Ceftalin

Approved Indications:

• Community-Acquired Bacterial Pneumonia (CABP):
  Treatment of adults and pediatric patients ≥2 months of age with CABP caused by susceptible isolates of Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible only), Haemophilus influenzae, Klebsiella pneumoniae, and Escherichia coli.
• Acute Bacterial Skin and Skin Structure Infections (ABSSSI):
  Indicated for adults and pediatric patients ≥2 months of age with ABSSSI due to susceptible isolates of Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus [MRSA]), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca.

Important Off-label/Investigational Uses:

• Bacteremia secondary to ABSSSI or CABP (based on clinical practice experience).
• Off-label use in resistant gram-positive infections such as MRSA where other options are limited or contraindicated.

Adults:

• CABP or ABSSSI: 600 mg IV every 12 hours for 5 to 14 days, depending on the severity and clinical response.

Pediatric Patients (≥2 months to <18 years):

• CABP or ABSSSI:
• 2 months to <2 years: 8 mg/kg IV every 8 hours (maximum 400 mg/dose)
• 2 to <18 years: 12 mg/kg IV every 8 hours (maximum 600 mg/dose)

Renal Impairment (Adults):

• CrCl ≥50 mL/min: No dose adjustment
• CrCl 30–49 mL/min: 400 mg IV every 12 hours
• CrCl 15–29 mL/min: 300 mg IV every 12 hours
• ESRD (on hemodialysis): 200 mg IV every 12 hours, after dialysis on dialysis days

Hepatic Impairment:

• No dose adjustment needed.

Route of Administration:

• Intravenous infusion over 5 to 60 minutes.

Duration:

• CABP: Typically 5–7 days
• ABSSSI: Typically 5–14 days

Ceftaroline Fosamil is a broad-spectrum cephalosporin prodrug that, upon conversion to its active form (ceftaroline), binds to penicillin-binding proteins (PBPs), including PBP 2a in MRSA. This binding inhibits bacterial cell wall synthesis through interference with the transpeptidation step of peptidoglycan synthesis, leading to cell lysis and death. Its unique affinity for PBP 2a differentiates it from other β-lactams, granting it bactericidal activity against MRSA and resistant Streptococcus pneumoniae strains.

• Absorption: Administered IV; complete systemic availability.
• Distribution: Widely distributed; protein binding ~20%.
• Metabolism: Ceftaroline Fosamil is rapidly hydrolyzed by plasma phosphatases to active ceftaroline.
• Elimination: Primarily renal.
• Half-life: ~2.5 hours in adults with normal renal function.
• Bioavailability: Not applicable (IV only).
• Excretion: ~88% excreted unchanged in urine.
• Onset of Action: Rapid, typically within hours of IV infusion.

• Pregnancy:
  No FDA pregnancy category; animal studies did not show harm to the fetus. Human data are limited. Use only if clearly needed.
• Lactation:
  Unknown whether ceftaroline is excreted in human milk. Due to potential risk to the infant, caution is advised. Consider benefits vs. risks when prescribing to breastfeeding mothers.

• Primary Class: 5th Generation Cephalosporin Antibiotic
• Subclass: Advanced-generation beta-lactam; MRSA-active cephalosporin

• Known hypersensitivity to ceftaroline fosamil or any component of the formulation
• History of anaphylactic reaction to β-lactam antibiotics (e.g., penicillins, cephalosporins)

• Hypersensitivity Reactions: Risk of anaphylaxis or serious skin reactions (e.g., Stevens-Johnson syndrome).
• Seizures: Reported in patients with renal impairment; monitor and adjust dose accordingly.
• Clostridioides difficile-associated diarrhea (CDAD): May occur with broad-spectrum antibiotic use.
• Coombs’ test seroconversion: Without hemolysis has been reported; monitor if anemia is suspected.
• Superinfection: Long-term use may result in fungal or bacterial superinfections.

Common:

• Hematologic: Positive Coombs test, anemia
• Gastrointestinal: Diarrhea, nausea
• Skin: Rash, pruritus
• Hepatic: Elevated liver enzymes

Serious:

• Allergic reactions: Anaphylaxis, angioedema
• Neurological: Seizures (especially in renal impairment)
• Gastrointestinal: Clostridioides difficile-associated diarrhea

Rare:

• Stevens-Johnson syndrome, toxic epidermal necrolysis

• Probenecid: Increases serum ceftaroline levels by inhibiting renal tubular secretion.
• Other Nephrotoxic Agents: May increase nephrotoxicity risk if co-administered.
• Live Vaccines: May reduce vaccine efficacy; avoid concurrent use of live bacterial vaccines.
• No significant CYP450 interactions; not a substrate, inducer, or inhibitor of major CYP enzymes.

• Recent Guidance (IDSA 2023): Ceftaroline is recommended as an alternative agent in MRSA-related pneumonia and skin infections, especially where vancomycin or linezolid is contraindicated.
• Dose Adjustments Reinforced: EMA and FDA have reaffirmed renal dosing thresholds, particularly in pediatric and dialysis-dependent populations.
• Expanded Use in Pediatrics: Approval extended to include children ≥2 months of age.

• Unreconstituted Vials: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
• Reconstituted Solution (in vials): Use within 6 hours at room temperature or within 24 hours if refrigerated (2°C to 8°C).
• Reconstituted & Diluted for Infusion: Stable up to 6 hours at room temperature or 24 hours refrigerated.
• Do Not Freeze. Protect from excessive light and heat.