Flucloxacillin or azithromycin for uncomplicated cellulitis
Date First Published:
November 15, 2000
Last Updated:
October 3, 2001
Report by:
Vince Choudhery, Specialist Registrar (Ninewells Hospital, Dundee)
Search checked by:
Colin Fleming, Ninewells Hospital, Dundee
Three-Part Question:
In [patients with uncomplicated cellulitis] is [flucloxacillin or azithromycin] better [at improving outcome]?
Clinical Scenario:
An eighteen-year old presents to the emergency department with a two-day history of redness and swelling in their left arm after a scratch. They are systemically well, and apyrexial. A diagnosis of cellulitis is made and you feel you can discharge the patient on oral antibiotics with outpatient follow up. You wonder whether flucloxacillin or azithromycin would be better at improving outcome.
Search Strategy:
Medline 1966-9/99 using the OVID interface.
Search Details:
([{exp azithromycin OR azithromycin.mp OR exp macrolide$ OR macorlide$.mp} AND {exp floxacillin OR flucloxacillin.mp OR exp penicillins OR pencillin.mp} AND {exp cellulitis OR celluliti$.mp OR exp skin diseases, bacterial OR exp staphlococcal skin infections OR skin infection.mp}]) LIMIT to human AND English language.
Outcome:
5 papers of which 2 irrelevant to question.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Azithromycin, erythromycin and cloxacillin in the treatment of infections and associated soft tissues. European Azithromycin Study Group. Daniel R. 1991, UK | 2 separate studies, one of erythromycin vs azithromycin and one of flucloxacillin vs azithromycin studied. Only 2nd examined. 223 adult patients with acute skin infections (cellulitis, abscess) 105 given fluclox 500mg q.i.d. for 7 days. 218 given azithromycin 500mg day one then 250mg o.d. for 4 days. | Prospective randomised trial | Side effects reported up to 35 days after treatment. | Flucloxacilliin had severe side effects as opposed to 16% of azithromycin group. | Drug company funded study No explanation of any blinding Similar time period of dosage administration Not just cellulitis examined |
| Pathogen isolation, and evidence of eradication. | No significant difference in efficacy of both drugs. | ||||
| Clinical response 4-9 days after treatment: cured, improved or failed. | |||||
| Once daily azithromycin in the treatment of adult skin and skin structure infections. Amaya-Tapia G, Aguirre-Avalos G, Andrade-Villanueva J, et al. 1993, Mexico | 62 adult patients with acute skin infection (cellulitis, abscess, infected ulcers, wounds and furuncles). 31 given azithromycin 500mg o.d. for 3 days. 31 given dicloxacillin 250mg q.i.d. for 7 days. | Prospective randomised blinded trial | Bacteriological eradication, persistence or superinfection. | Results compatible. | At beginning states 7-day course diclox given at end states 10 days No real description of blinding process Not just cellulitis studied |
| Clinical resolution, improvement, or failure. | Clinical resolution in 83.3% azithromycin, and 83.9% dicloxacillin. All other results compatible. | ||||
| A comparative study of the efficacy, safety and tolerance of azithromycin, dicloxacillin and flucloxacillin in the treatment of children with acute skin and skin structure infections. Rodriguez-Solares A, Perez-Gutierrez F, Prosperi J, et al. 1993 Venezuela | 118 Children aged 2-12 yrs with a diagnosis of acute skin infection. (Excluding those with relevant allergy reduced drug absorption or recent antibiotic treatment) 60 azithromycin (10mg/kg o.d. for three days) 49 dicloxacillin (12.5-25mg/kg q.i.d. for 7 days. 9 flucloxacillin (500-2000mg q.i.d.). |
Prospective randomised trial | Response graded clinically by investigators at 0 day, at 3-5 days and at 7-10 days. On third visit response graded as 'cure', 'improvement' or 'failure'. | No significant difference in efficacy. | Patients excluded from trial if pre-treatment cultures showed resistant pathogens, with no mention of intention to treat No mention of power calculation No mention of blinding of investigators when grading response Not just cellulitis studied, but abcess, impetigo, pyoderma and skin ulcers |
| Reported side effects within 35 days of treatment. | Only 2 patients in each group had side effects rated mild. |
Author Commentary:
There seems to be no significant difference in the efficacy of flucloxacillin and azithromycin. The main difference clinically is the much shorter treatment period with only once daily dosing of azithromycin. However azithromycin is considerably more expensive than flucloxacillin, a fact which will prohibit its use first line in most cases.
Bottom Line:
Consider use of azithromycin in cases of cellulitis where compliance will be a problem, otherwise its price may effectively exclude its use.
References:
- Daniel R.. Azithromycin, erythromycin and cloxacillin in the treatment of infections and associated soft tissues. European Azithromycin Study Group.
- Amaya-Tapia G, Aguirre-Avalos G, Andrade-Villanueva J, et al.. Once daily azithromycin in the treatment of adult skin and skin structure infections.
- Rodriguez-Solares A, Perez-Gutierrez F, Prosperi J, et al.. A comparative study of the efficacy, safety and tolerance of azithromycin, dicloxacillin and flucloxacillin in the treatment of children with acute skin and skin structure infections.