title: A combination of silver nanoparticles and visible blue light enhances the antibacterial efficacy of ineffective antibiotics against methicillin-resistant Staphylococcus aureus (MRSA).
abstract: BACKGROUND
  Silver nanoparticles (AgNPs) are potential antimicrobials agents, which can be considered as an alternative to antibiotics for the treatment of infections caused by multi-drug resistant bacteria. The antimicrobial effects of double and triple combinations of AgNPs, visible blue light, and the conventional antibiotics amoxicillin, azithromycin, clarithromycin, linezolid, and vancomycin, against ten clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) were investigated.
  
  
  METHODS
  The antimicrobial activity of AgNPs, applied in combination with blue light, against selected isolates of MRSA was investigated at 1/2-1/128 of its minimal inhibitory concentration (MIC) in 24-well plates. The wells were exposed to blue light source at 460 nm and 250 mW for 1 h using a photon emitting diode. Samples were taken at different time intervals, and viable bacterial counts were determined. The double combinations of AgNPs and each of the antibiotics were assessed by the checkerboard method. The killing assay was used to test possible synergistic effects when blue light was further combined to AgNPs and each antibiotic at a time against selected isolates of MRSA.
  
  
  RESULTS
  The bactericidal activity of AgNPs, at sub-MIC, and blue light was significantly (p < 0.001) enhanced when both agents were applied in combination compared to each agent alone. Similarly, synergistic interactions were observed when AgNPs were combined with amoxicillin, azithromycin, clarithromycin or linezolid in 30-40 % of the double combinations with no observed antagonistic interaction against the tested isolates. Combination of the AgNPs with vancomycin did not result in enhanced killing against all isolates tested. The antimicrobial activity against MRSA isolates was significantly enhanced in triple combinations of AgNPs, blue light and antibiotic, compared to treatments involving one or two agents. The bactericidal activities were highest when azithromycin or clarithromycin was included in the triple therapy compared to the other antibiotics tested.
  
  
  CONCLUSIONS
  A new strategy can be used to combat serious infections caused by MRSA by combining AgNPs, blue light, and antibiotics. This triple therapy may include antibiotics, which have been proven to be ineffective against MRSA. The suggested approach would be useful to face the fast-growing drug-resistance with the slow development of new antimicrobial agents, and to preserve last resort antibiotics such as vancomycin.
authors.affiliation: Department of Microbiology, Immunology, and Biotechnology, German University in Cairo, GUC, New Cairo City, Cairo, Egypt.
authors.forename: Fatma Elzahraa
authors.initials: FE
authors.lastname: Akram
authors.affiliation: National Institute for Laser Enhanced Sciences, Cairo University, Cairo, Egypt.
authors.forename: Tarek
authors.initials: T
authors.lastname: El-Tayeb
authors.affiliation: Department of Microbiology, Immunology, and Biotechnology, German University in Cairo, GUC, New Cairo City, Cairo, Egypt.
authors.forename: Khaled
authors.initials: K
authors.lastname: Abou-Aisha
authors.affiliation: Department of Microbiology, Immunology, and Biotechnology, German University in Cairo, GUC, New Cairo City, Cairo, Egypt. mohamed.el-azizi@guc.edu.eg.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Azizi
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology*; D003131:Combined Modality Therapy / Q000379:methods; D004338:Drug Combinations; D004357:Drug Synergism; D008027:Light; D000069349:Linezolid / Q000494:pharmacology; D053768:Metal Nanoparticles / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000528:radiation effects*; D008826:Microbial Sensitivity Tests; D010789:Phototherapy / Q000379:methods; D012834:Silver / Q000494:pharmacology*; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D012834:Silver; D014640:Vancomycin; D000658:Amoxicillin; D017963:Azithromycin; D017291:Clarithromycin; D000069349:Linezolid
keywords: Azithromycin; Checkerboard assay; Clarithromycin; Double and triple combinations; Linezolid; Multidrug-resistance; Nonconventional antimicrobials; Vancomycin