What is the recommended intravenous cefazolin dosing, duration, renal dose adjustment, and alternative therapy for an adult with uncomplicated cellulitis, including management of a documented type I IgE allergy to penicillins or cephalosporins?

IV Cefazolin for Uncomplicated Cellulitis: Dosing, Duration, and Allergy Management

For uncomplicated cellulitis requiring IV therapy, cefazolin 1–2 g IV every 8 hours for 5 days is the preferred beta-lactam regimen, achieving approximately 96% clinical success in typical cases caused by streptococci and methicillin-sensitive Staphylococcus aureus. 1, 2

Standard IV Cefazolin Dosing

Administer cefazolin 1–2 g IV every 8 hours for hospitalized adults with uncomplicated cellulitis requiring parenteral therapy. 3, 1 This dosing provides excellent tissue penetration, with wound tissue concentrations achieving a mean tissue-to-serum ratio of 1.06, ensuring adequate drug exposure at the infection site. 4

For moderate-to-severe infections, the FDA-approved dosing is 500 mg to 1 gram every 6 to 8 hours. 5 In clinical practice, the 1–2 g every 8 hours regimen is preferred for cellulitis because it simplifies administration while maintaining therapeutic levels. 3, 1

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs (resolution of warmth and tenderness, decreasing erythema, absence of fever); extend only if symptoms have not improved within this timeframe. 1 High-quality randomized controlled trial evidence demonstrates that 5-day courses achieve 98% clinical resolution with no relapse by 28 days, making traditional 7–14-day regimens unnecessary for uncomplicated cases. 1

For complicated skin and soft tissue infections requiring hospitalization, 7–14 days of therapy is recommended, individualized based on clinical response. 1

Renal Dose Adjustment

Patients with creatinine clearance ≥55 mL/min or serum creatinine ≤1.5 mg/dL can receive full doses. 5

For creatinine clearance 35–54 mL/min (serum creatinine 1.6–3.0 mg/dL): Give full doses but restrict dosing intervals to at least every 8 hours. 5

For creatinine clearance 11–34 mL/min (serum creatinine 3.1–4.5 mg/dL): Administer half the usual dose every 12 hours after an initial loading dose. 5

For creatinine clearance ≤10 mL/min (serum creatinine ≥4.6 mg/dL): Give half the usual dose every 18–24 hours after an initial loading dose. 5

All reduced-dosage recommendations apply after an initial loading dose appropriate to infection severity—do not reduce the first dose even in renal impairment. 5

Management of Type I IgE Penicillin Allergy

When Cefazolin Is Contraindicated

Avoid cefazolin in patients with documented type I IgE-mediated penicillin allergy (anaphylaxis, angioedema, urticaria, bronchospasm) because cross-reactivity, although low (2–4%), can be clinically significant in severe reactions. 1, 6

Alternative IV Regimens for Penicillin-Allergic Patients

Vancomycin 15–20 mg/kg IV every 8–12 hours is first-line for hospitalized penicillin-allergic patients with cellulitis, targeting trough concentrations of 15–20 mg/L (A-I evidence). 1, 6, 7

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
• Clindamycin 600 mg IV every 8 hours (A-III evidence), but only if local MRSA clindamycin resistance is <10% 1

Oral Alternatives for Penicillin-Allergic Outpatients

Clindamycin 300–450 mg orally every 6 hours for 5 days is the optimal first-line choice for penicillin-allergic patients with typical nonpurulent cellulitis, providing single-agent coverage for both streptococci and MRSA without requiring combination therapy. 6 Use only when local MRSA clindamycin resistance rates are <10%. 1, 6

Levofloxacin 500 mg orally once daily for 5 days provides excellent streptococcal coverage but lacks reliable MRSA activity; reserve fluoroquinolones for beta-lactam-allergic patients to minimize resistance. 6

Management of Cephalosporin Allergy

Patients with suspected immediate-type cephalosporin allergy can receive penicillins with dissimilar side chains, irrespective of severity and time since the index reaction (strong recommendation, moderate-quality evidence). 1

Any carbapenem can be used safely in cephalosporin-allergic patients in a clinical setting, irrespective of severity or time since the index reaction. 1

Cross-reactivity among beta-lactams is less common than historically believed, allowing safe use of penicillins with dissimilar side chains or carbapenems in many cases. 1

When MRSA Coverage Is Unnecessary

Routine MRSA-active antibiotics are not required for typical cellulitis, even in hospitals with high MRSA prevalence, because MRSA is an uncommon cause of nonpurulent cellulitis. 1 Beta-lactam monotherapy with cefazolin achieves 96% clinical success in typical cases. 1, 2

Add MRSA-active therapy only when specific risk factors are present:

• Penetrating trauma or injection drug use 1
• Visible purulent drainage or exudate 1
• Known MRSA colonization or prior MRSA infection 1
• Systemic inflammatory response syndrome (fever >38°C, heart rate >90 bpm, respiratory rate >24 breaths/min) 1
• Failure to respond to beta-lactam therapy after 48–72 hours 1

Severe Cellulitis Requiring Broad-Spectrum Coverage

For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, initiate mandatory broad-spectrum combination therapy:

• Vancomycin 15–20 mg/kg IV every 8–12 hours PLUS piperacillin-tazobactam 3.375–4.5 g IV every 6 hours 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

Do not delay surgical consultation when any signs of necrotizing infection are present (severe pain out of proportion, skin anesthesia, rapid progression, "wooden-hard" tissue, gas, or bullae)—these infections progress rapidly and require debridement. 1

Essential Adjunctive Measures

Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances, which hastens clinical improvement. 1, 6

Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration and treat these conditions to eradicate colonization and reduce recurrent infection. 1

Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, obesity, and eczema to reduce recurrence risk. 1

Critical Pitfalls to Avoid

Do not add MRSA coverage reflexively for typical cellulitis without the specified risk factors—this overtreats approximately 96% of cases and drives antimicrobial resistance. 1, 2

Do not automatically extend therapy to 7–10 days based on residual erythema alone—some inflammation persists even after bacterial eradication; extend only if warmth, tenderness, or erythema have not improved after 5 days. 1

Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection than initially recognized. 1

Do not use vancomycin alone for open-wound cellulitis—it lacks activity against gram-negative and anaerobic pathogens that commonly colonize such wounds. 1