FDA Grants New Cephalosporin Fast-Track Status

Monotherapy with ceftobiprole was found to be as effective as vancomycin plus ceftazidime for treating patients with a broad range of complicated skin and skin-structure infections caused by gram-positive and gram-negative bacteria.

Following the completion of successful phase III registration trials, the Food and Drug Administration granted ceftobiprole fast-track status for the treatment of both complicated skin and skin-structure infections caused by methicillin-resistant staphylococci and hospital-acquired pneumonia.

Ceftobiprole is a novel, broad-spectrum cephalosporin developed jointly by Basilea Pharmaceutica AG and Cilag AG International (a Johnson & Johnson company).

The randomized, double-blind, multicenter trial included 828 patients with diabetic foot infections, abscess, cellulitis, and wound infection, reported Gary J. Noel and his fellow researchers, all full-time employees of Johnson & Johnson Pharmaceutical Research and Development, Raritan, N.J., which funded the study (Clin. Infect. Dis. 2008;46:647–55).

Infecting pathogen types—identified in at least 10 patients at baseline—included coagulase-negative and coagulase-positive staphylococci, Pseudomonas aeruginosa, β-hemolytic streptococci, and enterobacteriaceae. The most prevalent pathogens were gram-positive bacteria, specifically methicillin-resistant Staphylococcus aureus (MRSA) (123 patients) and methicillin-susceptible S. aureus (MSSA) (250 patients).

The patient cohort, accumulated over 129 international sites, was divided into two arms, with 547 patients receiving ceftobiprole and 281 receiving the glycopeptide antibiotic vancomycin plus the third-generation cephalosporin ceftazidime, according to the researchers.

Patients in the ceftobiprole arm received 500 mg for 120 minutes every 8 hours, while in the comparator group, the starting dose was 1,000 mg vancomycin infused over 60 minutes every 12 hours plus 1,000 mg ceftazidime infused over 120 minutes every 8 hours.

The mean duration of treatment in the clinically evaluable population was about 9 days in both arms, the authors noted.

At the investigating physicians' discretion, empirical treatment with metronidazole (Flagyl, Pfizer) was permitted to provide activity against anaerobic bacteria. The nitroimidazole anti-infective was given to 39 of the ceftobiprole-treated patients and 17 of the comparator-treated patients, the researchers wrote.

At the test-of-cure (TOC) visit (after 6–17 days of treatment) for the evaluable patients, clinical cure occurred for 439 of 485 (91%) ceftobiprole-treated patients and for 220 of 244 (90%) comparator-treated patients, the researchers noted, adding that cure rates in the intent-to-treat population at the TOC visit were about 81% in both groups.

The cure rates exceeded 90% among ceftobiprole-treated patients with abscess, cellulitis, or wound infections, and among patients who had surgical debridement of their infections performed within 48 hours after study enrollment, the authors reported, adding that these rates were comparable with those observed among comparator-treated patients.

Among patients with S. aureus, MRSA, and MSSA infections, cure rates at the TOC visit among ceftobiprole-treated patients and among comparator-treated patients were also comparable.

The difference in cure rates of complicated skin and skin-structure infections associated with bacteremia was not statistically significant.

Among the 30 ceftobiprole-treated individuals from whom P. aeruginosa was isolated at baseline, 26 (87%) were clinically cured, according to the researchers. Among the 12 ceftobiprole-treated patients from whom P. aeruginosa was isolated as the sole pathogen at baseline, 9 (75%) were determined to be clinically cured at the TOC visit.

In an accompanying editorial, Dr. Andreas F. Widmer concurred with the researchers and noted that for infections involving enterobacteriaceae, ceftobiprole may become the drug of choice if currently unknown adverse effects do not limit its use in the future (Clin. Infect. Dis. 2008;46:656–8).

MRSA coverage with ceftobiprole may improve outcomes in complicated skin and skin-structure infections by enabling early bactericidal therapy in patients admitted to emergency departments with infections not yet identified as being caused by MRSA, said Dr. Widmer of the division of infectious disease and hospital epidemiology at University Hospital in Basel, Switzerland.

"This promising new agent may be regarded as the first clinically effective cephalosporin against MRSA for treatment of complicated skin and skin-structure infections, with two randomized clinical trials supporting its efficacy," he said, referring to a trial published this year by the same group of investigators that compared ceftobiprole with vancomycin alone (Antimicrob. Agents Chemother. 2008;52:37–44).

Dr. Widmer has been a member of an expert group for Novartis and has served on the advisory board for Arpida Ltd.

