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The clinical use of alkyl-dimethyl-benzyl-ammonium chloride (zephiran)
THE CLINICAL USE OF ALKYLdDIMETHYLBENZYL/ AMMONIUM CHLORIDE (ZEPHIRAN) A PRELIMINARY
REPORT
CHARLES S. WHITE, M.D., J. LLOYD COLLINS, M.D., AND HOWARD E. NEWMAN, M.D. WASHINGTON,D. C. ITHIN the past severa years our 275, against EbertheIIa typhosa 176, and concept of the bactericida1 properagainst E. cob 318. Somewhat higher ties of antiseptic soIutions and their figures under the same conditions were use in surgical procedures has undergone a obtained by Dunn3v4 and Deskowitzl decided change. WhiIe the action of some In penetration and inhibition tests, using of the newer antiseptics and germicides the agar cup-pIate method, the resuIts may not be thoroughIy understood, their were convincing and paraIIeIed the pheno1 efficacy and non-toxic action has given coefficient tests. The Iargest zones were them first rank. In this category faIIs a new formed by the StaphyIococcus aureus, the type of antiseptic, a mixture of aIkyIsmaIIest by the Streptococcus pyogenes. dimethy - benzyl - ammonium chIorides Ten per cent aIcohoIic and IO per cent (zephiran). aqueous zephiran soIutions were used in The product is obtained as a mixture of skin disinfection tests, which were carried homoIogues in which the aIkyIs represent out in the foIIowing manner: After the the radicaIs derived from the fatty acids of hands were scrubbed with a brush, soap coconut oi1. This compound is an amberand water for eight minutes, they were coIored soIid of soap-like consistency. The dried with a sterile towe and the fingers mixture is quite uniform in composition, immersed five minutes in the test soIution and is fuIIy soIubIe in water, aIcoho1, and and then washed with steriIe water. Agar acetone. The aqueous soIution is sIightIy was Iiquefied, poured over the fingers, and aIkaIine, possesses a faint aromatic odor, coIIected in steriIe petri dishes. No coIonies and imparts a soapy sensation to the skin. couId be detected in five days. This conGermicidaI soIutions for cIinica1 use have firms the work of Domagk,5 which was a surface tension of approximateIy 36 carried out under simiIar conditions. dynes/cm. Tests were made with the object of PharmacoIogic studies invoIving ora determining the destructive effect of a toxicity and effect on the skin and mucous soIution of the ammonium chIoride commembranes of the Iaboratory animaIs re- pound on spores of BaciIIus subtiIis, veaIed that this compound in germicida1 Trichophyton gypseum, and a Mucor, concentration is reIativeIy non-toxic and which was isoIated from miIk. The resuIts non-irritating.’ showed that in a concentration of I :goo Heineman2 has contributed a concise but (distiIIed water) the ammonium chIoride thorough evaIuation of zephiran. His compound destroyed the spores of BaciIIus studies embraced the foIIowing: (I) pheno1 subtilis and those of the two types of fungi coefficient determination; (2) inhibition and in five minutes. With the facts of an extensive bacteriopenetration tests; (3) tests for disinfection of the human skin; and (4) destruction of Iogic background before us, we felt that a clinica test was warranted. It has been spores of bacteria and fungi. truthfuIIy stated that no amount of IaboraThe pheno1 coefficient was determined by the method as described by the Food tory tests can repIace actua1 cIinica1 experience in evaluating a germicide. There is no and Drug Administration. Against StaphyIococcus aureus the pheno1 coefficient was test-tube comparable to Iiving tissue for 607
W
608
American Journal of Surgery
White,
et aI.-Zephiran
this purpose. There is no test that can replace the routine use of a sohrtion over a considerabIe period of time, embracing as it must, many variabIe conditions, unapproached by any Iaboratory. We inaugurated a skin test which, in spite of its inherent fauhs, we considered as the nearest approach to an actuaI cIinica1 test. The surgeons, assistants and nurses scrubbed up in the usual manner, except that the ammonium chIoride compound soIution I : IOOO (Tincture zephiran) was used for immersing the hands and forearms, instead of the usua1 mercuria1 soIution and aIcoho1. In every case, immediateIy before operation, a smaI1 piece of fuI1 thickness untreated skin was removed with steriIe forceps and scaIpe1 and pIaced in a steriIe test-tube marked in code in order that the bacterioIogist couId not possibIy know anything of the treatment of this specimen. The surface to be operated upon was then scrubbed with soap and water, benzine, and aIcoho1. When the surface was dry, tincture of zephiran I : IOOO was we11 appIied with a sterile sponge and aIIowed to dry. Then a smaI1 piece of fuI1 thickness of skin was removed, dropped into a sterile test tube, marked in code, and sent to the Iaboratory. We shaI1 designate these sections of skin as “contro1” and “treated.” There were hfty-one such cases and the skin, in most instances, was removed from the abdomen. In the fifty-one cases in which cuItures were made from the untreated skin by excising a piece, there was growth in every instance, as foIIows : StaphyIococcus aIbus.. Staphylococcus aIbus and aureus.. Staphylococcus albus and citreus.. Staphylococcusaureus.......................... Staphylococcus albus and Streptococci.. Budding yeast.. Gram-positive cocci in chains..
