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Identification
- Summary
Ceftolozane is a cephalosporin antibiotic used to treat complicated intra-abdominal infections in combination with metronidazole, complicated urinary tract infections, and hospital-acquired pneumonia.
- Brand Names
- Zerbaxa
- Generic Name
- Ceftolozane
- DrugBank Accession Number
- DB09050
- Background
Ceftolozane is a semi-synthetic broad-spectrum fifth generation cephalosporin.10 It was approved by the FDA in 2014 for use in combination with Tazobactam for the treatment of serious infections, such as intra-abdominal infections and complicated urinary tract infections. The manufacturer of this drug is Cubist Pharmaceuticals.3 Most recently, in June 2019, ceftolozane-tazobactam was approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.13
Hospital-acquired pneumonia and ventilator-associated pneumonia are major causes of morbidity and mortality in hospitalized patients and the use of ceftolozane-tazobactam offers effective activity against various organisms causing these infections, such as Pseudomonas aeruginosa.12
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Ceftolozane (DB09050)
- Weight
- Average: 666.69
Monoisotopic: 666.175098322 - Chemical Formula
- C23H30N12O8S2
- Synonyms
- (6R,7R)-3-([3-Amino-4-(2-aminoethylcarbamoylamino)-2-methylpyrazol-1-ium-1-yl]methyl)-7-([(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
- Ceftolozane
- ceftolozano
- External IDs
- CXA-101
- FR-264,205
Pharmacology
- Indication
Ceftolozane is used in combination with tazobactam for the treatment of infections caused by designated susceptible microorganisms in adult and pediatric patients:13
- Complicated Intra-abdominal Infections (cIAI), used in combination with metronidazole
- Complicated Urinary Tract Infections (cUTI), including pyelonephritis
- Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP)
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Hospital acquired bacterial pneumonia Combination Product in combination with: Tazobactam (DB01606) •••••••••••• Used in combination to treat Ventilator associated bacterial pneumonia Combination Product in combination with: Tazobactam (DB01606) •••••••••••• Used in combination to treat Complicated bacterial urinary tract infections Combination Product in combination with: Tazobactam (DB01606) •••••••••••• Used in combination to treat Complicated pyelonephritis Combination Product in combination with: Tazobactam (DB01606) •••••••••••• Used in combination to treat Complicated intra-abdominal bacterial infections Regimen in combination with: Tazobactam (DB01606), Metronidazole (DB00916) •••••••••••• - Contraindications & Blackbox Warnings
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Ceftolozane exerts bactericidal activities against susceptible gram-negative and gram-positive infections by interfering with bacterial cell wall synthesis.13,5 When it is combined with tazobactam, it exerts further activity against beta-lactamase enzyme producing bacteria, which are normally resistant to beta-lactam antibiotics and interfere with infection treatment.13,11 The addition of tazobactam strengthens the therapeutic response to ceftolozane, giving it the ability to treat a broader range of bacterial infections and resistant organisms.5,7,9
- Mechanism of action
Ceftolozane belongs to the cephalosporin class of antibacterial drugs. Ceftolozane exerts antibacterial effects, preventing the formation of cell walls that protect bacteria from injury and confer resistance to some antibiotics. Its antibacterial activity is also mediated through ceftolozane binding to penicillin-binding proteins (PBPs), which are required for peptidoglycan cross-linking for bacterial cell wall synthesis. As a result of cell wall synthesis inhibition, bacterial cells are killed, treating various infections.7,6 Ceftolozane has a particularly high affinity to the penicillin-binding proteins for Pseudomonas aeruginosa and Escherichia coli as well as Klebsiella pneumoniae and other enteric bacteria.11 In particular, a high affinity has been seen in vitro for penicillin-binding proteins 1b, 1c, 2, and 3 when compared to other antibiotics, ceftazidime and imipenem. 8
Target Actions Organism APenicillin-binding protein 1B inhibitorPseudomonas aeruginosa ACell division protein inhibitorPseudomonas aeruginosa APenicillin-binding protein 1C inhibitorEscherichia coli (strain K12) APenicillin-binding protein 2 inhibitorEscherichia coli (strain K12) UPenicillin-binding protein Not Available Gram positive and gram negative bacteria - Absorption
