Ceftaroline 600 mg every 8 hours, via 2 hour intravenous infusion, has demonstrated tolerability in individuals with complicated skin and soft tissue infection, according to a study published in the Journal of Antimicrobial Chemotherapy. It achieved noninferiority compared with the 12-hour regimen in terms of tolerability and safety.
This pooled analysis included 6 Phase III randomized controlled trials, 3 of which evaluated with complicated skin and soft tissue infection and 3 of which assessed community-acquired pneumonia. The 2 sets of studies showed internal similarity in their respective inclusion criteria and designs, though the COVERS study included a proportionally greater number of individuals with acute infection compared with the other 2 complicated skin and soft tissue infection studies.
Safety data was pooled and evaluated from any patients who were randomly assigned to receive ceftaroline. The 8-hour regimen group included 506 individuals, whereas the 12-hour regimen group included 1686. Treatment-emergent adverse events, urinalysis, vital signs, electrocardiograms, and laboratory tests were used to assess safety and tolerability.
Both study groups showed a similar prevalence and pattern of adverse events, with 39.3% of the 8-hour group and 22.4% of the 12-hour group having systemic inflammatory response syndrome. In the 8-hour group, the most common treatment-emergent adverse events were nausea (n=20), headache (n=17), and hypokalaemia (n=15); in the 12-hour group, diarrhea (n=84), nausea (n=63), and headache (n=63) were most common. Overall, the most common adverse events were mild-to-moderate gastrointestinal events.
Both groups also showed similar intensity of rash, though Asian study sites in the 8-hour pool demonstrated a higher rate (18.5% Asian vs 5.5% non-Asian study sites) and largely mild rash prevalence that correlated with therapy duration ≥1 week. Vital signs and electrocardiogram readings were not abnormal in either regimen. Serious adverse events occurred in 5.1% of the 8-hour group and in 7.7% of the 12-hour group.
A potential limitation of this study was the small sample sizes, which did not allow for the detection of fine distinctions between the 2 regimens.
The study researchers concluded that “600 mg of ceftaroline fosamil [every 8 hours] was well tolerated. Incidence and severity of [adverse events] were similar to those observed with 600 mg of ceftaroline fosamil [every 12 hours]. The safety profile of the [every 8 hours] regimen was consistent with the known safety profile of ceftaroline fosamil and the cephalosporin class.”
This analysis was sponsored by Pfizer, with individual studies sponsored by Pfizer and Allergan.
Cheng K, Pypstra R, Yan JL, Hammond J. Summary of the safety and tolerability of two treatment regimens of ceftaroline fosamil: 600 mg every 8 h versus 600 mg every 12 h [published online December 28, 2018]. J Antimicrob Chemother. doi: 10.1093/jac/dky519