The Value of Antiseptics As Prophylactic Applications to Recent Wounds

[ 297 ] THE VALUE OF ANTISEPTICS AS PROPHYLACTIC APPLICATIONS TO RECENT WOUNDS BY J. GORDON, J. W. McLEOD, ANNA MAYR-HARTING, J. W. ORR AND K. ZINNEMANN Department of Pathology and Bacteriology, Leeds University There have been .groups of observers both in this concluded on this account that the penetration of country and in Germany who have been entirely bacteria from a wound into the deeper tissues was sceptical about the value of the prophylactic appli- so rapid that local treatment of the wound was cation of antiseptics to wounds and who seem to obviously futile. Schiemann & Wreschner (1922) incline to the opinion that such medication is likely and Weise (1922), however, who record these to be more harmful than useful; e.g. Colebrook in observations of Schimmelbusch, made similar ob- a special report to the Medical Research Council servations with streptococci but showed that with (1928) stated that 'the ordinary "antiseptics" have this micro-organism not only tail amputation but a higher affinity for the leucocytes than for the also local application of antiseptics was often microbes, and by combining with the former forfeit successful in saving mice so infected. They did not their microbicidal potential'. Further, he stated dispute the rapid penetration of the bacteria but that with the exception of optochin and neosal- concluded that in the case of the streptococcus the varsan, substances which have been tried as anti- body could deal with limited numbers of these septics are so rapidly fixed on serum proteins, blood micro-organisms, if the local lesions from which cells, and the fixed tissues, that they fail to impart they were reaching- the general circulation were bactericidal power to the serum. Fleming (1924, eliminated. Further, Browning (1943) in a discus- 1931) in a number of ingenious experiments showed sion of the antiseptic action of the amino acridine that injury to leucocytes is the most likely outcome compounds made an extensive survey of the of antiseptic applications to wounds, and has literature on the influence of these substances on argued that they are more likely to be harmful than leucocytes and concluded that in view of the wide useful for that reaon; later (1938), he pointed out variations in results the particular technique the superiority of the sulphonamides to the older adopted must be an important factor. Hence he antiseptics as tested by his 'slide cell' technique suggests there is need for much caution in accepting and in penicillin he has discovered an antiseptic such results as an indication of what will actually which in respect of a high ratio of bactericidal happen in the animal body. potency to its toxicity to mammalian tissues In 1940 Garrod in a very illuminating review of approaches the ideal. This has given the clinical the whole subject of antiseptics in wounds, stated results which would be expected on theoretical a strong case for discrimination between the pro- grounds. There are, however, limitations to the use phylactic use of antiseptics in wounds and the of penicillin as a general prophylactic antiseptic treatment of established infection of wounds. In application which depend on (a) its failure to the course of this review, in which he stressed destroy some types of bacteria which cause suppura- particularly the claims of proflavine, he suggested tion, (6) its relative lability, (c) its present cost. that the less caustic of the phenolic disinfectants There is therefore ground for further careful assess- such as 'Cyllin' and 'Izal', which consist of emul- ment of the best prophylactic antiseptic. Fleming sions of certain of the higher boiling homologues of (1940) has in fact admitted that there may be a phenol, and products such as 'Dettol' in which a place for proflavine in the interim dressing of cresol or xylenol has had its bactericidal power wounds pending surgical treatment. The German reinforced by halogenation, have a claim for con- opinion on the question of the prophylactic use of sideration in the treatment of wounds. Interest in antiseptics seems to have been considerably in- the prophylactic treatment of wounds by anti- fluenced by the observations of Schimmelbusch, septics was renewed by the introduction of the who had demonstrated that mice inoculated on a sulphonamides, which, unlike any other substances scarified area of the tail with anthrax bacilli could employed previously, had been proved effective in not be saved when the tail was amputated at a the treatment of established infection by several point proximal to the site of inoculation even types of bacteria. These have also been much 10 min. after the wound had been infected. It was recommended and used in the prophylaxis of Downloaded from https://www.cambridge.org/core. IP address: 170.106.202.126, on 29 Sep 2021 at 19:54:42, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0022172400013954 298 The value of antiseptics as prophylactic applications to recent wounds infection