Ceftolozane and tazobactam: Drug information

(For additional information see "Ceftolozane and tazobactam: Patient drug information" and see "Ceftolozane and tazobactam: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Zerbaxa

Brand Names: Canada

Zerbaxa

Pharmacologic Category

Cephalosporin Combination

Dosing: Adult

Note: Zerbaxa (ceftolozane/tazobactam) is a combination product. Dosage recommendations are expressed as grams of ceftolozane/tazobactam combination. Not recommended for routine empiric use. Reserve use for patients with or at risk for certain multidrug-resistant gram-negative organisms (eg, P. aeruginosa with difficult-to-treat resistance) with limited treatment options (Ref). When the 3 g dose is utilized for the treatment of multidrug-resistant gram-negative infections, it is recommended to extend infusion time (ie, over 3 hours instead of standard 1 hour) (Ref).

Intra-abdominal infection

Intra-abdominal infection (alternative agent): IV: 1.5 to 3 g every 8 hours in combination with metronidazole (Ref). Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Ref).

Pneumonia, hospital-acquired or ventilator-associated

Pneumonia, hospital-acquired or ventilator-associated (alternative agent): IV: 3 g every 8 hours (Ref). Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (Ref).

Serious infections due to multidrug-resistant P. aeruginosa

Serious infections (eg, bloodstream infection, skin and soft tissue infection) due to multi drug-resistant P. aeruginosa (off-label use): IV: 1.5 to 3 g every 8 hours (Ref); 3 g every 8 hours should be used for pulmonary infections (Ref).

Urinary tract infection, complicated

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms):

IV: 1.5 g every 8 hours. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Ref).

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Dosage recommendations are expressed as grams of ceftolozane/tazobactam combination.

Altered kidney function: IV:

**Ceftolozane/Tazobactam Dose Adjustments for Kidney Impairment^a**
CrCl^b (mL/minute)	If the usual recommended dose is 1.5 g every 8 hours	If the usual recommended dose is 3 g every 8 hours
^aChoose usual recommended dose based on indication and disease severity (see adult dosing), then choose the adjusted dose from that column corresponding to the patient's CrCl.
^bCrCl may be estimated using Cockcroft-Gault formula.
^c Note: May consider delaying dosage adjustment (eg, administer full doses for 48 hours after initiation) before decreasing the dose for acute kidney injury (AKI). In a subgroup analysis of ceftolozane/tazobactam clinical trials, cure rates were lower in subjects with CrCl 30 to 50 mL/minute compared to subjects with CrCl >50 mL/minute (Kullar 2017; Palchak 2015). It has been suggested that this may be due to underdosing of the medication at the beginning of treatment due to a falsely low estimate of CrCl based on an admission serum creatinine value. Elevated serum creatinine values quickly normalize in over half of patients thought to have AKI (Crass 2019).
>50 to 130 (usual recommended dosing schedule)	1.5 g every 8 hours	3 g every 8 hours
30 to 50	750 mg every 8 hours^c	1.5 g every 8 hours^c
15 to 29	375 mg every 8 hours^c	750 mg every 8 hours^c
<15 mL/minute not on dialysis	There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m²): IV: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematological malignancies. A measured urinary clearance is necessary to identify these patients.

Empiric therapy: Monte Carlo simulation suggests that a 1.5 g loading dose followed by 4.5 g continuous infusion over 24 hours will meet pharmacodynamic targets. If unable to administer by continuous infusion, the more aggressive intermittent dose (3 g every 8 hours) is preferred over the 1.5 g every 8-hour regimen (Ref).

Directed therapy (pathogen is susceptible): 3 g every 8 hours (Ref).

Hemodialysis, intermittent (thrice weekly): IV: Dialyzable (ceftolozane 66%; tazobactam 56%) (Ref).

If the usual recommended dose is 1.5 g every 8 hours: Initial: 750 mg as a single dose, followed by 150 mg every 8 hours. Administer dose immediately after dialysis on dialysis days (Ref).

If the usual recommended dose is 3 g every 8 hours: Initial: 2.25 g as a single dose, followed by 450 mg every 8 hours. Administer dose immediately after dialysis on dialysis days (Ref).

CRRT: Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations assume high-flux dialyzers and flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection), organism minimum inhibitory concentration (MIC), residual kidney function, and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.

CVVH/CVVHD/CVVHDF: IV: 1.5 g every 8 hours (Ref).

