Best IV Antibiotic for Cellulitis
For typical uncomplicated cellulitis requiring IV therapy, cefazolin 1-2 g IV every 8 hours is the preferred first-line agent, as beta-lactam monotherapy successfully treats 96% of cases and MRSA coverage is unnecessary unless specific risk factors are present. 1
Standard IV Therapy Algorithm
For Uncomplicated Cellulitis (No MRSA Risk Factors)
Use beta-lactam monotherapy alone:
- Cefazolin 1-2 g IV every 8 hours is the preferred agent 1
- Alternative: Oxacillin 2 g IV every 6 hours 1
- Duration: 5 days if clinical improvement occurs; extend only if no improvement 1
This approach is appropriate even in hospitals with high MRSA prevalence, as MRSA remains an uncommon cause of typical nonpurulent cellulitis 1. The 96% success rate with beta-lactam monotherapy confirms that reflexively adding MRSA coverage represents overtreatment 1.
For Complicated Cellulitis Requiring MRSA Coverage
Add MRSA-active therapy ONLY when these specific risk factors are present: 1
- Penetrating trauma or injection drug use 1, 2
- Purulent drainage or exudate 1
- Known MRSA colonization or infection elsewhere 1
- Failure of beta-lactam therapy after 48-72 hours 1
- Systemic inflammatory response syndrome (SIRS) 1
MRSA-active IV options (all equally effective per IDSA A-I evidence): 1
- Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line) 1
- Linezolid 600 mg IV twice daily 1
- Daptomycin 4 mg/kg IV once daily 1
- Clindamycin 600 mg IV three times daily (only if local MRSA resistance <10%) 1
For Severe Cellulitis with Systemic Toxicity
Mandatory broad-spectrum combination therapy when any of these are present: 1
- Fever, hypotension, altered mental status 1
- Rapid progression or skin necrosis 1
- Suspected necrotizing fasciitis 1
- Severe immunocompromise or neutropenia 1
Recommended IV combinations: 1
- Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1, 3
- Alternative: Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
- Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
- Alternative: Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 1
Duration for severe infections: 7-14 days, guided by clinical response 1, 3
Pediatric IV Antibiotic Selection
- Vancomycin 15 mg/kg IV every 6 hours is first-line for hospitalized children with complicated cellulitis 1
- Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (only if stable, no bacteremia, local resistance <10%) 1
- Linezolid 600 mg IV twice daily (>12 years) or 10 mg/kg/dose IV every 8 hours (<12 years) 1
Critical Pitfalls to Avoid
Do not add MRSA coverage reflexively just because the patient is hospitalized - even in high MRSA-prevalence hospitals, typical cellulitis is caused by streptococci and responds to beta-lactams in 96% of cases 1. Adding unnecessary MRSA coverage increases costs, adverse effects, and antibiotic resistance without improving outcomes 1.
Do not use piperacillin-tazobactam for uncomplicated cellulitis - this represents significant overtreatment and should be reserved only for severe infections with systemic toxicity or suspected necrotizing fasciitis 1, 3. Piperacillin-tazobactam lacks MRSA activity and must always be combined with vancomycin or linezolid when used 1.
Reassess at 48-72 hours - if the patient is not improving on appropriate therapy, consider MRSA coverage, deeper infection, or necrotizing fasciitis rather than simply continuing ineffective antibiotics 1.
Transition to Oral Therapy
Once clinical improvement is demonstrated (typically after minimum 4 days IV treatment), transition to oral antibiotics: 1
- Cephalexin, dicloxacillin, or clindamycin for continued therapy 1
- If MRSA coverage needed: clindamycin alone OR doxycycline/TMP-SMX plus a beta-lactam 1
- Never use doxycycline or TMP-SMX as monotherapy - unreliable streptococcal activity 1