VIENNA — Ceftaroline, an investigational fifth-generation cephalosporin in late-stage development, is likely to become a major drug in the treatment of infections caused by Staphylococcus aureus and Streptococcus pneumoniae, including the strains resistant to current widely prescribed antimicrobials.
Ceftaroline exhibited impressive in vitro activity in standardized antimicrobial susceptibility testing involving 8,842 isolates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus(MSSA) from 56 U.S. and European medical centers during 2008–2009, Dr. Helio S. Sader reported at the meeting.
In a separate laboratory study presented at the congress, Dr. Michael R. Jacobs reported that ceftaroline showed more in vitro activity against the prevailing U.S. pediatric and adult serotypes of S. pneumoniae than any of the other 13 agents tested.
The investigational drug's performance was particularly strong against the isolates from pediatric patients, which tend to be among the most resistant to currently available antimicrobials. Indeed, the often multidrug-resistant serotype 19A accounted for 32.6% of all S. pneumoniae isolates from pediatric patients, compared with 15% in adults.
Ceftaroline had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL against serotype 19A, compared with 65.6 mcg/mL for ceftriaxone. The MIC90s for 12 other currently marketed antimicrobials ranged from 13.8 to 100 mcg/mL, noted Dr. Jacobs, professor of clinical microbiology at Case Western Reserve University, Cleveland.
The study included 891 S. pneumoniae isolates that were obtained from patients in 22 U.S. cities in 2008. The isolates came from infections at all body sites, and one-third were from pediatric patients. Pediatric isolates were significantly less susceptible to amoxicillin, penicillin, and ceftriaxone than were adult isolates. Serotypes covered in the seven-valent pneumococcal conjugate vaccine were uncommon in both adults and children.
Ceftaroline is now under Food and Drug Administration review for two potential indications: community-acquired pneumonia and complicated skin and skin structure infections.
In the S. aureus study, ceftaroline was 16-fold more active than was ceftriaxone against MSSA strains. It also showed strong potency against MRSA strains, with MIC90s of 1–2 mg/L, making it at least 64-fold more potent than ceftriaxone, according to Dr. Sader of JMI Laboratories, North Liberty, Iowa.
He drew particular attention to the investigational agent's outstanding performance against MRSA isolates with SCCmec type IV, which is found in the U.S. pandemic community-associated MRSA clone USA300, as well as in several problematic clones circulating in Europe. Ceftaroline's MIC90 of 1 mg/L against these isolates was the most favorable of the 10 drugs tested.
Ceftaroline is being developed by Forest Laboratories, which supported both studies.