Monte Carlo simulation suggests that after 24 hours of therapy clinicians may consider reducing the dose to 750 mg every 8 hours to minimize accumulation at steady state (Ref). Alternatively, these simulations also suggest that a 3 g loading dose followed by a maintenance dose of 750 mg every 8 hours will ensure adequate initial concentrations while minimizing accumulation (Ref).

PIRRT: Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection), organism MIC, residual kidney function, and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.

IV: 750 mg loading dose, followed by 150 mg every 8 hours while off prolonged intermittent renal replacement therapy (PIRRT). For PIRRT sessions, give 750 mg at the start (within first hour) of PIRRT and an additional 750 mg within an hour after PIRRT session ends.

Note: Limited data available: Dosing based on a single case report describing a patient receiving PIRRT with blood and dialysate flow rates of 200 mL/minute for 7.5-hour treatments. Ceftolozane and tazobactam were extensively cleared by PIRRT; however, appropriate serum concentrations were maintained throughout the treatment (Ref).

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Ceftolozane and tazobactam: Pediatric drug information")

Note: Zerbaxa (ceftolozane and tazobactam) is a combination product; dosage recommendations are provided in mg of ceftolozane. Each 1.5 g vial of ceftolozane/tazobactam contains 1 g ceftolozane and 0.5 g tazobactam in a 2:1 ratio.

Intra-abdominal infection

Intra-abdominal infection:

Infants, Children, and Adolescents <18 years: IV: 20 mg ceftolozane/kg/dose every 8 hours in combination with metronidazole for 5 to 14 days; maximum dose: 1,000 mg ceftolozane per dose.

Adolescents ≥18 years: IV: 1,000 mg ceftolozane every 8 hours in combination with metronidazole for 4 to 14 days.

Pneumonia, hospital-acquired or ventilator-associated

Pneumonia, hospital-acquired or ventilator-associated: Adolescents ≥18 years: IV: 2,000 mg ceftolozane every 8 hours for 8 to 14 days.

Urinary tract infection, complicated

Urinary tract infection, complicated:

Infants, Children, and Adolescents <18 years: IV: 20 mg ceftolozane/kg/dose every 8 hours for 7 to 14 days; maximum dose: 1,000 mg ceftolozane per dose.

Adolescents ≥18 years: IV: 1,000 mg ceftolozane every 8 hours for 7 days.

Dosing: Kidney Impairment: Pediatric

Note: Zerbaxa (ceftolozane and tazobactam) is a combination product; dosage recommendations are provided in mg of ceftolozane; use caution. Each 1.5 g vial of ceftolozane/tazobactam contains 1 g ceftolozane and 0.5 g tazobactam in a 2:1 ratio.

Altered kidney function:

Infants, Children, and Adolescents <18 years: IV:

eGFR >50 mL/minute/1.73 m²: No dosage adjustment necessary.

eGFR ≤50 mL/minute/1.73 m²: Use is not recommended. Based on adult data, dosage adjustment is necessary, but pediatric-specific adjustments have not been determined.

Adolescents ≥18 years: Note: Dosing recommendations are provided in terms of ceftolozane component.

Intra-abdominal infection or complicated urinary tract infection: IV:

CrCl >50 mL/minute: No dosage adjustment necessary.

CrCl 30 to 50 mL/minute: 500 mg ceftolozane every 8 hours.

CrCl 15 to 29 mL/minute: 250 mg ceftolozane every 8 hours.

Hospital-acquired or ventilator-associated bacterial pneumonia: IV:

CrCl >50 mL/minute: No dosage adjustment necessary.

CrCl 30 to 50 mL/minute: 1,000 mg ceftolozane every 8 hours.

CrCl 15 to 29 mL/minute: 500 mg ceftolozane every 8 hours.

Hemodialysis: Dialyzable (ceftolozane: 66%; tazobactam: 56%) (Ref).

Infants, Children, and Adolescents <18 years: Use is not recommended. Based on adult data, dosage adjustment is necessary, but pediatric-specific adjustments have not been determined.

Adolescents ≥18 years: Note: Dosing recommendations are provided in terms of ceftolozane component. IV:

Intra-abdominal infection or complicated urinary tract infection: Loading dose: 500 mg ceftolozane as a single dose, followed by 100 mg ceftolozane every 8 hours. Administer dose immediately after dialysis on dialysis days.

Hospital-acquired or ventilator-associated bacterial pneumonia: Loading dose: 1,500 mg ceftolozane as a single dose, followed by 300 mg ceftolozane every 8 hours. Administer dose immediately after dialysis on dialysis days.

