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Flucloxacillin or azithromycin for uncomplicated cellulitis

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.
([{exp azithromycin OR OR exp macrolide$ OR macorlide$.mp} AND {exp floxacillin OR OR exp penicillins OR} AND {exp cellulitis OR celluliti$.mp OR exp skin diseases, bacterial OR exp staphlococcal skin infections OR skin}]) LIMIT to human AND English language.

Search Outcome

5 papers of which 2 irrelevant to question.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Daniel R,
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 trialSide 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.
Clinical response 4-9 days after treatment: cured, improved or failed. No significant difference in efficacy of both drugs.
Amaya-Tapia G et al,
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 trialBacteriological 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.
Rodriguez-Solares A et al,
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 trialResponse 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.


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.

Clinical Bottom Line

Consider use of azithromycin in cases of cellulitis where compliance will be a problem, otherwise its price may effectively exclude its use.


  1. Daniel R. Azithromycin, erythromycin and cloxacillin in the treatment of infections and associated soft tissues. European Azithromycin Study Group. Journal of International Medical Research 1991;19(6):433-45.
  2. Amaya-Tapia G, Aguirre-Avalos G, Andrade-Villanueva J, et al. Once daily azithromycin in the treatment of adult skin and skin structure infections. Journal of Antimicrobial Chemotherapy 1993;31(SupplE):129-35.
  3. 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. Journal of Antimicrobial Chemotherapy 1993;31(SupplE):103-9.