TOPICAL USES OF SEVERAL ANTIBIOTICS 315 Drug Resistance and Sensitivity: In the dermatological field it has been noted, by and large, that resistance of susceptible bacteria appears to be inconsequential with bacitracin (3, 11). In the use of bacitracin, many dermatologists had been impressed from the early days of usage by the low incidence of allergic reactions, as contrasted with other agents, whether antibiotics or chemicals. This good impression dealing with low incidence of sensitivity has been maintained with continued experiences, during the past several years, and right up to the present time (1, 4, 6, 8, 10, 12-15). To select an example, one group of investigators studied bacitracin for sensitivity in 288 individuals, patch testing with bacitracin ointments (1000 units per gram) for forty-eight hours. All of those tested were nega- tive for sensitivity, except one. However, this exceptional individual was also allergic to the petrolatum in the ointment and also reacted violently to liquid petrolatum, olive oil, wool fat, soybean oil bases, lard, carbowax, greaseless ointment bases, sulfonamides and quinolines (10). Another study noted that not a single instance of allergy or irritation occurred in 400 individuals, and concluded that either the incidence of total hypersensitivity of the drug is extremely low, or else the time required for local allergy to develop, if it develops, is an unusually long time (16). Still other investigators have stated that bacitracin is the least allergenic of local agents currently used, and place the sensitization rate at less than 0.5 per cent (15). Another worker pointed out that it is noteworthy that lack of irritation is an important attribute of bacitracin, since it is manda- tory to avoid agents which have any tendency to irritate the skin (17). NEOMYCIN Uses: Neomycin is a broad spectrum antibiotic. It has been shown to have a wide range of activity, in vitro and in vivo, against Gram-negative and Gram-positive organisms (5, 18, 22, 29-33). While Gram-negative bacilli, especially, exhibit a wide range of susceptibility toward neomycin, the drug is said to have no effect against fhngi (18). Neomycin is said to be bactericidal in a concentration equal to or only slightly higher than that in which it is bacteriostatic (34, 35). In some of the early published work on neomycin used topically, 200 cases were first reported (36), followed by a report totaling 675 cases, with the conclusion that neomycin was more effective for certain skin conditions than other topical agents (37). Also, later dermatoloõical studies with neomycin confirmed its valuable effects in 264 individuals with various types of cutaneous conditions. Many other published reports have further confirmed the highly satis- factory topical effects of neomycin, especially when applied either as an ointment or in aqueous solution (1, 5, 17, 35, 36, 38, 39, 40, 41, 42, 43, 44).

316 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS One of these groups of investigators not only considers neomycin a very effective and safe antibiotic for topical use in cutaneous conditions, but also calls attention to this antibiotic's apparent low potential for irritant and/or sensitization reactions (4:4). Toxicity, Sensitivity, Drug Resistance: The findings of many investigators are that toxicity following topical application of neomycin has not been noted (5, 39, 4:548). Evidently the extremely low rate of absorption ren- ders its toxic possibilities of no significance unless it would be applied to large denuded areas for prolonged periods of time (1, 18, 4:6). In cases of very extensive dermatological involvement, one viewpoint is that the topi- cal treatment should not be continued for more than six to eight days (4:9). As in the case of bacitracin applied topically, neomycin rarely induces sensitivity (5, 29, 35, 50). It can be used generally without fear of allergic. reactions (35), and it is well tolerated by patients known to be sensitive to certain other antibiotics (18). In the previously mentioned 675 cases treated for skin conditions, the individuals were surprisingly tolerant to the drug (37). In the series of 264 individuals mentioned, not a single instance of allergic sensitivity and/or primary irritant reaction was noted, and patch test reactions were completely negative in all cases (29). In still another study of 335 individ- uals, employing neomycin ointment and neomycin cream, only two patients showed irritation, one due to the ointment and the other to the cream. In both instances the preparations were stopped, neomycin lotion was sub- stituted, and the irritation and infection cleared (4:9). These latter few instances would indicate that some degree of care should be given to the nature of the bases used and, indeed, sensitivity to certain bases such as the synthetic waxes has also been implied by one investigator (51). V.ery few organisms appear to become resistant to neomycin, which is in contrast to certain other antibiotics (22, 52, 53). One explanation given is that since neomycin is bactericidal as well as bacteriostatic, organisms do not remain to become resistant (35). Several reports do make reference to the development of resistance by a few organisms, when used in medical conditions. For instance, although neomycin is said to be efficacious against Pseudomonas and Proteus, in cutaneous and pyogenic infections, resistance is said to have been demon- strated in certain species of the organisms (15). Also, certain strains of hemolytic streptococci have been noted to be resistant, and the occasional occurrence of secondary activation of Candida albicans (monilia) and Asper- gilli organisms is reported (1). When neomycin is used over a long period of time, such as may be neces- sary in the treatment of certain skin infections, several investigators have reported or mentioned a small percentage of cases of cutaneous moniliasis