Ceftaroline is the Only Cephalosporin with MRSA Coverage
Ceftaroline (also known as ceftaroline fosamil) is the sole cephalosporin antibiotic that provides reliable activity against methicillin-resistant Staphylococcus aureus (MRSA). 1
Mechanism of MRSA Activity
Ceftaroline achieves its unique anti-MRSA activity through high-affinity binding to penicillin-binding protein 2a (PBP2a), the altered PBP that confers methicillin resistance in MRSA and has low affinity for other beta-lactam antibiotics 2, 3. This binding affinity (median inhibitory concentration 0.90 mcg/mL to PBP2a) correlates directly with its low minimum inhibitory concentrations against MRSA isolates 2.
Classification and Spectrum
- Generation: Ceftaroline is classified as a fifth-generation or "advanced-generation" cephalosporin 1
- Gram-positive coverage: Active against MRSA, methicillin-susceptible S. aureus (MSSA), multidrug-resistant Streptococcus pneumoniae, and other streptococci 1, 4
- Gram-negative coverage: Active against common pathogens including Haemophilus influenzae, Escherichia coli, Klebsiella species, and Moraxella catarrhalis 4, 5
- Notable gaps: Not active against extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, Pseudomonas aeruginosa, or most anaerobes 2, 5
FDA-Approved Indications and Dosing
Approved uses 4:
- Acute bacterial skin and skin structure infections (ABSSSI)
- Community-acquired bacterial pneumonia (CABP)
Standard dosing 1:
- Adults: 600 mg IV every 12 hours
- Pediatrics: 10 mg/kg/dose IV every 8 hours (not to exceed 600 mg/dose) 1
- Renal adjustment required: For creatinine clearance 30-50 mL/min 2
Clinical Efficacy Against MRSA
In Phase III trials for complicated skin and soft tissue infections, ceftaroline demonstrated non-inferiority to vancomycin plus aztreonam, with clinical cure rates of 96.7% versus 88.9% in Phase II studies 2. A meta-analysis showed ceftaroline was superior to ceftriaxone for severe pneumonia (OR: 1.66; 95% CI 1.34,2.06) 1.
Importantly, ceftaroline demonstrated superior activity compared to vancomycin against MRSA isolates in pharmacokinetic/pharmacodynamic models, with lower potential to select resistant mutants 6. Against heterogeneous vancomycin-intermediate S. aureus (hVISA) isolates, ceftaroline maintained activity while vancomycin showed MIC elevations up to 8-12 mcg/mL 6.
Critical Limitations for Clinical Use
Practical constraints 7:
- IV administration only: No oral formulation available
- Short stability: Reconstituted solution stable for only 6 hours, limiting outpatient parenteral antibiotic therapy (OPAT) use
- Cost considerations: Generally more expensive than vancomycin for inpatient use
Clinical Positioning
Ceftaroline occupies niche roles rather than first-line empiric therapy 7:
- Culture-directed treatment of documented MRSA infections when vancomycin alternatives are needed
- Patients with vancomycin intolerance or treatment failure
- MRSA infections in patients with renal dysfunction where vancomycin dosing is problematic
- Potential role in MRSA bacteremia and endocarditis based on case reports, though not FDA-approved for these indications 7
Not recommended as first-line empiric therapy because vancomycin, linezolid, and daptomycin remain the guideline-recommended first-line agents for empiric MRSA coverage in most clinical scenarios 1.
Important Caveat
While ceftobiprole (another advanced-generation cephalosporin) has activity against some MRSA strains, it has limited efficacy against MRSA compared to ceftaroline and is not approved for use in pneumonia in the United States 1. Therefore, ceftaroline remains the only clinically reliable cephalosporin option for MRSA coverage in the US.