Document 1: Post-1950 Sources Which Demonstrate the Antimicrobial
Properties of Silver
Robert C. Holladay, MS
Copyright 2004 Robert C. Holladay
(1) Thompson, N.R.
1973. Silver. In Comprehensive Inorganic Chemsitry Vol .3.
“The germicidal properties of silver, although not recognized as such, have been utilized since the times of the ancient Mediterranean and Asiatic cultures, references being made to the use of silver vessels to prevent spoilage of beverages, and silver foil or plates in the surgical treatment of wounds and broken bones…To primitive life forms oligodynamic silver is as toxic as the most powerful chemical disinfectants and this, coupled with its relative harmlessness to animate life, gives it great potential as a disinfectant”.
(2) Grier, N.
1983. Silver and Its
compounds. In Disinfection, Sterilization and
Preservation. Third Edition.
In 1887 it was reported that a 1:10000 solution of silver nitrate destroyed highly resistant anthrax spores in 48 hours.
Mild silver protein solutions, and strong protein silver solutions were made using silver oxide and protein. Silver oxide as a colloidal solution was used to treat infections. Metallic silver can serve as a source of silver ions.
“In veterinary medicine, claims have been made that an ionic Ag aerosol, upon inhalation, has protected chickens against coli-bacteriosis and pullorosis-typhus infections…Thus, one may extrapolate to the future and predict a further development and significant place for silver compounds in the prevention and treatment of at least some infectious diseases”. Mechanism of action and silver resistance is discussed.
Comment: Other than the literature written by Robert C. Holladay, this article is the best overall summation of the antimicrobial effectiveness of silver.
(3) Tredget, Edward, et al. 1998. A matched-pair, randomized study evaluating the efficiacy and safety of acticoat silver-coated dressing for the treatment of burn wounds. Journal of Burn Care & Rehabilitation, 19(6), 531-537.
Thirty burn patients were treated with either silver nitrate, or a silver-coated dressing. The silver-coated dressing was more effective in preventing bacterial growth.
(4) Davies, Richard, and Etris, Samuel. 1997. The development and functions of silver in water purification and disease control. Catalysis Today, 36, 107-114.
Silver thiosulfate is effective against E. coli, S. aureus, and HIV-1103. Viruses with sulfhydryl terminuses would react to silver in a fashion similar to bacteria. The antimicrobial mechanism of silver ions is unknown. It is not known how many types of bacteria or viral structures are inactivated by silver. It is not known how many diseases can be successfully treated by silver colloids.
“In recent decades, studies have revealed the biochemical reactions of ionic silver that result in the inactivation of bacteria, fungi, protozoa, spirochetes, viruses, etc…However, the broad use of silver as a powerful clinical tool is still in the future because its full range of activity remains to be elucidated”
Silver becomes far more potent when combined with oxygen. Silver peroxide, a black oxide long marketed as AgO actually consists of Ag4O4. 50%of the silver in Ag4O4 has a charge of +1 and 50% has a charge of +3. Ag+3 is 200 times as effective a disinfectant as Ag+1. In 78 A.D. Pliny the Elder wrote that the slag of silver “has healing properties as an ingredient in plasters, being extremely effective in causing wounds to close up.”
“Tens of thousands of swimming
pools in
Silver nitrate is mentioned in Roman pharmacopoeia written in 69 B.C.
(5) Haeger, Knut. 1963. Preoperative treatment of leg ulcers with silver spray and aluminum foil. Acta Chirurgica Scandinavica, 125, 32-41.
“During the westward migration in the U.S.A., it was widely believed that suspected infection of drinking water could be counteracted by allowing a silver dollar to lie overnight in the water glass.”
Sixteen patients with leg ulcers were treated with a colloidal silver spray. The solution was applied once daily for the first few days, then twice weekly. The infection subsided in all cases. After instruction, patients performed the therapy at home without supervision. No discomfort or side effects were observed. There was no persistent discoloration of the skin that could be attributed to silver.
“in all cases the infection subsided.”
(6) Klasen, H.J. 2000. Historical review of the use of silver in the treatment of burns. Burns. 26: 117-130.
