ceftolozane

Action and Spectrum

Actions and Spectrum: 

ceftolozane is a cephalosporin antibiotic that is used to treat bacterial infections. It exerts its antibacterial effects by inhibiting bacterial cell wall synthesis. Specifically, it targets penicillin-binding proteins in the bacterial cell wall. Peptidoglycan is a crucial component of the bacterial cell wall, providing structural integrity and protection. 

ceftolozane exhibits a broad spectrum of activity against both Gram-negative and some Gram-positive bacteria. It is particularly effective against Enterobacteriaceae and Pseudomonas aeruginosa, including strains that may be resistant to other antibiotics. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% (HABP/VABP) 

Increased hepatic transaminase (11.9%) 

1-10% (cIAI/cUTI) 

Headache (2.5-5.8%) 

Pyrexia (1.7-5.6%) 

Insomnia (1.3-3.5%) 

Nausea (2.8-7.9%) 

Diarrhea (1.9-6.2%) 

Constipation (1.9-3.9%) 

Hypokalemia (0.8-3.3%) 

AST increased (1-1.7%) 

Thrombocytosis (0.4-1.9%) 

Anxiety (0.2-1.9%) 

Vomiting (1.1-3.3%) 

ALT increased (1.7-1.5%) 

Anemia (0.4-1.5%) 

Abdominal pain (0.8-1.2%) 

1-10% (HABP/VABP) 

Diarrhea (6.4%) 

Vomiting (3.3%) 

Renal impairment/failure (8.9%) 

Intracranial hemorrhage (4.4%) 

Clostridioides difficile-associated diarrhea (2.8%) 

Post-marketing reports 

Candidiasis candidiasis 

Renal impairment 

Urticaria 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

Hypersensitivity 

Allergic Reactions 

Caution: 

Renal impairment 

Seizures 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

ceftolozane inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). PBPs are enzymes involved in the final steps of peptidoglycan synthesis, an essential component of the bacterial cell wall. This inhibition weakens the cell wall, leading to bacterial cell lysis and death. The addition of tazobactam enhances the spectrum of activity by inhibiting beta-lactamases, enzymes produced by bacteria to resist beta-lactam antibiotics. 

Pharmacodynamics:  

• Bactericidal Activity: ceftolozane kills susceptible bacteria by interfering with cell wall synthesis. 
• Time-Dependent Killing: ceftolozane’s efficacy relies on maintaining drug concentration above the minimum inhibitory concentration (MIC) with multiple daily doses. 
• Post-Antibiotic effect: ceftolozane continues to suppress bacterial growth even after concentrations fall below MIC, influencing dosing frequency and duration. 
• Synergy with Tazobactam: Combined with tazobactam, ceftolozane’s spectrum expands as tazobactam protects it from bacterial beta-lactamases. 
• Concentration-Dependent Killing: ceftolozane’s efficacy increases with higher drug concentrations, impacting dosing strategies.

Pharmacokinetics: 

Absorption 

Peak plasma time: Approximately 1.02 hours after administration. 

Peak plasma concentration: 

• For cIAI and cUTI indications: 

ceftolozane: 65.7 mcg/mL 

tazobactam: 17.8 mcg/mL 

• For HABP/VABP indication: 

ceftolozane: 105 mcg/mL 

tazobactam: 26.4 mcg/mL 

Area Under the Curve: 

• For cIAI and cUTI indications: 

ceftolozane: 186 mcg•h/mL 

tazobactam: 35.8 mcg•h/mL 

• For HABP/VABP indication: 

ceftolozane: 392 mcg•h/mL 

tazobactam: 73.3 mcg•h/mL 

Distribution 

Approximately 16-21% of ceftolozane bound to plasma proteins. 

Volume of distribution (Vd): 

ceftolozane: 13.5 L 

Metabolism 

ceftolozane is not metabolized to a significant extent. 

Elimination/Excretion 

The half-life of ceftolozane is approximately 2.77 hours.  

The renal clearance ranges from 3.41 to 5.59 L/hr. More than 95% of ceftolozane is excreted unchanged in the urine. Over 80% of tazobactam is excreted as the parent compound in the urine, while the remaining portion is excreted as the M1 metabolite. 

Adminstartion

Administration: 

ceftolozane/tazobactam is given by intravenous infusion. It should not be administered by other routes, such as intramuscularly or subcutaneously. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: ceftolozane 

Why do we use ceftolozane? 

ceftolozane is a cephalosporin antibiotic often used in combination with tazobactam, a beta-lactamase inhibitor. It is used to treat certain bacterial infections.  

• Complicated Intra-abdominal Infections (cIAI): ceftolozane/tazobactam is combined with metronidazole to treat cIAI caused by susceptible Gram-negative and Gram-positive bacteria, including multidrug-resistant pathogens. 
• Complicated Urinary Tract Infections (cUTI), including pyelonephritis: ceftolozane/tazobactam treats cUTI caused by susceptible Gram-negative bacteria, including multidrug-resistant strains. 
• Hospital-Acquired Bacterial Pneumonia/Ventilator-Associated Bacterial Pneumonia (HABP/VABP): ceftolozane/tazobactam is indicated for the treatment of HABP/VABP caused by susceptible Gram-negative pathogens, including multidrug-resistant strains.