Efficacy of a novel lantibiotic, CMB001, against MRSA
| Autor: | Christine M Brown, Stephen P Krasucki, Stephen J Streatfield, Jerzy Karczewski, Yukari Maezato |
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| Rok vydání: | 2021 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine Microbiology (medical) Staphylococcus aureus 030106 microbiology Microbial Sensitivity Tests Neutropenia medicine.disease_cause Microbiology Mice 03 medical and health sciences Bacteriocins Pharmacokinetics Vancomycin In vivo Animals Medicine Pharmacology (medical) Whole blood Pharmacology biology business.industry Staphylococcal Infections biology.organism_classification medicine.disease Methicillin-resistant Staphylococcus aureus Anti-Bacterial Agents Acinetobacter baumannii 030104 developmental biology Infectious Diseases business medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 76:1532-1538 |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | Objectives To evaluate the efficacy of a novel lantibiotic, CMB001, against MRSA biofilms in vitro and in an in vivo experimental model of bacterial infection. Methods Antibacterial activity of CMB001 was measured in vitro after its exposure to whole blood or to platelet-poor plasma. In vitro efficacy of CMB001 against a Staphylococcus aureus biofilm was studied using scanning electron microscopy. The maximum tolerable dose in mice was determined and a preliminary pharmacokinetic analysis for CMB001 was performed in mice. In vivo efficacy was evaluated in a neutropenic mouse thigh model of infection. Results CMB001 maintained its antibacterial activity in the presence of blood or plasma for up to 24 h at 37°C. CMB001 efficiently killed S. aureus within the biofilm by causing significant damage to the bacterial cell wall. The maximum tolerable dose in mice was established to be 10 mg/kg and could be increased to 30 mg/kg in mice pretreated with antihistamines. In neutropenic mice infected with MRSA, treatment with CMB001 reduced the bacterial burden with an efficacy equivalent to that of vancomycin. Conclusions CMB001 offers potential as an alternative treatment option to combat MRSA. It will be of interest to evaluate the in vivo efficacy of CMB001 against infections caused by other pathogens, including Clostridioides difficile and Acinetobacter baumannii, and to expand its pharmacokinetic/pharmacodynamic parameters and safety profile. |
| Databáze: | OpenAIRE |
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