M. Glenn Koenig

Nocardia infections in a general hospital.

A number of recent reports have stressed the importance of Nocardia asteroides both as a primary pathogen and as an opportunistic invader.l-s Indeed, the incidence of nocardiosis appears to be increasing, presumably because of a greater prevalence of patients with compromised host defenses.2 Of major significance is the fact that nocardiosis, though frequently life-threatening, shows a gratifying response to therapy if it is recognized early enough. Nocardiosis most often presents as a pulmonary infection, but involvement of nearly every organ and tissue in the body has been recogni~ed.~,~.~ The resultant clinical picture can be extremely varied, and the correct etiology may go unrecognized for a prolonged period of time. We have seen an impressive array of nocardial infections at the Vanderbilt University Medical Center, many of which had unusual presentations. Our experience with the diagnosis and management of these cases is the basis of this report.

THE IMPORTANCE OF SURFACE ANTIGENS IN STAPHYLOCOCCAL VIRULENCE

While certain biological characteristics of staphylococci such as coagulase and hemolysin production correlate reasonably well with “pathogenicity,” the precise factors which define staphylococcal virulence remain obscure. Although Gilbert in 1931 suggested that the possession of a capsule might be a determinant of staphylococcal virulence,’ until recently i t has generally been thought that surface or capsular antigens played no role in determining pathogenicity of staphylococci. Since 1961, however, the virulence of an unusual group of staphylococcal strains has been shown to be directly related to the presence of surface or capsular antigens which retard phagocytosis. I t is the purpose of this paper to summarize the work we have done with these strains and to indicate how these microorganisms may relate to the problem of human staphylococcal disease. In 1958 Hunt and Moses‘ observed that the Smith strain of Staphylococcus aureus produced two colonial variants in serum or plasma soft agar which differed markedly in their virulence for mice. The diffuse colonial variant (see FIGURE 1) consistantly killed mice when injected intraperitoneally, while similar numbers of the compact colonial variant failed to produce fatal disease. Because this appeared to be a unique model in which to study factors correlating with virulence among staphylococci, the biologic characteristics and the experimental infections produced by these two colonial variants of the Smith strain have been closely scrutinized in our lab~ora tory .~ The observation of Hunt and Moses was readily confirmed. Marked differences in mortality were noted after the intraperitoneal administration of the Smith diffuse and compact variants. Injection of approximately 5 x 10’ or more diffuse variant staphylococci resulted in the death of most animals 5.5 to 12 hours later; while injection of similar numbers of compact variant staphylococci failed to kill mice. The results of such an experiment are shown in TABLE 1. The majority of the biologic characteristics of the two variants were found to be identical. Both strains produced similar amounts of alpha hemolysin; both produced delta hemoIysin; both produced simiIar quantities of free coagulase; the antibiotic sensitivities of both strains were almost identical; and neither strain could be typed by the standard typing phages either at

Staphylococcal clumping and fibrinogen and fibrin degradation products in inflammatory exudate.

Summary Sterile peritoneal exudate induced in rabbits by infusion of glycogen was found to contain a material causing staphylococcal clumping. Removal of fibrinogen from the exudate partially diminished the clumping titer. The remaining active material was not clottable by thrombin, evoked a precipitation line with antifibrinogen serum in double gel diffusion tests, and was sensitive to heating at 60°. A similar material interacting with staphylococci possessing clumping factor was detected in a cytoplasmic fraction (8200g supernatant) of PMN leukocytes. These data indicate that rabbit peritoneal exudate contains not only fibrinogen but its derivatives. Such derivatives are also present in exudative leukocytes probably due to the phagocytosis and digestion of fibrin. The presence of degradation products of fibrinogen and fibrin in exudative fluid reflects local activation of fibrinolysis in inflammatory foci.

The Clinical Aspects of Botulism

Botulism may have been known to antiquity. K. F. Meyer (1928) suggests that Emperor Leo VI of Byzantium (886–911 A.D.) earned the sobriquet, “The Wise,” or “The Philosopher,” possibly because of an edict that forbade the eating of blood sausage due to its harmfulness to health. Nine centuries later physicians of southern Germany recognized the disease as the often fatal syndrome that sometimes followed the consumption of a regionally popular blood sausage. As a consequence the manufacture of that dangerous food product came under strict government surveillance, and the term botulism (botulus is Latin for sausage) was applied to the illness. In 1895 an outbreak of a strange neuroparalytic disorder occurred among 34 members of a musical society who, after performing at a funeral in the Belgium village of Ellezelles, had eaten some raw, salted ham. Three of the musicians died, while 10 became critically ill. The Belgian bacteriologist van Ermengem investigated the outbreak and, in a paper that remains a classic in the annals of bacteriology, showed that a spore-forming anaerobic bacillus produced a toxin responsible for the disease in the sick musicians and caused the illness previously termed botulism (van Ermengem, 1897).

The Hepatic Uptake of Bacterial Endotoxin I. The Influence of Humoral and Cellular Factors

Summary An isolated perfused rabbit liver model was utilized to study the hepatic uptake of 51Cr-endotoxin. Perfusates containing 5% normal rabbit serum produced relatively low uptake of endotoxin compared to the striking enhancement of uptake caused by 5% serum from endotoxin-tolerant rabbits. The serum factor (or factors) responsible for hepatic uptake of endotoxin was heat-stable. There was not a close correlation between the “O” agglutinin titer of serum samples and their effect on hepatic uptake. There was no significant difference between endotoxin uptake recorded in perfused livers from normal rabbits and those from endotoxin-tolerant rabbits. We wish to thank Miss Laura Treanor and Mrs. Sheila Timmons for their valuable assistance in the performance of these studies.

The Treatment of Blastomycosis with Amphotericin B

Although antibiotic agents were introduced beginning in the mid-1930s, there was no really useful agent for the treatment of deepseated mycotic infections such as histoplasmosis, cryptococcosis, coccidioidomycosis, and blastomycosis until the introduction of amphotericin B in the late 1950s. The present report will review some of the available information concerning amphotericin B and will present our ideas about its use in the treatment of blastomycosis.