Ceftobiprole: An Emerging Therapeutic Option for Resistant and Complicated Infections

2011 ◽  
Vol 3 ◽  
pp. CMT.S5032 ◽  
Author(s):  
Wanda C. Reygaert
Keyword(s):  
Antimicrobial Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Therapeutic Option ◽  
Generation Cephalosporin ◽  
Final Approval ◽  
Cure Rate ◽  
Skin Structure ◽  
Fifth Generation ◽  
Complicated Skin ◽  
Mrsa Strains

Ceftobiprole is a new parenterally administered fifth generation cephalosporin which has been shown to have antimicrobial activity against a broad range of bacteria, and specifically against methicillin-resistant Staphylococcus aureus (MRSA) in complicated skin and skin structure infections (cSSSIs), with a cure rate non-inferior to vancomycin and ceftazidime. It has increased stability against β-lactamases and an increased affinity for PBP2’ in MRSA strains. Ceftobiprole has shown a low tendency to select for resistance, and because it is excreted mainly in the urine, a low potential for adverse drug interactions. It has been shown to cause few mild to moderate adverse effects in patients. The broad-spectrum of activity makes it an excellent choice for initial monotherapy in cSSSIs. There is also promise for use in all types of pneumonia, and synergistic possibilities with aminoglycoside and fluoroquinolone drugs. It is awaiting final approval by the FDA.

scholarly journals Phase 2 Study of Ceftaroline versus Standard Therapy in Treatment of Complicated Skin and Skin Structure Infections

2007 ◽  
Vol 51 (10) ◽  
pp. 3612-3616 ◽  
Author(s):  
George H. Talbot ◽  
Dirk Thye ◽  
Anita Das ◽  
Yigong Ge
Keyword(s):  
Success Rate ◽  
Standard Therapy ◽  
Clinical Cure ◽  
Clinical Cure Rate ◽  
Tolerability Profile ◽  
Clinical Relapse ◽  
Cure Rate ◽  
Ceftaroline Fosamil ◽  
Skin Structure ◽  
Complicated Skin

ABSTRACT Ceftaroline, the bioactive metabolite of ceftaroline fosamil (previously PPI-0903, TAK-599), is a broad-spectrum cephalosporin with potent in vitro activity against multidrug-resistant gram-positive aerobic pathogens, including methicillin-resistant Staphylococcus aureus. A randomized, observer-blinded study to evaluate the safety and efficacy of ceftaroline versus standard therapy in treating complicated skin and skin structure infections (cSSSI) was performed. Adults with cSSSI, including at least one systemic marker of inflammation, were randomized (2:1) to receive intravenous (i.v.) ceftaroline (600 mg every 12 h) or i.v. vancomycin (1 g every 12 h) with or without adjunctive i.v. aztreonam (1 g every 8 h) for 7 to 14 days. The primary outcome measure was the clinical cure rate at a test-of-cure (TOC) visit 8 to 14 days after treatment. Secondary outcomes included the microbiological success rate (eradication or presumed eradication) at TOC and the clinical relapse rate 21 to 28 days following treatment. Of 100 subjects enrolled, 88 were clinically evaluable; the clinical cure rate was 96.7% (59/61) for ceftaroline versus 88.9% (24/27) for standard therapy. Among the microbiologically evaluable subjects (i.e., clinically evaluable and having had at least one susceptible pathogen isolated at baseline), the microbiological success rate was 95.2% (40/42) for ceftaroline versus 85.7% (18/21) for standard therapy. Relapse occurred in one subject in each group (ceftaroline, 1.8%; standard therapy, 4.3%). Ceftaroline exhibited a very favorable safety and tolerability profile, consistent with that of marketed cephalosporins. Most adverse events from ceftaroline were mild and not related to treatment. Ceftaroline holds promise as a new therapy for treatment of cSSSI and other serious polymicrobial infections.

scholarly journals Prospective Study of the Wilson Severity-of-Illness Scoring System for Complicated Skin and Skin Structure Infections

2012 ◽  
Vol 57 (1) ◽  
pp. 647-650 ◽  
Author(s):  
George H. Talbot ◽  
Tanya O'Neal ◽  
Anita F. Das ◽  
Dirk Thye
Keyword(s):  
Clinical Cure ◽  
Clinical Cure Rate ◽  
Severity Of Illness ◽  
Cure Rate ◽  
Two Phase ◽  
Ceftaroline Fosamil ◽  
Risk Class ◽  
Skin Structure ◽  
Complicated Skin ◽  
Cure Rates

