The efficacy of the new cephalosporin ceftaroline in the treatment of community-acquired pneumonia
The results of two phase 3 clinical trials have demonstrated the efficacy of a new cephalosporin ceftaroline antibiotic in the treatment of community-acquired pneumonia.
Results from two Phase 3 clinical trials (FOCUS 1,2), presented at the 49th Interdisciplinary Conference on Antimicrobial Drugs and Chemotherapy (The 49th Interscience Conference on Antimicrobial Agents and Chemotherapy), demonstrated the effectiveness of the new ceftaroline cephalosporin antibiotic for the treatment of community-acquired pneumonia. However, according to the researchers, the role of the drug may be limited.
Ceftaroline (Forest Laboratories) is equivalent to ceftriaxone (Rocephin, Hoffman-La Roche) in the treatment of community-acquired pneumonia, acting on the causative agents typical of community-acquired pneumonia , including Streptococcus pneumoniae and Staphylococcus aureus. This drug has a high affinity for the penicillin binding protein 2a and potent bactericidal activity against many antibiotic resistant Gram-positive microorganisms, including resistant and multidrug-resistant penicillin S. pneumoniae and methicillin-resistant S. aureus isolates. However, compared to other new cephalosporins, ceftaroline is not active enough against certain gram negative microorganisms.
In two FOCUS clinical trials, 1228 patients were admitted to a hospital with moderate to severe community-acquired pneumonia requiring intravenous antibiotic therapy. All patients were randomized into two groups. The first group received ceftaroline intravenously 600 mg every 12 hours for 5-7 days, the second group received ceftriaxone intravenously 1 g once a day also for 5-7 days. The baseline characteristics of the patients, including concomitant pathology, organic lung disease, previous pneumonia or bronchial asthma, did not differ between the groups compared.
The overall clinical cure rate in the ceftaroline group was 84.3% and in the ceftriaxone group 77.7%. Both drugs were well tolerated, but adverse events were recorded more often in the ceftaroline group. Among the adverse events, diarrhea (4.2% in the ceftaroline group and 2.6% in the ceftriaxone group), headache (3.4% and 1.5%, respectively) and insomnia (3.1 % and 2.3%, respectively).
The frequency of clinical recovery was analyzed according to the pathogen. Thus, in patients with community acquired pneumonia caused by S. pneumoniae, the clinical cure rate was 85.5% and 68.6% in the ceftaroline and ceftriaxone group, respectively, with S. pneumoniae - 100% and 22.2%, respectively, of S. aureus - 72% and 60%, respectively. The cure rate for patients with typical Gram negative respiratory pathogens such as Haemophilus influenzae, Haemophilus parainfluenzae and Klebsiella pneumoniae was comparable for both drugs.
However, the activity of ceftaroline is lower than that of other generation III-IV cephalosporins compared to certain resistant gram-negative microorganisms (Pseudomonas aeruginosa, pathogenic agents producing AmpC or micro-organisms producing extended spectrum beta-lactamases).
Results of two clinical trials indicate that ceftarolin is a promising new drug for the treatment of community-acquired pneumonia, however, limited activity against gram-negative bacteria and a lack of activity against P. aeruginosa considerably limits the possibility of its use for the treatment of nosocomial pneumonia.