What about Ceftaroline (Cefaroline) for treating infections, specifically acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP)?

Ceftaroline for Bacterial Infections

Ceftaroline fosamil is a highly effective, FDA-approved advanced-generation cephalosporin with unique anti-MRSA activity, indicated for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP), dosed at 600 mg IV every 12 hours. 1

FDA-Approved Indications and Dosing

Standard dosing is 600 mg IV infused over 60 minutes every 12 hours for both ABSSSI (5-14 days) and CABP (5-7 days). 1, 2 This represents the only cephalosporin with proven efficacy against methicillin-resistant Staphylococcus aureus (MRSA), earning designation as a new subclass: "cephalosporins with anti-MRSA activity." 3

Renal Dosing Adjustments

• Moderate to severe renal impairment requires dose reduction since ceftaroline is primarily renally excreted 1, 4
• Clinical effectiveness remains high (78-91% success) in patients with renal insufficiency, though specific adjusted doses must follow FDA guidance 4
• Over 50% of renally impaired patients were successfully discharged home 4

Role in Community-Acquired Pneumonia

For hospitalized adults with non-severe CAP without MRSA/Pseudomonas risk factors, ceftaroline 600 mg every 12 hours combined with a macrolide is a first-line option with strong recommendation and high-quality evidence. 5

The 2019 ATS/IDSA guidelines position ceftaroline equivalently alongside ceftriaxone, cefotaxime, and ampicillin-sulbactam as acceptable β-lactam options 5. However, ceftaroline offers the distinct advantage of MRSA coverage, which the traditional cephalosporins lack 6, 7.

CAP Treatment Algorithm:

• Non-severe CAP (hospitalized): Ceftaroline + macrolide OR respiratory fluoroquinolone monotherapy 5
• Severe CAP: Ceftaroline + macrolide OR ceftaroline + respiratory fluoroquinolone 5
• Contraindications to macrolides/fluoroquinolones: Ceftaroline + doxycycline (conditional recommendation) 5

Clinical Trial Evidence:

Phase III trials (FOCUS 1 and 2) demonstrated ceftaroline achieved 84.3% clinical cure versus 77.7% for ceftriaxone (difference 6.7%, 95% CI 1.6-11.8), establishing noninferiority 3. Notably, patients with moderate-to-severe CABP showed day 4 clinical response of 69.5% versus 59.4% for ceftriaxone 3.

Role in Skin and Skin Structure Infections

For ABSSSI, ceftaroline 600 mg IV every 12 hours is listed as a first-line intravenous option alongside vancomycin, daptomycin, and linezolid. 5

The 2018 WSES/SIS-E consensus specifically notes ceftaroline's effectiveness against both S. aureus and MRSA in complicated skin infections, with a safety profile consistent with the cephalosporin class 5.

ABSSSI Clinical Trial Data:

The CANVAS trials (1 and 2) enrolled 1,378 adults and demonstrated 91.6% clinical response with ceftaroline versus 92.7% with vancomycin plus aztreonam (difference -1.1%, 95% CI -4.2.0), establishing noninferiority 3. More importantly, at day 3, ceftaroline achieved 74.0% cessation of lesion spread versus 66.2% for comparators (difference 7.8%, 95% CI 1.3,14.0) 3.

Spectrum of Activity and Microbiological Considerations

Ceftaroline has exceptional activity against resistant Gram-positive organisms through high-affinity binding to PBP2a, the protein conferring methicillin resistance. 7, 3

Gram-Positive Coverage:

• MRSA, including vancomycin-intermediate, linezolid-resistant, and daptomycin-nonsusceptible strains 7, 3
• Multidrug-resistant Streptococcus pneumoniae with penicillin MICs ≤2 mg/L 6, 7
• Methicillin-susceptible S. aureus 6
• Limited activity against Enterococcus faecalis and faecium 3

Gram-Negative Coverage:

• Active against 90-95% of Haemophilus influenzae 6
• Many common Enterobacteriaceae 7, 3
• NOT active against extended-spectrum β-lactamase producers, AmpC-producing organisms, or most nonfermentative Gram-negatives 2, 3

Critical Gap:

Ceftaroline lacks activity against atypical pathogens (Mycoplasma, Chlamydophila, Legionella), necessitating combination therapy with macrolides or fluoroquinolones for CAP 6.

Real-World Effectiveness Data

A large retrospective study of 527 patients revealed 88% clinical success across both FDA-approved and off-label indications 8. Notably:

• 67% were treated for off-label uses with favorable outcomes 8
• 88.9% of S. aureus isolates were MRSA, highlighting real-world prevalence 8
• Hospital mortality was only 8% 8
• 80% received ceftaroline as second-line therapy after disease progression on initial antibiotics 8

Safety Profile

Adverse events occurred in only 8% of patients, consistent with the excellent tolerability of the cephalosporin class. 3, 8

Common adverse effects mirror other cephalosporins, with warnings for:

• Hypersensitivity reactions (cross-reactivity with other β-lactams) 1
• Clostridioides difficile-associated diarrhea 1
• Direct Coombs' test seroconversion 1
• Neurological adverse reactions 1

30-day readmission for the same infection occurred in only 9% of discharged patients, suggesting durable clinical response 8.

Clinical Positioning and Practical Considerations

Ceftaroline fills a unique niche as the only β-lactam with anti-MRSA activity, making it invaluable when β-lactam therapy is preferred over vancomycin or daptomycin. 5, 7, 3

When to Choose Ceftaroline:

• MRSA infections where β-lactam mechanism is desired over glycopeptides
• Second-line therapy after vancomycin failure or intolerance 8
• Patients with renal impairment requiring MRSA coverage (with dose adjustment) 4
• CAP requiring MRSA coverage in combination regimens 5

Key Limitations:

• Requires IV administration (no oral formulation) 1, 2
• Must be combined with macrolide or fluoroquinolone for CAP due to lack of atypical coverage 6
• Ineffective against ESBL and AmpC producers 2, 3
• More expensive than traditional cephalosporins, though cost-effectiveness may be favorable given efficacy 5