Dosing: Hepatic Impairment: Pediatric

Infants, Children, and Adolescents: IV: No dosage adjustment necessary.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults or pediatrics with complicated intra-abdominal infection (cIAI) and urinary tract infection (UTI) unless otherwise indicated for adults with hospital-acquired bacterial pneumonia (HAP) and ventilator-associated bacterial pneumonia (VAP).

>10%:

Gastrointestinal: Abdominal pain (neonates, infants, children, adolescents: 2% to 11%; adults: ≤1%), diarrhea (neonates, infants, children, adolescents: 7% to 17%; adults: cIAI, UTI: 2% to 6%, HAP, VAP: 6%)

Hematologic & oncologic: Positive direct Coombs’ test (neonates, infants, children, adolescents: cIAI: 45%, UTI: 30%; adults: cIAI, UTI: <1%, HAP, VAP: 31%) thrombocythemia (neonates, infants, children, adolescents: 9% to 16%; adults: ≤2%)

Hepatic: Increased serum transaminases (including increased serum alanine aminotransferase and increased serum aspartate aminotransferase: neonates, infants, children, adolescents: 4% to 7%; adults: cIAI, UTI: 1% to 2%, HAP, VAP: 12%)

Miscellaneous: Fever (neonates, infants, children, adolescents: 7% to 13%; adults: 2% to 6%)

1% to 10%:

Cardiovascular: Atrial fibrillation (adults: ≤1%), hypertension (neonates, infants, children, adolescents: 4%), hypotension (adults: ≤2%), phlebitis (neonates, infants, children, adolescents: 1% to 6%)

Dermatologic: Skin rash (adults: ≤2%)

Endocrine & metabolic: Hypokalemia (neonates, infants, children, adolescents: 4%; adults: ≤3%), increased gamma-glutamyl transferase (adults: cIAI, UTI: <1%, HAP, VAP: <2%)

Gastrointestinal: Clostridioides difficile-associated diarrhea (adults: HAP, VAP: 3%), constipation (adults: 2% to 4%), gastritis (neonates, infants, children, adolescents: 4%; adults: <1%), nausea (adults: 3% to 8%), vomiting (neonates, infants, children, adolescents: 1% to 10%; adults: cIAI, UTI: 1% to 3%, HAP, VAP: 3%)

Hematologic & oncologic: Anemia (neonates, infants, children, adolescents: 2% to 7%; adults: ≤2%), leukopenia (neonates, infants, children, adolescents: ≤8%), neutropenia (neonates, infants, children, adolescents: ≤8%)

Hepatic: Increased serum alkaline phosphatase (adults: cIAI, UTI: <1%, HAP, VAP: <2%)

Nervous system: Anxiety (adults: ≤2%), dizziness (adults: ≤1%), headache (adults: 3% to 6%), insomnia (adults: 1% to 4%), intracranial hemorrhage (adults: HAP, VAP: 4%)

Renal: Renal failure syndrome (adults: cIAI, UTI: <1%, HAP, VAP: ≤9%) renal insufficiency (adults: cIAI, UTIs: <1%, HAP, VAP: ≤9%)

Respiratory: Bradypnea (neonates, infants, children, adolescents: 4%)

<1% (adults):

Cardiovascular: Angina pectoris, tachycardia, venous thrombosis

Dermatologic: Urticaria

Endocrine & metabolic: Hyperglycemia, hypomagnesemia, hypophosphatemia

Gastrointestinal: Abdominal distention, dyspepsia, flatulence, paralytic ileus

Genitourinary: Fungal urinary tract infection, vulvovaginal candidiasis

Infection: Candidiasis

Local: Infusion-site reaction

Nervous system: Ischemic stroke

Respiratory: Dyspnea, oropharyngeal candidiasis

Contraindications

Serious hypersensitivity to ceftolozane/tazobactam, piperacillin/tazobactam, other members of the beta-lactam class, or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Hypersensitivity and anaphylaxis (serious and sometimes fatal) have been reported in patients receiving beta-lactam drugs. Question patient about previous hypersensitivity reactions to other cephalosporins, penicillins or other beta-lactams. Cross-sensitivity has been established. If administered, use with caution and if anaphylaxis occurs, discontinue and institute appropriate supportive therapy.

