Novel antimicrobial strategies to treat multi‐drug resistant Staphylococcus aureus infections

Abstract

Antimicrobial resistance is a major obstacle for the treatment of infectious diseases and currently represents one of the most significant threats to global health. Staphylococcus aureus remains a formidable human pathogen with high mortality rates associated with severe systemic infections. S. aureus has become notorious as a multidrug resistant bacterium, which when combined with its extensive arsenal of virulence factors that exacerbate disease, culminates in an incredibly challenging pathogen to treat clinically. Compounding this major health issue is the lack of antibiotic discovery and development, with only two new classes of antibiotics approved for clinical use in the last 20 years. Combined efforts from the scientific community have reacted to the threat of dwindling treatment options to combat S. aureus disease in several innovative and exciting developments. This review describes current and future antimicrobial strategies aimed at treating staphylococcal colonization and/or disease, examining therapies that show significant promise at the preclinical development stage to approaches that are currently being investigated in clinical trials.

Improved Antibacterial Activity of 1,3,4-Oxadiazole-Based Compounds That Restrict Staphylococcus aureus Growth Independent of LtaS Function

“…Therefore, more concerted efforts are required to identify alternative Gram-positive and or specific S. aureus targets for the design of therapeutic compounds, which we have recently reviewed. 8 Teichoic acids are glycopolymeric structures that form an integral part of the Gram-positive cell envelope and can either be attached to peptidoglycan as wall teichoic acids or anchored to membrane lipids as lipoteichoic acids (LTAs). 9,10 Both structures have been shown to be important for S. aureus growth and virulence and therefore are considered attractive druggable targets.…”

“…Therefore, more concerted efforts are required to identify alternative Gram-positive and or specific S. aureus targets for the design of therapeutic compounds, which we have recently reviewed …”

Staph wars: the antibiotic pipeline strikes back

“…Also not included are alternatives to antibiotics, such as vaccines, neutralizing antibodies, bacteriophage and anti-virulence strategies. Recent reviews on alternatives to antibiotics currently in the clinical pipeline are provided by Ghosh et al, Douglas et al and Czaplewski et al [236–238]…”

Binding to the immutable targets: a novel strategy to combat surgical-site infections caused by multidrug-resistant superbugs

“…The major risk factors leading to antibiotic resistance include prior antibiotic administrations and previous infections 5 . Among the various bacterial strains causing SSIs, Staphylococcus aureus and Escherichia coli are the widespread ones with resistance ranging from 42.7 to 44.7% and from 13.3 to 15.3%, respectively 6 . Similarly, vancomycin-resistant Enterococci, MDR Enterococci and methicillin-resistant Staphylococcus aureus remain other major concerns 7 .…”

“…Healthcare professionals are shifting towards vancomycin, to treat methicillin-resistant S. aureus . However, uncontrolled use of vancomycin is leading to the development of resistance among S. aureus strains 6 . In this scenario, antibiotic development strategies must be modified.…”