Reviews the use of silver in the treatment of burns.
(7) Romans, I.B.
1954. Oligodynamic
metals. In Antiseptics, Disinfectants, Fungicides, and
Chemical and Physical Sterilization.
The antimicrobial properties of silver are due to the silver ion, and oxidized silver possesses increased antimicrobial capabilities.
Other metallic ions also have antimicrobial characteristics, but are generally inferior to silver. A mixture of several different metal particles can be extremely effective.
Metal particles including lead, silver, and copper, cause hemolysis when placed in human blood.
The silver in silver solutions can adsorb onto glass surfaces.
The antimicrobial properties of a silver solution become inactivated when placed in tap water.
Comment: This article compiles much of the early literature on the antimicrobial effectiveness of silver and other metals. Over 200 references are cited.
(8) Feng, Qing Ling, et al. 1998. Antibacterial effects of Ag-hap thin films on alumina substrates. Thin Solid Films, 335, 214-219.
“An obvious
antimicrobial effect against Escherichia
coli, Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus
epidermidis was observed in the samples treated
with 20 ppm silver nitrate solution. In contrast to this, the untreated samples
did not show any bactericidal effect”.
(9) Lansdown, A.B.G., et al. 1997. Silver aids healing in the sterile skin wound: experimental studies in the laboratory rat. British Journal of Dermatology, 137, 728-735.
15mm wounds were induced on the back skin of young rats. Silver sulphadiazine, silver nylon, and deionized water (control) was applied. Wounds treated with silver nylon or silver sulphadiazine healed faster than controls.
(10) Cason, J.S., et al. 1966. Antiseptic and aseptic prophylaxis for burns: use of silver nitrate and of isolators. British Medical Journal, 1288-1294.
“Controlled trials showed the outstanding prophylactic value of 0.5% silver nitrate compresses to burns…a trial in patients with extensive burns showed Ps. Aeruginosa in 70% of swabs from the control series (treated with penicillin cream), but in only 3.1% of swabs from the series treated with silver nitrate compresses…No toxic effects attributable to silver nitrate were detected”.
(11) Moyer, Carl A. et al. 1965. Treatment of large human burns with 0.5% silver nitrate solution. Archives of Surgery, 90, 812-867.
“An aqueous solution of silver nitrate (0.5%) is an effective bacteriostatic agent in vitro, and on burn wounds in vivo…It is nontoxic to man, and argyria does not occur during or after its continuous application to burn wounds for as long as 120 days. At this concentration, silver nitrate approaches the ideal antiseptic; it prevents the growth of such bacteria as Staphylococcus aureus, Pseudomonas aeruginosa”.
(12) Ricketts, C.R. et al. 1970. Mechanism of prophylaxis by silver compounds against infections in burns. British Medical Journal, 2, 444-446.
“The antibacterial effect was found to depend on the availability of silver ions from solution in contact with precipitate…silver nitrate solution in water was rapidly bactericidal…It seems probable that the outstanding prophylactic effectiveness of silver nitrate compresses is due to the high concentration of silver ions present in the dressings for a short while after each replenishment of silver nitrate solution”.
(13)
“The therapeutic and prophylactic effects of nylon dressings coated with metallic silver in a direct current circuit have been examined in a rat model of fatal burn wound sepsis…Silver nylon dressings placed at 4 hours after inoculation but without applied current showed significant effectiveness…Silver in the form of sulfadiazine or nitrate salt is the most common topical agent used in the treatment of burn wounds…This surface effect is probably due to the limited tissue penetration of silver ions…the availability and limited penetration of silver may be the clinically limiting factor”.
Silver nylon exerted a stronger antimicrobial effect when it was used as a cathode as opposed to an anode.
(14) Russell, A.D., et al. 1994. Antimicrobial activity and action of silver. Progress in Medicinal Chemistry, 31, 351-370.
When molten silver is cooled in hydrogen, it does not possess antimicrobial activity. When cooled in air, silver exhibits antimicrobial activity…The addition of nitric acid to silver enhances its activity…“The general conclusion to be reached from this set of experiments was that pure silver is devoid of activity but that tarnished and/or surface-oxidised silver was active.”
