Infections of the kidney are produced by bacteria that seldom infect other organs. This fact is evident from an analysis of the relative frequency with which different bacterial species are isolated in infected urines. Studies summarized in table 1 disclosed that Escherichia coli was the most frequent cause of urinary infection and Proteus species are next. Then in diminishing order there were Aerobacter aerogenes, Klebsiella pneumoniae, paracolon organisms, Pseudomonas aeruginosa, enterococci, and Alcaligenes faecalis.

The study of experimental pyelonephritis has been generally restricted to that form of the disease which develops after ligation of the ureter (1-3). When pyelonephritis is complicated by ureteral ligation, however, a clear distinction cannot be made between the effects of urinary obstruction and those of infection. We have attempted, therefore, to establish experimental pyelonephritis in the absence of hydronephrosis and have succeeded by subjecting rats to a simple new technique requiring only two steps: 1) Injection of bacteria into the blood and 2) Massage of the kidneys through the intact abdominal wall. This method has provided an experimental model which appears to reproduce closely that form of human pyelonephritis occurring in patients with no manifest hydronephrosis. In addition, it dispenses with the cumbersome surgical procedures previously required for the production of experimental pyelonephritis.This report describes the pathogenesis of pyelonephritis in rats when renal massage is combined with the inoculation of strains of Escherichia coli isolated from human infections. METHODSI. The effect of renal massage on the incidence of pyelonephritis in rats inoculated uith E. coli Sprague-Dawley rats weighing 150 to 200 gm. were divided into two groups of 15 each, and inoculated intracardially with 0.5 ml. of an 18-hour tryptose broth culture of E. coli, or approximately 10' living bacterial cells as determined by plate counts. This strain of E. coli had been isolated from the blood of a patient a few days before the experiment and had been subcultured only twice. Immediately after the bacterial inoculation, one group of 15 rats were subjected to bilateral renal massage. The kidneys of each rat were grasped by thumb 1 Aided by research grant from Public Health Service, H-1955. 2 Presented in part at the 27th Annual Meeting of The Central Society for Clinical Research, October 30, 1954. and forefinger through the intact abdominal wall (Figure 1) and gently but firmly massaged during ether anesthesia for exactly 5 minutes. In order to maintain a uniform degree of pressure on the massaged kidneys, each period of 5 minutes was divided between two of us instead of confining the total period of massage for each animal to one of several persons. The 15 rats in the second group were anesthetized under ether for 5 minutes but their kidneys were not massaged. The kidneys of a third group were massaged for 5 minutes under ether anesthesia but the rats were not inoculated with bacteria. This third group also served as controls for the experiments in section 3b and are described there.Within 48 hours, 4 rats in each group had died after the inoculation of E. coli. The survivors recovered fully and appeared in excellent condition. At the end of two weeks, the rats were sacrificed by exposure to ether and exsanguination. Approximately 1.0 ml. of blood was divided between trypticase soy broth and blood agar for culture and 0.5 ml. was used for determining urea nitrogen. The kidneys were examined grossly and then each...

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The gram-negative bacteria in the bowel, urine, and tissues in healthy and infected subjects elaborate powerful antibacterial substances known as colicins. Colicins kill gram-negative bacilli of the same, or closely related, species in vitro and have been examined for antibacterial action in vivo. Halbert and Swick (1) found that antibacterial substances, similar to colicins, were elaborated in the tissues of mice with peritoneal and subcutaneous infections produced by Escherichia coli. Branche, Young, Robinet, and Massey (2) obtained evidence that the ability of some E. coli strains to maintain themselves in the human intestine is associated with the production of colicins that suppress competing strains. In order to obtain more definite information on the activity of colicins in vivo, it would be advantageous to administer these substances to animals and examine their effect on the antibacterial properties of the body fluids. Until now, such experiments have been limited by the toxicity that results from an intimate association of colicins with the somatic 0 antigen, or endotoxin. In the present studies, an attempt was made to separate the bactericidal substance from the toxic 0 antigen, so that the colicin could be inoculated into mice and its effect observed on the bactericidal power of their sera. Mice were chosen for this purpose because their sera normally lack bactericidal power (3).

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