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

  • IV: 600 mg q12hrs IV

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

  • xxxx