Enhancement of penicillin effectiveness by traces of cobalt

Cytochemical Interpretation of the Mechanism of Penicillin Action 1

“…Some of these enhancing factors may prove to be subtances that affect the systems regulating the respiratory processes of the pathogen cells, so that the cells become more susceptible to the action of penicillin. It has been shown, for example, that small amounts of cobalt salts, which have been long known to function in oxygen transfer, when appropriately used, increase several fold the bactericidal activity of low concentrations of penicillin in vitro (179). Similarly the therapeutic effectiveness of penicillin in vivo may be doubled by appropriate use of cobalt (150).…”

“…Thus it tends to increase the action of a given concentration of penicillin. For example, co-1948] baltous salts increase two to four or more times the response in vitro to penicillin, and its effectiveness in vivo (150,179).…”

Cytochemical Mechanisms of Penicillin Action

“…It has been shown that the antibacterial action of penicillin in vitro and in vivo may be markedly enhanced by the presence of appropriately low concentrations of cobalt that do not themselves inhibit proliferation of the test organisms (Pratt and Dufrenoy, 1947b; Strait, Dufrenoy, and Pratt, 1948). This paper presents further evidence of the enhancing action of cobalt on penicillin activity and offers an explanation of the phenomenon.…”

The Enhancement of Penicillin Effectiveness in Vivo by Traces of Cobalt

“…It has been shown that the in vitro activity of dilute solutions of penicillin against Staphylococcus aureus may be increased 4-to 8-fold in the presence of trace amounts of cobalt chloride (Strait, Dufrenoy, and Pratt, 1947) and that the enhancing effect is even more pronounced when gram-negative, penicillin-Tesistant organisms such as Eberthella typhosa, Proteus vulgaris, or Escherichia .coli are used as test organisms (Pratt and Dufrenoy, 1947b). This effect seems to be specific to cobalt among the ions studied, since salts of Ni, Mn, Pt, Ir, Fe, Zn, Sr, Cd, Li, Cu, Ag, Au, and Bi have been studied, and none has been so ,effective in producing a similar enhancement of penicillin activity in the range -from 0.01 to 10 ppm.…”

“…first few hours: 70 per cent via the urine in the first 10 hours and approximately only an additional 10 per cent in the next 14 hours. It was observed in vitro (Strait, Dufrenoy, and Pratt, 1947) that there is an optimum concentration of cobalt for securing the maximum enhancement of penicillin activity and that to secure the best effect a period during which the cobalt is in contact with the pathogen before the application of penicillin is desirable. Thus it may be surmised that, in vivo, appropriate doses of cobalt chloride administered before and periodically for several hours after appropriate doses of penicillin would be effective in increasing und prolonging the effect of the penicillin.…”