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

TOPICAL USES OF SEVERAL ANTIBIOTICS 317 at the site of application (1, 17, 29, 35, 39, 49). For instance, one of the dermatologists noted only one case of localized moniliasis in 125 cases, an incidence of 0.8 per cent (35, 49). One of the other groups (29) noted localized cutaneous moniliasis in seven patients out of 264 (2.6 per cent) 3 after prolonged local application. They stated that experiments conducted do not indicate that neomycin enhances the growth of fungi, nevertheless the drug should be omitted for local use if a cutaneous moniliasis is suspected. One report (49) suggested that an antimonilial agent be incorporated in the neomycin formula, and in this case methyl and butyl parahydroxybenzoate were employed in a lotion formula. Therefore, moniliasis is not a serious complication of neomycin usage, and the incidence is very low when•"the antibiotic is used dermatologically. ?•" TYROTHRICIN Tyrothricin is not one of the "newer" antibiotics on the contrary, it is one of the oldest. Nevertheless, it is fitting to include tyrothricin in this commentary of relatively newer antibiotics because: (a) it continues to enjoy wide-scale usage for its action against Gram-positive organisms (b) it is an antibiotic strictly for local use, and not systemic, this property being similar to neomycin (c) it bears further similarity in certain properties to bacitracin and neomycin, such as freedom from toxicity and a very low in- cidence of sensitivity when employed for local use (d) it is synergistic with certain other antibiotics and chemicals and (e) the main active antibiotic extracted from tyrothricin, gramicidin, is gaining in usage, at least in the pharmaceutical field. Uses: Tyrothricin is widely active against most Gram-positive organ- isms, and this action is almost wholly due to its gramicidin content (12, 59). In fact, there are early instances in literature where, apparently, the nam• gramicidin was mistakenly used synonymously with tyrothricin (60, 61). The tyrocidine in tyrothricin shows activity against certain Gram-ne'er'- rive organisms (62), but also it has much less antibacterial ability that •n gramicidin. In fact, the bactericidal ability of tyrocidine is pract•callj negligible. However, tyrocidine has the ability to lower the surface ten-' sion of aqueous solutions (63). As stated before, the use of tyrothricin is restricted to local application. It must make a direct contact in order to be of maximum effectiveness be- cause, being insoluble in water, it does not penetrate the tissues when ap- plied locally (59, 64). It is nontoxic when used, for example, in throat lozenges and mouth washes or where indicated for internal use when ingested orally. It is also non-toxic and virtually free from sensitizing action when employed in the usual dosages in topical pharmaceutical products, for dermatological therapy, for infected wounds and similar conditions.