Frequently asked questions
What are the indications and usage for ZERBAXA?
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.
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.
What is the recommended dosing for ZERBAXA when treating adult patients (18 years and older) with HABP/VABP?
The recommended dose of ZERBAXA in adult patients 18 years and older with HABP/VABP and creatinine clearance (CrCl) greater than 50 mL/min is 3 grams (two 1.5-g vials) over 1-hour period intravenously every 8 hours for 8 to 14 days. The duration of therapy should be guided by the severity and site of infection and the patient’s clinical and bacteriological progress.
Renal dosing adjustments for adult patients (18 years and older) with HABP/VABP per estimated CrCL (mL/min)a,b
- 30 to 50 CrCl (mL/min) 1.5 g (1 g and 0.5 g) intravenously every 8 hours for 8 to 14 days.
- 15 to 29 CrCl (mL/min) 750 mg (500 mg and 250 mg) intravenously every 8 hours for 8 to 14 days.
- For adult patients (18 years and older) with end-stage renal disease on hemodialysis: a single loading dose of 2.25 g (1.5 g and 0.75 g) followed by a 450-mg (300 mg and 150 mg) maintenance dose administered intravenously every 8 hours for the remainder of the treatment period (on hemodialysis days, administer the dose at the earliest possible time following completion of dialysis).
aCreatinine Clearance (CrCl) estimated using Cockcroft-Gault formula.
bAll doses of ZERBAXA are administered over 1 hour.
To view complete dosing information, visit the Dosing overview.
What is the recommended dosing for ZERBAXA when treating adult patients (18 years and older) with cIAI and cUTI?
Dosage for adult patients (18 years and older) with cIAI and cUTI with CrCla greater than 50 mL/min
| Infection | Dose | Frequency | Infusion time | Duration of treatmentd |
|---|---|---|---|---|
| Complicated intra-abdominal infectionsc | 1.5g | Every 8 hours | 1 hour | 4-14 days |
| Complicated urinary tract infections, including pyelonephritis | 1.5g | Every 8 hours | 1 hour | 7 days |
cUsed in conjunction with metronidazole 500 mg intravenously every 8 hours.
dThe duration of therapy should be guided by the severity and site of infection and the patient’s clinical and bacteriological progress.
Dosage adjustments in adult patients (18 years and older) with renal impairment
- Dose adjustment is required for adult patients (18 years and older) with CrCl 50 mL/min or less. All doses of ZERBAXA are administered over 1 hour. For patients with changing renal function, monitor CrCl at least daily and adjust the dosage of ZERBAXA accordingly.
Renal dosing adjustments for adult patients (18 years and older) with cIAI and cUTI with CrCl 50 mL/min or lessa,b
- 30 to 50 CrCl (mL/min) 750 mg (500 mg and 250 mg) intravenously every 8 hours
- 15 to 29 CrCl (mL/min) 375 mg (250 mg and 125 mg) intravenously every 8 hours
- For adult patients (18 years and older) with end-stage renal disease (ESRD) on hemodialysis (HD): a single loading dose of 750 mg (500 mg and 250 mg) followed by a 150 mg (100 mg and 50 mg) maintenance dose administered intravenously every 8 hours for the remainder of the treatment period (on hemodialysis days, administer the dose at the earliest possible time following completion of dialysis).
aCreatinine Clearance (CrCl) estimated using Cockcroft-Gault formula.
bAll doses of ZERBAXA are administered over 1 hour.
To view complete dosing information, visit the Dosing overview.
What is the recommended dosing for ZERBAXA when treating pediatric patients with cIAI and cUTI?
Dosage for pediatric patients (birth to less than 18 years of age) with eGFRd greater than 50 mL/min/1.73 m2
Complicated intra-abdominal infectionse
| Dose (g) | 30 mg/kg up to a maximum dose of 1.5 gf |
| Frequency | Every 8 hours |
| Infusion time | 1 hour |
| Duration of treatment | 5 to 14 days |
Complicated urinary tract infections, including pyelonephritis
| Dose (g) | 30 mg/kg up to a maximum dose of 1.5 gf |
| Frequency | Every 8 hours |
| Infusion time | 1 hour |
| Duration of treatment | 7 to 14 days |
eUsed in conjunction with metronidazole.
fPediatric patients weighing greater than 50 kg should not exceed a maximum dose of 1.5 g.
Dosage adjustments in pediatric patients (birth to less than 18 years of age) with renal impairment
Dosage adjustment of ZERBAXA in pediatric patients (birth to less than 18 years of age) with eGFR 50 mL/min/1.73 m2 or less has not been determined.
ZERBAXA is not recommended in pediatric patients who have an eGFR 50 mL/min/1.73m2 or less.
To view complete dosing information, visit the Dosing overview.
What is the Important Safety Information for ZERBAXA?
