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Ceftolozane and Tazobactam

Medically reviewed by Drugs.com. Last updated on Jun 25, 2019.

Pronunciation

(sef TOL oh zane & taz oh BAK tam)

Index Terms

  • Ceftolozane/Tazobactam
  • CXA 201
  • Tazobactam and Ceftolozane

Dosage Forms

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)

Brand Names: U.S.

  • Zerbaxa

Pharmacologic Category

  • Cephalosporin Combination

Pharmacology

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.

Distribution

Vd: Ceftolozane: 13.5 L; Tazobactam: 18.2 L

Metabolism

Ceftolozane: Not metabolized; Tazobactam: Hydrolyzed to inactive metabolite

Excretion

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

Half-Life Elimination

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

Protein Binding

Ceftolozane: 16% to 21%; Tazobactam: 30%

Special Populations: Renal Function Impairment

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.

Use: Labeled Indications

Intra-abdominal infection: Treatment of complicated intra-abdominal infection in patients ≥18 years, 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, caused by E. cloacae, E. coli, Haemophilus influenzae, K. oxytoca, K. pneumoniae, P. mirabilis, P. aeruginosa, and Serratia marcescens.

Urinary tract infection: Treatment of complicated urinary tract infection, including pyelonephritis, in patients ≥18 years caused by E. coli, K. pneumoniae, P. mirabilis, and P. aeruginosa.

Off Label Uses

Serious infections due to multi-drug resistant Pseudomonas aeruginosa

Data from a limited number of patients studied suggest that ceftolozane/tazobactam may be beneficial for the treatment of infections (eg, bloodstream infection, skin and soft tissue infection) caused by multidrug-resistant Pseudomonas aeruginosa [Hernandez-Tejedor 2017], [Patel 2016], [Sousa Dominguez 2017].

Contraindications

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

Documentation of allergenic cross-reactivity for beta-lactams (eg, penicillins and cephalosporins) is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Note: Zerbaxa (ceftolozane/tazobactam) is a combination product. Dosage recommendations are expressed as grams of ceftolozane/tazobactam combination.

Intra-abdominal infection, empiric or pathogen-directed therapy for resistant gram-negative organisms: IV: 1.5 g every 8 hours in combination with metronidazole (Lucasti 2014; SIS [Mazuski 2017]; manufacturer's labeling). Total duration of therapy is 4 to 7 days following adequate source control (SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]); for infections managed without surgical or percutaneous intervention, a longer duration may be necessary (Barshak 2019; Pemberton 2019).

Pneumonia, hospital-acquired or ventilator-associated: IV: 3 g every 8 hours (manufacturer's labeling). Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (IDSA/ATS [Kalil 2016]), but a longer course may be required.

Serious infections (eg, bloodstream infection, skin and soft tissue infection) due to multidrug-resistant P. aeruginosa (off-label use): IV: 1.5 to 3 g every 8 hours (Hernandez-Tejedor 2017; Patel 2016; Soliman 2015; Sousa Dominguez 2017; Vickery 2016); 3 g every 8 hours should be used for pulmonary infections (Soliman 2015; Vickery 2016; Xiao 2016).

Urinary tract infection (complicated, including pyelonephritis): IV: 1.5 g every 8 hours (manufacturer's labeling); duration of therapy depends on the antimicrobial chosen to complete the regimen and ranges from 5 to 14 days (Hooton 2019).

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Reconstitute the vial with 10 mL SWFI or NS and gently shake to dissolve. The final volume is approximately 11.4 mL and contains ceftolozane/tazobactam 1.5 g (ceftolozane 1 g and tazobactam 500 mg).

To prepare the required dose, withdraw the appropriate volume from the reconstituted vial(s). Add the withdrawn volume to an infusion bag containing 100 mL of NS or D5W.

Infusions range from clear, colorless solutions to solutions that are clear and slightly yellow. Variations in color within this range do not affect the potency of the product.

Administration

IV: Administer by IV infusion over 1 hour.

Dietary Considerations

Some products may contain sodium.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F); protect from light. Reconstituted solution may be held for 1 hour prior to transfer and further dilution in an infusion bag. Diluted solution in D5W or NS may be stored for 24 hours at room temperature or for 7 days at 2°C to 8°C (36°F to 46°F); do not freeze.

Drug Interactions

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

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). 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. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. 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. 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. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

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

Adverse Reactions

1% to 10%:

Cardiovascular: Hypotension (≤2%), atrial fibrillation (≤1%)

Central nervous system: Headache (3% to 6%), insomnia (complicated intra-abdominal infections: 4%; complicated UTIs: 1%), anxiety (≤2%), dizziness (≤1%)

Dermatologic: Skin rash (≤2%)

Endocrine: Hypokalemia (complicated intra-abdominal infections: 3%; complicated UTIs: <1%)

Gastrointestinal: Nausea (3% to 8%), diarrhea (complicated intra-abdominal infections: 6%; complicated UTIs: 2%), constipation (2% to 4%), vomiting (complicated intra-abdominal infections: 3%, complicated UTIs: 1%), abdominal pain (≤1%)

Hematologic & oncologic: Anemia (≤2%), thrombocythemia (≤2%)

Hepatic: Increased serum ALT (2%), increased serum AST (1% to 2%)

Miscellaneous: Fever (complicated intra-abdominal infections: 6%; complicated UTIs: 2%)

<1%, postmarketing, and/or case reports: Abdominal distention, angina pectoris, candidiasis, Clostridioides (formerly Clostridium) difficile-associated diarrhea, dyspepsia, dyspnea, flatulence, fungal urinary tract infection, gastritis, hyperglycemia, hypomagnesemia, hypophosphatemia, increased gamma-glutamyl transferase, increased serum alkaline phosphatase, infusion site reaction, nonhemorrhagic stroke, oropharyngeal candidiasis, paralytic ileus, positive direct Coombs test, renal failure, renal insufficiency, tachycardia, urticaria, venous thrombosis, vulvovaginal candidiasis

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.

Monitoring Parameters

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

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

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

Frequently reported side effects of this drug

• Headache

• Nausea

• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like urinary retention, hematuria, change in amount of urine passed, or weight gain

Clostridioides (formerly Clostridium) difficile (C. diff)--associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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