Which IV antibiotics should I start for severe facial cellulitis?

IV Antibiotic Selection for Severe Facial Cellulitis

For severe facial cellulitis requiring IV therapy, initiate vancomycin 15–20 mg/kg IV every 8–12 hours PLUS piperacillin-tazobactam 3.375–4.5 g IV every 6 hours immediately. 1

Rationale for Combination Therapy

Severe facial cellulitis with systemic toxicity mandates broad-spectrum combination therapy because:

• Facial infections can rapidly progress to involve deeper structures, orbital complications, or intracranial spread, making aggressive empiric coverage essential 1
• Vancomycin provides MRSA coverage (15–20 mg/kg IV every 8–12 hours, targeting trough 15–20 mg/L), which is critical given the potential for resistant organisms in severe presentations 1, 2
• Piperacillin-tazobactam adds polymicrobial coverage for gram-negative and anaerobic organisms that may be present, particularly if there is any history of trauma, dental involvement, or concern for deeper infection 3, 1

Alternative IV Regimens

If vancomycin plus piperacillin-tazobactam is contraindicated or unavailable:

• Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam provides equivalent MRSA coverage with A-I evidence 1, 2
• Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) is another acceptable combination 1
• Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours offers broad coverage when beta-lactam/beta-lactamase inhibitors are not suitable 3, 1

When Monotherapy May Be Sufficient

If the patient lacks systemic toxicity (no fever >38°C, no tachycardia >90 bpm, no hypotension, no altered mental status) and the cellulitis is non-purulent without MRSA risk factors:

• Cefazolin 1–2 g IV every 8 hours is the preferred IV beta-lactam for uncomplicated cellulitis requiring hospitalization 1, 2
• Nafcillin 2 g IV every 6 hours or oxacillin 2 g IV every 6 hours are alternatives 1, 2
• Beta-lactam monotherapy achieves 96% clinical success in typical cellulitis, even in hospitalized patients, when MRSA risk factors are absent 1

MRSA Risk Factors Requiring Coverage

Add MRSA-active therapy (vancomycin or linezolid) when any of these are present:

• Penetrating facial trauma or recent facial surgery 1, 2
• Purulent drainage or exudate visible at the infection site 1, 2
• Known MRSA colonization or prior MRSA infection 1, 2
• Systemic inflammatory response syndrome (SIRS): fever, tachycardia, tachypnea, or altered mental status 1, 2
• Failure to respond to beta-lactam therapy after 48–72 hours 1, 2

Treatment Duration

• For severe cellulitis with systemic toxicity: 7–10 days total, reassessing at 5 days for clinical improvement 1
• For uncomplicated cellulitis: 5 days if clinical improvement occurs, extending only if warmth, tenderness, or erythema have not improved 1, 2
• High-quality RCT evidence confirms 5-day courses are as effective as 10-day courses for uncomplicated cases 1

Transition to Oral Therapy

Once clinical improvement is demonstrated (typically after 4–5 days of IV therapy):

• Clindamycin 300–450 mg orally every 6 hours if local MRSA clindamycin resistance is <10% 1, 2
• Linezolid 600 mg orally twice daily as an alternative for continued MRSA coverage 1, 2
• Cephalexin 500 mg orally every 6 hours if MRSA coverage is no longer needed and the patient is improving 1, 2

Critical Red Flags Requiring Surgical Consultation

Obtain emergent surgical evaluation if any of these warning signs are present:

• Severe pain out of proportion to examination findings 1, 2
• Skin anesthesia or "wooden-hard" subcutaneous tissue 1, 2
• Rapid progression despite appropriate antibiotics 1, 2
• Violaceous bullae, cutaneous hemorrhage, or skin sloughing 2
• Gas in soft tissue on imaging 1

These findings suggest necrotizing fasciitis, which requires immediate surgical debridement in addition to antibiotics 3, 1.

Common Pitfalls to Avoid

• Do not use ceftriaxone monotherapy for severe facial cellulitis—it lacks MRSA coverage and is not first-line even for MSSA in severe infections 2
• Do not delay antibiotics to obtain imaging when clinical presentation is straightforward; imaging is reserved for suspected deeper infection or necrotizing fasciitis 1, 2
• Do not continue ineffective antibiotics beyond 48 hours if the infection is progressing; reassess for resistant organisms or deeper infection 1, 2
• Do not use doxycycline or TMP-SMX as monotherapy for facial cellulitis, as they lack reliable streptococcal coverage 1, 2

Adjunctive Measures

• Elevate the head of the bed to promote gravity drainage of facial edema 1, 2
• Obtain blood cultures before initiating antibiotics in patients with systemic toxicity, though they are positive in only ~5% of typical cellulitis cases 1, 2
• Verify tetanus prophylaxis is up-to-date if there is any history of facial trauma 1