ZERBAXA®

(ceftolozane and tazobactam) for injection (1.5 g), for intravenous use

Clinical Efficacy of ZERBAXA® (ceftolozane and tazobactam) Against HABP/VABP

Treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP)

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Study design

ZERBAXA was studied in critically ill patients.

Study Design for ZERBAXA® (ceftolozane and tazobactam)

Primary efficacy endpoint: all-cause mortality at day 28. Objective was to demonstrate the noninferiority of ZERBAXA versus meropenem in adults with HABP/VABP. For analysis of the overall treatment differences, 2-sided 95% confidence intervals (Cls) were calculated as stratified Newcombe Cls.

100% of patients in the trial were ventilated

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Current antibiotic failure

Approximately 13% of patients were failing current antibacterial therapy for HABP/VABP

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APACHE II score

Patients had a median baseline APACHE II score of 17, indicating a 24% mortality rate (1/3 of patients had a score of ≥20, a 40% mortality rate)1,2

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Hospitalized for ≥5 days

77% of patients had been hospitalized for ≥5 days, 92% in the ICU

Primary endpoint

In a Phase 3 study, ZERBAXA achieved primary endpoint of noninferiority to meropenem in day 28 all-cause mortality.1

Phase 3 Clinical Study ZERBAXA® (ceftolozane and tazobactam) Study 24.0% Overall ITT Primary Endpoint Subgroup Analysis 1. 1 Treatment Difference 95% CI (-5.13, 7.39) vHABP VABP 87/362 25.3% 92/364 1 2.8 Treatment Difference 95% CI (0.18, 24.75) 24.2% 37.0% 40/108 24/99 -3.6 Treatment Difference 95% CI (-10.74, 3.52) 24.0% 20.3% 52/256 63/263 ZERBAXA Meropenem Day 28 all-cause mortality in the ITT population

The analysis population for the primary endpoint was the ITT population, which included all randomized patients

  • In the vHABP subgroup of patients (~28.5%), there was a favorable response for ZERBAXA in all-cause mortality through day 28.
  • – ZERBAXA 24.2% (24/99) meropenem 37.0% (40/108)
  • In the VABP subgroup, 28-day all-cause mortality was 24.0% (63/263) for ZERBAXA and 20.3% (52/256) for meropenem

References

1. Kollef MH, Nováček M, Kivistik Ü, et al. Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, doubleblind, phase 3, non-inferiority trial. Lancet Infect Dis. 2019;19(12):1299-1311.

2. APACHE II Calculator: Acute Physiology and Chronic Health Evaluation (APACHE) II score to predict hospital mortality. Updated November 10, 2018. Accessed July 29, 2022. https://clincalc.com/IcuMortality/APACHEII.aspx

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Indications and Usage

ZERBAXA is indicated for the treatment of adult patients (18 years and older) with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by the following susceptible Gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens.

ZERBAXA is indicated for the treatment of adult and pediatric patients (birth to less than 18 years old) with complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa.

ZERBAXA used in combination with metronidazole is indicated for the treatment of adult and pediatric patients (birth to less than 18 years old) with complicated intra-abdominal infections (cIAI) caused by the following 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.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZERBAXA and other antibacterial drugs, ZERBAXA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Important Safety Information for ZERBAXA® (ceftolozane and tazobactam)

  • Patients with renal impairment: Decreased efficacy of ZERBAXA has been observed in patients with baseline CrCl of 30 to ≤50 mL/min. In a clinical trial of adult patients, patients with cIAIs with CrCl >50 mL/min had a clinical cure rate of 85.2% when treated with ZERBAXA plus metronidazole vs 87.9% when treated with meropenem. In the same trial, patients with CrCl 30 to ≤50 mL/min had a clinical cure rate of 47.8% when treated with ZERBAXA plus metronidazole vs 69.2% when treated with meropenem. A similar trend was also seen in the cUTI trial. Dose adjustment is required for adult patients with CrCl 50 mL/min or less. All doses of ZERBAXA are administered over 1 hour. Monitor CrCl at least daily in patients with changing renal function and adjust the dose of ZERBAXA accordingly.
  • Hypersensitivity: ZERBAXA is contraindicated in patients with known serious hypersensitivity to the components of ZERBAXA (ceftolozane/ tazobactam), piperacillin/tazobactam, or other members of the beta-lactam class. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. Before initiating therapy with ZERBAXA, make careful inquiry about previous hypersensitivity reactions to cephalosporins, penicillins, or other beta-lactams. If an anaphylactic reaction to ZERBAXA occurs, discontinue use and institute appropriate therapy.
  • Clostridioides difficile-associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including ZERBAXA. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is confirmed, antibacterial use not directed against C. difficile should be discontinued, if possible.
  • Development of drug-resistant bacteria: Prescribing ZERBAXA in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and risks the development of drug-resistant bacteria.
  • Adverse reactions in adult patients with HABP/VABP: The most common adverse reactions occurring in ≥5% of adult patients receiving ZERBAXA in the HABP/VABP trial were hepatic transaminase increased (11.9%), renal impairment/renal failure (8.9%), and diarrhea (6.4%).
  • Adverse reactions in adult patients with cIAI or cUTI: The most common adverse reactions occurring in ≥5% of adult patients receiving ZERBAXA in the cUTI and cIAI trials were headache (5.8%) in the cUTI trial, and nausea (7.9%), diarrhea (6.2%), and pyrexia (5.6%) in the cIAI trial.
  • Adverse reactions in pediatric patients with cIAI or cUTI: The most common adverse reactions occurring in ≥7% of pediatric patients receiving ZERBAXA in the cIAI trial were diarrhea (17%), thrombocytosis (16%), pyrexia (13%), abdominal pain (11%), vomiting (10%), increased aspartate aminotransferase (7%), and anemia (7%). The most common adverse reactions occurring in ≥7% of pediatric patients receiving ZERBAXA in the cUTI trial were thrombocytosis (9%), leukopenia (8%), diarrhea (7%), and pyrexia (7%).
  • Pediatric Use: There is insufficient information to recommend dosage adjustment for pediatric patients younger than 18 years of age with cIAI and cUTI with eGFR 50 mL/min/1.73m2 or less. ZERBAXA is not recommended in pediatric patients who have an eGFR 50 mL/min/1.73m2 or less. Pediatric patients born at term or pre-term may not have an eGFR of 50 mL/min/1.73m2 or greater at birth or within the first few months of life.

Before prescribing ZERBAXA, please read the accompanying Prescribing Information.

US-ZER-0162606/23