What is the recommended use and dosage of Ceftaroline (Cefaroline) for treating complicated skin and skin structure infections, including those caused by Methicillin-resistant Staphylococcus aureus (MRSA)?

Ceftaroline for Complicated Skin and Skin Structure Infections

Ceftaroline (600 mg intravenously every 12 hours for 5-14 days) is recommended as an effective treatment for complicated skin and skin structure infections (cSSSIs), including those caused by methicillin-resistant Staphylococcus aureus (MRSA). 1

Mechanism and Spectrum of Activity

Ceftaroline is a fifth-generation cephalosporin with unique properties that distinguish it from other antibiotics:

• Binds to penicillin-binding protein (PBP) 2a of MRSA with high affinity, giving it activity against MRSA unlike other cephalosporins 2
• Broad-spectrum activity against both gram-positive and gram-negative pathogens 3
• Particularly effective against:
  • MRSA and other resistant staphylococci
  • Streptococcus pneumoniae (including drug-resistant strains)
  • Common gram-negative pathogens involved in skin infections 4

Dosage and Administration

For complicated skin and skin structure infections:

• Standard dosage: 600 mg IV every 12 hours for 5-14 days 1, 5
• Renal adjustment: Required for moderate renal impairment (CrCl 30-50 mL/min) 2
• Administration: Given as intravenous infusion over 1 hour 2

Clinical Evidence for cSSSI

Ceftaroline has demonstrated excellent efficacy in clinical trials for complicated skin infections:

• In phase III trials, ceftaroline was non-inferior to vancomycin plus aztreonam in treating cSSSIs caused by both gram-positive and gram-negative pathogens 2
• Clinical cure rates of 96.7% were observed with ceftaroline compared to 88.9% for standard therapy (vancomycin with or without aztreonam) in phase II studies 5
• Particularly effective against MRSA skin infections, with high microbiological success rates of 95.2% 5

Advantages Over Other Antibiotics

• Monotherapy option: Can be used as single-agent therapy for polymicrobial infections due to its broad-spectrum coverage 2
• MRSA coverage: Provides effective coverage against MRSA without requiring combination therapy 6
• Safety profile: Well-tolerated with adverse events similar to other cephalosporins 4
• Resistance: Low propensity to select for resistant subpopulations 2

Place in Therapy for cSSSI

Ceftaroline is particularly valuable in the following scenarios:

1. MRSA infections: When MRSA is confirmed or suspected in complicated skin infections 1
2. Polymicrobial infections: When both gram-positive (including MRSA) and gram-negative pathogens are suspected 2
3. Alternative to vancomycin: When vancomycin is contraindicated or not tolerated 6

Duration of Therapy

• For uncomplicated cSSSIs: 5-10 days 1
• For severe or complicated infections: 7-14 days 5
• Treatment should continue until clinical signs and symptoms of infection have resolved 1

Limitations and Precautions

• Not active against extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae or Pseudomonas aeruginosa 2
• Limited activity against anaerobes such as Bacteroides species 2
• Requires dosage adjustment in moderate to severe renal impairment 2
• Monitor hematological parameters with prolonged courses 6

Comparison to Alternative Agents

For MRSA skin infections, alternative options include:

• Vancomycin: 15 mg/kg IV every 12 hours (traditional standard of care) 1
• Linezolid: 600 mg IV/PO every 12 hours (alternative with oral option) 1
• Daptomycin: 4-6 mg/kg IV every 24 hours (alternative for MRSA) 1
• Telavancin: 10 mg/kg IV every 24 hours 7

Ceftaroline offers the advantage of broader gram-negative coverage compared to these alternatives, potentially eliminating the need for combination therapy in polymicrobial infections.

Common Pitfalls to Avoid

• Failing to adjust dosage in patients with renal impairment
• Using ceftaroline for infections caused by ESBL-producing organisms or Pseudomonas
• Not considering surgical drainage for purulent collections, which remains essential regardless of antibiotic choice 1
• Unnecessarily prolonged antibiotic courses after clinical resolution 1

Ceftaroline represents an important addition to the antimicrobial armamentarium for complicated skin infections, particularly those involving MRSA, with proven efficacy and a favorable safety profile.