Advances in MRSA drug discovery: where are we and where do we need to be?

Abstract

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) have been on the increase during the past decade, due to the steady growth of the elderly and immunocompromised patients, and the emergence of multidrug-resistant (MDR) bacterial strains. Although there are a limited number of anti-MRSA drugs available, a number of different combination antimicrobial drug regimens have been used to treat serious MRSA infections. Thus, the addition of several new antistaphylococcal drugs into clinical practice should broaden clinician's therapeutic options. As MRSA is one of the most common and problematic bacteria associated with increasing antimicrobial resistance, continuous efforts for the discovery of lead compounds as well as development of alternative therapies and faster diagnostics are required.

Areas covered: This article summarizes the FDA-approved drugs to treat MRSA infections, the drugs in clinical trials, and the drug leads for MRSA and related Gram-positive bacterial infections. In addition, the article discusses the mode of action of antistaphylococcal molecules and the resistant mechanisms of some molecules.

Expert opinion: The number of pipeline drugs presently undergoing clinical trials is not particularly encouraging. There are limited and rather expensive therapeutic options for MRSA infections in the critically ill. Further research efforts are required for effective phage therapy on MRSA infections in clinical use, which seem to be attractive therapeutic options for the future.

Keywords::

• acyl t-RNA synthase inhibitor
• antibacterial agents
• antibacterial vaccine
• antibiotics
• antimicrobial peptides
• Clp protease inhibitor
• combination therapy
• daptomycin
• dihydrofolate reductase inhibitor
• dihydropteroate synthase inhibitor
• electron transport inhibitor
• elongation factor G inhibitor
• FAS II inhibitor
• Gram-positive pathogens
• linezolid
• menaquinone biosynthesis inhibitor
• methicillin-resistant Staphylococcus aureus
• peptide deformylase inhibitor
• peptidoglycan biosynthesis inhibitor
• phage therapy
• Pol IIIC inhibitor
• RNA-polymerase inhibitor
• two-component system inhibitor
• vancomycin
• β-lactamase inhibitor

Acknowledgments

The authors would like to thank the reviewers for their useful suggestions and critiques to improve this manuscript.

Notes

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