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Published on: April 18, 2019
New Synergistic Combination Therapy of Mupirocin and α-Pinene Against Multidrug-Resistant Clinical Strains of
Paulo Cáceres-Guido1, Nicolás Martín-Vázquez2, Adriana Ojeda-Sana3
1Pharmacokinetics and Clinical Pharmacology Research Unit, Pharmacy - Integrative Medicine Group, Hospital de Pediatría Prof. Dr. J. P. Garrahan, Buenos Aires, Argentina.
Objective:
Increased mupirocin use leads to mupirocin resistance and is associated with persistence of methicillin-resistant Staphylococcus aureus (MRSA) carriers, prolonged hospitalization, and significant economic burdens for health systems. The study aimed to investigate the antimicrobial activity of compounds of Salvia rosmarinus L. ("rosemary", formerly Rosmarinus officinalis), alone or in combination with mupirocin, against multidrug resistant MRSA using isolates obtained from pediatric patients.
Methods:
The in vitro antibacterial activity of the monoterpene α-pinene (α-Pi), a rosemary essential oil constituent, alone and in combination with mupirocin, was evaluated by determining the minimum inhibitory concentrations and minimum bactericidal concentrations (MBCs) and the fractional inhibitory concentration indices (FICIs) and fractional bactericidal concentration indices against multidrug-resistant clinical MRSA strains. The in vivo efficacy of α-Pi, alone and in combination with mupirocin, to eradicate MRSA infection was determined using an optimized mouse model of MRSA-infected wounds. Mouse skin samples (obtained via biopsy) were assessed for toxicity, and rabbit skin samples for irritation.
Results:
Both in vitro and in vivo, α-Pi was active against MRSA strains and acted synergistically with mupirocin against MRSA strains. Mupirocin-monoterpene combinations exhibited FICI values of 0.2 to 0.4, reducing the MBC of topical mupirocin 33-fold. A topical formulation containing α-Pi and mupirocin enhanced the efficacy of mupirocin in an in vivo MRSA-infected mouse skin model without significantly harming the skin of mice and rabbits.
Conclusions:
A topical formulation combining mupirocin and α-Pi may aid in the development of innovative agents for treating MRSA infections.
Insights
Rosemary
Area of Science:
- Phytochemistry
- Microbiology
- Pharmacology
Background:
- Increased mupirocin use drives resistance in methicillin-resistant Staphylococcus aureus (MRSA).
- MRSA infections lead to prolonged hospital stays and significant healthcare costs.
- Alternative treatments are needed to combat multidrug-resistant MRSA strains.
Purpose of the Study:
- To evaluate the antimicrobial activity of Salvia rosmarinus (rosemary) compounds against multidrug-resistant MRSA.
- To investigate the synergistic effects of rosemary constituents with mupirocin.
- To assess the efficacy and safety of a combined topical formulation in an in vivo model.
Main Methods:
- In vitro testing of α-pinene (α-Pi) and mupirocin using MIC, MBC, and FICI.
- In vivo efficacy study using a mouse model of MRSA-infected wounds.
- Assessment of skin toxicity in mice and rabbits for topical formulations.
Main Results:
- α-Pinene demonstrated in vitro and in vivo activity against MRSA.
- Synergistic antimicrobial activity was observed between α-Pi and mupirocin.
- A topical formulation of α-Pi and mupirocin enhanced MRSA eradication in vivo without significant toxicity.
Conclusions:
- A topical formulation combining mupirocin and α-pinene shows potential for treating MRSA infections.
- This combination may offer an innovative approach to overcome mupirocin resistance.
- Further development could lead to new therapeutic agents against resistant bacterial strains.
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