of war wounds, and advantage has been been executed before the sulphonamides were taken of their limited toxicity to apply them in the available. form of powder, which has been shown by Botterel, It is clear that unless enormous numbers of Carmichael & Cone (1941) to produce very little animals are to be used it is not possible to get damage even •when introduced experimentally in results which are statistically significant with a relatively large amounts to -wounds of the brain. large number of different compounds; hence the This conclusion has also been established in careful range of antiseptics tested was inevitably restricted. experimental •work by Russell & Falconer (1940-1, Those examined were the following: Deosan, Dettol, 1943) and Russell & Beck (1944), who. also note Izal, Milton, tincture of iodine; a solution of equal that the admixture of even 1 % of proflavine to the parts of crystal violet and brilliant green, proflavine, powder makes it much more irritant. The use of quinanil; sulphanilamide solution and sulphanil- sulphonamides in wounds in the form of powder amide powder, sulphathiazole. The investigation of was first adopted by Jensen, Johnsrud & Nelson Izal and Dettol seemed to be indicated in view of (1939) and probably first suggested for war wounds Garrod's suggestion quoted above, especially as we by Legroux (1940). could find no record of investigation of these It has been widely adopted and favourable substances previously in experiments of this type. reports on experimental results are recorded, Tincture of iodine was included because of its wide amongst others, by Bonnin & Fenner (1941), use as a prophylactic antiseptic and because of its Bisgard & Baker (1942), McSwain & Glenn (1942), marked capacity for sterilizing the intact skin after Colebrook (1940-1), Colebrook & Francis (1941), infection with the more resistant spore-bearing Key & Burford (1941), Baker (1942). Schneider bacteria (McLeod & Bevan-Brown, 1918). Milton (1941) and Goldberger (1942) strike an original and Deosan, which are solutions of sodium hypo- note in recommending the combination of hydrogen chlorite prepared by special methods, were included peroxide solutions and sulphanilamide powder for in view of the wide use of antiseptics of this kind, •wound treatment. e.g. Dakin's solution, in the war of 1914-18. The mixed solutions of triphenylmethane dyes (first It seems altogether probable that in the case of ' suggested to one of us by C. H. Browning) were infections by streptococci, bacteria which can be included because of the remarkable potency of these controlled by sulphonamides when they have compounds against the Gram-positive coccal forms succeeded in invading the body generally, the effect and also because of long personal experience of their of local application of these drugs should be superior value in everyday use as a prophylactic antiseptic to that of most other known antiseptics. That they application to minor wounds. Iodine was the only are in fact capable when given by mouth of con- antiseptic of those tried by McLeod & Bevan -Brown trolling local streptococcal lesions tending to which approached this dye mixture in efficiency in generalization with fatal issue, was of course killing off sporing aerobes on the surface of the skin. demonstrated by Berger (1937) and others for It has in any case had wide use in surface disinfec- prontosil. The same is not necessarily true of other tion under the name of Bonney's paint (Bonney & bacteria such as staphylococci and anaerobes which Browning, 1918). It was obvious that one of the are much less sensitive to sulphonamides. In fact, acridine dyes should be included in such a series, under the experimental conditions adopted by since so many records are extant of their ability to Mclntosh & Selbie (1942, 1943), it has been found terminate experimental infections in animals which that even -with sulphathiazole, in some ways the proved fatal in all controls or in a very high most effective of the sulphonamide group, the percentage of the controls. results with Cl. welchii and Cl. novyi infections are inferior to those obtained with proflavine, and Without attempting an exhaustive list of these Heggie & Heggie (1942) record that although local the following may be quoted: Browning & Gulbran- staphylococci infection of burns is not prevented sen (1925) on the control of diphtheria infection of by a full course of sulphapyridine by mouth, it is wounds; Browning, Cohen, Ellingworth & Gulbran- usually cleared up rapidly by the local use of sen (1931) on the control of intraperitoneal strepto- lymphagogues followed by 0-1 % proflavine in coccal infection; Weise (1922) and Schiemann & buffered isotonic solution. Wreschner (1922) on the control of streptococcal There appears, therefore, still to be ground for infection of superficial wounds in mice; Reinhardt studying the best possible prophylactic treatment (1922) on the control of chicken cholera and pneu- for all •wounds.

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