Preferred Analgesic for Uncomplicated Cellulitis
For uncomplicated cellulitis in an otherwise healthy adult, NSAIDs (specifically ibuprofen 400 mg three times daily) may provide modest early benefit in accelerating clinical response within the first 3 days, though this effect does not persist beyond 4-5 days and does not improve overall cure rates. 1
Evidence for NSAIDs as Adjunctive Therapy
The most recent systematic review and meta-analysis (2024) demonstrates that oral NSAIDs as adjunct to antibiotics significantly improve early clinical response at day 3 (risk ratio 1.81,95% CI 1.42-2.31), but this benefit disappears by day 5. 1
A 2017 double-blind RCT comparing ibuprofen 400 mg three times daily for 5 days versus placebo showed a non-significant trend toward faster regression of inflammation at 48 hours (80% vs 65%), though the study was underpowered to detect smaller effects. 2
An earlier 2005 pilot study found that ibuprofen 400 mg every 6 hours for 5 days combined with antibiotics resulted in 82.8% of patients showing regression of inflammation within 1-2 days compared to only 9.1% with antibiotics alone, with complete resolution in 4-5 days versus 6-7+ days. 3
Importantly, NSAIDs appear safe in cellulitis treatment, with no patients developing renal impairment or necrotizing fasciitis in the available trials. 2
Practical Dosing Algorithm
If you choose to use adjunctive NSAIDs for symptom relief:
- Ibuprofen 400 mg orally three times daily for 3-5 days is the most studied regimen. 2, 3, 1
- Limit duration to 5 days maximum, as benefit does not extend beyond this timeframe. 1
- Reserve for patients without contraindications to NSAIDs (no renal impairment, no GI bleeding history, no anticoagulation). 2
Role of Corticosteroids
Current IDSA guidelines suggest considering systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though this carries only a weak recommendation based on limited evidence. 4
- There is insufficient data to support routine corticosteroid use for cellulitis, and the single trial supporting this recommendation has low certainty of evidence. 1
- Corticosteroids should be avoided in diabetic patients due to concerns about glycemic control and infection clearance. 4
Standard Analgesic Approach
For routine pain management in cellulitis:
- Acetaminophen (paracetamol) 500-1000 mg every 6 hours remains a safe first-line option for pain relief without anti-inflammatory effects that might theoretically mask worsening infection. [General medical knowledge]
- Elevation of the affected extremity above heart level for at least 30 minutes three times daily is a critical adjunctive measure that hastens improvement by promoting gravity drainage of edema and inflammatory substances—this is often more effective than analgesics alone. 4, 5
Critical Caveats
Inflammation may paradoxically worsen in the first 24-48 hours after starting antibiotics due to bacterial destruction releasing enzymes that increase local inflammation—this is expected and does not indicate treatment failure. 5
- Reassessment at 48-72 hours is crucial to verify clinical response, as most patients should demonstrate reduction in fever, decreased pain, and stabilization of erythema spread by this timepoint. 5
- If pain is severe or out of proportion to examination findings, consider necrotizing fasciitis and obtain emergent surgical consultation rather than escalating analgesics. 4
What NOT to Do
- Do not use NSAIDs as a substitute for appropriate antibiotic therapy—they are purely adjunctive and do not treat the underlying infection. 1
- Do not continue NSAIDs beyond 5 days, as there is no evidence of sustained benefit and risk of adverse effects increases. 1
- Do not use NSAIDs in patients with renal impairment, volume depletion, or concurrent nephrotoxic antibiotics (e.g., vancomycin), as this increases acute kidney injury risk. 2