General Information

Teflaro is specifically indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of applicable Gram-positive and Gram-negative microorganisms and for the treatment of community-acquired bacterial pneumonia caused by susceptible isolates of the applicable Gram-positive and Gram-negative microorganisms.

Teflaro is supplied as 600 mg or 400 mg of sterile powder for reconstitution into a solution designed for intravenous administration. The recommended dosage of Teflaro is 600 mg administered every 12 hours by intravenous (IV) infusion over 1 hour in patients >18 years of age. The duration of therapy should be guided by the severity and site of infection and the patient’s clinical and bacteriological progress.

Clinical Results

FDA Approval
The FDA approval of Teflaro was based on the following trials:

Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
Two identical randomized, multi-center, multinational, double-blind, noninferiority trials (Trials 1 and 2) enrolled 1,396 adults with clinically documented complicated ABSSSI. The subjects received Teflaro (600 mg administered IV over 1 hour every 12 hours) or vancomycin plus aztreonam (1 g vancomycin administered IV over 1 hour followed by 1 g aztreonam administered IV over 1 hour every 12 hours). Treatment duration was 5 to 14 days. Trial One: at Study day 3 in the Teflaro arm, 74% of the subjects were clinical responders while 64.6% of subjects in the vancomycin plus aztreonam arm were clinical responders. Trial Two: at Study day 3 in the Teflaro arm, 74% of the subjects were clinical responders while 68.1% of subjects in the vancomycin plus aztreonam arm were clinical responders.

Community-Acquired Bacterial Pneumonia (CABP)
Two randomized, multi-center, multinational, double blind, noninferiority trials enrolled 1,231 adults. The trials were designed to compare Teflaro (600 mg administered IV over 1 hour every 12 hours) with ceftriaxone (1 g ceftriaxone administered IV over 30 minutes every 24 hours). In both treatment groups of Trial 1, two doses of oral clarithromycin (500 mg every 12 hours), were administered as adjunctive therapy starting on Study Day 1. No adjunctive macrolide therapy was used in CABP Trial 2. Treatment duration was 5 to 7 days. The Response Rates at Study Day 4 (72-96 hours) were as follows: Trial One: Teflaro 69.6% responders and Ceftriaxone 58.3% responders. Trial Two: Teflaro 69.0% responders and Ceftriaxone 61.4% responders.

Mechanism of Action

Teflaro is a cephalosporin antibiotic with in vitro activity against Gram-positive and -negative bacteria. The bactericidal action of ceftaroline is mediated through binding to essential penicillin-binding proteins (PBPs). Ceftaroline is bactericidal against S. aureus due to its affinity for PBP2a and against Streptococcus pneumoniae due to its affinity for PBP2x.

Literature References

File TM Jr, Low DE, Eckburg PB, Talbot GH, David Friedland H, Lee J, Llorens L, Critchley I, Thye D Integrated Analysis of FOCUS 1 and FOCUS 2: Randomized, Doubled-Blinded, Multicenter Phase 3 Trials of the Efficacy and Safety of Ceftaroline Fosamil versus Ceftriaxone in Patients with Community-Acquired Pneumonia. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2010 Dec 15;51(12):1395-405

Steed ME, Rybak MJ Ceftaroline: a new cephalosporin with activity against resistant gram-positive pathogens. Pharmacotherapy 2010 Apr;30(4):375-89

Talbot GH, Thye D, Das A, Ge Y Phase 2 study of ceftaroline versus standard therapy in treatment of complicated skin and skin structure infections. Antimicrobial agents and chemotherapy 2007 Oct;51(10):3612-6.