Are two penicillins better than one? A systematic review of oral flucloxacillin and penicillin V versus oral flucloxacillin alone for the emergency department treatment of cellulitis

Eur J Emerg Med. 2014 Jun;21(3):170-4. doi: 10.1097/MEJ.0b013e328360d980.


Background: Flucloxacillin either alone or combined with penicillin V is still the first-line antibiotic drug of choice for the treatment of cellulitis in emergency departments (EDs) in Ireland. The rationale for this antibiotic regimen is their anti-staphylococcal and anti-streptococcal activity.

Objective: To determine the clinical efficacy, tolerability and safety of oral flucloxacillin alone (monotherapy) compared with a combination of flucloxacillin with penicillin V (dual therapy) in the ED-directed outpatient treatment of cellulitis.

Methods: We searched the following electronic databases: MEDLINE (1950 to August 2011), EMBASE (1980 to August 2011), Cochrane Central Register of Controlled Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue), OpenGrey, Current Controlled Trials metaRegister of Clinical Trials (August 2011) and reference lists and websites of potential trials. We performed cross-referencing from the reference lists of major articles on the subject. We imposed no language restriction.

Results: Despite a comprehensive literature search to identify relevant studies, no randomized-controlled trials that fulfilled the inclusion criteria were found.

Conclusions: Despite its common use, there are no published randomized-controlled trials comparing flucloxacillin monotherapy with a combination of flucloxacillin and penicillin V in the ED management of cellulitis. We discuss existing European and North American prescribing rationale and current guidelines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Cellulitis / diagnosis*
  • Cellulitis / drug therapy*
  • Cellulitis / microbiology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination / methods
  • Emergency Service, Hospital
  • Female
  • Floxacillin / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Ireland
  • Male
  • Penicillin V / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Treatment Outcome
  • Wound Healing / drug effects*


  • Floxacillin
  • Penicillin V