Development of the Drug Fast Character in Vitro and its Bearing Upon Drug Rotation in the Management of Chronic Urinary Infections

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Abstract
Three strains of Bacillus coli and 1 of Bacillus lactis aerogenes were cultured on sub-lethal concentrations of 5 germicides generally used in the treatment of urinary infections, namely: silver nitrate, mercuro-chrome, formaldehyde (to represent hexamethylenamin), acrifiavin, and hexylresorcinol. An astonishing degree of resistance to the action of certain of these germicides was developed in many of the substrains and in not a single instance did any of the original cultures fail to yield 5 sub strains, each possessed of the capacity to grow in the presence of concentrations of germicides which completely prevented growth of the original culture. An enormous increase in resistance to silver nitrate was developed. The cultures showed a 500-2500-fold increase in resistance to the drug. Each of the cultures yielded substrains which continued to grow vigorously through 60 daily transfers upon agar to which 1% of silver nitrate by volume had been added. On mercurochrome the cultures showed a 16-65-fold increased resistance. The cultures yielded sub-strains showing a 5-10-fold increase in resistance to formaldehyde. Substrains developed in acriflavin were found to increase their tolerance 11-14-fold. In hexyl-resorcinol, however, none of the cultures could be made to yield substrains whose resistance was increased to anything like the degree of drug-fastness developed in the other germicides. The drug-fast character when developed was found to be highly specific. Practically none of the drug-fast substrains showed any increase in tolerance to any of the germicides other than the one to which it had been exposed. The acquirement by bacteria of a specific drug-fast character is, in some cases, accompanied by an increased sensitiveness to the action of other germicides. The results of these experiments suggest a logical plan of drug rotation in the treatment of chronic urinary infections, and also show that future research looking to the development of new urinary antiseptics should be directed toward the synthesis of organic compounds of the phenolic type rather than derivatives of the heavy metals.

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