THE PRESERVATION OF OPHTHALMIC PREPARATIONS 385 There is no evidence of resistance by Ps.aeruginosa to polymyxin B sulphate. This antibiotic is limited by its relatively low activity against gram-positive organisms, and some species of Proteus (47). The U.S.P. XI suggests the use of a combination of 1000 units/ml polymyxin B sulphate and 0.01% benzalkonium chloride. The newer recommended ophthalmic preservatives include several promising compounds, nearly all of which require more work before their acceptance. Chlorhexidine is an exception in that it has been introduced into the Australian Pharmaceutical Formulary, and experience in practice has been gained. Nevertheless there are problems of compatibility with this compound, and it is not uniformly satisfactory with all ophthalmic solutions (50). When suitably formulated, the following compounds have reasonable scientific support for their use as ophthalmic preservatives in some in- stances: 0.05% Chlorocresol, 0.5% chlorbutol, 0.01% benzalkonium chloride, 0.005% chlorhexidine. Experimental evidence is required about mercury deposition on the lens before the mercurials may be used with confidence. Little attention has been paid to the use of combinations of agents. The recommendation of a combination of polymyxin B sulphate and benzalkonium chloride by U.S.N.F. XI would seem to be based on attain- ing broad spectrum activity rather than an expectation of synergism against any particular organism. Attention has been drawn to the dangers of indiscriminately combining antimicrobial agents (56,57). Preliminary work has shown synergism between phenylethyl alcohol and the organic mercurials (58). It would appear that the future lies more in the understanding of the nature of the resistance of Ps.aeruginosa to chemical inactivation than in the discovering of other new agents. The literature possesses several monuments to the capacity of this beast, literally to eat the agents used against it. The acquired resistance to a quaternary ammonium compound has been eliminated in the presence of E.D.T.A. (59), and the U.S.N.F. XI has suggested its use for that purpose. It has been shown that cells grown in the presence of Tween 80 are much less resistant to the action of several agents than are cells grown in plain broth (60,61). It has been suggested that the resistance of Ps.aeruginosa is connected with its slime production and its membrane permeability, both of which may be affected by Tween 80. The problems of sterilization and preservation have for too long been

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