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 multi-drug-resistant (MDR) bacterial strains. Although, only a limited number of anti-MRSA drugs are available, a number of different combination antimicrobial drug regimens have been used to treat serious MRSA infections. Thus, addition of several new antistaphylococcal drugs into clinical practice should broaden therapeutic options. Because MRSA is one of the most common and problematic bacteria associated with increasing antimicrobial resistance, continuous efforts on discovery of lead compounds as well as development of alternative therapies and faster diagnostics to ensure effective antistaphylococcal therapy 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 mode of action of antistaphylococcal molecules and resistant mechanisms of some molecules are briefly discussed. Expert opinion The number of pipeline drugs presently undergoing clinical trials is not particularly encouraging. There are limited and rather expensive therapeutic options for the infections by MRSA in the critically ill. This review article provides an update on antistaphylococcal drugs in clinical trials and antibacterial molecules effective against Gram-positive bacteria including MRSA. The structural and biological information of antibacterials summarized here are very useful for designing drug leads to develop into new anti-MRSA drugs.

Staphylococcus aureus: Overview of Bacteriology, Clinical Diseases, Epidemiology, Antibiotic Resistance and Therapeutic Approach

“…The continued efforts of researchers in discovering novel anti-MRSA drugs fructified resulting in arrival of number of newer anti-MRSA drugs for clinical use in the last 15 years [78,[123][124][125]. The following Table 3 lists the newer anti-MRSA drugs that were approved by U.S. FDA for clinical use.…”

A Bright Future for Antibiotics?

“…The methicillin-resistant S. aureus (MRSA) strain is considered to be one of the most common and problematic bacteria associated with increasing antimicrobial resistance. Consequently, continuous efforts are required to discover lead compounds for antistaphylococcal therapy (87). Popular among these efforts are attempts to create libraries of potential drugs by mining underexplored microbial niches or designing chemical probes for improving known molecular scaffolds.…”

Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus

“…antibiotic resistance | potential advanced pleuoromutilin | species specificity | protein biosynthesis T he emergence of bacterial resistance to antibiotics threatens to cause regression to the preantibiotic era, as the treatment of infections with the available arsenal of clinically used antibiotics has been badly affected by the appearance of multidrug-resistant strains (1)(2)(3). Consequently, today many infections are caused by highly resistant bacterial strains of Staphylococcus aureus.…”