What are the preferred intravenous (IV) antibiotics for the treatment of cellulitis?

Preferred IV Antibiotics for Cellulitis

For hospitalized adults with complicated cellulitis requiring IV therapy, vancomycin is the first-line agent, with alternatives including linezolid, daptomycin, or clindamycin depending on MRSA risk and severity. 1, 2

Standard IV Therapy for Complicated Cellulitis

First-Line Options for Adults

Vancomycin remains the gold standard IV antibiotic for hospitalized patients with complicated skin and soft tissue infections, dosed at 15-20 mg/kg IV every 8-12 hours. 1 This recommendation comes from the Infectious Diseases Society of America with A-I level evidence, representing the strongest possible recommendation. 1

Alternative IV agents with equivalent efficacy include:

• Linezolid 600 mg IV twice daily (A-I evidence) 1
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1
• Telavancin 10 mg/kg IV once daily (A-I evidence) 1
• Clindamycin 600 mg IV three times daily (A-III evidence) 1

When Beta-Lactam Monotherapy is Appropriate

For nonpurulent cellulitis without MRSA risk factors, a beta-lactam such as cefazolin may be considered as initial therapy, with modification to MRSA-active agents only if clinical response is inadequate. 1 The Infectious Diseases Society of America confirms that beta-lactam treatment succeeds in 96% of typical cellulitis cases, making MRSA coverage unnecessary in most hospitalized patients without specific risk factors. 2

Cefazolin 2 g IV once daily (with oral probenecid 1 g) or ceftriaxone 1 g IV once daily are effective options for moderate-to-severe cellulitis when MRSA is not suspected. 3 These regimens demonstrated 86-96% clinical cure rates in randomized trials. 3

Severe Infections Requiring Broad-Spectrum Coverage

Systemic Toxicity or Necrotizing Infection

For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy includes vancomycin or linezolid PLUS piperacillin-tazobactam, a carbapenem, or ceftriaxone plus metronidazole. 2 This represents significant escalation beyond standard cellulitis treatment and should be reserved for truly severe presentations. 2

For documented group A streptococcal necrotizing fasciitis specifically, the recommended combination is penicillin plus clindamycin. 2

Critical Caveat on Overtreatment

Using both piperacillin-tazobactam AND daptomycin simultaneously for simple cellulitis represents significant overtreatment—this combination should be reserved exclusively for life-threatening infections or documented resistant organisms. 2 If you are considering this combination, you are likely treating something more severe than typical cellulitis, which would warrant 7-14 days rather than the standard 5-day course. 2

Pediatric IV Antibiotic Selection

Standard Pediatric Dosing

For hospitalized children with complicated cellulitis, vancomycin 15 mg/kg IV every 6 hours is the recommended first-line agent. 1

If the patient is stable without ongoing bacteremia or intravascular infection, clindamycin 10-13 mg/kg/dose IV every 6-8 hours (maximum 40 mg/kg/day) is an option if local clindamycin resistance rates are low (e.g., <10%), with transition to oral therapy if the strain is susceptible. 1

Linezolid is an alternative, dosed at 600 mg IV twice daily for children >12 years, or 10 mg/kg/dose IV every 8 hours for children <12 years. 1

Treatment Duration

The standard duration for IV cellulitis treatment is 5 days if clinical improvement has occurred, with extension only if symptoms have not improved. 2 This applies regardless of whether vancomycin, daptomycin, or other agents are used. 2

For severe cellulitis with systemic toxicity requiring combination therapy (such as vancomycin plus piperacillin-tazobactam), plan for 7-10 days minimum, reassessing at 5 days. 2

For complicated skin and soft tissue infections in hospitalized patients, 7-14 days of therapy is recommended but should be guided by clinical response. 1

Key Decision Points

When to Add MRSA Coverage

MRSA-active IV therapy is indicated for cellulitis associated with:

• Purulent drainage or exudate 1
• Penetrating trauma 2
• Known MRSA colonization or prior infection 4
• Failure to respond to beta-lactam therapy 1
• Specific high-risk populations (athletes, prisoners, military recruits, long-term care residents, IV drug users, men who have sex with men) 4

Common Pitfall to Avoid

Do not reflexively add MRSA coverage to all hospitalized cellulitis patients—the Infectious Diseases Society of America confirms that adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases without risk factors. 2 This represents unnecessary broad-spectrum therapy that promotes resistance and increases costs without improving outcomes. 2