Efficacy and safety of ceftaroline: systematic review and meta-analysis

Background: Resistance to antibiotics is steadily increasing. Ceftaroline has a broad spectrum of activity against clinically relevant gram-positive strains including methicillin-resistant Staphylococcus aureus. Objectives: This systematic review was conducted to evaluate whether ceftaroline is effective and safe, leading to a lower rate of treatment failures than comparators. Material and methods: Studies were included if they were comparing the efficacy and safety of ceftaroline with other antibiotics. Data sources: Using the search terms 'ceftaroline' or 'ceftaroline fosamil', a search strategy was developed. The efficacy endpoint was the rate of treatment failure, while the safety endpoint was the incidence of adverse events. Heterogeneity bias was estimated using the Q-test, and publication bias was estimated using Egger's test. Null hypothesis was rejected if p value was less than 0.05. Results: Only 10 studies were included. Synthesis of results: The risk of treatment failure was significantly lower for ceftaroline than for comparators, and cumulative meta-analysis showed that the effect size was relevant and precise. Pooled risk ratio was 0.79 (95% confidence interval = 0.65-0.95). The rates of adverse events were similar among the studies, and there were no statistically significant differences between groups. For this endpoint, there was a significant heterogeneity among studies (p = 0.03). Pooled risk ratio for adverse events was 0.98 (95% confidence interval = 0.87-1.10), without a statistical difference. Discussion: The risk of treatment failure was significantly lower for ceftaroline than comparators, while the rate of adverse events was similar. To the best of our knowledge, this is the first systematic review on the efficacy and safety of ceftaroline including children and adults. A limitation is that no randomized controlled trials were found in non-complicated skin- and soft-tissue infection and non-community-acquired pneumonia infections; only few cases with methicillin-resistant Staphylococcus aureus isolations and no patients admitted to the intensive care unit were evaluated. Interpretation: Ceftaroline may be an option of treatment in complicated skin- and soft-tissue infection and community-acquired pneumonia.