The area under the curve (AUC) of ceftolozane-tazobactam after an injected dose of 1 g/0.5 g every 8 hours for 1 day was 172 mcg•h/mL. The Cmax (peak concentration) and AUC are dose-dependent. The Cmax on day one of the above dose of ceftolozane-tazobactam was 69.1 mcg/mL.13
- Volume of distribution
13.5 L.13 Tissue distribution of ceftalozone-tazobactam is rapid and shows good penetration into the lung, rendering it an ideal treatment for bacterial pneumonia.7
- Protein binding
16% to 21% bound to plasma proteins.13
- Metabolism
Certolozane is not metabolized to any significant extent.13 The beta-lactam ring of tazobactam, when administered as ceftolozane-tazobactam, is hydrolyzed to form an inactive metabolite.13
- Route of elimination
- Half-life
2.77 hours on day 1 of treatment on a dose of 1 g/0.5 g every 8 hours.13,6 3.12 hours on day 10 of treatment on a dose of 1 g/0.5 g every 8 hours.13
- Clearance
The renal clearance of was measured to be 3.41 – 6.69 L/h after a single dose of ceftolozane-tazobactam. Dose adjustments of this drug are required in patients with impaired renal function with a creatinine clearance of 50 mL/min or below. Consult official labeling for dosing adjustment guidelines.13,7
- Adverse Effects
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A note on nephrotoxicity
This drug is mainly excreted by the kidneys6, and if administered to a patient with a creatinine clearance of less than 50 mL/min, may cause renal damage. Consult official product labeling for dosing adjustments in patients with renal impairment.13,7
Overdose information
If an overdose occurs, discontinue the drug and follow this with supportive treatment. Dialysis may be used.13
Use in pregnancy
Ceftolozane-tazobactam is a pregnancy category B drug, but human studies have not been performed to validate this in humans. At doses equivalent to 4-7 the standard dose administered in humans, no developmental abnormalities were seen. Since animal studies are not always predictive of drug response in humans, it is advisable to exercise caution if this drug is prescribed during pregnancy. The mother's clinical need should be assessed as well as possible risks to the fetus.13
Use in lactation
Whether this drug is excreted in human breast milk is unknown. Caution is advised if this drug is administered during lactation, as many other drugs are known to be secreted into breast milk.13
Carcinogenesis/mutagenesis
Formal studies have not been conducted in humans to assess mutagenicity or carcinogenicity. Studies in mice and rats did not reveal any mutagenic or carcinogenic potential, however, the potential risks resulting from long-term use have not been studied.13
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Ceftolozane which could result in a higher serum level. Abciximab The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftolozane. Aceclofenac Aceclofenac may decrease the excretion rate of Ceftolozane which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Ceftolozane which could result in a higher serum level. Acenocoumarol The risk or severity of bleeding can be increased when Ceftolozane is combined with Acenocoumarol. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Ceftolozane sulfate 7R247U84HY 936111-69-2 UJDQGRLTPBVSFN-TVNHLQOTSA-N - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Zerbaxa Ceftolozane sulfate (1 g) + Tazobactam sodium (0.5 g) Injection, powder, for solution Intravenous Merck Sharp & Dohme B.V. 2020-12-22 Not applicable EU 
ZERBAXA Ceftolozane (1 G) + Tazobactam sodium (0.5 G) Injection, solution, concentrate Intravenous บริษัท เอ็มเอสดี (ประเทศไทย) จำกัด 2017-06-17 Not applicable Thailand 
ZERBAXA Ceftolozane (1 G) + Tazobactam (0.5 G) Injection, powder, for solution Intravenous; Parenteral Merck Sharp & Dohme B.V. 2016-05-07 Not applicable Italy 
Zerbaxa Ceftolozane sulfate (1 g/10mL) + Tazobactam sodium (0.5 g/10mL) Injection, powder, lyophilized, for solution Intravenous Merck Sharp & Dohme Llc 2014-12-19 Not applicable US 
Zerbaxa Ceftolozane sulfate (1 g / vial) + Tazobactam sodium (0.5 g / vial) Powder, for solution Intravenous Merck Ltd. 2016-01-12 Not applicable Canada 
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cephalosporins. These are compounds containing a 1,2-thiazine fused to a 2-azetidinone to for a oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid moiety or a derivative thereof.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Lactams