Monotherapy with ceftobiprole was found to be as effective as vancomycin plus ceftazidime for treating patients with a broad range of complicated skin and skin-structure infections caused by gram-positive and gram-negative bacteria.

Following the completion of successful phase III registration trials, the Food and Drug Administration granted ceftobiprole fast-track status for the treatment of both complicated skin and skin-structure infections caused by methicillin-resistant staphylococci and hospital-acquired pneumonia.

Ceftobiprole is a novel, broad-spectrum cephalosporin developed jointly by Basilea Pharmaceutica AG and Cilag AG International (a Johnson & Johnson company).

The randomized, double-blind, multicenter trial included 828 patients with diabetic foot infections, abscess, cellulitis, and wound infection, reported Gary J. Noel and his fellow researchers, all full-time employees of Johnson & Johnson Pharmaceutical Research and Development, Raritan, N.J., which funded the study (Clin. Infect. Dis. 2008;46:647–55).

Infecting pathogen types—identified in at least 10 patients at baseline—included coagulase-negative and coagulase-positive staphylococci, Pseudomonas aeruginosa, β-hemolytic streptococci, and enterobacteriaceae. The most prevalent pathogens were gram-positive bacteria, specifically methicillin-resistant Staphylococcus aureus (MRSA) (123 patients) and methicillin-susceptible S. aureus (MSSA) (250 patients).

The patient cohort, accumulated over 129 international sites, was divided into two arms, with 547 patients receiving ceftobiprole and 281 receiving the glycopeptide antibiotic vancomycin plus the third-generation cephalosporin ceftazidime, according to the researchers.

Patients in the ceftobiprole arm received 500 mg for 120 minutes every 8 hours, while in the comparator group, the starting dose was 1,000 mg vancomycin infused over 60 minutes every 12 hours plus 1,000 mg ceftazidime infused over 120 minutes every 8 hours.

The mean duration of treatment in the clinically evaluable population was about 9 days in both arms, the authors noted.

At the investigating physicians' discretion, empirical treatment with metronidazole (Flagyl, Pfizer) was permitted to provide activity against anaerobic bacteria. The nitroimidazole anti-infective was given to 39 of the ceftobiprole-treated patients and 17 of the comparator-treated patients, the researchers wrote.

At the test-of-cure (TOC) visit (after 6–17 days of treatment) for the evaluable patients, clinical cure occurred for 439 of 485 (91%) ceftobiprole-treated patients and for 220 of 244 (90%) comparator-treated patients, the researchers noted, adding that cure rates in the intent-to-treat population at the TOC visit were about 81% in both groups.

The cure rates exceeded 90% among ceftobiprole-treated patients with abscess, cellulitis, or wound infections, and among patients who had surgical debridement of their infections performed within 48 hours after study enrollment, the authors reported, adding that these rates were comparable with those observed among comparator-treated patients.

Among patients with S. aureus, MRSA, and MSSA infections, cure rates at the TOC visit among ceftobiprole-treated patients and among comparator-treated patients were also comparable.

The difference in cure rates of complicated skin and skin-structure infections associated with bacteremia was not statistically significant.

Among the 30 ceftobiprole-treated individuals from whom P. aeruginosa was isolated at baseline, 26 (87%) were clinically cured, according to the researchers. Among the 12 ceftobiprole-treated patients from whom P. aeruginosa was isolated as the sole pathogen at baseline, 9 (75%) were determined to be clinically cured at the TOC visit.

In an accompanying editorial, Dr. Andreas F. Widmer concurred with the researchers and noted that for infections involving enterobacteriaceae, ceftobiprole may become the drug of choice if currently unknown adverse effects do not limit its use in the future (Clin. Infect. Dis. 2008;46:656–8).

MRSA coverage with ceftobiprole may improve outcomes in complicated skin and skin-structure infections by enabling early bactericidal therapy in patients admitted to emergency departments with infections not yet identified as being caused by MRSA, said Dr. Widmer of the division of infectious disease and hospital epidemiology at University Hospital in Basel, Switzerland.

"This promising new agent may be regarded as the first clinically effective cephalosporin against MRSA for treatment of complicated skin and skin-structure infections, with two randomized clinical trials supporting its efficacy," he said, referring to a trial published this year by the same group of investigators that compared ceftobiprole with vancomycin alone (Antimicrob. Agents Chemother. 2008;52:37–44).

Dr. Widmer has been a member of an expert group for Novartis and has served on the advisory board for Arpida Ltd.

