Ceftaroline: A Novel Cephalosporin with Activity Against MRSA
Ceftaroline is a fifth-generation cephalosporin antibiotic with unique activity against methicillin-resistant Staphylococcus aureus (MRSA) that is FDA-approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). 1
Mechanism of Action
Ceftaroline works through a unique mechanism that differentiates it from other cephalosporins:
- Binds to penicillin-binding proteins (PBPs) in bacteria, inhibiting cell wall synthesis 1
- Has high affinity for PBP2a, which is responsible for methicillin resistance in Staphylococcus aureus 1
- Bactericidal against S. aureus (including MRSA) and Streptococcus pneumoniae 1
Antimicrobial Spectrum
Ceftaroline demonstrates activity against:
Gram-positive bacteria
- Staphylococcus aureus (including MRSA and methicillin-susceptible strains)
- Streptococcus pneumoniae (including penicillin-resistant strains)
- Streptococcus pyogenes
- Streptococcus agalactiae
Gram-negative bacteria
- Haemophilus influenzae
- Escherichia coli
- Klebsiella pneumoniae
- Klebsiella oxytoca
- Moraxella catarrhalis 1
Important limitations
- Not active against extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae
- Not active against AmpC-producing organisms
- Limited activity against anaerobes like Bacteroides fragilis 1
Clinical Applications
Ceftaroline is FDA-approved for:
- Acute Bacterial Skin and Skin Structure Infections (ABSSSI) - including those caused by MRSA 2, 1
- Community-Acquired Bacterial Pneumonia (CABP) 1
In clinical trials, ceftaroline demonstrated:
Dosage and Administration
- Standard dose: 600 mg IV every 12 hours 2, 1
- Administration: Intravenous infusion over 1 hour 1
- Duration: 5-14 days depending on infection type and severity 1
- Renal adjustment required for moderate to severe renal impairment 1
Pharmacokinetics
- Rapidly converted from prodrug (ceftaroline fosamil) to active form by plasma phosphatases
- Maximum plasma concentration: 19-21 μg/mL
- Half-life: approximately 2.6 hours
- Volume of distribution: 20.3 L
- Protein binding: approximately 20%
- Elimination: primarily renal (49.6%) 1
Advantages Over Other Antibiotics
The key advantage of ceftaroline is its activity against MRSA while maintaining the safety profile of a cephalosporin:
- Effective against MRSA, vancomycin-intermediate S. aureus (VISA), and heteroresistant VISA 2
- May be effective in cases where vancomycin has failed 2
- Provides broad-spectrum coverage that can be used as monotherapy for polymicrobial infections 2
- Lower potential to select for resistant mutants compared to vancomycin 2
Safety and Adverse Effects
Ceftaroline demonstrates a safety profile consistent with other cephalosporins:
- Well-tolerated in clinical trials 1
- Common adverse effects include diarrhea, nausea, and rash
- Cross-reactivity possible in patients with penicillin allergies
- No antagonism observed with other commonly used antibacterial agents 1
Clinical Considerations
- Ceftaroline should be considered for complicated skin and skin structure infections where MRSA is suspected or confirmed 2
- For community-acquired pneumonia where MRSA is a concern, ceftaroline provides coverage against both typical and atypical pathogens 1
- Several case series suggest potential utility in complicated S. aureus infections, including infective endocarditis, although this remains an off-label use 2
Limitations
- Requires intravenous administration
- Not effective against extended-spectrum beta-lactamase (ESBL) producing organisms
- Limited data on use in pediatric populations
- More expensive than older cephalosporins 2
Ceftaroline represents an important addition to the antimicrobial arsenal, particularly for infections caused by resistant gram-positive pathogens like MRSA, while maintaining activity against common respiratory pathogens.