Harry N. Beaty

Staphylococcus aureus bacteremia: Current clinical patterns☆

One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics.

Further Characterization of the Impaired Bactericidal Function of Granulocytes in Patients with Poorly Controlled Diabetes

Granulocytes of patients with diabetes mellitus have an impaired capability to engulf bacteria, but it is not clear whether subsequent intracellular killing, which has separate energy sources, is also defective. We separately assayed engulfment and intracellular killing of Staphylococcus aureus 502a by granulocytes of 17 diabetic patients with fasting hyperglycemia to better characterize the phagocytic defect. Diabetic granulocytes engulfed a smaller proportion than controls of a 106 inoculum of bacteria after 20 minutes of incubation in vitro (56.8 ± 9.4 per cent versus 72.4 ± 3.6 per cent, mean ± S.E. of 10 patients and paired controls, p < 0.05), but after 60 minutes of incubation this defect had disappeared. Intracellular killing of staphylococci by granulocytes from seven diabetics (68.6 ± 8.9 per cent of a 106 inoculum) was less (p < 0.01) than that of paired controls (80.3 ± 4.5 per cent) after two hours of incubation. Seven patients were retested during a period of improved diabetes control; intracellular killing of staphylococci by granulocytes of six of the seven increased considerably and either exceeded the paired control value or approached it to within 75 per cent. These data suggest that a primary defect exists in intracellular killing of staphylococci by granulocytes from poorly controlled diabetics in addition to that previously shown in engulfment. This bactericidal activity becomes more efficient when the diabetes is brought under better control.

Experimental pneumococcal meningitis: III. Chemotactic activity in cerebrospinal fluid

Summary Chemotactic activity was assayed in CSF of rabbits with pneumococcal meningitis to further characterize the inflammatory response in this infection. CSF chemotactic activity was detected in increasing levels for 72 hr after infection. Activity was stable at 56° and was inactivated by agents which denature proteins. Gel filtration demonstrated two chemotactically active fractions in infected CSF with mol wts of approximately 3000 and 11,000. Bacterial products appear to account for a portion of the observed CSF chemotactic activity, but the role of host factors remains to be clarified.

Effect of Experimental Pneumococcal Meningitis on Respiration and Circulation in the Rabbit

Pathophysiological studies in bacterial meningitis in man have been limited by clinical variability and the necessity for immediate therapy. After the development of a reliable animal model of pneumococcal meningitis, we studied respiration and circulation in 25 anesthetized New Zealand white rabbits during untreated pneumococcal meningitis and in 33 healthy controls. In meningitis, we found increased lactic acid in cerebrospinal fluid (CSF). Increased ventilation, perhaps due to CSF lactic acid accumulation, resulted in respiratory alkalosis; the concomitant lowering of Pco(2) acted as a homeostatic mechanism to restore pH toward normality in the CSF. Hyperventilation increased with the duration of the illness. Cardiac output was also increased with decreased peripheral vascular resistance but with only slight reduction in mean systemic and pulmonary arterial pressures. In the final hour of life, peripheral vascular resistance fell further; ventilation declined and then abruptly ceased while cardiac activity continued. Lactic acid accumulation in the CSF, found in both experimental and human pneumococcal meningitis, may cause the hyperventilation found in this disease and may contribute to death.

Serologic reactions of bovine procarboxypeptidase A and carboxypeptidase A

Abstract Serologic reactions of bovine procarboxypeptidase A and carboxypeptidase A (peptidyl- L -amino-acid hydrolase, EC 3.4.2.1) are compared through immunological reactions in agar and studies of the inhibition of enzymic reactions by antibody. 1. 1. Rabbits immunized with carboxypeptidase A α or procarboxypeptidase A-S 6 form antibodies with physical and immunological properties of 7-S γ-globulin. A procedure for the isolation of 7-S γ-globulin from the serum of immunized rabbits is described and utilized for the evaluation of the serologic reactions of the antigens and related proteins in a system relatively free of non-specific protein. 2. 2. Some of the antigenic relationships between carboxypeptidase A α , procarboxypeptidase A-S 6 , procarboxypeptidase A-S 5 and Fraction II of procarboxypeptidase A are demonstrated by immunologic reactions in agar. The effect of homologous and heterologous antibody on the enzymic activity of carboxypeptidase A and partially activated procarboxypeptidase A-S 6 are compared.

The Effect of Uremia on the Pyrogenic Response of Rabbits

Summary In order to determine the effect of uremia on the febrile response to pyrogen-ic stimuli, normal rabbits and animals made uremic with cephaloridine were challenged with endotoxin and leukocyte pyrogen and their febrile response was recorded. In addition, the ability of granulocytes from untreated and uremic antimals to elaborate leukocyte pyrogen in vitro was evaluated. No difference was observed in the febrile response of normal or uremic animals to these pyrogens nor was any impairment noted in the ability of granulocytes from uremic animals to generate leukocyte pyrogen. A correlation between high levels of blood urea nitrogen, low values of serum calcium, and a lowered basal body temperature was found.

Effect of inhibitors of protein synthesis on pyrogen production by granulocytes.

Summary The formation of pyrogen by rabbit leukocytes can be inhibited significantly by treating animals with high doses of chloramphenicol. The mechanism of this effect probably involves inhibition of protein synthesis at some point during the development of granulocytes. On the basis of experiments with inhibitors of protein synthesis it appears that leukocytes from inflammatory exudates do not synthesize much additional pyrogen during incubation in vitro.