• Superinfection: Use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Exposure to ceftolozane is increased with increasing degrees of renal impairment; monitor creatinine clearance (CrCl) at least daily in patients with changing renal function and adjust the dose. In clinical trials, cure rates were lower in patients with a baseline CrCl of 30 to 50 mL/minute.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Zerbaxa: 1.5 g: Ceftolozane 1 g and tazobactam 0.5 g (1 ea)

Generic Equivalent Available: US

Pricing: US

Solution (reconstituted) (Zerbaxa Intravenous)

1.5 (1-0.5) g (per each): $190.38

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Zerbaxa: 1.5 g: Ceftolozane 1 g and tazobactam 0.5 g (1 ea)

Administration: Adult

IV: Administer over 1 hour (Ref); for the treatment of multidrug-resistant gram-negative organisms (eg, P. aeruginosa with difficult-to-treat resistance) and administration of 3 g doses, administer 3 g by IV infusion over 3 hours (Ref).

Administration: Pediatric

Parenteral: IV: Administer over 1 hour (Ref). Consider administration over 3 hours if treating multidrug-resistant gram-negative bacteria or in adolescents receiving 2,000 mg ceftolozane per dose (3,000 mg ceftolozane/tazobactam) (Ref).

Use: Labeled Indications

Intra-abdominal infection: Treatment of complicated intra-abdominal infection in adult and pediatric patients, in combination with metronidazole, caused by Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius.

Pneumonia, hospital- acquired or ventilator-associated: Treatment of hospital-acquired pneumonia and ventilator-associated bacterial pneumonia in patients ≥18 years of age, caused by E. cloacae, E. coli, Haemophilus influenzae, K. oxytoca, K. pneumoniae, P . mirabilis, P. aeruginosa, and Serratia marcescens.

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): Treatment of complicated urinary tract infection, including pyelonephritis, in adult and pediatric patients caused by E. coli, K. pneumoniae, P. mirabilis, and P. aeruginosa.

Use: Off-Label: Adult

Serious infections due to multi-drug resistant Pseudomonas aeruginosa

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy

Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination

Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination

Furosemide: May enhance the nephrotoxic effect of Cephalosporins. Risk C: Monitor therapy

Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

Probenecid: May increase the serum concentration of Betalactamase Inhibitors. Management: Coadministration of probenecid with amoxicillin/clavulanate is not recommended per official package labeling. Risk D: Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Pregnancy Considerations

Tazobactam crosses the placenta (Bourget 1998).

In general, an increased risk of major birth defects or other adverse fetal or maternal outcomes has not been observed following maternal use of cephalosporin antibiotics

Breastfeeding Considerations

It is not known if ceftolozane or tazobactam are present in breast milk.

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Dietary Considerations

Some products may contain sodium.

Monitoring Parameters

Serum creatinine and CrCl at baseline and daily in patients with changing renal function

Mechanism of Action

Ceftolozane inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Ceftolozane is an inhibitor of PBPs of Pseudomonas aeruginosa (eg, PBP1b, PBP1c, and PBP3) and Escherichia coli (eg, PBP3). Tazobactam irreversibly inhibits some beta-lactamases (eg, certain penicillinases and cephalosporinases), and can covalently bind to some plasmid-mediated and chromosomal bacterial beta-lactamases.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_d:

Preterm neonates and infants <3 months (GA: ≤32 weeks): Geometric mean: Ceftolozane: 0.344 to 0.388 L/kg; Tazobactam: 0.338 to 0.667 L/kg (Bradley 2018).

Term neonates and infants <3 months (GA >32 weeks): Geometric mean: Ceftolozane: 0.394 L/kg; Tazobactam: 0.668 L/kg (Bradley 2018).

Infants ≥3 months and children <2 years: Geometric mean: Ceftolozane: 0.282 to 0.34 L/kg; Tazobactam: 0.421 to 0.574 L/kg (Bradley 2018).

Children 2 to <7 years: Geometric mean: Ceftolozane: 0.312 to 0.331 L/kg; Tazobactam: 0.488 to 0.513 L/kg (Bradley 2018).

Children 7 to <12 years: Geometric mean: Ceftolozane: 0.296 L/kg; Tazobactam: 0.74 L/kg (Bradley 2018).

Children ≥12 years and adolescents <18 years: Geometric mean: Ceftolozane: 0.274 L/kg; Tazobactam: 0.474 L/kg (Bradley 2018).

Adults: Ceftolozane: 13.5 L; Tazobactam: 18.2 L.

Protein binding: Ceftolozane: 16% to 21%; Tazobactam: 30%.

Metabolism: Ceftolozane: Not metabolized; Tazobactam: Hydrolyzed to inactive metabolite.

