Functional medicine providers are always searching for silver linings in medical research to share with their patients. In this case, the silver lining is literal: silver nanoparticles have been found to synergize with a class of somewhat toxic antibiotics, making it easier to use the antibiotics at a lower dose. Building on the centuries long recognition that silver exerted antimicrobial properties, researchers applied contemporary nanotechnology to potentially improve their effects. Combined with the aminoglycoside antibiotics, a 22-fold reduction in the dose of the antimicrobial could be used, avoiding the medications side effect risk.
Aminoglycosides like gentamicin come in handy for some difficult to treat drug resistant infections but have a variety of concerning side effects. Hearing loss and kidney damage are two of the more dangerous effects. Pharmacists and doctors have searched for the right doses to allow success against a number of infections without leaving permanent damage to the patient. Any approach that enables a lower dose of these drugs without sacrificing efficacy would enable easier and safer therapy for numerous dangerous infections.
Silver stands out as a relatively safe antimicrobial used over the centuries, but which declined in use with the advent of antibiotics in the 1940’s. Various uses have included and still include implanting silver on medical implants as an antimicrobial surface and to treat burn wounds. With the increase in drug resistant bacteria and the dearth of new antibiotics to combat them, silver has reemerged as a potential therapy (Franci et al. 2015). Drug resistant bacteria like Acinetobacter, Pseudomonas, Listeria, Klebsiella, Enterobacter and others are needing effective therapies.
Prior research has not pinpointed the exact mechanism of antimicrobial activity for silver. Many suspect different possible mechanisms. Some believe silver targets the cell membranes (Jung et al., 2008; Bondarenko et al, 2018). Some believe it targets the ribosomes where proteins are made (Yamanaka et al, 2005). Some evidence points to a contribution of silver to the generation of oxidative species that damage the DNA and proteins of bacteria (Park et al, 2009). Of note, the size and shape of silver nanoparticles seem to affect their antibacterial powers. Smaller spherical particles, along with triangular particles, seem to be the best (Pal et al, 2007; Raza et al, 2016; Dong et al, 2019)
In prior studies, these silver nanoparticles were able to enhance the effectiveness of several other antibiotic classes. These includes penicillin, amoxicillin, clindamycin, vancomycin, erythromycin, cefixime, and imipenem (Shahverdi et al, 2007; Naqvi etal., 2018; Ali et al., 2020). The current study in focus looked at the synergy of silver nanoparticles with the aminoglycoside class of antibiotics against several different bacteria. They found that on average a 22-fold reduction in the dose of the aminoglycoside could be used to combat the infections. While the efficacy was increased, there appeared to be no signficant toxicity in the model. This opens up a lot of possibilities for treating some drug resistant life-threatening infections.
Finding silver linings in old-fashioned silver makes a lot of sense. Combining old-fashioned silver with newer nanotechnology also makes sense. By making the actual particle size of the silver smaller and smaller, we improve the efficacy and also avoid the fact that even a natural substance like silver can eventually cause toxic effects. Overdosing on silver can lead to blue-man syndrome in which the silver deposits in the skin turning it gray-blue. This can be permanent unless a very long process of detoxification is applied. Our suggestion… don’t take any old sliver off the silver. Get guidance from a knowledgeable practitioner and use only when necessary. Helping our patient live healthier more abundant lives requires using the right therapies in the right ways at the right times. As we do so, we love silver linings like this research.
Autumn S. Dove, Dominika I. Dzurny, Wren R. Dees, Nan Qin, Carmen C. Nunez Rodriguez, Lauren A. Alt, Garrett L. Ellward, Jacob A. Best, Nicholas G. Rudawski, Kotaro Fujii, Daniel M. Czyż. Silver nanoparticles enhance the efficacy of aminoglycosides against antibiotic-resistant bacteria. Frontiers in Microbiology, 2023; 13 DOI: 10.3389/fmicb.2022.1064095
Thanks to Science Daily:
University of Florida. “Silver nanoparticles show promise in fighting antibiotic-resistant bacteria.” ScienceDaily. ScienceDaily, 31 January 2023. <www.sciencedaily.com/releases/2023/01/230131183142.htm>.
Ali, S., Perveen, S., Shah, M. R., Zareef, M., Arslan, M., Basheer, S., et al. (2020). Bactericidal potentials of silver and gold nanoparticles stabilized with cefixime: a strategy against antibiotic-resistant bacteria. J. Nanopart. Res. 22:201. doi: 10.1007/s11051-020-04939-y
Bondarenko, O. M., Sihtmäe, M., Kuzmičiova, J., Ragelienė, L., Kahru, A., and Daugelavičius, R. (2018). Plasma membrane is the target of rapid antibacterial action of silver nanoparticles in Escherichia coli and Pseudomonas aeruginosa. Int. J. Nanomedicine 13, 6779–6790. doi: 10.2147/ijn.S177163
Dong, Y., Zhu, H., Shen, Y., Zhang, W., and Zhang, L. (2019). Antibacterial activity of silver nanoparticles of different particle size against Vibrio natriegens. PLoS One 14:e0222322. doi: 10.1371/journal.pone.0222322
Franci, G., Falanga, A., Galdiero, S., Palomba, L., Rai, M., Morelli, G., et al. (2015). Silver nanoparticles as potential antibacterial agents. Molecules 20, 8856–8874. doi: 10.3390/molecules20058856
Jung, W. K., Koo, H. C., Kim, K. W., Shin, S., Kim, S. H., and Park, Y. H. (2008). Antibacterial activity and mechanism of action of the silver ion in Staphylococcus aureus and Escherichia coli. Appl. Environ. Microbiol. 74, 2171–2178. doi: 10.1128/aem.02001-07
Naqvi, S. Z. H., Kiran, U., Ali, M. I., Jamal, A., Hameed, A., Ahmed, S., et al. (2013). Combined efficacy of biologically synthesized silver nanoparticles and different antibiotics against multidrug-resistant bacteria. Int. J. Nanomedicine 8, 3187–3195. doi: 10.2147/IJN.S49284
Pal, S., Tak, Y., and Song, J. (2007). Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the gram-negative bacterium Escherichia coli. Appl. Environ. Microbiol. 73, 1712–1720. doi: 10.1128/aem.02218-06
Park, H.-J., Kim, J. Y., Kim, J., Lee, J.-H., Hahn, J.-S., Gu, M. B., et al. (2009). Silver-ion-mediated reactive oxygen species generation affecting bactericidal activity. Water Res. 43, 1027–1032. doi: 10.1016/j.watres.2008.12.002
Raza, M. A., Kanwal, Z., Rauf, A., Sabri, A. N., Riaz, S., and Naseem, S. (2016). Size- and shape-dependent antibacterial studies of silver nanoparticles synthesized by wet chemical routes. Nanomaterials (Basel) 6:74. doi: 10.3390/nano6040074
Shahverdi, A. R., Fakhimi, A., Shahverdi, H. R., and Minaian, S. (2007). Synthesis and effect of silver nanoparticles on the antibacterial activity of different antibiotics against Staphylococcus aureus and Escherichia coli. Nanomedicine 3, 168–171. doi: 10.1016/j.nano.2007.02.001
Yamanaka, M., Hara, K., and Kudo, J. (2005). Bactericidal actions of a silver ion solution on Escherichia coli, studied by energy-filtering transmission electron microscopy and proteomic analysis. Appl. Environ. Microbiol. 71, 7589–7593. doi: 10.1128/AEM.71.11.7589-7593.2005
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.