In the continuous battle against antibiotic-resistant bacteria, a recent study published in BMC Pharmacology & Toxicology offers a potential strategy against one of the most notorious pathogens—methicillin-resistant Staphylococcus aureus (MRSA). The study provides promising results on the use of daptomycin in combination with other antimicrobial agents. As published on 30th January 2020 and updated on 9th March 2020 in BMC Pharmacology & Toxicology (DOI: 10.1186/s40360-019-0305-y), researchers have analyzed the in vitro synergistic effects of combining daptomycin with selected antimicrobial agents to counteract MRSA strains with a minimum inhibitory concentration (MIC) of 1 mg/L against daptomycin—shedding new light on effective MRSA treatment options.

The study, conducted by Yi-Chien Lee from the Department of Internal Medicine, Fu Jen Catholic University Hospital, and colleagues from the National Taiwan University Hospital and the Institute of Infectious Diseases and Vaccinology, National Health Research Institutes in Taiwan, tested the effects of daptomycin combinations on 100 MRSA isolates. The combinations included daptomycin with fosfomycin, oxacillin, gentamicin, linezolid, and rifampicin, with a view to determining whether these combinations might produce an enhanced inhibitory effect on bacterial growth.

Daptomycin Versus MRSA

Daptomycin is a lipopeptide antibiotic that has been used as a last-line treatment for various bacterial infections caused by MRSA—a bacterial strain resistant to many standard antibiotics, including methicillin. Typically, it is effective against Gram-positive bacteria, including Staphylococcus aureus strains that are resistant to methicillin. However, MRSA’s ability to evolve and develop resistance even to powerful antibiotics like daptomycin necessitates the search for alternative treatment strategies.

Combo Therapy: The Synergistic Approach

A microbroth checkerboard assay was used to evaluate the interactions between daptomycin and the selected antimicrobial agents. The researchers assessed the potential synergistic activities using the fractional inhibitory concentration index (FICI).

Key Findings

1. All MRSA isolates were found to be susceptible to linezolid.
2. A significant 85% exhibited susceptibility to fosfomycin.
3. Gentamicin and rifampicin had lower susceptibility rates at 8% and 69%, respectively.
4. None of the isolates was susceptible to oxacillin.
5. The most significant synergistic effect was found with the daptomycin-fosfomycin combination, followed by daptomycin in combination with oxacillin, gentamicin, linezolid, and rifampicin, in decreasing order of efficacy.

Ethics and Publication Conduct

The study (Reference: NTUH-IRB No. 201110043RD) was performed in line with the Helsinki Declaration, with the Ethical Committee of National Taiwan University Hospital waiving informed consent due to the retrospective design and minimal risk posed by the research. No competing interests were reported by the authors, and the publisher claimed neutrality on jurisdictional claims in published maps and institutional affiliations.

The Important Role of Combination Therapy

Combination therapy is not entirely a new concept. It is often used in the treatment of complex infections to broaden the spectrum of activity, reduce the potential for developing resistance, and achieve synergistic effects. In the case of MRSA, it is especially crucial due to the pathogen’s resilience and adaptability against monotherapy antibiotic treatments.

The Implications of the Study

With a 37% synergy rate, the combination of daptomycin and fosfomycin shows potential as an effective therapeutic option that could eventually translate into clinical practice for managing MRSA infections, especially those that demonstrate a high MIC to daptomycin. These findings could also lead to the development of new treatment guidelines that integrate combination therapies to deal with resistant strains.

Relevance in Current Medical Practice

The CDC has recognized MRSA as a serious threat, and the strain’s resistance to common antibiotics has significantly complicated infection control and treatment. The results of this study are thus particularly relevant for clinical practice, offering an alternative in treating persistent or severe cases of MRSA infections. Combination therapies might also alleviate the pressure on using higher doses of single agents, potentially reducing the associated toxicities and side effects.

Keywords

1. MRSA treatment
2. Daptomycin MRSA synergy
3. Antibiotic combination therapy
4. Daptomycin-fosfomycin combination
5. Methicillin-resistant Staphylococcus aureus

References

1. Lee, Y.-C., Chen, P.-Y., Wang, J.-T., & Chang, S.-C. (2020). A study on combination of daptomycin with selected antimicrobial agents: in vitro synergistic effect of MIC value of 1 mg/L against MRSA strains. BMC Pharmacol Toxicol, 20(1), 25. https://doi.org/10.1186/s40360-019-0305-y
2. Lowy, F. D. (1998). Staphylococcus aureus infections. N Engl J Med, 339, 520–532. https://doi.org/10.1056/NEJM199808203390806
3. Wang, J. T., Lauderdale, T. L., Lee, W. S., Huang, J. H., Wang, T. H., Chang, S. C. (2010). Impact of active surveillance and contact isolation on transmission of methicillin-resistant Staphylococcus aureus in intensive care units in an area with high prevalence. J Formos Med Assoc, 109, 258–268. https://doi.org/10.1016/S0929-6646(10)60051-4
4. Stefani, S., & Goglio, A. (2010). Methicillin-resistant Staphylococcus aureus: related infections and antibiotic resistance. Int J Infect Dis, 14(Suppl 4), S19–S22. https://doi.org/10.1016/j.ijid.2010.05.009
5. Davis, J. S., Van Hal, S., Tong, S. Y. (2015). Combination antibiotic treatment of serious methicillin-resistant Staphylococcus aureus infections. Semin Respir Crit Care Med, 36, 3–16. https://doi.org/10.1055/s-0034-1396906

Conclusion

This pivotal study serves as an exemplar of the advances in microbiological research that hold promise for future treatments of MRSA. As antibiotic resistance continues to pose a severe health threat, the exploration and validation of combination therapies, like the promising daptomycin-fosfomycin regimen, mark critical steps toward more effective medical interventions against resilient pathogens such as MRSA. Further clinical trials and in vivo studies are needed to confirm the efficacy and safety of these combinations. But for now, the research provides a hopeful perspective on managing a formidable foe in the microbial world.