Ceftaroline Fosamil for Treatment of Pediatric Complicated Skin and Soft Tissue Infections and Community-Acquired Pneumonia

Abstract

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. Supplementary Information The online version contains supplementary material available at 10.1007/s40272-021-00468-w.

New Antibiotics for Staphylococcus aureus Infection: An Update from the World Association of Infectious Diseases and Immunological Disorders (WAidid) and the Italian Society of Anti-Infective Therapy (SITA)

“…However, the superiority of this regimen has never been demonstrated. Similar variations have been suggested for the treatment of children [ 50 ]. For complicated pneumonia or other serious MRSA infections in children, some experts recommend administering ceftaroline over 2 h at a dose of 15 mg/kg (not to exceed 600 mg) every 8 h.…”

Ceftaroline fosamil in the treatment of methicillin-resistant Staphylococcus aureus

“…Despite its effectiveness, modification of the PBP binding site can cause resistance, which may limit its usefulness. 10,11…”

“…These findings highlight the need for further randomized controlled trials with larger numbers of patients to better understand the efficacy of ceftaroline in pediatric MRSA infections. 8,11…”

Microbiological, Clinical, and PK/PD Features of the New Anti-Gram-Negative Antibiotics: β-Lactam/β-Lactamase Inhibitors in Combination and Cefiderocol—An All-Inclusive Guide for Clinicians

“…In healthy volunteers, the PK parameters relative to the distribution of ceftarolinefosamil/avibactam in the fixed-dose combination (600 mg/600 mg) are a Vd of 19.8 (±2.9) L when administered in a single dose and of 16.9 (±2.4) L when administered in multiple doses [23]. Ceftaroline-fosamil was approved in 2010 for the treatment of adults and children with community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections [89]. In addition, the combination has been used off-label in serious infections such as nosocomial pneumonia, osteoarticular infections, meningitis, and endocarditis.…”