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Document 1: Post-1950 Sources Which Demonstrate the Antimicrobial Properties of Silver

May 3, 2004

Robert C. Holladay, MS

Copyright 2004 Robert C. Holladay

 

(1) Thompson, N.R.  1973.  Silver.  In Comprehensive Inorganic Chemsitry Vol .3.  New York, Pergamon, 79-80.

            “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.  Philadelphia, Lea & Febiger, 375-389.

            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 Europe and the United States have used electrically driven silver-copper ion systems to provide satisfactory sanitation for decades.”

            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.  Philadelphia, Lea & Febiger, 388-428.

            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) Chu, Chi-sing et al.  1988.  Therapeutic effects of silver nylon dressings with weak direct current on Pseudonomas aeruginosa-infected burn wounds.  The Journal of Trauma, 28(10), 1488-1492.

            “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 American College of Surgeons, 179,  305-312.

            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) Buckley, S.C., Scott, S., and Das, K.  2000.  Late review of the use of silver sulphadiazine dressings for the treatment of fingertip injuries.  Injury, International Journal of the Care of the Injured, 31, 301-304.

            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 fusidateIt  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) Chu, C.C., et al.  1987.  Newly made antibacterial braided nylon sutures.  In vitro qualitative and in vivo preliminary biocompatibility study.  Journal of Biomedical Materials Research, 21, 1281-1300.

            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 summarizes some of the results.

Species

MIC (micrograms of silver sulfadiazine per milliliter)

Aspergillus fumigatus

100

Mucor pusillus

50

Rhizopus nigricans

100

            None of the strains was inhibited by sodium sulfadiazine.

 

(30) Miller, Lawrence P., and McCallan, S.E.A.  1957.  Toxic action of metal ions to fungus spores.  Agricultural and Food Chemistry, 5(2), 116-122.

            “Silver is taken up rapidly by fungus spores, so that germination can be completely inhibited after a contact time of 1 minute or less.  Only mercury(I) and (II), and to a lesser extent copper, offer serious competition”.

 

(31) Slade, S.J., and Pegg, G.F.  1993.  The effect of silver and other metal ions on the in vitro growth of root-rotting Phytophthora and other fungal species.  Annals of Applied Biology, 122, 233-251.

            Silver was the most toxic ion to zoospores of Phytophthora nicotianae parasitica. Nickel, cobalt, zinc and copper ions were also tested.  The LD50 for Ag+ was 11.4ppb.  “Silver was similarly toxic to a range of pathogens including Pythium aphanidermatum, Thielaviopsis basicola and Fusarium oxysporum f.spp.  Most zoospores of phytophthora spp. Were killed by Ag+ in the range 5-50 ppb, bursting at the higher concentrations”.  All zoospores  of nicotianae parasitica were killed at an Ag+ concentration of 500 ppb.  A population of P. cryptogea were all killed at 100 ppb Ag+.  “Zoospore cysts and germlings showed the same sensitivity to silver.  Oospores were mostly killed over the range 25-100 ppb…Ionic silver was lost from solution during a microscope slide bioassay by binding to the glass surface…It is surprising that no silver-based fungicide has been developed”. 

 

(32) Scalzo, M., et al.  1996.  Antimicrobial activity of electrochemical silver ions in nonionic surfactant solutions and in model dispersions.  Journal of Pharmacy and Pharmacology, 48, 60-63.

            Electrically generated silver ions were introduced to the following microorganisms: E. coli, P. aeruginosa, S. epidermidis, C albicans.

            “The wide antimicrobial spectrum, the high microbicidal potency, the good water solubility and the safety of anodic silver, therefore, provide an encouraging background to the investigation of the use of this ion as a preservative in pharmaceutical or cosmetic formulations…The high rate of kill of anodic silver is very useful to ensure a rapid reduction of microorganisms.  However, the effectiveness of silver in keeping the number of surviving organisms at less than 0.01% of the starting inoculum after repeated inocula, even in the presence of strong interfering additives, appears the most interesting feature for its possible use as a preserving agent in multiple-dose products”.

 

(33) Chang, Te-Wen, and Weinstein, Louis.  1975.  In vitro activity of silver sulfadiazine against Herpesvirus hominis.  The Journal of Infectious Diseases, 132(1), 79-81.

            “Silver sulfadiazine at a concentration of 10 micrograms/ml suppresses or completely inactivates the infectivity of Herpesvirus hominis…Because sulfadiazine does not have antiviral activity, the inhibitory activity of the silver salt of this agent is probably related to the presence of the silver ion…Silver sulfadiazine has been shown to be effective in the prevention of herpetic keratoconjunctivitis and encephalitis in rabbits…Because of the wide spectrum of antimicrobial activity (Treponema, yeast, Neisseria gonorrhoeae, and Herpesvirus), the use of silver sulfadiazine as a prophylactic agent for genital infections merits serious considerations”.

 

(34) Chang, Te-Wen, and Weinstein, Louis.  1975.  Prevention of Herpes Keratoconjunctivitus in rabbits by silver sulfadiazine.  Antimicrobial Agents and Chemotherapy, 8(6), 677-678.

            “Silver sulfadiazine, at a concentration of 10 micrograms/ml when applied immediately after infection by Herpesvirus hominis, prevented the development of acute herpetic keratoconjunctivitis in rabbits”.

 

(35) Tokumaru, T., Shimizu, Y., and Fox, C.L. Jr.  1974.  Antiviral activities of silver sulfadiazine in ocular infection.  Research Communications in Chemical Pathology and Pharmacology, 8(1), 151-158.

            “Among viruses affecting the eyes, herpes simplex (HSV) and vesicular stomatitis viruses (VSV) were found to be susceptible to direct inactivation by this compound.  At 1 microgram/ml it suppressed HSV growth I tissue culture…In the rabbit eye, infection by Pseudomonas aerugionsa was suppressed by similar applications of AgSD”.

 

(36) Chang, Te-Wen, and Weinstein, Louis.  1975.  Inactivation of Treponema pallidum by silver sulfadiazine.  Antimicrobial Agents and Chemotherapy, 7(5), 538-539.

