Daily Medication Pearl: Ceftolozane and Tazobactam (Zerbaxa)

Indication: Zerbaxa is a combination of ceftolozane, a cephalosporin antibacterial, and tazobactam, a beta-lactamase inhibitor, indicated for the treatment of patients 18 years of age and older with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by the susceptible Gram-negative microorganisms Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens; for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa; and in combination with metronidazole for the treatment of patients 18 years of age and older with complicated intra-abdominal infections (cIAI) caused by the susceptible Gram-negative and Gram-positive microorganisms Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius.

Insight:

• Dosing: 1.5 to 3 g.
• Dosage forms: Zerbaxa 1.5 g for injection is supplied as a sterile powder for reconstitution in single-dose vials containing ceftolozane 1 g (equivalent to 1.147 g ceftolozane sulfate) and tazobactam 0.5 g (equivalent to 0.537 g tazobactam sodium).
• Adverse events: The most common adverse reactions in adult patients (≥5% in either the cIAI or cUTI indication) are nausea, diarrhea, headache, and pyrexia.
• Mechanism of action: Ceftolozane belongs to the cephalosporin class of antibacterial drugs. The bactericidal action of ceftolozane results from inhibition of cell wall biosynthesis and is mediated through binding to penicillin-binding proteins (PBPs). Ceftolozane is an inhibitor of PBPs of P. aeruginosa (e.g., PBP1b, PBP1c, and PBP3) and E. coli (e.g., PBP3). Tazobactam sodium has little clinically relevant in vitro activity against bacteria due to its reduced affinity to penicillin-binding proteins. It is an irreversible inhibitor of some beta-lactamases (e.g., certain penicillinases and cephalosporinases), and can bind covalently to some chromosomal and plasmid-mediated bacterial beta-lactamases.

Source: zerbaxa_pi.pdf (merck.com)