Protein inhibits the action of silver.
Silver protein solutions are antimicrobial because they possess small quantities of silver ions.
Silver ions are bactericidal, antifungal, protozoicidal, and active against herpes simplex virus, but are not effective against spores, cysts of Entamoeba histolytica and mycobacteria.
Ricketts (1970) found that silver cations were bactericidal in water, but not in broth.
Silver will adsorb to surfaces and its antimicrobial action is diminished in the presence of phosphates, chlorides, sulfides and hard water.
Silver and copper ions are effective agents as drinking water and swimming pool disinfectants.
Silver
reacts with sulphydryl groups in bacteria in both
structural and functional proteins.
Silver also produces structural changes in bacteria and interacts with
nucleic acids.
Comment: This source provides an extensive literature review on the mechanism of action of silver and a shorter review on resistance to it. 141 references are cited.
(15) Geronemus, Roy G., Mertz, Patricia M., and Eaglstein, William H. 1979. Wound healing. Archives of Dermatology, 115, 1311-1314.
An experiment was performed in which pigs were given rectangular wounds and different antimicrobial agents were applied. Silver sulfadiazine (Silvadene) is superior to Neosporin and Furacin. “Silvadene promoted healing at the fastest rate of the agents in the study, being 28% faster that the control. Both the agent and its base were significantly faster than the untreated control.”
(16) Kjolseth, Dorthe,
et al. 1994. Comparison of the effects of commonly used
wound agents on epitheliazation and neovascularization. Journal of the
Mice were wounded and six commonly used topical antimicrobial agents were applied: bacitracin, sodium hypochlorite, silver nitrate, silver sulfadiazine, mafenide acetate, and povine-iodine.
“In our model, we found that, of all drugs studied, silver sulfadiazine lead to the most rapid epithelialization and was one of the fastest neovascularizing agents. These findings support most of the aforementioned studies”.
(17) Hamilton-Miller, J.M.T., Shah, Saroj, and Smith, Craig. 1993. Silver sulphadiazine: a comprehensive in vitro reassessment. Chemotherapy, 39, 405-409.
Silver sulphadiazine was applied to 409 strains from 12 different genera of bacteria. Species resistant to multiple antibiotics were uniformly sensitive. No resistant strains were found. The minimum inhibitory concentration was usually in the range of 16-64 ppm. The table below summarizes some of the results.
|
Species |
# of Strains Tested |
MIC in micrograms/ml |
|
Staphylococcus aureus (methicillin resistant) |
97 |
64-128 |
|
Coagulase-negative staphylococci |
20 |
16 |
|
Streptococcus pyogenes |
20 |
8-128 |
|
Enterococci |
20 |
32-128 |
|
Candida Albicans |
20 |
64 |
|
Escheri coli |
20 |
16-32 |
|
Klebsiella pnemoniae |
20 |
32-128 |
|
Enterobacter spp. |
20 |
64-128 |
|
Pseudomonas aeruginosa |
20 |
16-32 |
Numerous
details of experimental procedures were omitted in the 12 publications
describing the in vitro effectiveness
of silver sulphadiazine between 1973 and 1991, and
this casts doubt on the numerical results obtained.
(18) de Boer, P., and Collinson, P.O. 1981. The use of silver sulphadiazine occlusive dressings for finger-tip injuries. The Journal of Bone and Joint Surgery, 63B(4), 545-547.
64 patients with fingertip injuries were treated with either Fucidin gauze or silver sulphadiazine cream. Silver sulphadiazine cream proved to be more effective.
4 patients treated with Fucidin developed sepsis, whereas none of the patients treated with silver sulphadiazine developed sepsis.
(19)
Silver sulphadiazine was applied to fingertip wounds. “21 patients were reviewed between 2 and 8 years after injury…the cosmetic results were good…There were no infections in our group…We recommend this method of treatment”.
(20) Coward, Joe E., Carr, Howard S., and Rosenkranz, Herbert S. 1973. Silver sulfadiazine: effect on the growth and ultrastructure of Staphylococci. Chemotherapy 19, 348-353.