            6.2 micrograms/ml of silver sulfadiazine completely inactivated T. pallidum in 30 minutes.  “At 37 C, the amounts of silver sulfadiazine required for inactivation were two- to fourfold less” (than at 28 degrees C)

 

(37) Montes, Leopoldo F., Muchinik, Guillermo, and Fox, Charles L.  1986.  Response of varicella zoster virus and herpes zoster to silver sulfadiazine.  Cutis, 38, 363-365.

            Silver sulfadiazine inactivates the infectivity of varicella zoster virus.  “At a concentration of 10 micrograms/ml or higher the virus was inactivated after thirty minutes…Forty-two patients with herpes zoster were treated topically with 1 percent silver sulfadiazine cream applied four times a day.  All patients experienced complete drying of vesicles, marked reduction of erythema and edema, and striking elimination of pain and burning sensation within twenty-four to seventy-two hours…Because sulfadiazine alone does not have known antiviral activity, the inhibitory action of the silver salt of sulfadiazine is believed to be related to the presence of the silver ion”.

 

(38) Hussain, Saber, Anner, Rolf M., and Anner, Beatrice M.  1992.  Cysteine protects Na, K-ATPase and isolated human lymphocytes from silver toxicity.  Biochemical and Biophysical Research Communications, 189(3), 1444-1449.

            “Metal-binding proteins are important components of retroviruses such as human immunodeficiency  virus (HIV).  Therefore, metals could be used as antiviral agents.  However, most metals are toxic for humans with the exception of silver which is toxic only to prokaryotic cells and viruses…Thus, non-toxic silver cysteine could be used as an anti-viral and cysteine-replenishing agent…silver is a highly active bactericidal metal with little toxicity for humans.  Silver has also been shown to be a potent inhibitor of HIV protease…silver is expected to interact potently with HIV proteins and to interrupt thereby the cellular replication of HIV at various stages such as interaction with surface receptors, gene expression or cellular biosynthesis of viruses.  Possible therapeutic forms of silver-cysteine and evalutation of this new compound in cells from patients infected with HIV remain to be investigated”.

 

(39) Bogdanchikova, N.Y., et al.  1992.  Activity of colloidal silver preparations against variolovaccine virus.  Khimiko-Farmatsevticheskii Zhurnal, 26(9-10), 90-91.

            This article is in Russian but it has an English abstract which states: “The drugs of colloidal silver collargol and protargol were found to have activity against smallpox virus…silver metal particles may make a great contribution to the mechanism responsible for antiviral effects”.  The same authors published the following article:

 

(40) Bogdanchikova, N.Y., et al.  1992.  Activity of colloidal silver preparations toward smallpox.  Pharmaceutical Chemistry Journal, 26(9-10), 778.

            “The drugs of colloidal silver collargol and protargol were found to have activity against the smallpox virus.  The activity of the drugs which was calculated per unit weight of silver was equal…It is suggested from the calculated activity ratio that silver metal particles may make a great contribution to the mechanism responsible for antiviral effects.”

Comment: Russian article with English abstract.

 

(41) Simonetti, N., et al.  1992.  Electrochemical Ag+ for preservative use.  Applied and Environmental Microbiology, 58(12), 3834-3836.

            Ag+ was tested against the following microorganisms: E. coli, P. aeruginosa, C Albicans, A. niger. 

            “Ag+ solutions exhibited better antimicrobial effectiveness against bacteria, a yeast species, and a mold than did analogous silver solutions from inorganic salts(silver nitrate and silver chloride)…Ag+ could be used effectively in preservatives…the microbicidal activity of silver is significantly ion influenced ”.

            A method of manufacturing colloidal silver and testing it for silver content is described.

 

(42) Bosetti, M., et al.  2002.  Silver coated materials for external fixation devices: in vitro biocompatibility and genotoxicity.  Biomaterials, 23, 887-892.

            “The hypothesis that coating a pin with a silver-containing compound will decrease colonization and/or pin tract infection has been confirmed in other studies in vitro and in vivo experiments…These studies have shown that silver is neither gentoxic or cytotoxic as compared to stainless steel, a material widely used as a metal implant…Silver has long been known to be a potent antibacterial agent with a very broad spectrum of activity and has been used safely in medicine for many years”.    

 

(43) Deitch, Edwin A., et al.  1983.  Silver-nylon: a new antimicrobial agent.  Antimicrobial Agents and Chemotherapy, 23(3), 356-359.

            “On the basis of these experiments, it appears that silver nylon is an effective antimicrobial agent…We presume that the release of silver ions from the silver nylon fabric was the basis of the antimicrobial action of silver nylon…Although the bacteriostatic and bacteriocidal sensitivity of organisms to silver vary widely, they are generally in the range of 10 to 20 micrograms/ml…Silver is not associated with significant side effects, is not an allergen, and is only rarely associated with the induction of resistant strains of bacteria”.

 

(44) Marino, Andrew A., et al.  1984.  Electrical augmentation of the antimicrobial activity of silver-nylon fabrics.  Journal of Biological Physics, 12, 93-98.

            Silver nylon exerted an antimicrobial effect on the following microorganisms: Pseudonomas aeruginosa, Staphylococcus aureus, and Candida albicans.

            “A significant enhancement of the fabrics’ antimicrobial effect was achieved by the passage of weak DC currents, which cause increased liberation of silver ions”.

 

(45) Tsai, W.C., et al.  1987.  In vitro quantitative study of newly made antibacterial braided nylon sutures.  Surgery, Gynecology & Obstetrics, 165, 207-211.

            “The previously demonstrated antibacterial property of the newly made silver compound coated nylon thread toward a wide range of bacterial species was further confirmed in the present quantitative study…This further supports the concept that it is the silver ions, not their associated compounds which possess or are largely responsible for this antibacterial property”.

 

(46) Falcone, Alfred E., and Spadaro, Joseph A.  1986.  Inhibitory effects of electrically activated silver material on cutaneous wound bacteria.  Plastic and Reconstructive Surgery, 77(3), 455-458.