Half-life elimination:

Neonates and infants <3 months: Ceftolozane: 2.7 ± 0.6 hours; Tazobactam: 1.2 ± 0.7 hours.

Infants ≥3 months and children <2 years: Ceftolozane: 2 ± 0.7 hours; Tazobactam: 1.1 ± 0.4 hours.

Children 2 to <6 years: Mean range: Ceftolozane: 1.7 to 1.8 hours; Tazobactam: 1 ± 0.3 hours.

Children 6 to <12 years: Mean range: Ceftolozane: 1.8 to 2 hours; Tazobactam: 1.1 to 1.2 hours.

Children ≥12 years and adolescents <18 years: Mean range: Ceftolozane: 2.2 to 2.3 hours; Tazobactam: 1.3 ± 0.5 hours.

Adults: Ceftolozane: ~3 to 4 hours; Tazobactam: ~2 to 3 hours.

Excretion: Ceftolozane: Urine (>95% as unchanged drug); Tazobactam: urine (>80% as unchanged drug).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Renal clearance was similar to plasma clearance and to the GFR for the unbound fraction suggesting that ceftolozane is eliminated by glomerular filtration. The mean AUC of both ceftolozane and tazobactam increases with decreasing renal function in mild, moderate, and severe renal impairment. In patients with end-stage renal disease, tazobactam's elimination pathway through metabolism becomes clinically significant; recommended doses in this population are designed to optimize tazobactam's pharmacodynamic targets (Xiao 2017).

Anti-infective considerations:

Parameters associated with efficacy:

Ceftolozane: time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC):

Organism specific:

Gram-negative organisms (eg, P. aeruginosa): ceftolozane (in combination with tazobactam): goal: 35% fT > MIC (1-log kill) (Craig 2013); ceftolozane (monotherapy): goal: ≥30% to 40% fT > MIC (1- to 2-log kill) (Craig 2013; Lepak 2014).

Gram-positive organisms (eg, Streptococcus pneumoniae): ceftolozane (monotherapy): goal: ≥27% fT > MIC (2-log kill) (Lepak 2014).

Population specific:

Critically ill patients in the ICU: minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Abdul-Aziz 2020; Al-Shaer 2020; Roberts 2014); some experts favor ≥100% fT > 4 × MIC (Guilhaumou 2019).

Tazobactam (in combination with ceftolozane): time dependent, associated with fT > threshold concentration, where threshold concentration is 0.5 × ceftolozane/tazobactam MIC.

Gram-negative organisms: goal: ≥77% fT > 0.5 × MIC (1-log kill); ≥90% fT > 0.5 × MIC (2-log kill) (Vanscoy 2013).

Expected drug exposure in normal renal function:

Expected drug exposure in healthy volunteers:

Pediatric patients: single dose (1-hour infusion): C_max(peak): IV:

Neonates and infants, GA: ≤32 weeks; PNA: 7 days to <3 months: ceftolozane 20 mg/tazobactam 10 mg/kg: ceftolozane: 45.2 mg/L (range 33.3 to 61.2 mg/L); tazobactam: 12.1 mg/L (range: 6.43 to 22.7 mg/L) (Bradley 2018).

Neonates and infants, GA: >32 weeks; PNA: 7 days to <3 months: ceftolozane 20 mg/tazobactam 10 mg/kg: ceftolozane: 45 mg/L (range: 36.3 to 55.9 mg/L); tazobactam: 11.7 mg/L (range: 7.48 to 18.3 mg/L) (Bradley 2018).

Infants and children 3 months to <2 years of age: ceftolozane 30 mg/tazobactam 15 mg/kg: ceftolozane: 91.3 mg/L (range: 72.1 to 116 mg/L); tazobactam: 22.4 mg/L (range: 13.8 to 36.6 mg/L) (Bradley 2018).

Children 2 to <7 years of age: ceftolozane 30 mg/tazobactam 15 mg/kg: ceftolozane: 96.6 mg/L (range: 71.2 to 131 mg/L); tazobactam: 24.8 mg/L (range: 13.2 to 46.6 mg/L) (Bradley 2018).

Children 7 to <12 years of age: ceftolozane 18 mg/tazobactam 9 mg/kg: ceftolozane: 56.2 mg/L (range: 45.3 to 69.7 mg/L); tazobactam: 9.25 mg/L (range: 5.92 to 14.5 mg/L) (Bradley 2018).