35 5 z 3
-
4 1 I
In the area treated by zephiran, in which a piece of sk in was removed, there was growth in two cases: (I) Gram-negative
MARCH. 1938
bacihus : a spore-bearing baciIIus and spores ; and (2) Gram-positive coccus in chains and clusters. The organisms appeared considerabIy smaIIer than those in the control. Of the fifty-one cases, forty-six were of the abdomina1 type, four were breast tumors, and one a Iipoma of the chest waI1. They were without exception “clean cases,” that is, no operation was done in the presence of known skin infections. There was but one infected wound in this series: this case was a choIecystogastrostomy for carcinoma of the head of the pancreas. The wound was definiteIy infected, but in a11 probabiIity the source of contamination was from the heId of operation rather than from the skin. There were twenty-one additional cases in which zephiran was empIoyed in skin preparation, but for very good reasons (many of these patients were employees of the institution) no skin was removed for Iaboratory tests. These cases a11 heaIed by primary union. In aI1, there were seventy-six cases of zephiran preparation with one wound infection. No irritation was noted on the skin of the patient or on the hands of the operator, assistants, or nurses. No pustuIation or other evidence of irritation was noted on the skin on which zephiran was used and upon which adhesive pIaster was apphed. Our percentage of infections in this hospita1, and in fact in most of our work elsewhere, is very much higher. This has occurred in spite of the fact that we require skin preparation for operation on two successive days unIess the operation is an urgent one and time wiI1 not permit deIay. The incidence of one infected wound in seventy-six cases, whiIe representing a smal1 series, is very gratifying to us. It is a11 the more remarkabIe when the type of patient is considered. They were all indigents, on the ward of a municipa1 hospita1, many feebIe, poorIy nourished, a fair percentage of them emergency cases, and many had not avaiIed themseIves for unknown periods of the usua1 sanitation afforded by soap and water.
NEW SERIES VOL.XXXIX,
No. 2
White,
et aI.-Zephiran
To check our results, we requested the gynecoIogic division to carry out a series of cases using the same details in skin preparation with 335 per cent iodine as the germicide. There were twenty-five such cases, a11 abdomina1 operations. In the contro1 biopsies there was growth in every case. No biopsies were taken from the iodine-treated skin, but seven infected wounds were present in the twenty-five cases. CONCLUSIONS
The reduction in wound infection, judging by our experience over a long period with many other antiseptics, is too striking to be termed an accident or a fortuitous crrcumstance. WhiIe the number of cases in which zephiran was used was a comparativeIy smaI1 one, there are sufficient data to warrant the statement that it is a safe and effective germicide and justifies an extended tria1. SUMMARY
In a series of seventy-six cases, using zephiran as a skin germicide, wound infection foIIowed in one case, an incidence of 1.3 per cent. There is reasonabIe doubt about skin contamination in this case.
American JournaI of Surgery
609
In fifty-one cases from skin cut from areas prepared with zephiran, cuItures showed growth in two cases. Growth was present in a11 controIs. In a comparative study of twenty-five cases in which Iaparotomy was performed with 334 per cent tincture of iodine, there were infected wounds in seven cases or 28 per cent. No skin irritation was noted with zephiran even under adhesive pIaster. We wish to express our thanks to Dr. H. H. LefNer for his vaIuabIe Iaboratory work. REFERENCES I. DESKOWITZ, M. W. Some germicidal and physiological properties of a mixture of high moIecuIar alkyI-dimethyLbenzyI-ammonium chlorides. UnpubIished report from the bacterioIogic Iaboratories of the CoIIeae of Phvsicians and Sureeons. CoIumbia University, New”York. 2. HEINEMAN, P. G. Antiseptic properties of akyIdimethyl-benzyI-ammonium chIorides. J. Am. Pbarm. A., 21: 71I (Aug.) 1937. 3. DUNN, CECIL G. A mixture of high moIecuIar alkyldimethyI-benzyI-ammonium chIorides as an antiseptic. Proc. Sot. Exper. Biol. @ Med., 35: 427, I
1936.
4. DUNN, CECIL G. Antiseptic and germicida1 properties of a mixture of aIkyI-dimethyl-benzyIammonium chlorides. Am. J. Hyg., 26: 46 (JuIy) 1937. 5. DOMAGK, GERHARDT. A new class of disinfectants. Deutscb. med. Wcbnscbr., 21: 827, 1935.