            “Electrically activated silver-coated fabric can effectively inhibit a number of bacterial species commonly found in cutaneous ulcers.  Electrical activation in all cases in our study increased the tendency for spontaneous inhibition of bacterial growth by the silver ion”.

 

(47) Deitch, Edwin A., et al.  1987.  Silver nylon cloth: In vitro and in vivo evaluation of antimicrobial activity.  The Journal of Trauma, 27(3), 301-304.

            “the antimicrobial effect of a silver compound is due to the constant presence of free silver ions in the local wound environment…Additionally, since silver ions released from a silver fabric would not be accompanied by a carrier molecule or anion, there would not be any associated potential side effects due to the carrier molecule, such as occurs with both silver nitrate and silver sulfadiazine”.

 

(48) Wright, J.B., et al.  1999.  Efficacy of topical silver against fungal burn wound pathogens.  American Journal of Infection Control, 27(4), 344-349.

            Topical silver was applied to Candida albicans, Candida glabrata, Candida tropicalis, and Saccharomyces cerevisiae.

            “Silver, a well-known antimicrobial agent, has been used in clinical settings for more than a century.  During this period, the safety of this agent has been well established…In addition to being effective against fungi, this method of silver application has also been demonstrated to be effacious against a broad spectrum of bacteria, including antibiotic-resistant strains…The results of the current study demonstrate the excellent in vitro performance of silver, particularly the nanocrystalline form, against a variety of common fungal pathogens.  The most remarkable aspect of the fungicidal experiments is that nanocrystalline silver appears to be effective against the resistant spores produced by some of these organisms”.

 

(49) Wright, J. Barry, Lam, Kan, and Burrell, Robert E.  1998.  Wound management in an era of increasing bacterial antibiotic resistance: a role for topical silver treatment.  American Journal of Infection Control, 26(6), 572-577.

            “To be bactericidal, the silver must be available as a solution, and the efficiacy of the solution is dependent on the concentration of silver ions present in the solution…silver is effective against a broad range of antibiotic-resistant organisms, which is expected because silver has been regularly found to be effective against antibiotic-resistant organisms”.

 

(50) Becker, Robert O., and Spadaro, Joseph A.  1978.  Treatment of orthopaedic infections with electrically generated silver ions.  The journal of Bone and Joint surgery, 60-A(7), 871-881.

            A silver wire was placed in an infected area of the bone, and electric current was applied which released silver ions.

            “Electrically generated silver ions have been shown previously to be a potent antibacterial agent with an exceptionally broad spectrum...The present study reports on clinical experience using electrically generated silver ions as adjunctive treatment in the management of chronic osteomyelitis…wound care (usually provided by the patient) resulted in control of the infection in twelve of the fifteen treatment attempts and in healing of the non-union after follow-up ranging from three to thirty-six months…In this small series, the silver ions seemed to have been an effective local antibacterial agent with advantages over other antibiotics that included: activity against all of the bacterial types encountered in these patients, negligible toxic effect on local tissues, and penetration of poorly vascularized tissue to the distance believed to be about one centimeter…the rapid subsidence of the infection once treatment with silver ions was initiated convinced us that the silver iontophoresis had had a beneficial antibacterial effect…An added benefit, which was unexpected, was the deposition of substantial amounts of new bone produced during treatment with the silver-nylon anode”.

 

(51) Nand, Sanjiv, et al.  1996.  Dual use of silver for management of chronic bone infections and infected non-unions.  Journal of the Indian Medical Association, 94(3), 91-95.

            A wire was placed in an infected wound and electric current was applied which released silver ions into the infected wounds of  920 patients with chronic osteomyelitis.

            “Broad spectrum antibacterial effect of electrically generated silver ions has been fully established…920 proved cases of chronic osteomyelitis with or without pathological fractures and septic non-unions…wound care yielded not only control of bone infections in 85% of cases, but also produced healing of pathological fractures in 83% of patients…In the present series, silver ions have been used as an effective local antibacterial agent with multiple advantages over many conventionally used methods with or without antibiotics.  Silver ions are not only effective in different cases, where bacteria had become resistant to most of the commonly used antibiotics but also have only negligible toxic effects on tissues…No patient was subject to this treatment without waiting for outcome from previous treatment”.

 

(52) Webster, Dwight A. et al.  1981.  Silver anode treatment of chronic osteomyelitis.  Clinical Orthopaedics and Related Research.  161: 105-114.

            25 patients with chronic bone infections who had received extensive conventional treatment unsuccessfully were used in this study.  Many of them were candidates for amputation and they had received an average of 4.1 prior operations.  Silver nylon was placed in the wound and electric current was applied to the silver nylon.  The electric current provided a constant supply of silver cations, which was necessary because silver ions react with chloride and proteins.  At the end of the study, 16 patients had healed, with no pain or drainage and a completely closed wound.  6 patients had not healed and were still receiving treatment, and 3 had received amputations.  Side effects were not seen.

            “The silver cation is known to have an exceptionally broad spectrum involving gram-positive, gram-negative, aerobic and anaerobic microorganisms.  A number of species have been found to have a minimum inhibitory concentration for anode-derived silver considerably lower than antibiotics in current use, and resistance to silver ions is rare.”   

 

(53) Becker, Robert O.  2000.  Effects of electrically generated silver ions on human cells and wound healing.  Electro- and Magnetobiology, 19(1), 1-19.

            “A method of producing local antibiotic effects by means of an iontophoretic technique using free silver ions has been evaluated in vitro and in vivo for more than two decades.  The antibiotic properties of the technique have proved useful in both animal and human studies…Beginning in 1973, in vitro studies demonstrated that such ions were an effective antibiotic with a very broad spectrum and favorable quantitative evaluations compared with synthetic antibiotics…The failure of other nontoxic metal ions to produce a similar alteration with the same electrical parameters strongly indicates that the electrically generated silver ion is the agent responsible for the observed cellular changes…Healing rates in these wounds are significantly accelerated and are accompanied by enhanced healing of the bone, soft tissue, nerve, and skin, with replacement of missing tissues by histologically normal tissues…The responsible agent for these cellular effects is believed to be the electrically generated silver ion”.

