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ZERBAXA® (ceftolozane and tazobactam) for injection (1.5 g), for intravenous use
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In vitro activity for ZERBAXA® (ceftolozane and tazobactam)

ZERBAXA demonstrated potent in vitro activity against P. aeruginosa1

  • The clinical significance of in vitro data is unknown.
  • Limitations of the SMART data include: lack of clinical information to confirm nosocomial versus community-acquired isolates, relatively small number of isolates tested each year (n=250 per site), small number of sites, and change of sites participating in SMART study over time.1
  • Culture and susceptibility information and local epidemiology should be considered in modifying antibacterial therapy.
  • ZERBAXA is not active against bacteria that produce serine carbapenemases (K. pneumoniae carbapenemase [KPC]), and metallo-beta-lactamases.

Susceptibility rates for select ICU respiratory tract isolates in U.S. surveillance data (2023-2024)1,a

Susceptibility Rates for Select ICU Respiratory Tract Isolates for ZERBAXA® (ceftolozane and tazobactam) vs. MeropenemSusceptibility Rates for Select ICU Respiratory Tract Isolates for ZERBAXA® (ceftolozane and tazobactam) vs. Meropenem

aIsolates were collected as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART 2023-2024).1

Study design1

The Study for Monitoring Antimicrobial Resistance Trends (SMART) represents the commitment of Merck to monitor the in vitro susceptibility of clinical bacterial Gram-negative isolates to antimicrobials in intra-abdominal (since 2002), urinary tract (since 2009), respiratory tract (since 2015), and bloodstream infections (since 2019). SMART was initiated in 2002 and is a global study. This report specifically focuses on isolates from respiratory tract infections (RTIs), collected from 2023 and 2024.

Minimum inhibitory concentration (MIC) values for ceftolozane/tazobactam and comparator agents were determined using the broth microdilution methodology recommended by the Clinical and Laboratory Standards Institute (CLSI) that was current in the year the data was collected. The following breakpoints were used to test for the susceptibility of P. aeruginosa for ZERBAXA (MICs [mcg/mL]): ≤4/4 (susceptible).

ZERBAXA: 9 years of P.aeruginosa susceptibility data

  • The clinical significance of in vitro data is unknown.
  • Limitations of the SMART data include: lack of clinical information to confirm nosocomial versus community-acquired isolates, relatively small number of isolates tested each year (n=250 per site), small number of sites, and change of sites participating in SMART study over time.2
  • Contributing centers collected consecutive Gram-negative bacilli from hospitalized patients with intra-abdominal, urinary, respiratory tract, or bloodstream infections.2
  • Culture and susceptibility information and local epidemiology should be considered in modifying antibacterial therapy.
  • ZERBAXA is not active against bacteria that produce serine carbapenemases (K. pneumoniae carbapenemase [KPC]), and metallo-beta-lactamases.

Susceptibility rates for select isolates in US surveillance data (2016-2024)2,a

Susceptibility Rates to P. aeruginosa Isolates From 2016 Through 2024

aIsolates were collected as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART 2016-2024).2

Study design2

The Study for Monitoring Antimicrobial Resistance Trends (SMART) was initiated by Merck in 2002 and represents the commitment of Merck to monitor the in vitro susceptibility of clinical aerobic and facultative Gram-negative bacterial isolates from intra-abdominal infections (IAIs) to selected antimicrobials internationally, enabling longitudinal analyses to determine if susceptibility patterns changed over time. Collection of isolates from urinary tract infections (UTIs), lower respiratory tract infections (RTIs), and bloodstream infections (BSIs) started in 2009, 2015, and 2019, respectively. Each participating site collected up to the indicated number of consecutive clinically relevant isolates of Gram-negative bacilli: 100 from patients with RTIs, 50 from IAIs, 50 from UTIs, and 50 from BSIs. 

The above collection of isolates represents the United States surveillance data of P. aeruginosa susceptibility to ceftolozane/tazobactam between 2016 and 2024. Minimum inhibitory concentration (MIC) was interpreted using current Clinical & Laboratory Standards Institute (CLSI) guidelines available in the United States. The following breakpoints were used to test for the susceptibility of P. aeruginosa for ZERBAXA (MICs [mcg/mL]): ≤4/4 (susceptible).

References

  1. Data available on request from the Merck National Service Center via email at daprequests@merck.com. Please specify information package US-ZER-02083.
  2. Data available on request from the Merck National Service Center via email at daprequests@merck.com. Please specify information package US-ZER-02140.

INDICATIONS AND USAGE

  • ZERBAXA® (ceftolozane and tazobactam) 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

  • 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/1.73 m2 or less. ZERBAXA is not recommended in pediatric patients who have an eGFR 50 mL/min/1.73 m2 or less. Pediatric patients born at term or pre-term may not have an eGFR of 50 mL/min/1.73 m2 or greater at birth or within the first few months of life.

Before prescribing ZERBAXA, please read the accompanying Prescribing Information.

INDICATIONS AND USAGE
IMPORTANT SAFETY INFORMATION

  • ZERBAXA® (ceftolozane and tazobactam) 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

  • 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/1.73 m2 or less. ZERBAXA is not recommended in pediatric patients who have an eGFR 50 mL/min/1.73 m2 or less. Pediatric patients born at term or pre-term may not have an eGFR of 50 mL/min/1.73 m2 or greater at birth or within the first few months of life.

Before prescribing ZERBAXA, please read the accompanying Prescribing Information.