Cellulitis is a common skin infection resulting in inflammation that may take weeks to resolve despite appropriate antibiotics. It is unclear whether the adjunctive use of nonsteroidal anti-inflammatory drugs hastens the resolution of inflammation in patients with cellulitis.
We conducted a double-blind, randomized controlled trial comparing ibuprofen 400 mg three times daily for 5 days with identical placebo in adults with uncomplicated cellulitis of the upper or lower limb who were treated with intravenous cefazolin via an outpatient parenteral antibiotic treatment service at one of two Australian hospitals. Participants were assessed twice daily by a study nurse. The primary outcome measure was the proportion of patients with regression of inflammation 48 hours after the first effective dose of parenteral antibiotics (trial registration ANZCTR 12611000515998).
Fifty-one patients were enrolled; 48 had sufficient data available to be included in the modified intention-to-treat analysis. Inflammation had begun to regress at 48 hours in 20 participants (80%) in the ibuprofen group compared to 15 (65%) in the placebo group (absolute risk difference +15%; 95% confidence interval -10 to +40; p >0.05). There was no significant difference in any secondary outcome. Ibuprofen appeared safe, with no patients developing renal impairment or necrotizing fasciitis.
This trial demonstrated no significant benefit of adjunctive ibuprofen in adults with uncomplicated cellulitis. The trial was powered to detect a large effect, and hence it is unclear whether the 15% absolute increase in the primary end point in the ibuprofen group was attributable to chance.
|Intention-to-treat population, n (%)||15/23 (65%)||20/25 (80%)||0.25|
|Per-protocol population||11/18 (61%)||15/20 (75%)||0.36|
|Duration of intravenous antibiotics, days, median (IQR)||3 (3–4)||3 (2–4)||0.43|
|Time to return to normal leg function, days, median (IQR)a||7 (4–10)||7.5 (6–9)||0.52|
|Return to usual activities at day 14||10/14 (71%)||19/20 (95%)||0.06|
|Cellulitis completely resolved at day 6||7/20 (35%)||5/19 (26%)||0.56|
|Cellulitis completely resolved at day 14||10/14 (71%)||13/20 (65%)||0.69|
|Leg pain score on day 6, median (range)||0 (0–1)||0 (0–1)||0.94|
|Decrease in leg pain score from baseline to day 6, mean (SD)||3.6 (3.6)||3.4 (2.2)||0.86|
|Leg tightness score on day 6, median (range)||0 (0–2)||1 (0–2)||0.63|
|Decrease in leg tightness score from baseline to day 6, mean (SD)||3.8 (3.8)||3.3 (2.1)||0.73|
|Safety end points|
|Need for hospital admission in first 14 days||1 (4%)||1 (4%)||0.73|
|Serum creatinine at day 6, μmol/L, mean (SD)||71 (11.8)||75 (12)||0.25|
|Proportion with serum creatinine >120 μmol/L at day 6||0||0||NA|
|Proportion with at least moderate epigastric pain or heartburn at any time during days 1–6||0||2 (8%)||0.16|