 

(54) Woodward, Richard L.  1963.  Review of the bactericidal effectiveness of silver.  Journal of the American Water Works Association, 55, 881-886.

            “Several properties of silver require special attention in studies of its bactericidal effectiveness.  A failure to appreciate this and to use appropriate technique probably accounts for many but not all of the contradictory results reported by various researchers.  Silver has a marked tendency to adsord on surfaces.  This can interfere seriously with any careful bacteriologic work”.

 

(55) Spadaro, J.A., et al.  1974.  Antibacterial effects of silver electrodes with weak direct current.  Antimicrobial Agents and Chemotherapy, 6(5), 637-642.

            Electrically generated silver ions were applied to S. aureus E. coli, P. vulgaris, and P. aeruginosa.  Silver ions were more effective at inhibiting bacteria than platinum, gold, copper and stainless steel ions.

            “Thus, it appears as if the electrically injected Ag ion is at least as effective as that carried by silver sulfadiazine…Finally, this study suggests that electrochemically injected silver ions in nanomolar concentrations be considered for further testing and for possible use as a “topically” applied bacteriostatic treatment for infections of poorly vascularized areas such as burns, chronic skin ulcerations, and osteomyelitis.  Advantages may include a greater depth of tissue penetration compared with the simple diffusion resulting from the topical applications of silver sulfadiazine, as well as the obviating need for the accompanying sulfonamide with its possible toxic reactions”.

 

(56) Berger, T.J., et al.  1976.  Antifungal properties of electrically generated metallic ions.  Antimicrobial Agents and Chemotherapy, 10(5), 856-860.

            Silver, copper, zinc, and titanium wires were placed in dishes containing microorganisms, and electric current was applied.  Silver ions were the most effective at inhibiting the microorganisms.  The application of electrically generated silver to several fungal species is summarized in the table below.

Microorganism

MIC of Anodic Ag in micrograms/ml

Candida parapsilosis

4.7

Torulopsis glabrata

1.6

C. albicans I

0.5

C. albicans II

3.5

“There is now strong evidence in the literature that the active component of any silver compound is the silver itself…The data show that electrically generated silver cations are more effective than silver sulafadiazine or silver nitrate”.

 

(57) Berger, T.J., et al.  1976.  Electrically generated silver ions: quantitative effects on bacterial and mammalian cells.  Antimicrobial Agents and Chemotherapy, 9(2), 357-358.

            Electrically generated silver ions were applied to several microorganisms and the MIC was 10 to 100 times lower than silver sulfadiazine.  Effects on mammalian cells were minimal.  The table below summarizes some of the data.

Organism

Strain identification no.

MIC of anodic Ag in micrograms/ml

MIC of silver sulfadiazine in micrograms/ml

Escherichia coli

ATCC 25922

0.50

 

E. coli

Dental

1.03

3.13

Providencia stuartii

A 21471

0.13

12.50

Proteus mirabilis

Clinical

0.08

1.56

Pseudonomas aeruginosa

ATCC 27853

0.31

1.56

Serratia

386 A

0.08

3.13

Staphylococcus albus

Dental

0.12

 

S. aureus

ATCC 25923

0.03

 

S. aureus

Dental

0.25

25

Streptoccocus group D

296

0.63

50

S. mitis

Dental

0.31

 

Mouse bone marrow cells were exposed to 4 micrograms/ml Ag.  Detrimental effects to the cells were not seen.  With exposure to silver, there was a slight different in types of cells arising from the bone marrow cells.

 

(58) Kusnetsov, Jaana, et al.  2001.  Copper and silver ions more effective against legionellae than against mycobacteria in a hospital warm water system.  Water Research, 35(17), 4217-4225.

            “Silver ion concentration of about 3 micrograms/liter was sufficient to control the growth of legionellae in circulating warm water”.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                

 

(59) Slawson, R.M., et al.  1992.  Germanium and silver resistance, accumulation, and toxicity in microorganisms.  Plasmid, 27, 72-79.

            Mechanism of antimicrobial action of the silver ion and silver resistance is reviewed extensively.  Different laboratory conditions used in assessing the antimicrobial properties of metals makes the literature difficult to compare.  Different growth media or buffers can have a significant impact on the results of various researchers.   

 

(60) Kushner, D.J.  1971.  Influence of solutes and ions on microorganisms.  In Inhibition and Destruction of the Microbial Cell.  New York, Academic Press, 279-280.

            Antimicrobial activities of several metallic ions are discussed.

 

(61) Doul, J.  1986.  Toxic effects of metals.  In Casarett and Doull’s Toxicology, The Basic Science of Poisons.  Third Edition.  New York, Macmillan, 625.

            “The use of silver nitrate for prophylaxis of opthalmia neonatorum is a legal requirement in some states.”

 

(62) Richards, R.M.E.  1981.  Antimicrobial action of silver nitrate.  Microbios, 31, 83-91.

            “Silver nitrate 3 micrograms/ml prevented the separation into two daughter cells of sensitive dying cells of Pseudomonas aeruginosa growing in nutrient broth plus the chemical.  Cell size of sensitive cells was increased and the cytoplasmic contents, cytoplasmic membrane and external cell envelope structures were all abnormal.”

 

(63) Pruitt, Basil A. Jr.  1987.  Opportunistic infections in burn patients: diagnosis and treatment.  In New Surgical and Medical Approaches in Infectious diseases.  New York, Churchill Livingstone, 245.

            “Infection is the most frequent cause of morbidity and mortality following burns”

 

(64) Fox, Charles L. Jr.  1968.  Silver sulfadiazine-a new topical therapy for Pseudomonas in burns.  Archives of Surgery, 96, 184-188.

            Mice with burns experienced a lower mortality rate when treated with silver sulfadiazine instead of sulfadiazine, mafenide, 0.9% sodium chloride, and other silver products.