REPORT
CHARLES S. WHITE, M.D., J. LLOYD COLLINS, M.D., AND HOWARD E. NEWMAN, M.D. WASHINGTON,D. C. ITHIN the past severa years our 275, against EbertheIIa typhosa 176, and concept of the bactericida1 properagainst E. cob 318. Somewhat higher ties of antiseptic soIutions and their figures under the same conditions were use in surgical procedures has undergone a obtained by Dunn3v4 and Deskowitzl decided change. WhiIe the action of some In penetration and inhibition tests, using of the newer antiseptics and germicides the agar cup-pIate method, the resuIts may not be thoroughIy understood, their were convincing and paraIIeIed the pheno1 efficacy and non-toxic action has given coefficient tests. The Iargest zones were them first rank. In this category faIIs a new formed by the StaphyIococcus aureus, the type of antiseptic, a mixture of aIkyIsmaIIest by the Streptococcus pyogenes. dimethy - benzyl - ammonium chIorides Ten per cent aIcohoIic and IO per cent (zephiran). aqueous zephiran soIutions were used in The product is obtained as a mixture of skin disinfection tests, which were carried homoIogues in which the aIkyIs represent out in the foIIowing manner: After the the radicaIs derived from the fatty acids of hands were scrubbed with a brush, soap coconut oi1. This compound is an amberand water for eight minutes, they were coIored soIid of soap-like consistency. The dried with a sterile towe and the fingers mixture is quite uniform in composition, immersed five minutes in the test soIution and is fuIIy soIubIe in water, aIcoho1, and and then washed with steriIe water. Agar acetone. The aqueous soIution is sIightIy was Iiquefied, poured over the fingers, and aIkaIine, possesses a faint aromatic odor, coIIected in steriIe petri dishes. No coIonies and imparts a soapy sensation to the skin. couId be detected in five days. This conGermicidaI soIutions for cIinica1 use have firms the work of Domagk,5 which was a surface tension of approximateIy 36 carried out under simiIar conditions. dynes/cm. Tests were made with the object of PharmacoIogic studies invoIving ora determining the destructive effect of a toxicity and effect on the skin and mucous soIution of the ammonium chIoride commembranes of the Iaboratory animaIs re- pound on spores of BaciIIus subtiIis, veaIed that this compound in germicida1 Trichophyton gypseum, and a Mucor, concentration is reIativeIy non-toxic and which was isoIated from miIk. The resuIts non-irritating.’ showed that in a concentration of I :goo Heineman2 has contributed a concise but (distiIIed water) the ammonium chIoride thorough evaIuation of zephiran. His compound destroyed the spores of BaciIIus studies embraced the foIIowing: (I) pheno1 subtilis and those of the two types of fungi coefficient determination; (2) inhibition and in five minutes. With the facts of an extensive bacteriopenetration tests; (3) tests for disinfection of the human skin; and (4) destruction of Iogic background before us, we felt that a clinica test was warranted. It has been spores of bacteria and fungi. truthfuIIy stated that no amount of IaboraThe pheno1 coefficient was determined by the method as described by the Food tory tests can repIace actua1 cIinica1 experience in evaluating a germicide. There is no and Drug Administration. Against StaphyIococcus aureus the pheno1 coefficient was test-tube comparable to Iiving tissue for 607
W
608
American Journal of Surgery
White,
et aI.-Zephiran
this purpose. There is no test that can replace the routine use of a sohrtion over a considerabIe period of time, embracing as it must, many variabIe conditions, unapproached by any Iaboratory. We inaugurated a skin test which, in spite of its inherent fauhs, we considered as the nearest approach to an actuaI cIinica1 test. The surgeons, assistants and nurses scrubbed up in the usual manner, except that the ammonium chIoride compound soIution I : IOOO (Tincture zephiran) was used for immersing the hands and forearms, instead of the usua1 mercuria1 soIution and aIcoho1. In every case, immediateIy before operation, a smaI1 piece of fuI1 thickness untreated skin was removed with steriIe forceps and scaIpe1 and pIaced in a steriIe test-tube marked in code in order that the bacterioIogist couId not possibIy know anything of the treatment of this specimen. The surface to be operated upon was then scrubbed with soap and water, benzine, and aIcoho1. When the surface was dry, tincture of zephiran I : IOOO was we11 appIied with a sterile sponge and aIIowed to dry. Then a smaI1 piece of fuI1 thickness of skin was removed, dropped into a sterile test tube, marked in code, and sent to the Iaboratory. We shaI1 designate these sections of skin as “contro1” and “treated.” There were hfty-one such cases and the skin, in most instances, was removed from the abdomen. In the fifty-one cases in which cuItures were made from the untreated skin by excising a piece, there was growth in every instance, as foIIows : StaphyIococcus aIbus.. Staphylococcus aIbus and aureus.. Staphylococcus albus and citreus.. Staphylococcusaureus.......................... Staphylococcus albus and Streptococci.. Budding yeast.. Gram-positive cocci in chains..
