Zerbaxa (Ceftolozane/Tazobactam) is NOT Recommended for Typical Wound Cellulitis
Zerbaxa is not indicated for wound cellulitis and should not be used for this indication. The FDA-approved indications for Zerbaxa are limited to complicated intra-abdominal infections (cIAI), complicated urinary tract infections (cUTI), and hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP)—cellulitis is notably absent from this list 1, 2, 3.
Why Zerbaxa is Inappropriate for Wound Cellulitis
Spectrum Mismatch with Cellulitis Pathogens
Beta-lactam monotherapy targeting streptococci and methicillin-sensitive Staphylococcus aureus (MSSA) is the standard of care for typical wound cellulitis, with a 96% success rate 4, 5.
The primary pathogens in wound cellulitis are beta-hemolytic streptococci (especially Streptococcus pyogenes) and MSSA—organisms that are exquisitely sensitive to simple beta-lactams like cephalexin, dicloxacillin, or cefazolin 6, 4, 5.
Zerbaxa's spectrum is designed for multidrug-resistant Gram-negative bacilli, particularly extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and drug-resistant Pseudomonas aeruginosa—organisms that are uncommon causes of typical cellulitis 2, 3.
Lack of MRSA Coverage
Zerbaxa does not provide coverage against methicillin-resistant Staphylococcus aureus (MRSA), which would be the only reason to deviate from standard beta-lactam therapy in wound cellulitis associated with specific risk factors 2, 3.
When MRSA coverage is needed (penetrating trauma, purulent drainage, injection drug use, known MRSA colonization), appropriate agents include vancomycin, linezolid, daptomycin, or clindamycin—not Zerbaxa 6, 4.
Correct Treatment Algorithm for Wound Cellulitis with Normal Renal Function
First-Line Therapy for Uncomplicated Wound Cellulitis
Oral cephalexin 500 mg every 6 hours for 5 days is the preferred first-line agent, providing excellent coverage against streptococci and MSSA 4.
Alternative oral beta-lactams include dicloxacillin 250-500 mg every 6 hours, amoxicillin, or penicillin V 250-500 mg four times daily 4.
Treatment duration is 5 days if clinical improvement occurs, extending only if symptoms have not improved within this timeframe 4.
When to Add MRSA Coverage
Add MRSA-active antibiotics ONLY when specific risk factors are present 4:
- Penetrating trauma or injection drug use
- Purulent drainage or exudate
- Evidence of MRSA infection elsewhere or known MRSA colonization
- Systemic inflammatory response syndrome (SIRS)
For MRSA coverage, use clindamycin 300-450 mg orally every 6 hours (if local resistance <10%), or combination therapy with trimethoprim-sulfamethoxazole plus a beta-lactam, or doxycycline plus a beta-lactam 4.
Hospitalized Patients Requiring IV Therapy
For uncomplicated wound cellulitis requiring hospitalization without MRSA risk factors, use IV cefazolin 1-2 g every 8 hours 4.
For complicated cellulitis with MRSA risk factors, use vancomycin 15-20 mg/kg IV every 8-12 hours (A-I evidence), with alternatives including linezolid 600 mg IV twice daily, daptomycin 4 mg/kg IV once daily, or clindamycin 600 mg IV every 8 hours if local resistance is low 6, 4.
Severe Cellulitis with Systemic Toxicity
For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, use vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours for 7-10 days 4.
This represents the only scenario where broad-spectrum coverage approaching Zerbaxa's spectrum might be considered, but even here, piperacillin-tazobactam (not Zerbaxa) is the recommended agent 4.
Critical Pitfalls to Avoid
Do not use Zerbaxa for cellulitis simply because it is available or because the patient is hospitalized—this represents significant overtreatment and inappropriate antimicrobial stewardship 4.
Do not reflexively add MRSA coverage for typical nonpurulent wound cellulitis without specific risk factors, as MRSA is an uncommon cause even in high-prevalence settings 4, 5.
Do not extend treatment beyond 5 days based on residual erythema alone, as some inflammation persists even after bacterial eradication 4.
Essential Adjunctive Measures
Elevate the affected extremity above heart level to promote gravity drainage of edema and inflammatory substances 4.
Examine interdigital toe spaces for tinea pedis, fissuring, or maceration, and treat these to eradicate colonization and reduce recurrent infection risk 4.
Address predisposing conditions including venous insufficiency, lymphedema, and chronic edema 4, 7.