Ceftaroline fosamil achieved high clinical cure and microbiological success rates, was efficacious for cSSSIs caused by MRSA and other common cSSSI pathogens and was generally well tolerated. Ceftaroline fosamil has the potential to provide a monotherapy alternative for treatment of cSSSIs.

Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.

Ceftaroline fosamil achieved high clinical cure and microbiological response rates in patients hospitalized with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile that is similar to that of ceftriaxone and other cephalosporins. Ceftaroline fosamil is a promising agent for the treatment of CAP.

Ceftaroline fosamil demonstrated high clinical cure and microbiological success rates, was efficacious against cSSSIs caused by MRSA and other common cSSSI pathogens and was generally well tolerated. Monotherapy with ceftaroline fosamil has the potential to provide an alternative treatment for cSSSIs.

ClinicalTrials.gov identifiers: NCT00424190 for CANVAS 1 and NCT00423657 for CANVAS 2.

Ceftaroline, the bioactive metabolite of ceftaroline fosamil (previously PPI-0903, TAK-599), is a broadspectrum cephalosporin with potent in vitro activity against multidrug-resistant gram-positive aerobic pathogens, including methicillin-resistant Staphylococcus aureus. A randomized, observer-blinded study to evaluate the safety and efficacy of ceftaroline versus standard therapy in treating complicated skin and skin structure infections (cSSSI) was performed. Adults with cSSSI, including at least one systemic marker of inflammation, were randomized (2:1) to receive intravenous (i.v.) ceftaroline (600 mg every 12 h) or i.v. vancomycin (1 g every 12 h) with or without adjunctive i.v. aztreonam (1 g every 8 h) for 7 to 14 days. The primary outcome measure was the clinical cure rate at a test-of-cure (TOC) visit 8 to 14 days after treatment. Secondary outcomes included the microbiological success rate (eradication or presumed eradication) at TOC and the clinical relapse rate 21 to 28 days following treatment. Of 100 subjects enrolled, 88 were clinically evaluable; the clinical cure rate was 96.7% (59/61) for ceftaroline versus 88.9% (24/27) for standard therapy. Among the microbiologically evaluable subjects (i.e., clinically evaluable and having had at least one susceptible pathogen isolated at baseline), the microbiological success rate was 95.2% (40/42) for ceftaroline versus 85.7% (18/21) for standard therapy. Relapse occurred in one subject in each group (ceftaroline, 1.8%; standard therapy, 4.3%). Ceftaroline exhibited a very favorable safety and tolerability profile, consistent with that of marketed cephalosporins. Most adverse events from ceftaroline were mild and not related to treatment. Ceftaroline holds promise as a new therapy for treatment of cSSSI and other serious polymicrobial infections.

CD101 IV is a novel echinocandin with distinctive pharmacokinetic properties that is being developed as a once-weekly treatment for candidemia and invasive candidiasis. CD101 has potent in vitro activity and in vivo efficacy against a broad range of Candida and Aspergillus species. The primary objective of two randomized, double-blind, placebo-controlled, dose-escalation studies in healthy adults was to determine the safety and tolerability of CD101 IV. Sequential cohorts of 8 subjects (n = 6, active; n = 2, placebo) were administered single (50, 100, 200, 400 mg) or multiple once-weekly (100 mg given once weekly for two weeks [×2], 200 mg ×2, 400 mg ×3) doses of CD101 IV infused over 1 h. There were no deaths, serious adverse events (SAEs), severe adverse events (AEs), or withdrawals from the study due to an AE. The majority of AEs were mild, and all completely resolved. There was a higher incidence of total AEs and mild transient infusion reactions in the 400-mg ×3 dose group. There were no clinically meaningful trends in postbaseline laboratory abnormalities and no safety issues related to electrocardiograms, vital signs, or physical exams. CD101 showed dose-proportional plasma exposures, minor accumulation (30% to 55%), low apparent clearance (<0.28 liter/h), long half-life (t1/2) (>80 h), and minimal urine excretion. CD101 IV was safe and well tolerated at single and multiple doses of up to 400 mg given once weekly for 3 weeks and exhibited a long t1/2, minimal accumulation over several weeks, negligible renal excretion, and high plasma exposures enabling once-weekly dosing.

Ceftaroline fosamil is a novel cephalosporin with broad-spectrum activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae, and common Gram-negative organisms. The activity of ceftaroline against MRSA is attributed to its ability to bind to penicillin-binding protein (PBP) 2a with high affinity and inhibit the biochemical activity of PBP 2a more efficiently than other presently available β-lactams. The activity of ceftaroline against MRSA and the β-haemolytic streptococci makes it an attractive monotherapy agent for the treatment of complicated skin and skin structure infections (cSSSIs). Recent profiling and surveillance studies have shown that ceftaroline is active against contemporary skin pathogens collected from US and European medical centres in 2008. The mean free drug %T > MIC (percentage of time the drug concentration remains above the MIC) needed for stasis ranged from 26% for S. aureus to 39% for S. pneumoniae in the murine thigh infection model. Pharmacokinetic and pharmacodynamic target attainment predictions for 600 mg of ceftaroline fosamil every 12 h showed that the mean %T > MICs for which plasma free-drug concentrations exceeded an MIC of 1 and 2 mg/L were 71% and 51% of the dosing interval, respectively. For a 40% T > MIC target, the predicted attainments for infections due to pathogens for which ceftaroline MICs were 1 or 2 mg/L were 100% and 90%, respectively. Clinical and microbiological successes of ceftaroline fosamil in treating cSSSIs were demonstrated in two Phase III clinical studies, in which 96.8% of all baseline cSSSI isolates from the microbiologically evaluable population were inhibited by ceftaroline at ≤ 2 mg/L. Ceftaroline fosamil is a promising broad-spectrum agent for the treatment of cSSSIs.