A Comparative Study of the Renal Damage Produced in Mice by Various Lots of Bacitracin 1

Abstract

In recent publications it has been suggested that bacitracin grown by the deep-tank method shows a higher degree of nephrotoxicity than the bacitracin produced by surface culture methods (1). The studies being reported were designed to compare the two types of material from a strictly objective standpoint. The survivors were sacrificed at the end of the experimental period and their kidneys fixed in 10% formalin. A series of 10 mice injected with saline served as the controls. RESULTSEvidence of gross pathology as expressed by the degree of ischemia present was noted and recorded on a four-plus graded scale at the time of autopsy. Histologic sections were made of the kidneys. These sections were stained with hematoxylineosin and were graded for evidence of renal changes independently (LWS) without knowledge of the gross renal classification. Very little, if any, correlation between the degree of renal ischemia grossly and the extent of renal damage microscopically was found.In Table I the acute toxicity of the various lots of bacitracin is shown along with the biologic activity of each lot.In Table II the incidence of microscopic renal injury in mice injected intravenously with various lots of bacitracin in dosages of 50, 100, and 200 TABLE I

The Effect of Bacitracin on Renal Function

“…Since this work was submitted for publication, a number of reports (21)(22)(23)(24)(25), relating to the toxicity of bacitracin have appeared.…”

“…It is of interest that proteinuria appeared at the same time in all groups. Also of interest is the rapid decline in the magnitude of proteinuria (Figure 1) Following baseline determinations of the above functions as well as of blood non-protein nitrogen and urea nitrogen, bacitracin2 was administered intramuscularly in a dosage of 1,500 units per kilogram body weight followed by a second injection of the same magnitude 24 hours later. This dosage was selected to correspond to the daily therapeutic dosage employed by others in the treatment of various surgical and medical infections (2,4,5).…”

Biochemistry of Antibiotics

“…Bacitracin ministration of bacitracin caused renal damage in humans (163) and in mice (164). CircuUn (Bacillus circulans) .-Mc Leod (165) and Murray et al (166) su bmitted papers almost simultaneously describing antibiotic substances from a Bacillus resembling B. circulans.…”