What cephalosporins (a type of beta-lactam antibiotic) have activity against Methicillin-resistant Staphylococcus aureus (MRSA)?

Cephalosporins with Anti-MRSA Activity

Ceftaroline is currently the only FDA-approved cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). 1

Ceftaroline: The Anti-MRSA Cephalosporin

Ceftaroline fosamil is a fifth-generation cephalosporin that has demonstrated significant activity against MRSA through its unique mechanism of action:

• Mechanism: Binds to penicillin-binding protein 2a (PBP2a) in MRSA, which is the altered PBP that confers methicillin resistance 1
• FDA Approval: Approved for:
  • Acute bacterial skin and skin structure infections (ABSSSI), including those caused by MRSA
  • Community-acquired bacterial pneumonia (CABP), though only for methicillin-susceptible S. aureus in this indication 1

Dosing for Ceftaroline

• Standard dose: 600 mg IV every 12 hours for 5-14 days 1
• Dose adjustment required for renal impairment
• Not available for oral administration or outpatient parenteral therapy due to limited stability (6 hours once reconstituted) 2

Clinical Efficacy Against MRSA

Ceftaroline has demonstrated effectiveness against MRSA in:

1. Skin and soft tissue infections: Clinical trials showed non-inferiority to vancomycin plus aztreonam for complicated skin infections, with particularly good results against MRSA 1

2. Off-label uses: While not FDA-approved for these indications, case series and retrospective studies have shown promising results in:

   • MRSA bacteremia
   • Endocarditis
   • Osteomyelitis
   • Deep-seated MRSA infections 3, 4

A systematic review of off-label use showed clinical success in 77% of cases across various deep-seated MRSA infections 4.

Antimicrobial Activity Profile

Ceftaroline demonstrates potent activity against:

• MRSA (MIC₅₀/₉₀: 1/2 μg/mL; 80.6% susceptible) 5
• Methicillin-susceptible S. aureus (MSSA)
• Streptococcus pneumoniae, including multidrug-resistant strains
• Beta-hemolytic streptococci
• Haemophilus influenzae
• Limited activity against extended-spectrum beta-lactamase (ESBL)-producing organisms 5

Limitations and Considerations

1. Not effective against:

   • Non-fermenting gram-negative bacteria (e.g., Pseudomonas)
   • ESBL-producing Enterobacteriaceae
   • Carbapenemase-producing organisms
   • Class B metallo-beta-lactamases
   • Class C (AmpC) cephalosporinases 1

2. Administration challenges:

   • IV-only formulation
   • Short stability after reconstitution
   • Cannot be used for outpatient therapy 2

3. Adverse effects:

   • Rash
   • Eosinophilia
   • Pruritus
   • Gastrointestinal effects (nausea, vomiting, diarrhea)
   • Neutropenia (with prolonged use) 4

Clinical Positioning

Ceftaroline is best positioned for:

• Culture-directed therapy for confirmed MRSA infections, particularly when:

  • Vancomycin has failed
  • Patients have contraindications to or intolerance of other anti-MRSA agents
  • Combination therapy is needed for deep-seated infections 6

• Second-line therapy after standard MRSA treatments (vancomycin, linezolid, daptomycin) for:

  • Persistent or recurrent MRSA infections
  • Infections with reduced susceptibility to first-line agents 4

Other Cephalosporins with Limited Anti-MRSA Activity

Ceftobiprole is another fifth-generation cephalosporin with activity against MRSA, but it has limited efficacy against MRSA compared to ceftaroline and is not FDA-approved in the US for pneumonia or other indications 6.

No other currently available cephalosporins have clinically significant activity against MRSA.