What is ZERBAXA?
ZERBAXA is a prescription antibiotic medication composed of two active ingredients:
- Ceftolozane: A next-generation cephalosporin antibiotic effective against a broad spectrum of Gram-negative bacteria, including multidrug-resistant strains such as Pseudomonas aeruginosa.
- Tazobactam: A beta-lactamase inhibitor that enhances ceftolozane’s activity by inhibiting enzymes produced by some resistant bacteria which would otherwise degrade ceftolozane.
Together, ceftolozane and tazobactam provide a powerful treatment option against complicated infections caused by resistant bacteria.
Uses of ZERBAXA
ZERBAXA is FDA-approved for the treatment of adults (18 years and older) with:
- Complicated intra-abdominal infections (cIAI), often used in combination with metronidazole.
- Complicated urinary tract infections (cUTI), including pyelonephritis.
- Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP), which are serious lung infections acquired in the hospital setting.
Clinicians may also use ZERBAXA off-label for other infections caused by susceptible bacteria under medical guidance.
Dosage and Administration
For HABP/VABP:
- Patients with normal renal function (creatinine clearance [CrCl] > 50 mL/min):
3 grams (2g ceftolozane / 1g tazobactam) IV every 8 hours over 1 hour, for 8–14 days. - For renal impairment, dosage adjustments are as follows:
- CrCl 30–50 mL/min: 1.5 g IV every 8 hours
- CrCl 15–29 mL/min: 750 mg IV every 8 hours
- End-stage renal disease on hemodialysis: Loading dose 2.25 g IV, then 450 mg IV every 8 hours; on dialysis days, dose is given post-dialysis.
All doses should be infused over 1 hour. Frequent monitoring of renal function is essential to guide dose adjustments, especially in patients with fluctuating kidney function.
Contraindications
- Known hypersensitivity to ceftolozane, tazobactam, other cephalosporins, or beta-lactam antibiotics (including penicillins and carbapenems).
- History of severe allergic reactions such as anaphylaxis or Stevens-Johnson syndrome to beta-lactams.
Safety and Precautions
- Renal impairment: Clinical trials showed reduced efficacy of ZERBAXA in patients with moderate renal impairment (CrCl 30–50 mL/min), with clinical cure rates lower than comparator antibiotics. Dose adjustments are critical in this population.
- Hypersensitivity reactions: Severe, potentially fatal allergic reactions have occurred. A detailed allergy history is mandatory before starting therapy. Discontinue immediately if severe hypersensitivity develops.
- Clostridioides difficile-associated diarrhea (CDAD): Like all systemic antibiotics, ZERBAXA can cause CDAD, which may occur during or weeks after treatment. If suspected, discontinue ZERBAXA and manage appropriately.
- Antibiotic resistance: Inappropriate use (e.g., for viral infections or without confirmed bacterial infection) increases risk of resistance development. Use only when bacterial infection is proven or strongly suspected.
Adverse Effects
Common adverse events observed in clinical trials (≥5% incidence) include:
- For HABP/VABP: Elevated liver enzymes (12%), renal impairment/failure (9%), diarrhea (6%).
- For cUTI: Headache (6%).
- For cIAI: Nausea (8%), diarrhea (6%), fever (6%).
These events were generally mild to moderate and manageable.
Cost Information
ZERBAXA is a high-cost intravenous antibiotic. The estimated cash price for ten vials (1 g ceftolozane / 0.5 g tazobactam each) is approximately $1,300 to $1,400, varying by pharmacy. Prices for insured patients will depend on coverage.
Summary
ZERBAXA is an advanced antibiotic option for treating complicated infections caused by resistant Gram-negative bacteria, including hospital-acquired pneumonias and complicated abdominal and urinary infections. Appropriate dosing and renal function monitoring are critical for safety and effectiveness. Awareness of hypersensitivity risks, potential for C. difficile infection, and stewardship principles is essential to optimize clinical outcomes.