Staphylococcus aureus and S. epidermis are sensitive to levels of silver sulfadiazine that can easily be achieved topically. “There was no relationship between sensitivity to silver sulfadiazine and to sulfadiazine”. The table below lists some of the results.
|
Species |
Strain No. |
AgSu, MIC, micrograms per milliliter |
GM |
CF |
AM |
Te |
C |
Pen |
E |
L |
M |
Su |
|
S. aureus |
1217 |
3.13 |
S |
S |
R |
S |
S |
R |
S |
S |
S |
S |
|
S. aureus |
1222 |
25.0 |
S |
S |
R |
R |
S |
R |
R |
R |
S |
S |
|
S. aureus |
1223 |
25.0 |
S |
S |
R |
S |
S |
R |
S |
S |
S |
S |
|
S. aureus |
1255 |
<0.78 |
S |
R |
R |
S |
S |
R |
R |
R |
R |
R |
|
S. aureus |
1293 |
3.13 |
S |
S |
R |
S |
R |
R |
S |
R |
S |
S |
|
S. epidermis |
1575 |
3.13 |
S |
S |
S |
R |
R |
R |
S |
S |
S |
R |
|
S. epidermis |
1593 |
3.13 |
S |
S |
R |
R |
R |
R |
R |
R |
R |
R |
Abbreviations: MIC= minimal inhibitory concentration; S= sensitive; R= resistant; AgSu= silver sulfadiazine; GM= gentamicin; Cf= cephalothin; AM= ampicillin; Te= tetracycline; C= chloramphenicol; Pen= penicillin G; E= erythromycin; L= lincomycin; M= methicillin; Su= sodium sulfadiazine.
(21) Kulick, Michael I., et al. 1985. Prospective study of side effects associated with the use of silver sulfadiazine in severely burned patients. Annals of Plastic Surgery, 14(5), 407-419.
“Reports of adverse effects associated with silver sulfadiazine are rare…leucopenia has been reported…Previous studies have documented renal tubular damage caused by sulfadiazine…Vilter reported on 116 patients who developed toxic reactions to sulfadiazine…Based on these previous studies, we cannot exclude renal damage and dysfunction owing to direct effects of sulfadiazine. A significant number of patients in our series had antibodies reacting with sulfadiazine”.
(22) Modak, Shanta M., and Fox, Charles L. Jr. 1973. Binding of silver sulfadiazine to the cellular components of Pseudonomas aeruginosa. Biochemical Pharmacology, 22, 2391-2404.
“Silver was bound in considerable amounts, mainly in the fraction containing the cell proteins and carbohydrates…The silver ion appears to be of central importance in the antibacterial effect of silver sulfadiazine…silver sulfadiazine dissociates in the culture medium and only silver is bound to the cells- no binding of sulfadiazine occurs; the antibacterial effect of silver sulfadiazine in vitro against various organisms is practically the same as that of silver nitrate; and while the MIC of silver sulfadiazine is near or identical to that of silver nitrate for most organisms tested, the MIC of sulfadiazine is considerably (200 x) higher”.
(23) Chambers, Cecil W., Proctor, Charles M., and Kabler, Paul W. 1962. Bactericidal effect of low concentrations of silver. Journal of the American Water Works Association, 208-216.
“The germicidal action of a specified amount of silver was found to be related to the concentration of silver ions rather than to the physical nature of the silver from which the ions were originally derived”.
Silver ions adsorb onto glass surfaces.
Exposure to light does not affect the germicidal efficacy of silver ions.
Germicidal capabilities of silver ions are affected by pH.
Phosphate interferes with the germicidal capabilities of silver ions.
(24) Wysor, M.S., and Zollinhofer, R.E. 1973. Silver phosphanilamidopyrimidine. Chemotherapy, 18, 342-347.
“An analogue of silver sulfadiazine, silver phosphanilamidopyrimidine, proved to be as effective as the parent compound in vitro and in vivo”.
(25) Kawahara, K., et al. 2000. Antibacterial effect of silver-zeolite on oral bacteria under anaerobic conditions. Dental Materials, 16, 452-455.