 

(65) Rosenkranz, Herbert S., and Carr, Howard S.  1972.  Silver sulfadiazine: effect on the growth and metabolism of bacteria.  Antimicrobial Agents and Chemotherapy, 2(5), 367-372.

            “Although silver sulfadiazine binds to purified DNA the present findings indicate that no such binding occurred when living bacteria were exposed to silver sulfadiazine…the principal evidence suggests that DNA is not primarily involved in the action of silver sulfadiazine…Most of the present data indicate that silver sulfadiazine was bound to the cell membrane fraction with some silver sulfadiazine bound to cell wall material.  It is known that the cell membrane plays a crucial role in controlling DNA and RNA synthesis.  It is not surprising, therefore, that an agent which affects the cell membrane should also cause a halt in the synthesis of DNA and RNA (and subsequently proteins).”

 

(66) Coward, Joe E. and Rosenkranz, Herbert S.  1975.  Electron microscopic appearance of silver sulfadiazine-treated Enterobacter clocae.  Chemotherapy 21, 231-235.

            Silver sulfadiazine exerts its antimicrobial ability by affecting the cell envelope.

 

(67) Kucan, John O., and Smoot, E. Clyde.  1989.  Topical antibacterials and soft-tissue wounds.  Surgical Rounds, April, 60-70.

            “The most commonly used topical antibacterial agent worldwide is silver sulfadiazine cream.”

 

(68) Rosenkranz, Herbert S., and Carr, Howard S.  1978.  The determination of the susceptibility of bacterial isolates to silver sulfadiazine.  Chemotherapy, 24, 143-145.

            “Silver sulfadiazine is a topical antimicrobial agent with a broad spectrum of activity against fungi as well as gram-positive and gram-negative bacteria.”

 

(69) Klasen, H.J.  2000.  A historical review of the use of silver in the treatment of burns, renewed interest for silver.  Burns, 26, 131-138.

            “Silver sulphadiazine was a combined formulation made from silver nitrate and sodium sulphadiazine by substituting a silver atom for a hydrogen atom in the sulphadiazine molecule…Temporary leucopenia is observed from time to time during silver sulphadiazine treatment.  The leucopenia usually begins two to three days after the start of the treatment and disappears spontaneously as the treatment is continued…Silver sulphadiazine had a cytotoxic effect on cultured bone marrow cells.  Gamelli et al. concluded on the basis of their study that silver sulphadiazine gave rise to changes in the myeloid cell compartment, with the hypothesis that the temporary leucopenia in burns patients treated with silver sulphadiazine might be a result of this.”

            Silver sulfadiazine is still the most commonly used topical antimicrobial in burn centers.

 

(70) Hoffman, Steen.  1984.  Silver Sulfadiazine: an antibacterial agent for topical use in burns.  Scandinavian Journal of Plastic and Reconstructive Surgery, 18, 119-126.

            This review discusses mechanism of action, antimicrobial activity, pharmacology, treatment of burns, frequency and methods of application, adverse effects, bacterial resistance, modifications, and treatments of wounds other than burns.

 

(71) Kucan, John O., et al.  1981.  Comparison of silver sulfadiazine, povine-iodine and physiologic saline in the treatment of chronic pressure ulcers.  Journal of the American Geriatrics Society, 29(5), 232-235.

            “In 100 percent of the ulcers treated with silver sulfadiazine cream (15 patients) the bacterial counts were reduced to 105 or less per gram of tissue within the three-week test period, compared to 78.6 percent in those treated with saline (14 patients) and 63.6 percent in those treated with povine-iodine solution (11 patients).  Moreover, the ulcers treated with silver sulfadiazine cream responded more rapidly.”

 

(72) Bishop, John B., et al.  1992.  A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers.  Journal of Vascular Surgery, 16(2), 251-257.

            “Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo.” 

 

(73) Carr, Howard S., Wlodkowski, Theodore J., and Rosenkranz, Herbert S.  1973.  Silver sulfadiazine: in vitro antibacterial activity.  Antimicrobial Agents and Chemotherapy, 4(5), 585-587.

            657 different types of bacteria from 22 different bacterial species were exposed to silver sulfadiazine.  All strains were inhibited by levels which can easily be obtained topically.  Strains resistant to sulfadiazine or multiple antibiotics were sensitive to silver sulfadiazine.  The table below summarizes some of the data.

 

Bacterial

Strain

 

No.

AgSu

MIC

(micro-

grams

per ml)

CB

CF

AM

P

M

L

E

GM

K

ST

C

TE

CL

NA

NI

SU

Serratia

1101

6.25

R

R

R

R

R

R

R

S

R

R

R

R

R

 

 

 

Serratia

1254

3.13

R

R

R

 

 

 

 

S

R

 

R

R

 

 

 

R

Escherichia

Coli

RTF

3.13

S

S

S

R

R

R

S

S

S

R

R

R

S

 

 

 

E. Coli

1200

25

R

R

R

 

 

 

 

S

R

 

R

R

S

S

 

R

E. Coli

1334

6.25

S

S

R

 

 

 

 

S

S

 

R

R

S

R

 

S

Pseudomonas

Aeruginosa

1186

1.56

R

R

R

 

 

 

 

R

R

 

R

R

S

R

 

R

P. multiphilia

1422

<0.78

R

R

R

 

 

 

 

S

R

 

R

R

R

S

R

S

P. multiphilia

1610

25

R

R

R

 

 

 

 

R

R

 

S

R

S

 

 

S

Klebsiella

1415

50

R

R

R

 

 

 

 

S

R

 

R

R

S

 

 

R

Enterobacter

1249

1.56

R

R

R

 

 

 

 

S

S

 

R

S

 

 

 

S

Enterobacter

1521

1.56

S

R

R

 

 

 

 

S

R

 

S

R

S

 

 

S

Proteus

Mirabilis

1231

1.56

R

R

R

 

 

 

 

S

R

 

R

R

 

 

 

R

P. rettgeri

1157

6.25

S

R

R

 

 

 

 

S

R

 

R

R

R

S

 

R

Providencia

1505

12.5

S

R

R

 

 

 

 

S

S

 

R

R

R

R

R

R

Herellea

1642

6.25

R

R

R

 

 

 

 

S

S

 

R

S

R

S

R

R

Staphylococcus

Aureus

1212

50

 

S

R

R

R

R

R

S

 

 

R

R

 

 

 

R

S. aureus

1436

25

 

S

R

R

R

R

R

S

 

 

S

R

 

 

 

S

S. epidermidis

1202

25

 

S

R

R

R

R

R

S

 

 

R

R

 

 

 

R

Enterococcus

(group D.