35 5 z 3
-
4 1 I
In the area treated by zephiran, in which a piece of sk in was removed, there was growth in two cases: (I) Gram-negative
MARCH. 1938
bacihus : a spore-bearing baciIIus and spores ; and (2) Gram-positive coccus in chains and clusters. The organisms appeared considerabIy smaIIer than those in the control. Of the fifty-one cases, forty-six were of the abdomina1 type, four were breast tumors, and one a Iipoma of the chest waI1. They were without exception “clean cases,” that is, no operation was done in the presence of known skin infections. There was but one infected wound in this series: this case was a choIecystogastrostomy for carcinoma of the head of the pancreas. The wound was definiteIy infected, but in a11 probabiIity the source of contamination was from the heId of operation rather than from the skin. There were twenty-one additional cases in which zephiran was empIoyed in skin preparation, but for very good reasons (many of these patients were employees of the institution) no skin was removed for Iaboratory tests. These cases a11 heaIed by primary union. In aI1, there were seventy-six cases of zephiran preparation with one wound infection. No irritation was noted on the skin of the patient or on the hands of the operator, assistants, or nurses. No pustuIation or other evidence of irritation was noted on the skin on which zephiran was used and upon which adhesive pIaster was apphed. Our percentage of infections in this hospita1, and in fact in most of our work elsewhere, is very much higher. This has occurred in spite of the fact that we require skin preparation for operation on two successive days unIess the operation is an urgent one and time wiI1 not permit deIay. The incidence of one infected wound in seventy-six cases, whiIe representing a smal1 series, is very gratifying to us. It is a11 the more remarkabIe when the type of patient is considered. They were all indigents, on the ward of a municipa1 hospita1, many feebIe, poorIy nourished, a fair percentage of them emergency cases, and many had not avaiIed themseIves for unknown periods of the usua1 sanitation afforded by soap and water.
NEW SERIES VOL.XXXIX,
No. 2
White,
et aI.-Zephiran
To check our results, we requested the gynecoIogic division to carry out a series of cases using the same details in skin preparation with 335 per cent iodine as the germicide. There were twenty-five such cases, a11 abdomina1 operations. In the contro1 biopsies there was growth in every case. No biopsies were taken from the iodine-treated skin, but seven infected wounds were present in the twenty-five cases. CONCLUSIONS
The reduction in wound infection, judging by our experience over a long period with many other antiseptics, is too striking to be termed an accident or a fortuitous crrcumstance. WhiIe the number of cases in which zephiran was used was a comparativeIy smaI1 one, there are sufficient data to warrant the statement that it is a safe and effective germicide and justifies an extended tria1. SUMMARY
In a series of seventy-six cases, using zephiran as a skin germicide, wound infection foIIowed in one case, an incidence of 1.3 per cent. There is reasonabIe doubt about skin contamination in this case.
American JournaI of Surgery
609
In fifty-one cases from skin cut from areas prepared with zephiran, cuItures showed growth in two cases. Growth was present in a11 controIs. In a comparative study of twenty-five cases in which Iaparotomy was performed with 334 per cent tincture of iodine, there were infected wounds in seven cases or 28 per cent. No skin irritation was noted with zephiran even under adhesive pIaster. We wish to express our thanks to Dr. H. H. LefNer for his vaIuabIe Iaboratory work. REFERENCES I. DESKOWITZ, M. W. Some germicidal and physiological properties of a mixture of high moIecuIar alkyI-dimethyLbenzyI-ammonium chlorides. UnpubIished report from the bacterioIogic Iaboratories of the CoIIeae of Phvsicians and Sureeons. CoIumbia University, New”York. 2. HEINEMAN, P. G. Antiseptic properties of akyIdimethyl-benzyI-ammonium chIorides. J. Am. Pbarm. A., 21: 71I (Aug.) 1937. 3. DUNN, CECIL G. A mixture of high moIecuIar alkyldimethyI-benzyI-ammonium chIorides as an antiseptic. Proc. Sot. Exper. Biol. @ Med., 35: 427, I
1936.
4. DUNN, CECIL G. Antiseptic and germicida1 properties of a mixture of aIkyI-dimethyl-benzyIammonium chlorides. Am. J. Hyg., 26: 46 (JuIy) 1937. 5. DOMAGK, GERHARDT. A new class of disinfectants. Deutscb. med. Wcbnscbr., 21: 827, 1935.