- Sub Class
- Beta lactams
- Direct Parent
- Cephalosporins
- Alternative Parents
- N-acyl-alpha amino acids and derivatives / 1,3-thiazines / Dicarboxylic acids and derivatives / Thiadiazoles / Tertiary carboxylic acid amides / Pyrazoles / Heteroaromatic compounds / Ureas / Secondary carboxylic acid amides / Amino acids show 13 more
- Substituents
- Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Azetidine / Azole / Carbonic acid derivative / Carbonyl group show 28 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 37A4IES95Q
- CAS number
- 689293-68-3
- InChI Key
- JHFNIHVVXRKLEF-DCZLAGFPSA-N
- InChI
- InChI=1S/C23H30N12O8S2/c1-23(2,20(40)41)43-31-11(15-30-21(26)45-32-15)16(36)29-12-17(37)35-13(19(38)39)9(8-44-18(12)35)6-34-7-10(14(25)33(34)3)28-22(42)27-5-4-24/h7,12,18,25H,4-6,8,24H2,1-3H3,(H7,26,27,28,29,30,32,36,38,39,40,41,42)/b31-11-/t12-,18-/m1/s1
- IUPAC Name
- 5-amino-2-{[(6R,7R)-7-[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetamido]-2-carboxylato-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl}-4-{[(2-aminoethyl)carbamoyl]amino}-1-methyl-1H-pyrazol-2-ium
- SMILES
- CN1C(N)=C(NC(=O)NCCN)C=[N+]1CC1=C(N2[C@H](SC1)[C@H](NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=NSC(N)=N1)C2=O)C([O-])=O
References
- General References
- Sorbera M, Chung E, Ho CW, Marzella N: Ceftolozane/Tazobactam: a new option in the treatment of complicated gram-negative infections. P T. 2014 Dec;39(12):825-32. [Article]
- Zhanel GG, Chung P, Adam H, Zelenitsky S, Denisuik A, Schweizer F, Lagace-Wiens PR, Rubinstein E, Gin AS, Walkty A, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Ceftolozane/tazobactam: a novel cephalosporin/beta-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs. 2014 Jan;74(1):31-51. doi: 10.1007/s40265-013-0168-2. [Article]
- Cluck D, Lewis P, Stayer B, Spivey J, Moorman J: Ceftolozane-tazobactam: A new-generation cephalosporin. Am J Health Syst Pharm. 2015 Dec 15;72(24):2135-46. doi: 10.2146/ajhp150049. [Article]
- Giacobbe DR, Bassetti M, De Rosa FG, Del Bono V, Grossi PA, Menichetti F, Pea F, Rossolini GM, Tumbarello M, Viale P, Viscoli C: Ceftolozane/tazobactam: place in therapy. Expert Rev Anti Infect Ther. 2018 Apr;16(4):307-320. doi: 10.1080/14787210.2018.1447381. Epub 2018 Mar 9. [Article]
- Shortridge D, Pfaller MA, Castanheira M, Flamm RK: Antimicrobial Activity of Ceftolozane-Tazobactam Tested Against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2013-2016) as Part of the Surveillance Program: Program to Assess Ceftolozane-Tazobactam Susceptibility. Microb Drug Resist. 2018 Jun;24(5):563-577. doi: 10.1089/mdr.2017.0266. Epub 2017 Oct 17. [Article]
- Miller B, Hershberger E, Benziger D, Trinh M, Friedland I: Pharmacokinetics and safety of intravenous ceftolozane-tazobactam in healthy adult subjects following single and multiple ascending doses. Antimicrob Agents Chemother. 2012 Jun;56(6):3086-91. doi: 10.1128/AAC.06349-11. Epub 2012 Mar 26. [Article]
- Hong MC, Hsu DI, Bounthavong M: Ceftolozane/tazobactam: a novel antipseudomonal cephalosporin and beta-lactamase-inhibitor combination. Infect Drug Resist. 2013 Nov 29;6:215-23. doi: 10.2147/IDR.S36140. [Article]
- Moya B, Zamorano L, Juan C, Ge Y, Oliver A: Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2010 Sep;54(9):3933-7. doi: 10.1128/AAC.00296-10. Epub 2010 Jun 14. [Article]
- Shlaes DM: New beta-lactam-beta-lactamase inhibitor combinations in clinical development. Ann N Y Acad Sci. 2013 Jan;1277:105-14. doi: 10.1111/nyas.12010. [Article]
- Ceftolozane Pubchem [Link]
- Zerbaxa MedSafe NZ data sheet [Link]
- FDA news [Link]
- FDA Approved Drug Products: ZERBAXA (ceftolozane and tazobactam) for injection, for intravenous use [Link]
- External Links
- KEGG Drug
- D10097
- PubChem Compound
- 53234134
- PubChem Substance
- 310264994
- ChemSpider
- 25999973
- 1597609
- ChEBI
- 134719
- ChEMBL
- CHEMBL2103872
- Wikipedia
- Ceftolozane/tazobactam
