Preservatives for Bacteriophage Suspensions

Abstract

That bacteriophage possesses therapeutic value in certain types of bacterial infections is becoming more and more evident. 1 The increasing demand for'phages intended for therapeutic use raises a question, applicable to all biological products, as to the choice of a suitable preservative. While filtration through a sound candle generally fulfills the requirements as to sterility, it is well known that this is not absolute proof against the development of so-called “secondary cultures”. Besides this there is also the possibility of accidentally introducing organisms in ampouling the filtrate for shipment.

In choosing preservatives for'phage products 2 considerations must be borne in mind: (1) The preservative must be bactericidal without in any way impairing the potency of the'phage and (2) the concentration of the germicide which is employed should be such that it will not be toxic for the patient in the amounts which would be administered with large doses of'phage. In studies designed to elicit the value of'phage as a therapeutic agent, a third consideration enters. Here it is important to reduce the concentration to a level which will insure bacteriostasis in the ampoule and will not, on further dilution by body fluids (urine, etc.) after administration of the'phage, exercise an appreciable bactericidal effect in vivo.

Of a number of substances tested merthiolate,∗ metaphen, and potassium mercuric iodide seemed essentially to fulfill the above requirements. Jamieson and Powell 2 have reported that merthiolate in a concentration of 1-5,000 has little effect on the activity of an antistaphylococcus bacteriophage at room or ice box temperature. They also reported that “bacteriophage containing as much as 1% merthiolate for several weeks produces high titered lysing of fresh cultures.”