Off-label use of ceftaroline fosamil: A systematic review.

• Review of studies on ceftaroline fosamil, a fifth-generation cephalosporin with anti-MRSA activity. • Prescribed off-label in bacteremia, endocarditis, osteoarticular infections, hospital-acquired pneumonia, meningitis. • 77% clinical success with off-label ceftaroline and few (9%) adverse events (AEs) reported but not all studies reported AEs. • Studies used different doses/dosing intervals because of renal adjustment and off-label use of higher doses. • Quality of included studies is low because of the retrospective nature of studies, case series and small sample sizes. • More evidence of ceftaroline efficacy and safety required from randomized controlled trials and PK/PD studies. Ceftaroline fosamil is a fifth-generation cephalosporin with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. It has been approved by the EMA and FDA for the treatment of adults and children with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). However, ceftaroline fosamil has a broad spectrum of activity, and a good safety and tolerability profile, so is frequently used off-label. The aim of this systematic review was to summarize the safety and efficacy of off-label use of ceftaroline. The review was conducted according to PRISMA guidelines. MEDLINE, EMBASE and CENTRAL databases (2010-2018) were searched using as the main term ceftaroline fosamil and its synonyms in combination with names of infectious diseases of interest. A total of 21 studies with 1901 patients were included: 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 reasons 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, and 724 (77%) of these reached this positive outcome. Incidence of adverse events (AEs) was reported in 11 studies. In 83 (9%) cases there were AEs related to the use of ceftaroline; the most common reported AEs were nausea, vomiting, diarrhea, rash and neutropenia. The review results show that ceftaroline may be used in clinical settings other than those currently approved; however, the use of ceftaroline in these contexts deserves further investigation. [ABSTRACT FROM AUTHOR]