OBJECTIVES: The mainstay of treatment for community acquired pneumonia (CAP) continues to be empiric antimicrobial therapy. Due to the ongoing emergence of antibiotic resistant pathogens there is a growing need for effective, advanced-spectrum antibacterial agents. This research aims to estimate the relative efficacy of Zinforo™ (ceftaroline fosamil), a fifth-generation cephalosporin, against empiric antibiotic therapy in adult patients admitted to hospital with moderate-to-severe CAP. METHODS: A systematic literature review was conducted in Medline, Medline-In-Process and Cochrane to identify all published RCTs in moderate-to-severe CAP between 2011 and 2015. These data supported an update to an existing NMA, conducted using the netmetapackage in the R project programme, where both random and fixed-effect (relative risk [RR]) models were outputted. The primary outcomes were test of cure (TOC) in the intent-to-treat (ITT), clinically evaluable (CE) and microbiologically evaluable (ME) populations. RESULTS:  The systematic literature review identified four relevant studies which supported the NMA. The pairwise relative effects and the relative treatment effects of ceftaroline fosamil versus other antibiotics (ceftriaxone, levofloxacin, moxifloxacin and amoxicillin-clavulanate) for clinical cure rates at TOC showed significant responses for ceftaroline fosamil compared with ceftriaxone (RR 1.11; 1.06-1.16) and was comparable to levofloxacin (RR 1.03; 0.90-1.16), moxifloxacin (RR 1.02; 0.93-1.16) and amoxicillin-clavulanate (RR 0.93; 0.80-1.08) in the ITT population. CONCLUSIONS: This study highlights that in adults with moderate-to-severe CAP, ceftaroline fosamil could provide an acceptable level of efficacy compared with ceftriaxone and was comparable to levofloxacin, moxifloxacin and amoxicillin-clavulanate in the ITT population. The overall findings from this review support ceftaroline fosamil as an alternative antibiotic in hospitalised adults with moderate-to-severe CAP.