Methods of Measuring Penicillin Concentrations in Body Fluids.

Inhibition of bacterial growth is the basis of the three methods commonly used for determining the potency of penicillin solutions. With the Oxford cup method (Abraham et al., 1941; Foster and Woodruff, 1944), penicillin is allowed to diffuse out into agar plates from small glass cups, and the diameters of the zones of inhibition of bacterial growth are measured. In dilution methods (Foster and Woodruff, 1943; Rammelkamp, 1942), the smallest amount of penicillin which will completely inhibit bacterial growth in solid or liquid media is the standard with which unknowns are compared. In turbidimetric methods, a range is selected in which bacterial growth is proportional to penicillin concentration, and a standard curve is constructed from turbidimetric measurements of the bacterial suspensions. These methods, developed for the titration of penicillin lots during production, have had to be modified for clinical use because the concentrations in body fluids are much smaller than those which can be most conveniently measured during penicillin manufacture. A search through the literature reveals that heretofore only the dilution method has been used clinically. In connection with extensive clinical studies, attempts have been made in thi.s laboratory to adapt all three methods to the measurement of penicillin in body fluids. The results of these studies will be presented briefly.