ABSTRACTWilson et al. (Am. J. Surg.185:369–375, 2003) developed a disease severity classification system for use in complicated skin and skin structure infections (cSSSI). Two phase 3 trials of ceftaroline fosamil in cSSSI provided the opportunity to evaluate the association between Wilson Severity Risk Class and clinical cure rates. Our analyses did not confirm that an association exists between Wilson Severity Risk Class and clinical cure rate and, thus, did not validate its predictive utility.

scholarly journals Use of Ribotyping To Retrospectively Identify Methicillin-Resistant Staphylococcus aureus Isolates from Phase 3 Clinical Trials for Tigecycline That Are Genotypically Related to Community-Associated Isolates

2005 ◽  
Vol 49 (11) ◽  
pp. 4521-4529 ◽  
Author(s):  
Fionnuala McAleese ◽  
Ellen Murphy ◽  
Timothy Babinchak ◽  
Guy Singh ◽  
Battouli Said-Salim ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Trials ◽  
Phase 3 ◽  
Double Blind ◽  
Methicillin Resistant ◽  
Skin Structure ◽  
Type Iv ◽  
Complicated Skin ◽  
Mrsa Strains ◽  
Encoding Genes

ABSTRACT A retrospective study was performed to identify methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained from patients enrolled in phase 3 clinical trials for tigecycline that were genotypically similar to known community-associated MRSA (CA-MRSA) strains. The clinical trials were double-blind comparator studies for complicated skin and skin structure infections or complicated intra-abdominal infections. We obtained 85% of the MRSA isolates from patients with complicated skin and skin structure infections. Using ribotyping, MRSA isolates were compared with well-characterized North American CA-MRSA strains and negative-control hospital-associated (HA) MRSA strains by cluster analysis; 91 of the 173 isolates clustered with two groups of known CA-MRSA strains, 60% of which shared an indistinguishable ribotype. These isolates were subsequently tested for the presence of SCCmec type IV and the Panton-Valentine leukocidin (PVL)-encoding genes as well as susceptibility to clindamycin, characteristics that are typically associated with CA-MRSA; 89 of the 91 isolates carried the type IV SCCmec element and 76 were also positive for the PVL-encoding genes; 73 of these isolates were susceptible to clindamycin. A similar analysis performed on 26 nonclustering isolates identified only four with these characteristics; 89 of the 91 clustering isolates were inhibited by tigecycline at MICs of ≤0.5 μg/ml. On the basis of clustering information and preliminary genetic characterization, it appears that ribotyping is a useful tool in identifying potential CA-MRSA isolates and 76 MRSA isolates from patients enrolled in the tigecycline phase 3 trials have genetic markers typically associated with CA-MRSA.

scholarly journals Cyclic and Acyclic Amine Oxide Alkyl Derivatives as Potential Adjuvants in Antimicrobial Chemotherapy against Methicillin-Resistant Staphylococcus aureus with an MDR Profile

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 952
Author(s):  
Lorenza Fagnani ◽  
Lisaurora Nazzicone ◽  
Fabrizia Brisdelli ◽  
Luisa Giansanti ◽  
Sara Battista ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Blood Cells ◽  
Pathogenic Bacteria ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Amine Oxide ◽  
Therapeutic Option ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Amphoteric Surfactants

The dramatic intensification of antimicrobial resistance occurrence in pathogenic bacteria concerns the global community. The revitalisation of inactive antibiotics is, at present, the only way to go through this health system crisis and the use of antimicrobial adjuvants is turning out the most promising approach. Due to their low toxicity, eco-friendly characteristics and antimicrobial activity, amphoteric surfactants are good candidates. This study investigated the adjuvant potentialities of commercial acyclic and newly cyclic N-oxide surfactants combined with therapeutically available antibiotics against MDR methicillin-resistant Staphylococcus aureus (MRSA). The safety profile of the new cyclic compounds, compared to commercial surfactants, was preliminarily assessed, evaluating the cytotoxicity on human peripheral mononuclear blood cells and the haemolysis in human red blood cells. The compounds show an efficacious antimicrobial activity strongly related to the length of the carbon atom chain. In drug–drug interaction assays, all surfactants act synergistically, restoring sensitivity to oxacillin in MRSA, with dodecyl acyclic and cyclic derivatives being the most effective. After evaluating the cytotoxicity and considering the antimicrobial action, the most promising compound is the L-prolinol amine-oxide C12NOX. These findings suggest that the combination of antibiotics with amphoteric surfactants is a valuable therapeutic option for topical infections sustained by multidrug-resistant S. aureus.

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