Streptococcus)

1561

50

 

R

R

R

R

R

R

R

 

 

R

R

 

 

 

R

Abbreviations: MIC Minimum Inhibitory Concentration; AgSu silver sulfadiazine; S sensitive; R resistant; CB carbenicillin; CF cephalothin; AM ampicilin; P penicillin G; M methicillin; L lincomycin; E erythromycin; GM gentamicin; K kanamycin; ST streptomycin; C chloramphenicol; TE tetracycline; CL colistin; NA nalidixic acid; NI nitrofurantoin; SU sulfadiazine 

 

(74) Rosenkranz, Herbert S. et al.  1974.  Properties of silver sulfadiazine-resistant Enterobacter clocae.  Antimicrobial Agents and Chemotherapy, 5(2), 199-201.  

            Two isolates of bacteria resistant to silver sulfadiazine were obtained.  The bacteria were also resistant to silver benzoate, but not silver nitrate.

            “Growth of the strains in nutritionally poor defined media sensitized them to the inhibitory action of the drug.”  

 

(75) Maple, P.A.C., Hamilton-Miller, J.M.T, and Brumfitt, W.  1992.  Comparison of the in-vitro activities of the topical antimicrobials azeliac acid, nitrofurazone, silver sulphadiazine and mupirocin against methicillin-resistant Staphylococcus aureus.  Journal of Antimicrobial Chemotherapy, 29, 661-668.

            “Silver sulphadiazine killed sulphonamide-sensitive and sulphonamide-resistant strains equally rapidly…The higher MICs we have obtained may indicate the poorer solubility of silver sulphadiazine in agar compared to broth”.

 

(76) Bult, Auke.  1982.  Silver sulfadiazine and related antibacterial metal sulfanilamides: facts and fancy.  Pharmacy International, December, 400-404.

            A review of the literature is presented. 

            3-5% of patients receiving silver sulfadiazine treatment are affected by leucopenia, however, leukocyte counts returned to normal within a week despite continuation of therapy.  The minimum inhibitory concentrations of ionic silver are very low, but in the presence of various media such as culture media, serum or wound components, MIC and MBC are much higher; they reduce the antimicrobial effectiveness of silver ions by a factor of 10 or more.  Proteins and amino acids, particularly those that contain SH react strongly with silver, as do phosphates, chlorides, and reducing species.  The antimicrobial activity of silver sulfadiazine is about five times lower than that of ionic silver. 

            Silver sulfadiazine slowly decomposes and releases silver and sulfadiazine into the wound.  Most of the silver becomes bound to wound components that are not microorganisms.  When silver nitrate is applied to a wound, the initial high concentration of silver ions becomes depleted without further replenishment.  The MIC of sulfadiazine is so high, that the amount of sulfadiazine released from silver sulfadiazine does not reach effective antibacterial levels.

            “Substitution of sulfadiazine in silver sulfadiazine by a biologically inactive component could result in a therapeutically safer drug”.

 

(77) Wysor, M.S., and Zollinhoffer, R.E.  1972.  Antibacterial properties of silver chelates of uracil and uracil derivatives in vitro, Chemotherapy, 17, 188-199. 

            “Silver uracils exhibit a broad spectrum of antibacterial properties against both gram-positive and gram-negative organisms in vitro”.

 

(78) Ballinger, Walter F., et al.  1970.  Silver allantoinate as an inhibitor of cutaneous bacteria upon the hands of operating room personnel.  Annals of Surgery, 171(6), 836-842.

            “Silver allantoinate was used because it has highly effective antibacterial properties when tested in vitro…The number of bacteria at the end of operations exceeded the number after scrubbing in 35% of the control hands but in only 8% of those treated with silver allantoinate powder”.

 

(79) Chu, C.S., et al.  1995.  Enhanced survival of autoepidermal-allodermal composite grafts in allosensitized animals by use of silver-nylon dressings and direct current.  The Journal of Trauma: Injury, Infection, and Critical Care, 39(2), 273-278.

            “Silver nylon dressings enhanced survival of meshed composite skin grafts”.

 

(80) Nomiya, Kenji, et al.  2000.  Synthesis and characterization of water-soluble silver(I) complexes with L-histidine (h2his) and (S)-(-)-2-pyrrolidone-5-carboxylic acid (h2pyrrld) showing a wide spectrum of effective antibacterial and antifungal activities.  Crystal structures of chiral helical polymers [ag(hhis)]n and {[ag(hprrld)]2}n in the solid state.  Inorganic Chemistry, 39, 3301-3311.

            A silver ion complex showed excellent antimicrobial activities against bacteria, yeast, and many molds except A. niger and A. terrus.

 

(81) Vermerie, N., et al.  1997.  Stability of nystatin in mouthrinses; effect of ph temperature, concentration and colloidal silver addition, studied using an in vitro antifungal activity.  Pharmacy World & Science, 19(4), 197-201.

            Colloidal silver is known for its antifungal potency.

 

(82) Wysor, Michael S.  1975.  Orally-administered silver sulfadiazine: chemotherapy and toxicology in cf-1 mice; Plasmodium berghei (malaria) and Pseudomonas Aeruginosa.  Chemotherapy, 21, 302-310.

            “No pathology or abnormal reactions were seen in CF-1 mice after receiving 1050 mg/kg orally and subcutaneously once a day for 30 days.  Silver sulfadiazine in doses of 1050 mg/kg once a day for 5 days cured mice of Plasmodium berghei even after splenoctemy”.

