Title:Therapeutic Options and Emerging Alternatives for Multidrug Resistant Staphylococcal Infections
VOLUME: 21 ISSUE: 16
Author(s):Maria Magana, Anastasios Ioannidis, Emmanouil Magiorkinis, Oleg Ursu, Cristian G. Bologa, Stylianos Chatzipanagiotou, Michael R. Hamblin and George P. Tegos
Affiliation:Torrey Pines Institute for Molecular Studies, Port St. Lucie, FL, USA; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston MA, USA.
Keywords:MRSA, multidrug resistance, staphylococcal infections, drug discovery.
Abstract:Methicillin-resistant Staphylococcus aureus (MRSA) remains the single biggest challenge in infectious
disease in the civilized world. Moreover, vancomycin resistance is also spreading, leading to fears of untreatable infections as were
common in ancient times. Molecular microbiology and bioinformatics have revealed many of the mechanisms involved in resistance development.
Mobile genetic elements, up-regulated virulence factors and multi-drug efflux pumps have been implicated. A range of approved
antibiotics from the glycopeptide, lipopeptide, pleuromutilin, macrolide, oxazolidinone, lincosamide, aminoglycoside, tetracycline,
steptogramin, and cephalosporin classes has been employed to treat MRSA infections. The upcoming pipeline of drugs for MRSA
includes some new compounds from the above classes, together with fluoroquinolones, antibacterial peptide mimetics, aminomethylciclines,
porphyrins, peptide deformylase inhibitors, oxadiazoles, and diaminopyrimidines. A range of non-drug alternative approaches has
emerged for MRSA treatment. Bacteriophage-therapy including purified lysins has made a comeback after being discovered in the 1930s.
Quorum-sensing inhibitors are under investigation. Small molecule inhibitors of multi-drug efflux pumps may potentiate existing antibiotics.
The relative failure of staphylococcal vaccines is being revisited by efforts with multi-valent vaccines and improved adjuvants.
Photodynamic therapy uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species that can nonspecifically
destroy bacteria while preserving host cells. Preparation of nanoparticles can kill bacteria themselves, as well as improve the
delivery of anti-bacterial drugs. Anti-MRSA drug discovery remains an exciting field with great promise for the future.
