ceftobiprole

Action and Spectrum

Actions and Spectrum: 

ceftobiprole is a broad-spectrum antibiotic belonging to the cephalosporin class, categorized as a fifth-generation cephalosporin. Its mechanism of action is like other beta-lactam antibiotics, as it interferes with bacterial cell wall synthesis.  

• Inhibition of Cell Wall Synthesis: ceftobiprole, like other cephalosporins, acts by inhibiting the synthesis of bacterial cell walls. It targets penicillin-binding proteins (PBPs), which are enzymes involved in the final steps of peptidoglycan synthesis. 
• Transpeptidase Inhibition: ceftobiprole binds to PBPs, especially PBP2a (associated with methicillin-resistant Staphylococcus aureus, MRSA), preventing the transpeptidation step in cell wall synthesis. Transpeptidation is crucial for the cross-linking of peptidoglycan chains, leading to the formation of a structurally intact cell wall. 

Spectrum of Activity: 

Gram-Positive Bacteria: 

ceftobiprole is effective against a wide range of Gram-positive bacteria, including: 

Staphylococcus aureus (including MRSA) 

Streptococcus pneumoniae 

Streptococcus pyogenes 

Streptococcus agalactiae 

Gram-Negative Bacteria: 

ceftobiprole also exhibits activity against certain Gram-negative bacteria, such as: 

Escherichia coli 

Klebsiella pneumoniae 

Haemophilus influenzae 

Drug Interaction

Adverse Reaction

Frequency not defined 

hypersensitivity (5.5%) 

diarrhea (4.2%) and vomiting (3.3%) 

phlebitis (2.3%) 

infusion site reactions (6.5%) 

nausea (4.3%) 

hyponatremia (2.7%) 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

Hypersensitivity 

Cross-Reactivity with Penicillins 

Caution: 

• Clostridium difficile-Associated Diarrhea (CDAD): Antibiotic therapy, including ceftobiprole, can be associated with the development of Clostridium difficile-associated diarrhea (CDAD). If CDAD is suspected or confirmed, appropriate measures, such as discontinuing ceftobiprole and initiating supportive therapy, should be taken. 
• Renal Impairment: ceftobiprole is primarily excreted through the kidneys. Dosage modifications can be required for patients with renal impairment. It is crucial in these situations to closely evaluate renal function and modify dosage in accordance with it. 
• Superinfection: When ceftobiprole is used for an extended period, non-susceptible organisms may proliferate. If superinfection happens, the right action needs to be done. 

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: 

ceftobiprole exerts its antibacterial effects by inhibiting cell wall synthesis in bacteria. It specifically targets and binds to penicillin-binding proteins (PBPs), enzymes involved in the final steps of peptidoglycan synthesis. 

ceftobiprole has a high affinity for a broad spectrum of PBPs, including PBP2a, which is often associated with methicillin-resistant Staphylococcus aureus (MRSA). 

Pharmacokinetics: 

Absorption 

ceftobiprole is administered intravenously, and information on oral bioavailability and time to peak plasma concentration may not be applicable. 

Distribution 

The volume of distribution for ceftobiprole is approximately 13.5 L to 21.4 L. ceftobiprole has a moderate protein binding capacity, primarily binding to serum albumin. The reported plasma protein binding is approximately 20%. 

Metabolism 

ceftobiprole is not extensively metabolized in the body. The primary form of ceftobiprole detected in the body is the unchanged drug. 

Elimination and Excretion 

The primary route of elimination for ceftobiprole is renal, with a significant portion (approximately 89%) of the unchanged drug excreted in the urine. The elimination half-life of ceftobiprole is in the range of 2 to 3 hours. 

Adminstartion

Administration: 

Intravenous administration 

• Intravenous Infusion: ceftobiprole is usually administered as an intravenous infusion over a specific period. 
• Dilution: ceftobiprole should be diluted before administration. It is typically diluted in a compatible intravenous solution, such as 0.9% sodium chloride (normal saline) or 5% dextrose. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: ceftobiprole 

Why do we use ceftobiprole? 

It is primarily indicated for the treatment of complicated skin and soft tissue infections caused by susceptible bacteria.  

• Hospital-Acquired Infections: ceftobiprole may be considered in the hospital setting for patients with complicated skin and soft tissue infections, including those acquired in a healthcare setting. 
• Mixed Infections: Due to its broad spectrum of activity, ceftobiprole may be effective in treating mixed infections involving both aerobic and anaerobic bacteria.