose of 2g probenecid. Probenecid reduces renal excretion of cefazolin, maintaining bactericidal concentrations in the blood for 24 hours. In one study, probenecid was administered with daily doses of ceftriaxione or cefazolin with similar treamtent failure rates of 7% and 8% respectively [5]. Another study found no significant difference in clinical cure rate between cefazolin/probenecid and ceftriaxone (86% and 96% respectively, p = 0.11). Despite the apparent trend towards an increased cure rate with ceftriaxone, the authors state that the study was sufficiently powered to exclude a significant difference between the two therapies. Adverse reactions such as nausea were more common with cefazolin/probenecid [6]. Also keep in mind that probenecid may potentially alter levels of other renally excreted medications.
There appears to be no solid evidence basis for oral versus intravenous antibiotic therapy regimens for cellulitis. Perhaps for this reason, wide practice variation has been noted in the treatment of cellulitis in urban emergency departments [7]. A large randomized prospective trial comparing pure oral therapy, single-dose IV therapy followed by oral, and outpatient IV therapy for efficacy, cost and patient satisfaction would go a long way towards resolving the issue.
It is important to remember that cellulitis is not the only condition that causes leg erythema. DVT is an obvious consideration with unilateral erythema and asymmetric swelling. It is well known to dermatologists that simple lower extremity edema may result in erythema in certain individuals [8], although this does not appear to have been formally studied. Nifedipine has been asssociated with erythematous edema of the lower extremities [9]. Another condition to keep in mind is varicose eczema, which is characterized by erythema along with crusting and/or scaling in one or both legs [10]. Small vesicles may frequently occur as well. While it can be difficult to distinguish erythematous edema or varicose eczema from cellulitis based on appearance, the diagnose of cellulitis should be reconsidered in a well-appearing patient without fever or leukocytosis. In addition, the simultaneous appearance of erythema on both legs should suggest a non-infectious etiology, although bilateral lower extremity cellulitis has been reported in large series [11].
One final point for cellulitis is that blood cultures are generally low yield and should not be routinely obtained. One study showed that only 2% of 553 patients with community-acquired cellulitis had positive blood cultures [12]. However, 3/10 patients with cellulitis superimposed on chronic lymphedema did have positive blood cultures [13], so this subgroup might require a different approach.

References
1. Gainer. (1991) Hosp Pract 26 Suppl 5:24
2. Bradsher et al. (1984) Am J Med 77:62
3. Gordin et al. (1985) Antimicrob Agents Chemother 27:648
4. Eron et al. (1983) Antimicrob Agents Chemother 23:731
5. Brown et al. [1996] J Emerg Med 14:547
6. Grayson et al. [2002] Clin Infect Dis 2002 34:440
7. Dong et al. (2001) Am J Emerg Med 19:535
8. Cox. (2002) Clin Med 2:23
9. Bridgman. (1978) Br Med J 1:578
10. Quartey-Papafio. (199) Br Med J 318:1672
11. Dupuy et al. (1999) Br Med J 318:1591
12. Perl et al. (199) Clin Infect Dis 29:1483
13. Woo et al. (2000) J Clin Microbiol Inf Dis 19:294