Pharmacological Class:
Cephalosporin + beta-lactamase inhibitor.
Active Ingredient(s):
1.5g (ceftolozane 1g and tazobactam 0.5g); per vial; pwd for IV infusion after reconstitution; preservative-free; contains sodium chloride 487mg/vial.
Company
Merck & Co., Inc.
Indication(s):
Susceptible complicated intra-abdominal infections in combination with metronidazole and complicated urinary tract infections, including pyelonephritis.
Pharmacology:
Ceftolozane is a cephalosporin antibacterial that exhibits bactericidal action by inhibiting cell wall biosynthesis and by binding to penicillin-binding proteins (PBPs). Ceftolozane is an inhibitor of PBPs of P. aeruginosa (PBP1b, PBP1c, and PBP3) and E. coli (PBP3).
Tazobactam is an irreversible inhibitor of some beta-lactamases and can bind covalently to some chromosomal and plasmid-mediated bacterial beta-lactamases. It has little clinically relevant in vitro activity against bacteria due to its reduced affinity to PBPs.
Clinical Trials:
In a multinational, double-blind study, adults hospitalized with complicated intra-abdominal infections (n=979) were randomized and compared Zerbaxa (1.5g IV every 8 hours) + metronidazole (500mg IV every 8 hours) to meropenem (1g IV every 8 hours) for 4–14 days of therapy.
The primary efficacy endpoint was clinical response, defined as complete resolution or significant improvement in signs and symptoms of the index infection at the test-of-cure (TOC) visit which occurred 24–32 days after the first dose.
Zerbaxa + metronidazole was non-inferior to meropenem (83% vs. 87.3%, respectively) with regard to clinical cure rates at the TOC visit in the microbiological intent-to-treat (MITT) population (n=806). The treatment difference was –4.3 % (95% CI: –9.2, 0.7).
In another multinational, double-blind study, adults hospitalized with complicated urinary tract infection including pyelonephritis (n=1,068) were randomized and compared Zerbaxa (1.5g IV every 8 hours) to levofloxacin (750mg IV once daily) for 7 days of therapy.
The primary efficacy endpoint was defined as complete resolution or marked improvement of the clinical symptoms and microbiological eradication at the TOC visit 7 (±2) days after the last dose.
Zerbaxa showed efficacy with regard to the composite endpoint of microbiological and clinical cure at the TOC visit in both the microbiologically modified intent-to-treat (mMITT) population (n=800) and the microbiologically eva luable (ME) population. In the mMITT population, 76.9% of the Zerbaxa-treated patients achieved clinical cure rates compared to 68.4% of the levofloxacin-treated patients. The treatment difference was 8.5% (95% CI: 2.3, 14.6).
For more clinical trial data, see full labeling.
Legal Classification:
Rx
Adults:
Give by IV infusion over 1 hour. ≥18 years (CrCl >50mL/min): complicated intra-abdominal infections: usually 1.5g every 8 hours for 4–14 days with IV metronidazole 500mg every 8 hours; complicated urinary tract infections: 1.5g every 8 hours for 7 days. Renal impairment (CrCl 30–50mL/min): 750mg every 8 hours; (CrCl 15–29mL/min): 375mg every 8 hours; ESRD on hemodialysis: 750mg loading dose, followed by 150mg maintenance dose every 8 hours for remainder of treatment (give on dialysis days).
Children:
<18 years: not established.
Contraindication(s):
Cephalosporin, penicillin, or other beta-lactam allergy.
Warnings/Precautions:
Discontinue if serious hypersensitivity reactions occur. Moderate or severe renal impairment; monitor renal function daily and adjust dose. Elderly. Pregnancy (Category B). Nursing mothers.
Adverse Reaction(s)
Nausea, diarrhea, headache, pyrexia, constipation, insomnia, vomiting; C. difficile-associated diarrhea, anaphylaxis.
How Supplied:
Single-use vials—10
LAST UPDATED:
7/14/2015
