title: Therapeutic options and emerging alternatives for multidrug resistant staphylococcal infections.
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.
authors.forename: Maria
authors.initials: M
authors.lastname: Magana
authors.forename: Anastasios
authors.initials: A
authors.lastname: Ioannidis
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Magiorkinis
authors.forename: Oleg
authors.initials: O
authors.lastname: Ursu
authors.forename: Cristian G
authors.initials: CG
authors.lastname: Bologa
authors.forename: Stylianos
authors.initials: S
authors.lastname: Chatzipanagiotou
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
authors.affiliation: Torrey Pines Institute for Molecular Studies, Port St. Lucie, FL, USA; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston MA, USA. gtegos@mgh.harvard.edu.
authors.forename: George P
authors.initials: GP
authors.lastname: Tegos
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000494:pharmacology / Q000627:therapeutic use; D001435:Bacteriophages / Q000502:physiology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D001428:Bacterial Vaccines