Monotherapy with ceftobiprole was found to be as effective as vancomycin plus ceftazidime for treating patients with a broad range of complicated skin and skin-structure infections caused by gram-positive and gram-negative bacteria.

Following the completion of successful phase III registration trials, the Food and Drug Administration granted ceftobiprole fast-track status for the treatment of both complicated skin and skin-structure infections caused by methicillin-resistant staphylococci and hospital-acquired pneumonia.

Ceftobiprole is a novel, broad-spectrum cephalosporin developed jointly by Basilea Pharmaceutica AG and Cilag AG International (a Johnson & Johnson company).

The randomized, double-blind, multicenter trial included 828 patients with diabetic foot infections, abscess, cellulitis, and wound infection, reported Gary J. Noel and his fellow researchers, all full-time employees of Johnson & Johnson Pharmaceutical Research and Development, Raritan, N.J., which funded the study (Clin. Infect. Dis. 2008;46:647–55).

Infecting pathogen types—identified in at least 10 patients at baseline—included coagulase-negative and coagulase-positive staphylococci, Pseudomonas aeruginosa, β-hemolytic streptococci, and enterobacteriaceae. The most prevalent pathogens were gram-positive bacteria, specifically methicillin-resistant Staphylococcus aureus (MRSA) (123 patients) and methicillin-susceptible S. aureus (MSSA) (250 patients).

The patient cohort, accumulated over 129 international sites, was divided into two arms, with 547 patients receiving ceftobiprole and 281 receiving the glycopeptide antibiotic vancomycin plus the third-generation cephalosporin ceftazidime, according to the researchers.

Patients in the ceftobiprole arm received 500 mg for 120 minutes every 8 hours, while in the comparator group, the starting dose was 1,000 mg vancomycin infused over 60 minutes every 12 hours plus 1,000 mg ceftazidime infused over 120 minutes every 8 hours.

The mean duration of treatment in the clinically evaluable population was about 9 days in both arms, the authors noted.

At the investigating physicians' discretion, empirical treatment with metronidazole (Flagyl, Pfizer) was permitted to provide activity against anaerobic bacteria. The nitroimidazole anti-infective was given to 39 of the ceftobiprole-treated patients and 17 of the comparator-treated patients, the researchers wrote.

At the test-of-cure (TOC) visit (after 6–17 days of treatment) for the evaluable patients, clinical cure occurred for 439 of 485 (91%) ceftobiprole-treated patients and for 220 of 244 (90%) comparator-treated patients, the researchers noted, adding that cure rates in the intent-to-treat population at the TOC visit were about 81% in both groups.

The cure rates exceeded 90% among ceftobiprole-treated patients with abscess, cellulitis, or wound infections, and among patients who had surgical debridement of their infections performed within 48 hours after study enrollment, the authors reported, adding that these rates were comparable with those observed among comparator-treated patients.

Among patients with S. aureus, MRSA, and MSSA infections, cure rates at the TOC visit among ceftobiprole-treated patients and among comparator-treated patients were also comparable.

The difference in cure rates of complicated skin and skin-structure infections associated with bacteremia was not statistically significant.

Among the 30 ceftobiprole-treated individuals from whom P. aeruginosa was isolated at baseline, 26 (87%) were clinically cured, according to the researchers. Among the 12 ceftobiprole-treated patients from whom P. aeruginosa was isolated as the sole pathogen at baseline, 9 (75%) were determined to be clinically cured at the TOC visit.

In an accompanying editorial, Dr. Andreas F. Widmer concurred with the researchers and noted that for infections involving enterobacteriaceae, ceftobiprole may become the drug of choice if currently unknown adverse effects do not limit its use in the future (Clin. Infect. Dis. 2008;46:656–8).

MRSA coverage with ceftobiprole may improve outcomes in complicated skin and skin-structure infections by enabling early bactericidal therapy in patients admitted to emergency departments with infections not yet identified as being caused by MRSA, said Dr. Widmer of the division of infectious disease and hospital epidemiology at University Hospital in Basel, Switzerland.

"This promising new agent may be regarded as the first clinically effective cephalosporin against MRSA for treatment of complicated skin and skin-structure infections, with two randomized clinical trials supporting its efficacy," he said, referring to a trial published this year by the same group of investigators that compared ceftobiprole with vancomycin alone (Antimicrob. Agents Chemother. 2008;52:37–44).

Dr. Widmer has been a member of an expert group for Novartis and has served on the advisory board for Arpida Ltd.