 

(83) Hurst, Christon J.  1991.  Disinfection of drinking water, swimming pool water, and treated sewage effluents.  In Disinfection, sterilization, and preservation. Fourth edition.  Philadelphia, Lea & Febiger, 713-729.

            “Generally the literature on the effectiveness of silver in water disinfection is confusing and rather contradictory.  This confusion reflects in part the variations in test procedures and, in some cases, is the result of failure to use a neutralizing agent in the reported tests.  Inability to recognize or appreciate some of the unique properties of silver has also contributed to this discrepancy…The tendency of silver to adsorb onto surfaces can seriously interfere with bacteriologic tests of its effectiveness.  This property of silver has been carefully studied by Chambers and Proctor (1960)”.

            Phosphates, calcium, and chlorides, ammonia, and organic matter can interfere with the bactericidal effectiveness of silver.

 

(84) Schoerner, C., et al.  1999.  Silver catheter study: methods and results of microbiological investigations.  Infection 27, Suppl.1, S54-S55.

            Bacterial growth is less common on silver catheters than control catheters.

 

(85) Bechert, T., et al.  1999.  The Erlanger silver catheter: in vitro results for antimicrobial activity.  Infection, 27, suppl. 1, S24.

            “Bacterial proliferation on the surface of the catheter and biofilm production are also substantially reduced by the elution of free silver ions from the catheter matrix.  Bacteriostatic and bactericidal activities can be determined…complexing silver ions with sulfur, which results in the formation of water insoluble Ag2S, abolishes the activity of silver ions.  We consider this phenomenon to be additional evidence for the antimicrobial activity of silver ions”.

 

(86) Maki, Dennis G., et al.  1988.  An attachable silver-impregnated cuff for prevention of infection with central venous catheters: a prospective randomized multi-center trial.  The American Journal of Medicine, 85, 307-314.

            “CONCLUSION: This novel, silver-impregnated, attachable cuff can substantially reduce the incidence of catheter-related infection with most percutaneously inserted central venous catheters”.

 

(87) Bach, A., et al.  1994.  Prevention of bacterial colonization of intravenous catheters by antiseptic impregnation of polyurethane polymers.  Journal of Antimicrobial Therapy, 33, 969-978.

            “Our results demonstrate that impregnation of intravenous catheters with silver sulphadiazine and chlorhexidine significantly reduces the rate and magnitude of bacterial colonization of the intravascular foreign body and of catheter-related infections in an animal model”.

 

(88) Kawashita, M., et al.  2000.  Antibacterial silver-containing silica glass prepared by sol-gel method.  Biomaterials, 21, 393-398.

            “Thus prepared silver-containing silica glass powders are believed to be useful as an antibacterial material for medical applications such as composite resin for dental restoration”.

 

(89) Bromberg, Lev E., et al.  2000.  Sustained release of silver from periodontal wafers for treatment of peridontitis.  Journal of Controlled Release, 68, 63-72.

            “An in vitro bacterial cell-killing assay shows that the released silver is biocidal.  In clinical evaluation, sustained release of silver at bactericidal levels for at least 21 days was observed, and efficacy was demonstrated with a significant reduction in anaerobic bacteria.  Staining due to the released silver was minimal and was reversible.  Hence, the developed wafer has potential for superior efficacy in the treatment of peridontitis”.

 

(90) Straub, A.M., et al.  2001.  Phase 1 evaluation of a local delivery device releasing silver ions in periodontal pockets: safety, pharmacokinetics and bioavailability.  Journal of Peridontal Research, 36(3), 187-193.

            “In summary, a bioresorbable LDD which releases silver ions in the periodontal pocket has been developed.  The results presented here suggest that the tested LDD possesses desirable silver release pharmacokinetics and that the delivery of silver to the periodontal pocket resulted in a reduction in the anaerobic as well as the aerobic microflora.  These results indicate that future clinical evaluations of this LDD are warranted”.

 

(91) Chu, Chi-Sing, et al.  1990.  Multiple graft harvestings from deep partial-thickness scald wounds healed under the influence of weak direct current.  The Journal of Trauma, 30(8), 1044-1050.

            Wounds treated with silver nylon cloth and direct current were more effective than wounds treated with silver nylon cloth alone.

 

(92) Chu, Chi-Sing, et al.  1991.  Weak direct current accelerates split-thickness graft healing on tangentially excised second-degree burns.  Journal of Burn Care & Rehabilitation, 12(4), 285-293.

            Wounds treated with silver nylon dressings and direct current were more effective than wounds treated with silver nylon dressings alone.

 

(93) Williams, Claire.  1994.  Actisorb plus.  British Journal of Nursing, 3(15), 786-788.

            Actisorb Plus consists of charcoal cloth impregnated with silver.  It is a wound dressing manufactured by Johnson & Johnson and exerts an antimicrobial effect on bacteria.

 

(94) Williams, Claire.  1997.  Arglaes controlled release dressing in the control of bacteria.  British Journal of Nursing, 6(2), 114-115.

            Arglaes is a wound dressing manufactured by Maersk Medical.  It contains silver, and an antimicrobial effect is exerted on pathogens in the wound by the release of silver ions.

 

(95) Yin, H.Q., Langford, R., and Burrell, R.E.  1999.  Comparative evaluation of the antimicrobial activity of acticoat antimicrobial barrier dressing.  Journal of Burn Care & Rehabilitation, 20(3), 195-200.

            Acticoat, a wound dressing coated with nanocrystalline silver, proved to be more effective than silver nitrate and silver sulfadiazine.

 

(96) Coward, Joe E., Carr, Howard S., and Rosenkranz, Herbert S.  1973.  Silver sulfadiazine: effect on the ultrastructure of Pseudonomas Aeruginosa.  Antimicrobial Agents and Chemotherapy, 3(5), 621-624.

            Silver sulfadiazine alters the cell membrane of bacteria.

 

(97) Rosenkranz, Herbert S., and Rosenkranz, Samuel.  1972.  Silver sulfadiazine: interaction with isolated deoxyribonucleic acid.  Antimicrobial Agents and Chemotherapy, 2(5), 373-383.

