What about Ceftolozane/Tazobactam (Zerbaxa)?

From the Guidelines

Ceftolozane/Tazobactam, also known as Zerbaxa, is a recommended first-line treatment option for patients with invasive infections caused by Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-PA) 1. This antibiotic combination is used to treat complicated intra-abdominal infections, complicated urinary tract infections, and hospital-acquired bacterial pneumonia. The typical adult dosage is 1.5 g (1 g ceftolozane/0.5 g tazobactam) administered intravenously every 8 hours for 4-14 days, depending on the infection type. Some key points to consider when using Ceftolozane/Tazobactam include:

• Dosage adjustments are required for patients with renal impairment.
• This medication works by inhibiting bacterial cell wall synthesis (ceftolozane component) while the tazobactam protects ceftolozane from degradation by certain beta-lactamase enzymes produced by resistant bacteria.
• Common side effects include nausea, diarrhea, headache, and fever.
• Patients should be monitored for allergic reactions, especially if they have a history of penicillin or cephalosporin allergies.
• This antibiotic should only be used under medical supervision for confirmed or strongly suspected bacterial infections to reduce the risk of developing antibiotic resistance. It's also important to note that Ceftolozane/Tazobactam has excellent in vitro activity against MDR P. aeruginosa 1, and is a valuable option for treating infections caused by MDR gram-negative bacteria, helping to preserve carbapenems 1.

From the FDA Drug Label

ZERBAXA (ceftolozane and tazobactam) is a combination of ceftolozane, a cephalosporin antibacterial, and tazobactam, a beta-lactamase inhibitor, indicated for the treatment of the following infections caused by designated susceptible microorganisms: Complicated Intra-abdominal Infections (cIAI), used in combination with metronidazole, in adult and pediatric patients (birth to less than 18 years old). Complicated Urinary Tract Infections (cUTI), Including Pyelonephritis, in adult and pediatric patients (birth to less than 18 years old). Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP), in adult patients 18 years and older.

Ceftolozane/Tazobactam (Zerbaxa) is indicated for the treatment of:

• Complicated Intra-abdominal Infections (cIAI) in adult and pediatric patients
• Complicated Urinary Tract Infections (cUTI) in adult and pediatric patients
• Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) in adult patients 18 years and older 2

From the Research

Overview of Ceftolozane/Tazobactam

• Ceftolozane/tazobactam is a novel antipseudomonal β-lactam/β-lactamase inhibitor combination approved for the treatment of complicated intraabdominal infections (cIAI) and complicated urinary tract infections (cUTI) 3.
• It exhibits bactericidal properties through inhibition of bacterial cell wall biosynthesis, which is mediated through penicillin-binding proteins (PBPs) 3.

Mechanism of Action and Pharmacokinetics

• Ceftolozane is a potent PBP3 inhibitor and has a higher affinity for PBP1b compared with other β-lactam agents 3.
• The addition of tazobactam provides enhanced activity against extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and certain anaerobic organisms 3.
• Ceftolozane/tazobactam follows a two-compartment model with linear elimination, and its pharmacokinetics are unaffected by the coadministration of tazobactam 4.

Clinical Efficacy and Safety

• Ceftolozane/tazobactam has demonstrated efficacy and safety in patients with cIAI, including those who are infected with ESBL-producing Enterobacteriaceae and P. aeruginosa 5.
• The clinical success rate of ceftolozane/tazobactam for resistant Pseudomonas aeruginosa respiratory infections was 72.6% across a wide range of comorbidities 6.
• Ceftolozane/tazobactam was well tolerated, with only six patients presenting adverse events, but none had to stop treatment 6.

Dosage and Administration

• The dose of ceftolozane/tazobactam is 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) intravenously every 8 hours given as a 1-hour infusion 3.
• Dosage adjustments are required for moderate-to-severe renal impairment and in patients receiving hemodialysis 3.
• The most common therapeutic regimens were 1.5 g every 8 h and 3 g every 8 h 6.

Resistance and Susceptibility

• Ceftolozane/tazobactam is active against multidrug-resistant Gram-negative bacilli, including Pseudomonas aeruginosa 4.
• The minimum inhibitory concentration (MIC) for the PSA was 2/4 for C/T, indicating susceptibility 7.
• Ceftolozane/tazobactam may be a valid therapeutic option to treat multidrug-resistant (MDR), extensively drug-resistant (XDR), pandrug-resistant (PDR), and carbapenem-resistant (CR) PA infections 6.