HerbertL Dupont

EXPERIMENTAL MODELS IN THE INVESTIGATION OF THE VIRULENCE OF DYSENTERY BACILLI AND ESCHERICHIA COLI

The knowledge gained from experiments in laboratory models has been very useful in helping us to reach our present understanding of the pathogenesis of some diarrheal diseases of human beings. This is especially true of bacillary dysentery. Dysentery may be defined as a syndrome in which blood, inflammatory cells, and mucus are present in the watery stool. A cardinal feature of classical shigellosis is an ulcerative lesion of the colonic mucosa, for it is through this defect in the epithelial barrier that the red blood cells reach the intestinal lumen. Thus, in order to gain some insight into at least one aspect of the pathogenesis of classical bacillary dysentery, one must understand how the ulcerative lesion evolves. The previous concept of the evolution of the colonic ulcer envisioned consecutive waves of absorption and excretion of heat-stable toxin across the intestinal wall, resulting in hypoxia and death of the epithe1ium.l For a variety of reasons2 we rejected this hypothesis and sought an alternate explanation. We started by using a virulent Shigella flexneri 2a strain and an avirulent mutant derived from it. As far as could be ascertained, the two strains were identical, with the exception that the parent strain caused disease when fed to starved, opiated guinea pigs or to rhesus monkeys, while the mutant failed to do so. When animals infected with either of the strains were studied using the fluorescent antibody technique, a distinctly different pattern of distribution of the organisms in the intestine was observed. The avirulent mutant was seen only in the lumen of the bowel. On the other hand the virulent bacteria were present in the epithelial cells of the intestine, and also both free and within phagocytic cells in the lamina propria. Rarely were the organisms viewed in the submucosa or in the mesenteric lymph nodes.2 From the results of these experiments we concluded that an essential step in the pathogenesis of bacillary dysentery is the penetration of the intestinal epithelial cell by the pathogen. If the organism is unable to enter the epithelium for one reason or another, few, if any, signs of disease are observed. Similar observations have been made independently by Voino-Yasenetsky and Khavkin and confirmed in extensive studies by Ogawa and colleague^.^ Other procedures are available to test for the ability of dysentery bacilli to

COMPARATIVE EFFICACY OF CHLORAMPHENICOL, AMPICILLIN, AND CO-TRIMOXAZOLE IN THE TREATMENT OF

Two clinical trials were conducted to compare the efficacy of 3 antimicrobial agents often recommended for the treatment of typhoid fever. Chloramphenicol was more effective than parenteral ampicillin or oral co-trimoxazole (trimethaprim/sulphamethoxazole) in reducing the duration of fever. Oral chloramphenicol was more effective than parenteral chloramphenicol probably because oral doses resulted in higher blood concentrations of the drug. However, parenteral chloramphenicol was given during the initial period of acute illness, without loss of efficacy.

Minocycline treatment failure in pneumonia caused by minocycline-sensitive Streptococcus pneumoniae.

A previously healthy 23-year-old white woman had fulminant pneumococcal pneumonia complicated by empyema and bilateral pneumothoraces. Despite early treatment with the recommended doses of minocycline, the disease progressed. The S pneumoniae isolate was resistant to a 30microgram tetracycline disk and showed an MIC of 3.13microgram/ml for minocycline and 12.5 microgram/ml for tetracycline; these levels are considered by the manufacturer to indicate sensitivity to minocycline and intermediate sensitivity to tetracycline. The tetracyclines, including minocycline, should not be used to treat bacterial pneumonia since resistant strains of pneumococci are not uncommon and inffective treatment can lead to rapid progression of the infection. This case suggests that the levels of minocycline considered to indicate sensitivity in vitro be reassessed.