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.
For full safety information on ZERBAXA, please see Prescribing information.
How should dosing for ZERBAXA be adjusted for adult patients (18 years and older) with renal impairment?
Renal dosing adjustments for adult patients (18 years and older) with cIAI and cUTI with CrCl 50 mL/min or lessa,b
- 30 to 50 CrCl (mL/min) 750 mg (500 mg and 250 mg) intravenously every 8 hours
- 15 to 29 CrCl (mL/min) 375 mg (250 mg and 125 mg) intravenously every 8 hours
- For adult patients (18 years and older) with end-stage renal disease (ESRD) on hemodialysis (HD): a single loading dose of 750 mg (500 mg and 250 mg) followed by a 150-mg (100 mg and 50 mg) maintenance dose administered intravenously every 8 hours for the remainder of the treatment period (on hemodialysis days, administer the dose at the earliest possible time following completion of dialysis).
aCreatinine Clearance (CrCl) estimated using Cockcroft-Gault formula.
bAll doses of ZERBAXA are administered over 1 hour.
Renal dosing adjustments for adult patients (18 years and older) with HABP/VABP per estimated CrCl (mL/min)a,b
- 30 to 50 CrCl (mL/min) 1.5 g (1 g and 0.5 g) intravenously every 8 hours for 8 to 14 days.
- 15 to 29 CrCl (mL/min) 750 mg (500 mg and 250 mg) intravenously every 8 hours for 8 to 14 days.
- For adult patients (18 years and older) with end-stage renal disease on hemodialysis: a single loading dose of 2.25 g (1.5 g and 0.75 g) followed by a 450-mg (300 mg and 150 mg) maintenance dose administered every 8 hours for the remainder of the treatment period (on hemodialysis days, administer the dose at the earliest possible time following completion of dialysis).
aCreatinine Clearance (CrCl) estimated using Cockcroft-Gault formula.
bAll doses of ZERBAXA are administered over 1 hour.
To view complete dosing information, visit the Dosing overview.
How should dosing for ZERBAXA be adjusted for pediatric patients with renal impairment?
Dosage adjustments in pediatric patients (birth to less than 18 years of age) with renal impairment
Dosage adjustment of ZERBAXA in pediatric patients (birth to less than 18 years of age) with eGFR 50 mL/min/1.73 m2 or less has not been determined.
ZERBAXA is not recommended in pediatric patients who have an eGFR 50 mL/min/1.73m2 or less.
To view complete dosing information, visit the Dosing overview.
Why were adult patients with HABP/VABP given a 3-g dose of ZERBAXA?
The 3 g dose was selected based on a Phase 1 PK/PD study where the 3 g dose achieved target concentrations in epithelial lining fluid for 100% of the dosing interval.1
What’s the difference between hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), and ventilated hospital-acquired bacterial pneumonia (vHABP)?
HABP is a bacterial pneumonia that occurs 48 hours or more after admission; which was not incubating at the time of admission; and is not associated with mechanical ventilation 2,3
VABP is a pneumonia that arises more than 48 hours after endotracheal intubation 2,3
vHABP is a bacterial pneumonia that occurs 48 hours or more after admission; which was not incubating at the time of admission; where the patient subsequently experiences acute respiratory failure and requires ventilation 2,3
Where can I find clinical data for ZERBAXA in HABP/VABP?
ZERBAXA was studied in a Phase 3, double-blind, multinational comparator-controlled noninferiority HABP/VABP study vs meropenem.
Which patients were included in the HABP/VABP study?
The baseline characteristics of patients in the study were:
- 100% ventilated
- Critically ill, median APACHE II score of 17
- 77% hospitalized for ≥5 days
- 92% in the ICU
- 13% failing current AB for HABP/VABP
- 100% of the patients were over 18 years of age, with the median age being 62 years of age
What is the mechanism of action for ZERBAXA?
ZERBAXA®(ceftolozane and tazobactam) combines a novel cephalosporin that has bactericidal action with a proven beta-lactamase inhibitor. Ceftolozane inhibits select penicillin-binding proteins, while tazobactam irreversibly inhibits some beta-lactamases.
Learn more about the Mechanism of Action.
References
- Caro L, Nicolau DP, De Waele JJ, et al. Lung penetration, bronchopulmonary pharmacokinetic/pharmacodynamic profile and safety of 3 g ceftolozane/tazobactam administered to ventilated, critically ill patients with pneumonia. J Antimicrob Chemother. 2020;75(6):1546-1553.
- FDA Guidance for Industry. Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia: developing drugs for treatment. Revised June 2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/hospital-acquired-bacterial-pneumonia-and-ventilator-associated-bacterial-pneumonia-developing-drugs Accessed 20 Sept 2023.
- Kalil AC, et al. Clin Infect Dis. 2016;63(5):e61-e111.