Off-label use of ceftaroline fosamil: a systematic review

Ceftaroline fosamil is a fifth-generation cephalosporin and the unique with anti-MRSA activity. It has been approved by EMA and FDA for the treatment of adults and children with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSI) However, given its broad spectrum of activity, safety and tolerability profile it is frequently used off-label. The aim of this systematic review is to summarize evidence regarding off-label use of ceftaroline, with regard to safety and efficacy. We performed the review according to PRISMA guidelines, we searched the MEDLINE, EMBASE and CENTRAL databases (2010-2018) using as main term ceftaroline fosamil and its synonyms in combination with names of infectious diseases of interest. Overall, 21 studies were included for total of 1901 patients: the most common off-label indications for ceftaroline use were bacteremia (n=595), endocarditis (n=171), osteoarticular infections (n=368), hospital acquired pneumonia (n=115) and meningitis (n=23). The most common reason for off-label use were persistent or recurrent infection after standard treatment or non-susceptibility to vancomycin and daptomycin. Clinical success was evaluated in 933 patients, of these 724 (77%) reached this positive outcome; incidence of adverse events was reported in 11 studies, in 83 (9%) cases there were adverse events (AEs) related to the use of ceftaroline; most common reported AEs were nausea, vomiting, diarrhea, rash and neutropenia. Our results show that ceftaroline may be used in other clinical settings than those currently approved. However, the use of ceftaroline in these contexts deserves further investigation.