Ceftaroline (Teflaro, Zinfloro)
Indications
Acute Skin/Skin Structure Infection (see Cellulitis, [[Cellulitis]])
Community-Acquired Pneumonia (CAP)
Pharmacology
- Fifth Generation Cephalosporin Antibiotic (see Cephalosporins, [[Cephalosporins]])
- Mechanism: inhibits bacterial cell wall synthesis
- Binds to Penicillin-binding proteins (PBP) 1-3 -> inhibits peptidoglycan synthesis in bacterial cell wall
- High affinity for PBP2a
- High affinity for a modified PBP in Methicillin-Resistant Staphylococcus Aureus (MRSA)
- High affinity for PBP2x in Streptococcus Pneumoniae
- Bacteria eventually lyse: due to activity of cell wall autolytic enzymes
Pharmacokinetics
- Time to Peak: 1 hr
- Elimination Half-Life: 2.7 hrs
Metabolism
- Conversion: ceftaroline fosamil (inactive prodrug) undergoes rapid conversion to ceftaroline in plasma by phosphatase enzyme
- Ceftaroline is hydrolyzed to form the inactive ceftaroline M-1 metabolite
- Renal: 88% is excreted in urine
- Hepatic: 6% is excreted in feces
Administration
Dose Adjustment
- Hepatic: none
- Renal
- CrCl >50 ml/min: no dose adjustment
- CrCl 30-50 ml/min: 400 mg q12hrs IV
- CrCl 15-30 ml/min: 300 mg q12hrs IV
- CrCl <15 ml/min: 200 mg q12hrs IV
Drug Interactions
- Coumadin (see Coumadin, [[Coumadin]]): ceftaroline may enhance the effect of coumadin
Adverse Effects
Dermatologic Adverse Effects
- Pruritus (see Pruritus, [[Pruritus]]): occurs in 3-4% of cases
- Rash: occurs in 3% of cases
Gastrointestinal Adverse Effects
- Constipation (see Constipation, [[Constipation]]): occurs in 2% of cases
- Diarrhea (see Diarrhea, [[Diarrhea]]): occurs in 5% of cases
- Elevated Liver Function Tests (LFT’s) (see xxxx, [[]]): occurs in 2% of cases
- Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]]): occurs in 4% of cases
Hematologic Adverse Effects
- Hemolysis (see Hemolytic Anemia, [[Hemolytic Anemia]])
- Diagnosis: positive Coombs test
Neurologic Adverse Effects
- Headache (see Headache, [[Headache]]): occurs in 3-5% of cases
Other Adverse Effects
- Hypokalemia (see Hypokalemia, [[Hypokalemia]]): occurs in 2% of cases
- Thrombophlebitis: occurs in 2% of cases
References