What is Zerbaxa (ceftolozane/tazobactam)?

Zerbaxa (Ceftolozane/Tazobactam): Clinical Overview

Zerbaxa is a combination antimicrobial agent consisting of ceftolozane (a novel cephalosporin) and tazobactam (a beta-lactamase inhibitor) that is particularly effective against multidrug-resistant gram-negative bacteria, including difficult-to-treat Pseudomonas aeruginosa. 1

Indications

Zerbaxa is FDA-approved for the treatment of:

1. Complicated Intra-abdominal Infections (cIAI) - used in combination with metronidazole in adult and pediatric patients (birth to <18 years) 1
2. Complicated Urinary Tract Infections (cUTI), including Pyelonephritis - in adult and pediatric patients (birth to <18 years) 1
3. Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) - in adult patients 18 years and older 1

Mechanism of Action

Zerbaxa combines:

• Ceftolozane: A cephalosporin that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs)
• Tazobactam: A beta-lactamase inhibitor that protects ceftolozane from degradation by certain beta-lactamases 1, 2

Antimicrobial Spectrum

Zerbaxa demonstrates potent activity against:

• Multidrug-resistant Pseudomonas aeruginosa, including carbapenem-resistant strains 3
• Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae 2
• Various gram-negative pathogens resistant to other antibiotics 4

The addition of tazobactam extends ceftolozane's activity to include most ESBL-producing organisms and some anaerobic species 2.

Dosing

Adult Dosing

• Standard dose: 1.5 g (1 g ceftolozane/0.5 g tazobactam) IV every 8 hours for cUTI and cIAI 1
• HABP/VABP dose: 3 g (2 g ceftolozane/1 g tazobactam) IV every 8 hours 3, 1

Pediatric Dosing

• Children ≥12 years: 1.5 g IV every 8 hours
• Children <12 years: 20/10 mg/kg IV every 8 hours 5

Renal Adjustment

Dosage adjustment is required in patients with CrCl ≤50 mL/min 1

Clinical Applications

Difficult-to-treat Pseudomonas aeruginosa (DTR-PA)

Zerbaxa is recommended as a treatment option for infections caused by difficult-to-treat P. aeruginosa with a dose of 1.5-3 g IV every 8 hours 3. This recommendation is based on its unique ability to evade multiple resistance mechanisms employed by P. aeruginosa, including efflux pumps, reduced porin uptake, and PBP modifications 2.

Complicated UTI/Pyelonephritis

For complicated UTI, Zerbaxa is an effective alternative to fluoroquinolones and carbapenems, particularly in areas with high resistance rates 3, 6. Treatment duration is typically 5-10 days 3.

Complicated Intra-abdominal Infections

For cIAI, Zerbaxa is used in combination with metronidazole and has demonstrated efficacy comparable to meropenem in clinical trials 4, 6. Treatment duration is typically 5-7 days 3.

Hospital-acquired and Ventilator-associated Pneumonia

For HABP/VABP, the higher dose of 3 g every 8 hours is recommended to achieve adequate lung penetration 3, 1.

Advantages Over Other Antimicrobials

1. Potent anti-pseudomonal activity: Maintains activity against many multidrug-resistant P. aeruginosa strains 2
2. Carbapenem-sparing option: Provides an alternative to carbapenems for ESBL-producing organisms, helping to reduce carbapenem resistance 7
3. Stable against various resistance mechanisms: Effective against pathogens with efflux pumps and porin channel mutations 2

Limitations

1. Not active against carbapenemase-producing organisms 2
2. Limited anaerobic coverage (requires metronidazole for cIAI) 1, 6
3. Requires dose adjustment in renal impairment 1

Safety Profile

The safety profile of Zerbaxa is consistent with that of other cephalosporins, with common adverse effects including:

• Hypersensitivity reactions
• Gastrointestinal effects (nausea, diarrhea)
• Headache 4

Clinical Pearls

• Zerbaxa should be reserved for infections caused by confirmed or suspected resistant pathogens to minimize development of resistance 1
• For cIAI, always combine with metronidazole for anaerobic coverage 1, 6
• Consider Zerbaxa as a carbapenem-sparing option for ESBL-producing organisms when susceptibility is confirmed 7
• The higher dose (3 g) is specifically indicated for HABP/VABP due to the need for increased lung penetration 3, 1

Zerbaxa represents an important addition to the antimicrobial armamentarium, particularly for treating resistant gram-negative infections while preserving carbapenem use for the most critical situations.