Health :: Antibiotic Ceftobiprole shows promise against MRSA infections
Johnson & Johnson Pharmaceutical Research and Development, L.L.C. today announced that ceftobiprole, a novel cephalosporin(1) antibiotic in Phase III clinical trials, was found to be active against complicated skin infections caused by common, potentially deadly bacteria, including MRSA. These data were from two poster presentations given at the 46th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). These data also were highlighted by ICAAC. Ceftobiprole is being co-developed with Basilea Pharmaceutica, Ltd. through an exclusive worldwide collaboration.
MRSA, which is the abbreviation for methicillin-resistant Staphylococcus aureus, is a growing public health threat both in hospital and community settings. While historically a cause of serious infections in hospitalized patients, it has become an increasingly common source of life-threatening infections in otherwise healthy people.
In the first presentation(2), ceftobiprole demonstrated high clinical cure rates comparable to a commonly used antibiotic, vancomycin, in treating patients with complicated skin and skin structure infections (cSSSI) due to Gram-positive bacteria, including MRSA. The primary objective of the study was to compare clinical cure rates 7-14 days after completion of therapy in patients given ceftobiprole (500 mg IV q 12hr) or vancomycin (1gm q IV 12hr).
In the second presentation(3) describing the baseline pathogens (bacteria) seen in the cSSSI study, ceftobiprole was microbiologically active against a wide range of both Gram-positive(4) and Gram-negative(5) bacteria, including many bacteria associated with common, serious skin infections.
“These trial data suggest that as an investigational broad-spectrum antibiotic, ceftobiprole is effective in treating patients with skin infections, including MRSA infections, a growing public health problem both inside and outside hospital settings,” said Gary J. Noel, M.D., Senior Director of Clinical Research and Development, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., who presented the findings.
The first presentation described a large, multi-center, randomized, double-blind clinical trial involving 784 patients with cSSSI in whom Gram-positive pathogens were documented and/or suspected based on microscopic examination. Forty-eight percent of the patients had abscesses and 33% had wound infections. Enrollment was stratified by patient type.
Cure rates in the ceftobiprole-treated (n=61) and vancomycin-treated (n=60) subjects in the clinically evaluable population with MRSA infections were 91.8% and 90.0% respectively. Overall cure rates in the ceftobiprole- treated (n=282) and vancomycin-treated (n=277) subjects in the clinically evaluable population were 93.3% and 93.5% respectively.
Serious treatment-related adverse events were 1% in the ceftobiprole- treated population and 3% in the vancomycin-treated population. The overall number of non-serious, treatment-emergent adverse events were similar. Adverse events associated with rashes (e.g. pruritis, erythema) occurred in 14% of vancomycin-treated subjects and in 9% of ceftobiprole-treated subjects. Nausea was reported by 14% of ceftobiprole-treated and 8% of vancomycin-treated patients. Taste disturbance was reported by 8% of ceftobiprole-treated and 1% of vancomycin-treated patients. Of the subjects who had normal serum creatinine levels at baseline, 4% of vancomycin-treated subjects had abnormal serum creatinine values during the study compared with 2% of ceftobiprole- treated subjects.
Discontinuation of therapy due to treatment-related adverse events was comparable in both groups (with 3% in ceftobiprole-treated subjects and 4% in vancomycin-treated subjects).
In the second presentation, baseline pathogens from the cSSSI study were examined for their susceptibility to ceftobiprole and selected antimicrobial agents. The predominant pathogen was S. aureus, and, of these staphylococcal isolates, 37% were methicillin-resistant. The Gram-negative isolates were identified as Enterobacteriaceae, Pseudomonas spp. and Acinetobacter baumannii. Among the baseline pathogens, ceftobiprole inhibited all staphylococcal and streptococcal isolates at clinically achievable concentrations.
In addition to these Phase III study results, data from multiple surveillance studies(6) are being presented demonstrating the broad-spectrum antibacterial activity of ceftobiprole against potentially life-threatening Gram-positive and Gram-negative isolates, including Enterobacteriaceae and Pseudomonas aeruginosa.
About Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) is part of Johnson & Johnson, the world’s most broad-based producer of healthcare products. J&JPRD is headquartered in Raritan, New Jersey (USA), and has facilities throughout Europe and the United States. J&JPRD is leveraging drug discovery and drug development in a variety of therapeutic areas to address unmet medical needs worldwide.
(1) Cephalosporins are a sub-class of antibacterial agents within the Beta-lactam class. Beta-lactam antibiotics are used to treat many different kinds of bacterial infections, including abdominal, ear, respiratory (including pneumonia), urinary tract, and skin infections.
(2) “Successful Treatment of Complicated Skin Infections (cSSSI) Due to Staphylococci, Including Methicillin-Resistant Staphylococcus aureus (MRSA) with Ceftobiprole” (Poster L-1212)
(3) “Ceftobiprole Activity against Baseline Pathogens from a Complicated Skin and Skin Structure Infection Clinical Trial” (Poster E-0116)
(4) Gram-positive indicates a group of bacteria that become violet-colored when the bacterial cells are treated with the Gram stain. This response is based on the chemical composition of their cell walls and is used to identify the type of bacteria. Some Gram-positive bacteria may cause serious infections.
(5) Gram-negative indicates a group of bacteria that become red when the bacterial cells are treated using the Gram stain method. This response is based on the chemical composition of their cell walls and is used to identify the type of bacteria. Some Gram-negative bacteria may cause serious infections.
(6) “Baseline Surveillance Profiles of Ceftobiprole (BPR) Activity Against Enterobacteriaceae and P. Aeruginosa (PA)” (Poster E-0122); “In vitro Activity of Ceftobiprole Tested Against a Recent Collection of North American Pseudomonas aeruginosa (PSA)” (Poster E-0115); “Susceptibilities of Most Prevalent Enterobacteriaceae-species to Ceftobiprole: Results of The Antimicrobial Resistance Surveillance Study of the Paul Ehrlich Society for Chemotherapy, 2004” (Poster E-0117).
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