ceftaroline fosamil
Regulatory sources consulted
Approved indications
- Complicated skin and soft-tissue infections and community-acquired pneumonia caused by susceptible organisms.
Contraindications
Absolute
- Hypersensitivity to ceftaroline fosamil or other cephalosporins.
Clinical warnings
- Major warning · Severe hypersensitivity or anaphylaxis may occur; review beta-lactam allergy history and discontinue if an allergic reaction develops. — CIMA/AEMPS, ficha técnica 12785001
- Major warning · Clostridioides difficile-associated diarrhea and colitis may occur during or after treatment; assess significant diarrhea. — CIMA/AEMPS, ficha técnica 12785001
- Major warning · It may cause encephalopathy and seizures, especially with renal impairment or unadjusted doses; adjust for renal function and monitor neurologic status. — CIMA/AEMPS, ficha técnica 12785001
Adverse events
Common (≥1%)
Nausea, diarrhea, and rash
Rare but serious
Anaphylaxis, C. difficile colitis, and severe cytopenias
Pregnancy and lactation
During pregnancy, use only when clinically indicated. Assess breastfeeding according to milk exposure and the infant’s condition described in the product information.
Recent literature (PubMed)
Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for an array of problematic community- and healthcare-acquired infections, including pneumonia, and is frequently associated with severe disease and high mortality rates. Standard recommended treatments for empiric and targeted coverage of suspected MRSA in patients with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), are vancomycin and linezolid. However, adverse events such as acute kidney injury and Clostridium difficile infection have been associated with these antibiotics. Ceftaroline fosamil is a β-lactam/extended-spectrum cephalosporin approved for the treatment of adults and children with CAP and complicated skin and soft tissue infections. Ceftaroline has in vitro activity against a range of common Gram-positive bacteria and is distinct among the β-lactams in retaining activity against MRSA. Due to the design of the pivotal randomised controlled trials of ceftaroline fosamil, outcomes in patients with MRSA CAP were not evaluated. However, various reports of real-world outcomes with ceftaroline fosamil for pneumonia caused by MRSA, including CAP and HAP/VAP, been published since its approval. A systematic literature review and qualitative analysis of relevant publications was undertaken to collate and summarise relevant published data on the efficacy and safety of ceftaroline fosamil in patients with MRSA pneumonia. While relatively few real-world outcomes studies are available, the available data suggest that ceftaroline fosamil is a possible alternative to linezolid and vancomycin for MRSA pneumonia. Specific scenarios in which ceftaroline fosamil might be considered include bacteraemia and complicating factors such as empyema.
This study conducted a network meta-analysis comparing linezolid, teicoplanin, daptomycin, tigecycline, and ceftaroline fosamil with vancomycin for treating MRSA-related diseases, addressing the lack of comprehensive evaluations in existing research on antibiotic therapy for MRSA infections. We systematically searched databases including PubMed, Embase, Web of Science, the Cochrane Librar up to August 22, 2023. All eligible randomized controlled trials of the six antibiotics were included in the NMA, and their effectiveness and safety were compared across various MRSA-related diseases. Categorical data were used for the odds ratio (OR), and continuous data were used for mean difference (SMD). The surface under the cumulative ranking (SUCRA) was employed to evaluate the incidence rate. According to SUCRA results, daptomycin was the most effective treatment (73.0%) in bloodstream infections. In pulmonary infections and skin and soft tissue infections, linezolid out-performed other antibiotics in effectiveness rate (90.6% and 86.3%), microbial killing rate (93.3% and 93.1%). Vancomycin showed lower adverse reactions than teicoplanin, with less hepatotoxicity compared to linezolid and tigecycline. Linezolid had higher thrombocytopenia risk but lower nephrotoxicity risk than others. Vancomycin was less effective in microbial killing rates than linezolid across various infections. The present research suggests that in pulmonary infections and skin and soft tissue infections, linezolid may be a better option for treating MRSA-related diseases. However, caution is warranted due to the association of linezolid with thrombocytopenia. Our study protocol was registered with the International Prospective Register of SystematicReviews (PROSPERO); Registration number: CRD42024535142.
This review discusses small molecule antibiotics approved for clinical use in the time frame 2010-2022. This time span saw the approval of four synthetic antibiotics (bedaquiline, pretomanid, delafloxacin, tedizolid), nine natural product derivatives (ceftaroline fosamil, cefiderocol, plazomicin, omadacycline, eravacycline, sarecycline, lefamulin, dalbavancin, oritavancin), and one natural product (fidaxomicin).
Ceftaroline and ceftobiprole are advanced generation cephalosporins with activity against methicillin-resistant Staphylococcus aureus (MRSA). This review summarizes their clinical efficacy for complicated skin and soft tissue infections (cSSTIs). Both these agents retain excellent in vitro activity against both MRSA and Gram-negative isolates from patients with CSSTIs. Both these agents are registered for the management of cSSTIs based on the results of large scale phase III noninferiority trials. Ceftaroline and ceftobiprole are noninferior to the combination of vancomycin and aztreonam as this was assessed by their clinical cure rate at the test-of-cure visits. Furthermore, ceftobiprole is noninferior to comparators for the achievement of early clinical success at 72 h. Ceftaroline achieves 81% clinical cure against diabetic foot infections. Ceftaroline and ceftobiprole can be used as monotherapy for the treatment of cSSTIs.
Community-acquired pneumonia (CAP)/community-acquired bacterial pneumonia (CABP) and complicated skin and soft tissue infection (cSSTI)/acute bacterial skin and skin structure infection (ABSSSI) represent major causes of morbidity and mortality in children. β-Lactams are the cornerstone of antibiotic treatment for many serious bacterial infections in children; however, most of these agents have no activity against methicillin-resistant Staphylococcus aureus (MRSA). Ceftaroline fosamil, a β-lactam with broad-spectrum in vitro activity against Gram-positive pathogens (including MRSA and multidrug-resistant Streptococcus pneumoniae) and common Gram-negative organisms, is approved in the European Union and the United States for children with CAP/CABP or cSSTI/ABSSSI. Ceftaroline fosamil has completed a pediatric investigation plan including safety, efficacy, and pharmacokinetic evaluations in patients with ages ranging from birth to 17 years. It has demonstrated similar clinical and microbiological efficacy to best available existing treatments in phase III-IV trials in patients aged ≥ 2 months to < 18 years with CABP or ABSSSI, with a safety profile consistent with the cephalosporin class. It is also approved in the European Union for neonates with CAP or cSSTI, and in the US for neonates with ABSSSI. Ceftaroline fosamil dosing for children (including renal function adjustments) is supported by pharmacokinetic/pharmacodynamic modeling and simulations in appropriate age groups, and includes the option of 5- to 60-min intravenous infusions for standard doses, and a high dose for cSSTI patients with MRSA isolates, with a ceftaroline minimum inhibitory concentration of 2-4 mg/L. Considered together, these data suggest ceftaroline fosamil may be beneficial in the management of CAP/CABP and cSSTI/ABSSSI in children.