Ceftaroline (Teflaro) - a Fifth generation Cephalosporin

Ceftaroline is the first fifth-generation cephalosporin that is used to treat the following conditions:

  • Community-acquired bacterial pneumonia caused by:

    • Streptococcus pneumoniae,
    • Methicillin-susceptible Staphylococcus aureus
    • Haemophilus influenzae,
    • Klebsiella pneumoniae,
    • Klebsiella oxytoca, and
    • Escherichia coli.
  • Skin and soft tissue infections caused by the following organisms:

    • methicillin-susceptible and methicillin-resistant isolates Staphylococcus aureus
    • Streptococcus pyogenes,
    • Streptococcus agalactiae,
    • Escherichia coli,
    • Klebsiella pneumoniae, and
    • Klebsiella oxytoca.

Ceftaroline Dose in Adults

Use of Ceftaroline for community acquired Pneumonia:

  • 600 mg intravenously two times each day for five to seven days

Use of Ceftaroline for treatment of Skin and soft tissue infections:

  • For 5 to 14 days, take 600 mg twice day.

Ceftaroline Dose in Children

Ceftaroline use for pulmonary exacerbations in Cystic fibrosis:

  • Children older than 6 years and Adolescents:
    • 15 mg/kg/dose intravenous thrice daily to a maximum dose of 600 mg/dose.

Use of Ceftaroline for the treatmnet of community-acquired Pneumonia:

  • Infants older than 2 months and Children less than 2 years:
    • 8 mg/kg/dose intravenously three times per day for five to fourteen days
  • Children older than 2 years and Adolescents less than 18 years of age:
    • less than 33 kgs:
      • 12 mg/kg/dose intravenously three times each day for five to fourteen days
    • more than 33 kgs:
      • 400 mg intravenous thrice daily or 600 mg twice daily for 5 to 14 days
  • Adolescents older than 18 years:
    • 600 mg intravenously two times each day for five to seven days

Use of Ceftaroline for the treatment of Skin and soft tissue infections:

  • Infants older than 2 months and Children less than 2 years:
    • 8 mg/kg/dose intravenous thrice daily.
  • Children older than 2 years and Adolescents less than 18 years:
    • less than 33 kg:
      • 12 mg/kg/dose intravenous thrice daily
    • more than 33 kgs:
      • 400 mg intravenous thrice daily or 600 mg twice daily
  • Adolescents older than 18 years of age:
    • 600 mg intravenous twice daily

Pregnancy Risk Factor B

  • Some animal studies have shown adverse effects, including skeletal deformities.
  • Ceftaroline use duringBreastfeeding:
  • It is unknown if ceftaroline can be found in breastmilk. Lactating mothers should avoid it.

Ceftaroline Dose in Renal Disease:

Ceftaroline dose in patients with kidney disease:

  • CrCl of more than 50 mL/minute:  Dose adjustment not required.
  • CrCl of 30 to 50 mL/minute: 400 mg every twice daily
  • CrCl 15 to 30 mL/minute: 300 mg every twice daily
  • CrCl less than 15 mL/minute: 200 mg every twice daily
  • ESRD patients receiving hemodialysis: 200 mg twice daily. The dose should be given after hemodialysis.

Ceftaroline Dose in Liver Disease:

The manufacturer has not recommended any dose adjustment in patients with liver disease. 

Common Side Effects of Ceftaroline include:

  • Hematologic & oncologic:
    • Positive direct Coombs test

Less Common Side Effects of Ceftaroline include:

  • Cardiovascular:
    • Bradycardia
    • Palpitations
    • Phlebitis
  • Central nervous system:
    • Insomnia
    • Headache
    • Dizziness
    • Seizure
  • Dermatologic:
  • Endocrine & metabolic:
  • Gastrointestinal:
    • Diarrhea
    • Vomiting
    • Nausea
    • Constipation
    • Abdominal pain
    • Pseudomembranous colitis
  • Hematologic & oncologic:
    • Anemia
    • Eosinophilia
    • Neutropenia
    • Thrombocytopenia
  • Hepatic:
    • Increased serum transaminases including ALT and AST
    • Hepatitis
  • Hypersensitivity:
    • Anaphylaxis
    • Hypersensitivity
  • Renal:
    • Renal failure
  • Miscellaneous:
    • Fever

Contraindications to Ceftaroline include:

  • Allergy/ Anaphylactic reactions to ceftaroline or other cephalosporins or any component of the formulations

Warnings and Precautions

  • Hemolytic anemia
    • Coombs Positive has been associated with autoimmune hemolytic anemia. It is important to stop using this therapy.
  • Hypersensitivity
    • Patients who are allergic to penicillins, cephalosporins, penicillins, or carbapenems should not use it.
    • If severe allergic reactions are observed, therapy should be stopped.
  • Superinfection
    • Ceftaroline treatment for longer periods (over 2 months) can lead to superinfections, including fungal or bacterial superinfections. C. difficile-associated diarrhea, (CDAD), and pseudomembranous collitis can occur.
  • Renal impairment
    • Patients with a CrCl lower than 50 ml/min should not use the drug. The dose should be adjusted.

Ceftaroline: Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).

BCG Vaccine (Immunization) Antibiotics may lessen the benefits of the BCG vaccine (Immunization).
Lactobacillus & Estriol The therapeutic effects of Lactobacillus or Estriol can be diminished by antibiotics.
Probenecid May raise serum levels of cephalosporins.
Vitamin K antagonists (eg warfarin) The anticoagulant effects of Vitamin K antagonists can be enhanced by cephalosporins.

Risk Factor D (Consider therapy modifications)

 
Sodium Picosulfate Antibiotics can reduce the therapeutic effects of Sodium Picosulfate. Patients who are currently using or have just finished using antibiotics should consider using an alternative product to cleanse the bowel before undergoing a colonoscopy.
Typhoid Vaccine The therapeutic effects of Typhoid vaccine may be diminished by antibiotics. The only affected strain is the live attenuated Ty21a. Patients being treated with systemic antibiotics should avoid vaccination with live attenuated Typhoid vaccine (Ty21a). This vaccine should not be used until at least three days after the cessation or discontinuation of antibacterial agent treatment.

Risk Factor X (Avoid Combination)

 
BCG (Intravesical). The therapeutic effects of BCG (Intravesical) may be diminished by antibiotics
Cholera Vaccine Cholera Vaccine may be less effective if taken with antibiotics. Treatment: Cholera vaccine should be avoided in patients who have received systemic antibiotics.

Monitoring Parameters:

  • Renal functions
  • Clincal indicators of anaphylaxis and allergic reactions
  • Prior to administering the drug, obtain appropriate cultures.

How to Administer Ceftaroline?

Give the medication intravenously during a 5- to 1-hour period in a gradual infusion.

Mecahnism of action of Ceftaroline:

  • A fifth-generation cephalosporin called ceftaroline prevents the construction of bacterial cell walls by attaching to penicillin-binding proteins (PBPs), which causes autolytic enzymes to destroy the bacteria.
  • Because of its strong affinity to PBP2a (a modified PBP found in MRSA) and PBP2x, it covers resistant Strep.pneumoniae.

Proteins bind 20% of the medication.

Initial activation of the inactive prodrug in plasma is followed by hydrolysis to create inactive metabolites. The Half-life eliminationThe time taken to complete a task can vary from 1.6 hours to 2.6 hours. TheTime to reach peak plasma concentrationIt takes one hour. It isexcretedIt is mainly found in the urine.  

International Brands of Ceftaroline:

  • Xafromil
  • Zinforo
  • Teflaro

Ceftaroline Brands in Pakistan:

No brands available in Pakistan   

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