Rifabutin: a repurposed antibiotic with high potential against planktonic and biofilm staphylococcal clinical
Magda Ferreira1,2,3, Margarida Pinto4, Frederico Aires-da-Silva1,2
1Center for Interdisciplinary Research in Animal Health (CIISA), Faculty of Veterinary Medicine, Universidade de Lisboa, Lisbon, Portugal.
Abstract:
Staphylococcus aureus poses a significant threat as an opportunistic pathogen in humans, and animal medicine, particularly in the context of hospital-acquired infections (HAIs). Effective treatment is a significant challenge, contributing substantially to the global health burden. While antibiotic therapy remains the primary approach for staphylococcal infections, its efficacy is often compromised by the emergence of resistant strains and biofilm formation. The anticipated solution is the discovery and development of new antibacterial agents. However, this is a time consuming and expensive process with limited success rates. One potential alternative for addressing this challenge is the repurposing of existing antibiotics. This study investigated the potential of rifabutin (RFB) as a repurposed antibiotic for treating S. aureus infections. The minimum inhibitory concentration (MIC) of rifabutin was assessed by the broth microdilution method, in parallel to vancomycin, against 114 clinical isolates in planktonic form. The minimum biofilm inhibitory concentration (MBIC50) was determined by an adaptation of the broth microdilution method, followed by MTT assay, against a subset of selected 40 clinical isolates organized in biofilms. The study demonstrated that RFB MIC ranged from 0.002 to 6.250 μg/mL with a MIC50 of 0.013 μg/mL. RFB also demonstrated high anti-biofilm activity in the subset of 40 clinical isolates, with confirmed biofilm formation, with no significant MBIC50 differences observed between the MSSA and MRSA strains, in contrast to that observed for the VAN. These results highlight the promising efficacy of RFB against staphylococcal clinical isolates with different resistance patterns, whether in planktonic and biofilm forms.
Insights
Rifabutin shows promise as a repurposed antibiotic against Staphylococcus aureus infections. It effectively inhibits both planktonic bacteria and biofilms, including resistant strains.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Staphylococcus aureus is a major cause of hospital-acquired infections (HAIs).
- Antibiotic resistance and biofilm formation in S. aureus present significant treatment challenges.
- Developing new antibiotics is costly and time-consuming.
Purpose of the Study:
- To evaluate rifabutin (RFB) as a repurposed antibiotic for S. aureus infections.
- To assess RFB's efficacy against planktonic and biofilm forms of S. aureus.
- To compare RFB's activity with vancomycin against clinical isolates.
Main Methods:
- Minimum Inhibitory Concentration (MIC) determined by broth microdilution for 114 isolates.
- Minimum Biofilm Inhibitory Concentration (MBIC50) assessed using broth microdilution and MTT assay on 40 isolates.
- Comparison of RFB and vancomycin (VAN) against Methicillin-Susceptible S. aureus (MSSA) and Methicillin-Resistant S. aureus (MRSA).
Main Results:
- RFB exhibited low MIC values (MIC50 = 0.013 μg/mL) against planktonic S. aureus.
- RFB demonstrated significant anti-biofilm activity against a subset of isolates.
- No significant difference in MBIC50 was observed between MSSA and MRSA strains for RFB, unlike vancomycin.
Conclusions:
- Rifabutin is a promising candidate for repurposing against S. aureus.
- RFB shows efficacy against both planktonic and biofilm forms of S. aureus, including resistant strains.
- RFB offers a potential alternative for treating challenging staphylococcal infections.
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