            “In the present study, it is shown that silver sulfadiazine interacts with isolated DNA but that the product is different in all respects from that obtained when silver nitrate is added to DNA”. 

 

(98) Feng, Q.L., et al.  2000.  A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus Aureus.  Journal of Biomedical Materials Research, 52, 662-668.

            Silver ions react with DNA and thiol groups in protein which produce the inactivation of bacterial proteins.

 

(99) Rendin, Larry J, Gamba, Carl L., and Johnson, Walllace M.  1958.  Colloidal oxide of silver in the treatment of peptic ulcer.  Pennsylvania Medical Journal.  61: 612-614.

            88 patients with peptic ulcers orally ingested tablets containing colloidal silver oxide over a period of 9 days.  Within 6 weeks, all cases except one were healed.  The particle size of the silver oxide was “three-tenths of a micron and smaller.”

Comment: This study was conducted before it was discovered that peptic ulcers are caused by bacteria.  Controls were not used.

 

(100) Brentano, Loreno et al.  1966.  Antibacterial efficacy of a colloidal silver complex.  Surgical Forum.  17: 76-78.

            Collargol (colloidal silver protein), silver nitrate, and a mixture of Collargol and silver nitrate (colloidal silver complex) were tested for antibacterial efficiency against S. aureus, A. aerogenes, and P. aeruginosa in water, human plasma, and trypticase soy broth.  The presence of proteins significantly decreased the antibacterial efficacy of all 3 agents tested.  Colloidal silver complex and silver nitrate inhibited the bacteria in water at 2.5 ppm, while a concentration of 100 ppm of Collargol was required to inhibit the bacteria in water.  In trypticase soy broth, the silver nitrate and colloidal silver complex required concentrations of 100 ppm to inhibit the bacteria, while the Collargol required a concentration of 1000 ppm to inhibit the bacteria in the same medium.  In human plasma, the inhibiting concentration of silver nitrate was 100 ppm, while the inhibiting concentration of colloidal silver complex was 1000 ppm, and the inhibiting concentration of Collargol was 5000 ppm. 

 

(101)Gravens, Dalien L. et al.  1973.  The antibacterial effect of treating sutures with silver.  Surgery.  73: 122-127.

            Sutures soaked in silver nitrate or a silver-zinc-allantion complex were exposed to S. aureus and P. aeruginosa.  With silk sutures soaked in a silver-zinc-allantion complex, the reduction of S. aureus and P. aeruginosa was 88.2% and 99.0% respectively.  In silk sutures soaked in silver nitrate, a 53.4% reduction in S. aureus was seen.  The silk soaked in silver nitrate was not exposed to P. aeruginosa.  Catheters exposed to a silver-zinc-allantion complex did not exhibit significant antibacterial activity.  The antibacterial effectiveness of silver compounds depends on the availability of silver ions, and a silver-zinc-allantion complex provides a continual release of silver ions.

 

(102) Thibodeau, E.A., S.L. Handelman, and R.E. Marquis.  1978.  Inhibition and killing of oral bacteria by silver ions generated with low intensity direct current.  Journal of Dental research.  57: 922-926.

            Electrically generated silver ions, silver nitrate, and silver fluoride were tested for antibacterial effectiveness against 5 different bacteria.  Based on silver content, no significant difference was found in the antibacterial effectiveness of the 3 agents.

            growth medium constituents have substantial effects on the effectiveness of silver ions.”

 

(103) Micheels, V., V. Moray and A. Castermans.  1979.  A ten year retrospective study of sepsis in severely burned patients treated with or without silver sulfadiazinate.  Scandinavian Journal of Plastic and Reconstructive Surgery.  13: 85-87.

            “In the beginning, silver sulfadiazinate reduced quantitative sepsis, but this benefit decreased after six years.”

 

(104) Tronstad L., M. Trope and B.F. Hammond.  1985.  Effect of electric current and silver electrodes on oral bacteria.  Endodonics & Dental Traumatology.  1: 112-115.

            Microorganisms commonly found in the root canal were placed in Petri dishes with agar.  2 silver electrodes were placed in the Petri dishes and an electric current was applied.  Zones of inhibition were seen for all bacteria at the positive electrode.  No zones of inhibition were seen at the negative electrode.  Silver ions were credited with the antimicrobial effect.  Bacteria tested consisted of: S. salivarius, S. sanguis, S. faecalis, A. viscosus, Ps. aeruginosa, P. jensenii, F. nucleatum, B. oralis and B. gingivalis.

 

(105) Adams, A.P., E.M. Santschi and M.A. Mellencamp.  1999.  Antibacterial properties of a silver chloride-coated nylon wound dressing.  Veterinary Surgery.  28: 219-225.

            A silver chloride-coated nylon wound dressing is effective at inhibiting E coli, Klebsiella Pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus.

 

(106) Tweden, Katherine S. et al.  1997.  Biocompatability of silver-modified polyester for antimicrobial protection of prosthetic valves.  Journal of Heart Valve Disease.  6: 553-561.

            Polyester coated with metallic silver was tested in vitro against Asperillus niger, Escheri coli, Serratia marcescens, Candida tropicalis, Streptococcus mitis and streptococcus bovis and was found to be effective. 

 

(107) Yamamoto, Kohji, et al.  1996.  Antibacterial activity of silver ions implanted in silicone dioxide filler on oral Streptococci.  Dental Materials.  12: 227-229.

            “The Ag+ filler showed significantly more antibacterial activity than the control filler without silver ions…The findings indicate that the antibacterial effect is due to silver ions released from the Ag+-containing filler.”

 

(108) Barranco, S.D. et al.  1974.  In vitro effect of weak direct current on Staphylococcus Aureus.  Clinical Orthopaedics and Related Research.  100: 250-255.

            Electrodes made from stainless steel, platinum, gold, and silver were placed in dishes containing bacteria.  Current was applied.  The silver electrode offered superior inhibition.

 

 

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