Ceftaroline fosamil for community-acquired pneumonia and skin and skin structure infections: a systematic review
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Background Ceftaroline is a parentally administered cephalosporin that has an in vitro expanded spectrum of activity compared with other cephalosporins yet data is conflicting regarding its place in therapy. Aim of the Review To compare the efficacy and safety of ceftaroline against standard antibiotic regimens for community-acquired pneumonia (CAP) and complicated skin and skin structure infections (cSSSIs). Method The databases of MEDLINE, EBSCO, and Embase were searched up to June 2016. Manual review of references was completed and experts in the field were contacted for unpublished data. Randomized controlled trials of ceftaroline in CAP or cSSSI populations were included. Outcomes included clinical cure, mortality, adverse events, serious adverse events, and discontinuation due to adverse events. Meta-analysis was used to pool results for these outcomes. We performed subgroup analyses for gram positive infections in CAP and infections caused by methicillin-resistant Staphylococcus aureus in cSSSIs. Risk of bias was assessed for all studies. Results Six trials (three for each indication) were included, each of which had an unclear or high risk of bias in at least one domain. For CAP, ceftaroline was significantly more efficacious in achieving clinical cure than ceftriaxone [risk ratio (RR) 1.11, 95% confidence interval (CI) 1.04–1.19; I2 = 47%]. For cSSSIs, there was no significant difference in clinical cure between ceftaroline and vancomycin plus aztreonam (RR 1.01, 95% CI 0.97–1.05; I2 = 0%). No differences were found for overall mortality, serious adverse events, discontinuation due to adverse events, and overall adverse events. Conclusion Ceftaroline is a viable therapeutic alternative for patients with CAP and cSSSIs, yet identified risks of bias and poor external validity preclude it from being recommended as a first-line agent.
KeywordsAntibiotics Ceftaroline fosamil Cephalosporins Community-acquired pneumonia Skin infections
No funding was received for this manuscript.
Conflicts of interest
All authors report no conflicts of interest.
- 1.World Health Orgnanization. WHO Antimicrobial Resistance Global Report on Surveillance. 2014. http://apps.who.int/iris/bitstream/10665/112642/1/9789241564748_eng.pdf?ua=1. Accessed 8 Sep 2016.
- 2.World Health Organization. The top 10 causes of death. 2016. http://www.who.int/mediacentre/factsheets/fs310/en/index3.html. Accessed 8 Sep 2016.
- 12.Sterne JAC, Egger M, Moher D. Chapter 10: addressing reporting biases. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0. Oxford: The Cochrane Collaboration; 2011.Google Scholar
- 13.File TM Jr, Low DE, Eckburg PB, Talbot GH, Friedland HD, Lee J, et al. FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011;66(3 suppl):iii19–32.PubMedGoogle Scholar
- 14.Low DE, File TM Jr, Eckburg PB, Talbot GH, Friedland HD, Lee J, et al. FOCUS 2: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011;66(3 suppl):iii33–44.PubMedGoogle Scholar
- 15.Zhong NS, Sun T, Zhuo C, D’Souza G, Lee SH, Lan NH, et al. Ceftaroline fosamil versus ceftriaxone for the treatment of Asian patients with community-acquired pneumonia: a randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial. Lancet Infect Dis. 2015;15:161–71.CrossRefPubMedGoogle Scholar
- 16.Corey GR, Wilcox MH, Talbot GH, Thye D, Friedland D, Baculik T, et al. CANVAS 1: the first Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother. 2010;65(4 suppl):iv41–51.PubMedGoogle Scholar
- 17.Wilcox MH, Corey GR, Talbot GH, Thye D, Friedland D, Baculik T, et al. CANVAS 2: the second Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother. 2010;65(4 suppl):iv53–65.PubMedGoogle Scholar