Children and adolescents 12 to <18 years of age: ceftolozane 1,000 mg/tazobactam 500 mg: ceftolozane: 63.5 mg/L (range: 50.2 to 80.4 mg/L); tazobactam: 14 mg/L (range: 8.59 to 22.9 mg/L) (Bradley 2018).

Adults: C_max(peak): IV (1-hour infusion):

Multiple doses (steady state):

Ceftolozane 1 g/tazobactam 500 mg every 8 hours: ceftolozane: 65.7 ± 27 mg/L; tazobactam: 17.8 ± 9 mg/L (manufacturer's labeling).

Ceftolozane 2 g/tazobactam 1 g every 8 hours: ceftolozane: 105 ± 46 mg/L; tazobactam: 26.4 ± 13 mg/L (manufacturer's labeling).

Critically ill patients with augmented renal clearance: C_max(peak): IV (1-hour infusion):

Single dose: ceftolozane 2 g/tazobactam 1 g: ceftolozane: 73.9 ± 25.4 mg/L; tazobactam: 18.7 ± 6.95 mg/L (Nicolau 2021).

Postantibiotic effect: gram-negative organisms (eg, E. coli): ~0.8 hours (Sader 2014).

Post–beta-lactamase-inhibitor effect: gram-negative organisms (eg, E. coli): ~1.3 to 2.1 hours (Sader 2014).

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Zerbaxa;
(AR) Argentina: Zerbaxa;
(AT) Austria: Zerbaxa;
(AU) Australia: Zerbaxa;
(BE) Belgium: Zerbaxa;
(BG) Bulgaria: Zerbaxa;
(BR) Brazil: Zerbaxa;
(CH) Switzerland: Zerbaxa;
(CL) Chile: Zerbaxa;
(CO) Colombia: Zerbaxa;
(CZ) Czech Republic: Zerbaxa;
(DE) Germany: Zerbaxa;
(DO) Dominican Republic: Zerbaxa;
(EE) Estonia: Zerbaxa;
(EG) Egypt: Zerbaxa;
(ES) Spain: Zerbaxa;
(FI) Finland: Zerbaxa;
(FR) France: Zerbaxa;
(GB) United Kingdom: Zerbaxa;
(GR) Greece: Zerbaxa;
(HK) Hong Kong: Zerbaxa;
(HR) Croatia: Zerbaxa;
(HU) Hungary: Zerbaxa;
(IE) Ireland: Zerbaxa;
(IT) Italy: Zerbaxa;
(JO) Jordan: Zerbaxa;
(JP) Japan: Zerbaxa;
(KR) Korea, Republic of: Zerbaxa;
(KW) Kuwait: Zerbaxa;
(LB) Lebanon: Zerbaxa;
(LV) Latvia: Zerbaxa;
(MX) Mexico: Zerbaxa;
(MY) Malaysia: Zerbaxa;
(NL) Netherlands: Zerbaxa;
(NO) Norway: Zerbaxa;
(NZ) New Zealand: Zerbaxa;
(PE) Peru: Zerbaxa;
(PH) Philippines: Zerbaxa;
(PL) Poland: Zerbaxa;
(PR) Puerto Rico: Zerbaxa;
(PT) Portugal: Zerbaxa;
(QA) Qatar: Zerbaxa;
(RO) Romania: Zerbaxa;
(RU) Russian Federation: Zerbaxa;
(SA) Saudi Arabia: Zerbaxa;
(SE) Sweden: Zerbaxa;
(SG) Singapore: Zerbaxa;
(SI) Slovenia: Zerbaxa;
(SK) Slovakia: Zerbaxa;
(TH) Thailand: Zerbaxa;
(TR) Turkey: Zerbaxa;
(TW) Taiwan: Zerbaxa

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Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
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Patel UC, Nicolau DP, Sabzwari RK. Successful treatment of multi-drug resistant pseudomonas aeruginosa bacteremia with the recommended renally adjusted ceftolozane/tazobactam regimen. Infect Dis Ther. 2016;5(1):73-79. doi:10.1007/s40121-016-0104-3 [PubMed 26935574]
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Refer to manufacturer's labeling.
Roberts JA, Paul SK, Akova M, et al; DALI Study. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014;58(8):1072-1083. doi:10.1093/cid/ciu027 [PubMed 24429437]
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Zerbaxa (ceftolozane/tazobactam) [prescribing information]. Syracuse, NY: Steri-Pharma LLC; May 2022.

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Ceftolozane and tazobactam: Drug information