“The MIC of silver zeolite ranged between 256 and 2048 micrograms/ml, which corresponded to a range of 4.8-38.4 micrograms/ml of Ag+”.
The substance was tested against Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, Streptococcus mutans, Streptococcus sangius, Actinomyces viscosus, and Staphylococcus aureus.
Other studies are cited in which silver zeolite has demonstrated antibacterial activity against S. mutans, S. mitis, C albicans, S. aureus, and P. aeruginosa in vitro.
(26) Hamilton-Miller, J.M.T, and Shah, Saroji. 1996. A microbiological assessment of silver fusidate, a novel topical antimicrobial agent. International Journal of Antimicrobial Agents, 7, 97-99.
“Silver fusidate at 1 g/l was bactericidal against eight strains of staphylococci, irrespective of their susceptibility to sodium fusidate…It is thought that the antimicrobial activity of silver sulphadiazine is due to the production of small amounts of free Ag+ by dissociation”.
The table below summarizes some of the test results.
|
Species [no.
tested] |
Antimicrobial
Compound |
MIC (mg/l) |
|
S. pyogenes [20] |
Silver fusidate |
4-16 |
|
|
Silver sulphadiazine |
4-64 |
|
Enterococci [20] |
Silver fusidate |
0.5-8 |
|
|
Silver sulphadiazine |
4-64 |
|
Enterobacter spp. [20] |
Silver fusidate |
32-64 |
|
|
Silver sulphadiazine |
32>128 |
|
K. pnemoniae [20] |
Silver fusidate |
32>128 |
|
|
Silver sulphadiazine |
32-64 |
|
Acinetobacter spp. [20] |
Silver fusidate |
4-32 |
|
|
Silver sulphadiazine |
4-16 |
|
Ps. Aeruginosa [20] |
Silver fusidate |
32 |
|
|
Silver sulphadiazine |
16-32 |
|
Pr. Mirabilis [20] |
Silver fusidate |
32 |
|
|
Silver sulphadiazine |
16-32 |
|
Prov. Stuartii [20] |
Silver fusidate |
32 |
|
|
Silver sulphadiazine |
16-32 |
|
Prov. Morganii [15] |
Silver fusidate |
32 |
|
|
Silver sulphadiazine |
16-32 |
|
Pr. Vulgaris [5] |
Silver fusidate |
32 |
|
|
Silver sulphadiazine |
16-32 |
|
Candida albicans [20] |
Silver fusidate |
128 |
|
|
Silver sulphadiazine |
64 |
(27)
Nylon material coated with silver was tested for antimicrobial action.
“Seven types of bacterial species were tested; S. aureus, E. coli, P. aeruginosa, K. pneumoniae, S. dysenteriae, S. marsuslene, and P. mirabilis…Silver ions released from the coated nylon thread were responsible for the observed antibacterial property; and the application of a weak direct current to the material enhanced this effect…the new material caused less inflammatory reaction than the control suture up to 60 days after implantation…The material exhibited very good to moderate in vitro bactericidal property toward seven bacterial species…The antibacterial property of the material always appeared in the anode site where Ag+ ions were released”.
(28) Speck, William T., and Rosenkranz, Herbert S. 1974. Activity of silver sulphadiazine against dermatophytes. The Lancet, 895-896.
Silver sulfadiazine is effective against fungi. The following table summarizes some of the results.
|
Species |
MIC (micrograms of
SSD/ml) in a liquid medium |
MIC (Micrograms of
SSD/ml) in a plate assay |
|
Microsporum audouinii |
100 |
25 |
|
Microsporum canis |
100 |
50 |
|
Microsporum ferrugineum |
100 |
- |
|
Trichophyton violaceum |
50 |
50 |
|
Trichophyton verrucosum |
50 |
50 |
|
Epidermophyton floccosum |
1.6 |
50 |
(29) Wlodkowski, Theodore J., and Rosenkranz, Herbert S. 1973. Antifungal activity of silver sulfadiazine. The Lancet, 739-740.
Silver sulfadiazine is effective against fungi. The following table summ