Rockefeller University scientists give thumbs-up to ‘superbug’ drug

A new drug called Ceftobiprole may fight bacteria that have developed resistance to antibiotics, according to researchers from Rockefeller University.

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NEW YORK— A new drug called Ceftobiprole may fight bacteria that have developed resistance to antibiotics, according to researchers from Rockefeller University.

Ceftobiprole, a broad-spectrum antibiotic discovered by Swiss biopharmaceutical company Basilea Pharmaceutica and being developed by Johnson & Johnson, held up against some of the deadliest strains of multidrug-resistant Staphylococcus aureus (MRSA) bacteria, often called "superbugs," according to the scientists. The new drug has completed clinical trials and has been granted fast-track status by the FDA.

Following recent media reports of "superbugs" that are resistant to some drugs, new antibiotics with high efficacy against such multidrug resistant strains are "urgently needed," the researchers wrote.

"The history of antibiotic use shows that sooner or later bacteria find a resistance mechanism against a previously successful antibiotic," says the study's lead investigator, Dr. Alexander Tomasz, head of Rockefeller's Laboratory of Microbiology. "The discovery of Ceftobiprole is a major 'score' in the armaments race against pathogenic bacteria."

Recent studies in several laboratories have already documented the powerful antimicrobial activity of Ceftobiprole against several species of bacteria, but the scientists knew that resistant MRSA strains appear before long. To this end, the researchers sought to identify a potential source of resistant strains that may emerge upon the introduction of Ceftobiprole into clinical use. They examined its activity against highly oxacillin-resistant subpopulations of staphylococci which are present in the relatively few major pandemic MRSA clones responsible for most MRSA cases worldwide.

The drug was shown to be uniformly effective against all these resistant MRSA strains, the researchers found.

"It just knocked out the cells 100 percent," Tomasz says. "To our great relief, we found that this new drug was able to kill these subpopulations of MRSA also. It is particularly reassuring that the new antibiotic has the basic core structure of the beta-lactam (penicillin type) chemistry which has been the basis of success in the past—in the case of penicillin, followed by methicillin, and now Ceftobiprole."

"The appearance of a cephalosporin such as BPR [Ceftobiprole] with powerful antimicrobial activity against MRSA strains should be encouraging for medicinal chemists since it suggests that modification of the β-lactam core structure may still be a rewarding avenue for producing effective counter weapons against the sophisticated resistance mechanism that has evolved in the methicillin resistant staphylococci," the researchers concluded.
The study, Comparative Study of the Susceptibility of Major Epidemic Clones of MRSA to Oxacillin and to the New Broad Spectrum Cephalosporin Ceftobiprole, will be published in the August 2008 edition of the American Society for Microbiology journal Antimicrobial Agents and Chemotherapy. The research was supported by Johnson & Johnson along with a grant from the U.S. Public Health Service.

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