Abstract
BackgroundSilver 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.MethodsThe 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.ResultsThe 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.ConclusionsA 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.
Highlights
Silver nanoparticles (AgNPs) are potential antimicrobials agents, which can be considered as an alter‐ native to antibiotics for the treatment of infections caused by multi-drug resistant bacteria
Vancomycin is the only antibiotic, which showed activity against the tested isolates with MIC90 and MBC90 values of 2 and 8 μg/mL, respectively (Table 2)
The isolates were resistant to linezolid with MIC90 of 32 μg/mL, and to amoxicillin, azithromycin and clarithromycin with MIC90 >64 μg/mL
Summary
Silver nanoparticles (AgNPs) are potential antimicrobials agents, which can be considered as an alter‐ native 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, azithromy‐ cin, clarithromycin, linezolid, and vancomycin, against ten clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Failure of antibiotics to manage infections caused by multidrug-resistant (MDR) pathogens, especially MRSA, has triggered much research effort for finding alternative antimicrobial approaches with higher efficiency and less resistance developed by the microorganisms. Silver has long been known to exhibit antimicrobial activity against wide range of microorganisms and has demonstrated considerable effectiveness in bactericidal applications [4] and silver nanoparticles (AgNPs) have been reconsidered as a potential alternative to conventional antimicrobial agents [5]. The use of AgNPs alone or in combination with other antimicrobial agents has been suggested as a potential alternative for traditional treatment of infections caused by MDR pathogens [5]. AgNPs were found to exhibit antibacterial activity against MRSA in vitro when tested alone or in combination with other antimicrobial agents [8,9,10]
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