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Acute Kidney Injury (AKI) / Haemodiafiltration / Sepsis 1 somestatus stop reason just information to hide Not Available Recruiting Treatment Neoplasms, Hematologic / Neutropenia 1 somestatus stop reason just information to hide Not Available Unknown Status Not Available Antibiotic Resistant Infection / Ventilator Associated Bacterial Pneumonia (VABP) 1 somestatus stop reason just information to hide Not Available Unknown Status Not Available Ceftolozane/Tazobactam / Hematology and Oncology / Imipenem/Relebactam 1 somestatus stop reason just information to hide Not Available Unknown Status Not Available Pseudomonas Aeruginosa / Pseudomonas Infections 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous; Parenteral Injection, powder, lyophilized, for solution Intravenous Injection, solution, concentrate Intravenous Powder, for solution Intravenous Solution Intravenous Injection, powder, for solution Intravenous Injection, powder, for solution Intravenous 1000 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US20140274993 No 2013-03-15 2033-03-15 US US2014144295 No 2013-03-15 2033-03-15 US US20140274991 No 2013-03-15 2033-03-15 US US20140262868 No 2013-03-15 2033-03-15 US US7129232 No 2006-10-31 2024-10-21 US US8685957 No 2014-04-01 2032-09-27 US US8968753 No 2015-03-03 2034-03-14 US US8476425 No 2013-07-02 2032-09-27 US US8906898 No 2014-12-09 2034-05-28 US US9320740 No 2016-04-26 2034-03-14 US US9872906 No 2018-01-23 2034-03-14 US US10125149 No 2018-11-13 2035-08-14 US US9724353 No 2017-08-08 2032-09-07 US US10028963 No 2018-07-24 2032-09-07 US US10376496 No 2019-08-13 2034-09-09 US US10420841 No 2019-09-24 2034-03-14 US US10933053 No 2021-03-02 2034-09-09 US US11278622 No 2014-03-14 2034-03-14 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP -6.17 https://www.chemsrc.com/en/cas/689293-68-3_1197589.html - Predicted Properties
Property Value Source Water Solubility 0.0884 mg/mL ALOGPS logP -1.2 ALOGPS logP -8.7 Chemaxon logS -3.9 ALOGPS pKa (Strongest Acidic) 2.49 Chemaxon pKa (Strongest Basic) 9.11 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 14 Chemaxon Hydrogen Donor Count 7 Chemaxon Polar Surface Area 302.21 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 194.51 m3·mol-1 Chemaxon Polarizability 62.04 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 241.16902 predictedDeepCCS 1.0 (2019) [M+H]+ 243.01685 predictedDeepCCS 1.0 (2019) [M+Na]+ 248.62267 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Pseudomonas aeruginosa
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Peptidoglycan glycosyltransferase activity
- Specific Function
- Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
- Gene Name
- ponB
- Uniprot ID
- Q9X6W0
- Uniprot Name
- Penicillin-binding protein 1B
- Molecular Weight
- 85486.615 Da
References
- Sorbera M, Chung E, Ho CW, Marzella N: Ceftolozane/Tazobactam: a new option in the treatment of complicated gram-negative infections. P T. 2014 Dec;39(12):825-32. [Article]
- Moya B, Zamorano L, Juan C, Ge Y, Oliver A: Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2010 Sep;54(9):3933-7. doi: 10.1128/AAC.00296-10. Epub 2010 Jun 14. [Article]
- FDA label, Zerbaxa [Link]
- Kind
- Protein
- Organism
- Pseudomonas aeruginosa
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Peptidoglycan glycosyltransferase activity
- Specific Function
- Not Available
- Gene Name
- pbpB
- Uniprot ID
- Q51504
- Uniprot Name
- Cell division protein
- Molecular Weight
- 62855.78 Da
References
- Sorbera M, Chung E, Ho CW, Marzella N: Ceftolozane/Tazobactam: a new option in the treatment of complicated gram-negative infections. P T. 2014 Dec;39(12):825-32. [Article]
- Moya B, Zamorano L, Juan C, Ge Y, Oliver A: Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2010 Sep;54(9):3933-7. doi: 10.1128/AAC.00296-10. Epub 2010 Jun 14. [Article]
- FDA label, Zerbaxa [Link]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Peptidoglycan glycosyltransferase activity
- Specific Function
- Cell wall formation. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a transpeptidase C-terminal domain which may not be functional.
- Gene Name
- pbpC
- Uniprot ID
- P76577
- Uniprot Name
- Penicillin-binding protein 1C
- Molecular Weight
- 85066.085 Da
References
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type d-ala-d-ala carboxypeptidase activity
- Specific Function
- Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. It synthesizes cross-linked peptidoglycan from lipid intermediates.
- Gene Name
- mrdA
- Uniprot ID
- P0AD65
- Uniprot Name
- Penicillin-binding protein 2
- Molecular Weight
- 70856.1 Da
References
- Kind
- Protein group
- Organism
- Gram positive and gram negative bacteria
- Pharmacological action
- Unknown
- General Function
- Serine-type d-ala-d-ala carboxypeptidase activity
- Specific Function
- Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
Components:
References
Drug created at May 06, 2015 16:29 / Updated at April 28, 2022 23:24