Silver sulphadiazine

Less study has been made of complexes with polydentate ligands. Ag-N linkages have been studied in relation to polynucleotide bases and the Ag-DNA interaction could be important in the use of the silver-sulphadiazine complex in burn treatment. Ethylenediamine is a bridging ligand in AgenC104 (2-coordinate silver) but essentially planar 5-coordination... 

Schaller, M., Korting, H. C. and Schmid, M. H., Interaction of cultured human keratinocytes with liposomes encapsulating silver sulphadiazine proof of the uptake of intact vesicles. Br. J. Dermatol, 134, 445-50, 1996. 

Applications of dressings soaked in aqueous silver nitrate solution have significant prophylactic action against infection in the treatment of major burns3 A salt other than the nitrate would seem to be preferable in order to avoid possible reduction to nitrite, with resulting toxicity. One such alternative is silver sulphadiazine. Because of its antibacterial action, silver nitrate is also sometimes used in eye drops. 

Dermal. Medical case histories indicate that dermal exposure to silver or silver compounds for extended periods of time can lead to local skin discoloration similar in nature to the generalized pigmentation seen after repeated oral exposure. However, the amount of silver and the duration of time required to produce this effect cannot be established with the existing information (Buckley 1963 McMahon and Bergfeld 1983). Moreover, adverse effects such as argyria have not been associated with the use of silver sulphadiazine as a bactericidal agent (Fox et al. 1969). No studies were located regarding dermal effects in animals after dermal exposure to silver or silver compounds. 

Absorption of silver nitrate across intact skin has been demonstrated in guinea pigs and is similar to that of intact human skin (Wahlberg 1965). The amount absorbed was estimated to be approximately 1 % of the applied dose within 5 hours of exposure. Silver administered in the form of silver sulphadiazine cream was minimally absorbed through both the intact and burned skin of rats and distributed throughout the body (Sano et al. 1982). The absorption of silver increased through burned skin after blister removal. The authors did not determine the percentage of the applied dose that was absorbed (Sano et al. 1982). 

Following the topical application of silver nitrate for the treatment of burns in two humans, silver was distributed to the muscles (0.03-2.3 ppm), liver (0.44 ppm), spleen (0.23 ppm), kidney (0.14 ppm), heart (0.032-0.04 ppm), and bones (0.025 ppm) (Bader 1966). No studies were located that quantitated the distribution of silver in animals following dermal exposure to silver or its compounds. However, Sano et al. (1982) detected silver in the same tissues of rats following topical application of silver sulphadiazine cream. 

Lockhart SP, Rushworth A, Azmy AAF, et al. 1983. Topical silver sulphadiazine Side effects and urinary excretion. Burns 10 9-12. 

Sano S, Fujimori R, Takashima M, et al. 1982. Absorption, excretion and tissue distribution of silver sulphadiazine. Burns 8 278-285. 

Fox C L, Modak S M. Mechanism of Silver Sulphadiazine Action on Bum Wound. Infections. Antimicrobial Agents Chemother. 5 582-588.1974. 

PROPERTIES AND USES OF SILVER COMPOUNDS Silver and silver salts Silver sulphadiazine... 

Silver and its compounds have long been used, in one form or another, as antimicrobial agents. The silver compound of major therapeutic interest at the present time is silver sulphadiazine. Many in health care, however, will... 

The first record of the medicinal but not antimicrobial use can be found in writings around 750 AD. An early scientific paper by Crede has already been alluded to [4] it involved the use of silver in the treatment of inflammation of the eyes (ophthalmia neonatorum) in new-born infants. In a further paper [8], silver was advocated as an internal antiseptic. During the following years, silver nitrate, citrate, lactate and proteinate have appeared in pharmacopoeias and formularies around the world. A silver nitrate lotion appeared in older editions of the British National Formulary. In the latest issues, however (no. 26, 1993 onwards [9]) only silver sulphadiazine is to be found. The USP XXII [10] lists silver sulphadiazine (used as a cream) and silver nitrate (used as an ophthalmic solution). 

Argyria, also called argyrism or argyrosis, which occurs as a result of prolonged silver therapy, was first reported in 1647 [11], and was reviewed in depth by Hill and Pillsbury [11] in 1939. It presents as an irreversible grey to blue-black colouring of the skin and mucous membranes, for example, the conjunctiva, and also of internal tissue. With the decline in use of many silver preparations in therapeutics, the condition is less likely to be encountered today. However, a recent case has been reported in a 59-year old patient undergoing silver sulphadiazine therapy for recurrent venous leg ulcers [12],... 

Bums. Infection may be reduced by application of silver sulphadiazine cream. Substantial absorption can occur from any raw surface and use of aminoglycoside, e.g. neomycin, preparations can cause ototoxicity. 

Infected burns are treated with a variety of antimicrobials, including silver-sulphadiazine and mupirocin. 

Eldad A, Neuman A, Weinberg A, Benmeir P, Rotem M, Wexler MR. Silver sulphadiazine-induced haemolytic anaemia in a glucose-6-phosphate dehydrogenase-deficient burn patient. Burns 1991 17(5) 430-2. 

Plasmid-mediated resistance to silver salts is of particular importance in the hospital environment, because silver nitrate and silver sulphadiazine may be used topically for preventing infections in severe burns. It may have increased relevance in the future arising from the use of silver-coated connectors in catheter systems. Silver reduction is not a primary resistance mechanism as sensitive and resistant cells can equally convert Ag+ to metallic silver. Plasmid-mediated resistance to silver salts is, in fact, difficult to demonstrate, but where it has been shown to occur, decreased accumulation rather than silver reduction is believed to be the mechanism involved. 

For areas of erythema and minor blistering, bland lotions (e.g. calamine) have been suggested. Silver sulphadiazine (Flamazine) 1% cream was used in the management (1986) of Iranian mustard gas casualties (Willems, 1989). This probably had value in reducing skin infection. 

Silver sulphadiazine + Mafenide Bum therapy prevention and treatment of bacterial infection. 

ShanmagasuDdaram, N., Sundaraseelan, J., Uma, S., Selvaraj, D., Babu, M., 2005. Design and delivery of silver sulphadiazine from alginate microsphetes impregnated collagen scaffolds. J. Biomed. Mater. Res. Appl. Biomater. 77B, 278—388. 

---