Frank A. Kapral

TOXIC-SHOCK SYNDROME ASSOCIATED WITH PHAGE-GROUP-I STAPHYLOCOCCI

Abstract Seven children (aged 8-17 years) presented with a high fever, headache, confusion, conjunctival hyperaemia, a scarlatiniform rash, subcutaneous œdema, vomiting, watery diarrhœa, oliguria, and a propensity to acute renal failure, hepatic abnormalities, disseminated intravascular coagulation, and severe prolonged shock. One patient died, one had gangrene of the toes, and all have had fine desquamation of affected skin and peeling of palms and soles during convalescence. Five patients were studied prospectively. Staphylococcus aureus related to phage-group I was isolated from mucosal (nasopharyngeal, vaginal, tracheal), or sequestered (empyema, abscess) sites, but not from blood. This organism produces an exotoxin which causes a positive Nikolsky sign in the newborn mouse and which is biochemically, pathologically, and immunologically distinct from phage-group-II stapphylococcal exfoliatin.

STAPHYLOCOCCUS AUREUS: SOME HOST‐PARASITE INTERACTIONS

The accumulation of detailed knowledge on host-parasite interactions is obviously a complex and difficult task that requires multiple efforts and is often dependent on progress in other areas. It has become increasingly clear that staphylococcal infections actually represent a group of diseases, each with its own set of parameters, though the same host and bacterium is involved. There is no simple answer to the question of what is responsible for virulence or what constitutes an immune mechanism. The organism is capable of producing a large array of biologically active substances, and the host can manifest many responses; the importance of all of these can vary markedly with different types of staphylococcal disease.

Inhibition of Staphylococcus aureus Delta Hemolysin by Phospholipids

Summary A number of unsaturated phospholipids were found to be selective inhibitors of Staphylococcus aureus delta hemolysin. This inhibitory effect was manifest promptly after addition to delta hemolysin. A synergism between alpha and delta hemolysin was evident in the kinetics of rabbit erythrocyte lysis.

Whipple's disease. Characterization of anaerobic corynebacteria and demonstration of Bacilli in vascular endothelium.

The first patient with a well documented case of Whipples disease, in whom an anaerobic Corynebacteria was successfully cultured both from the mucosa of the small intestine and from mesenteric lymph nodes is described. Electron microscopic studies demonstrated the organisms in the mucosa of the small intestine and in lymph nodes. In addition, vascular invasion was observed and the vascular endothelium contained a large number of bacilli. These observations support the concept that anaerobic Corynebacteria may be important in Whipples disease, but the precise role of this organism in the pathogenesis of this disorder remains to be elucidated.The first patient with a well documented case of Whipples disease, in whom an anaerobic Corynebacteria was successfully cultured both from the mucosa of the small intestine and from mesenteric lymph nodes is described. Electron microscopic studies demonstrated the organisms in the mucosa of the small intestine and in lymph nodes. In addition, vascular invasion was observed and the vascular endothelium contained a large number of bacilli. These observations support the concept that anaerobic Corynebacteria may be important in Whipples disease, but the precise role of this organism in the pathogenesis of this disorder remains to be elucidated.

THE NATURE OF ALPHA TOXIN PRODUCTION BY STAPHYLOCOCCUS AUREUS GROWN IN VIVO.

Summary When S. aureus 18Z grown within dialysis sacs was implanted in the peritoneal cavity of mice, alpha toxin was produced only during periods of multiplication. The amount of toxin produced per coccus increased markedly during the first 3 generations, was maximal by the fifth, and remained constant thereafter.

988 AMPICILLIN (A)|[sol]|NAFCILLIN (N) SYNERGY AGAINST AMPICILLIN-RESISTANT HAEMOPHILUS INFLUENZAE TYPE B (HibR)

Three infants with HibR bacteremic infections had good clinical responses to A and N therapy. This observation prompted in vitro evaluation of this combination against HibR clinical isolates. Minimal inhibitory concentrations (MICs) in μg/ml of A and N alone and in combination were determined by a microdilution method for 5 HibR isolates; A: 8-32, N: 8-16, A/N: 0.5-1/1-2 at a 104 colony forming unit/ml inoculum. Results indicate synergy since the MIC of each drug alone is at least 4 times greater than the MIC of the drug in combination. The proposed mechanism of A/N synergy is N inhibition of β-lactamase which protects A from hydrolysis allowing it to exert its antibacterial effect. A spectrophotometric assay of β-lactamase activity was used to study this proposal. The supernatant of sonified HibR cell preparations was the β-lactamase source; A served as substrate; and N, methicillin(M) and oxacillin(O) were studied as potential inhibitors. The hydrolysis of A in the absence and presence of the inhibitors obeyed Michaelis-Menten kinetics. N, M, and 0 acted as purely competitive inhibitors of A hydrolysis with N being the most effective and 0 the least as evidenced by KI values of 7.10 × 10−2, 3.16 × 10−1, and 3.35 μM respectively. These findings provide an explanation for the observed in vitro A/N synergy which in vivo may have been responsible for favorable outcomes in 3 infants with HibR bacteremic infections treated with A and N.

820 TOXIC SHOCK SYNDROME ASSOCIATED WITH PHAGE GROUP I STAPHYLOCOCCI

Six otherwise normal children (ages 8-16 years) have presented sporadically in 1977 with a clinically distinct syndrome of high fever (40-41°C), headache, confusion, conjuctival hyperemia, a diffuse scarlatinaform erythroderma, subcutaneous edema, vomiting, watery diarrhea, hypotension, oliguria, and a propensity to develop acute renal failure, hepatic abnormalities, D.I.C., and severe prolonged shock. One patient died, one developed gangrene of the toes, and all have had fine desquamation of affected skin surfaces as well as marked peeling of palms and soles during convalescence. All five patients studied prospectively have grown phage group I Staphylococcus aureus from mucosal sites (nasopharyngeal, vaginal, tracheal) but not from the blood or CSF. These organisms have been shown to produce a toxin which causes a positive Nikolskys sign in the newborn mouse model but is biochemically, pathologically, and immunologically distinct from the phage group II staphylococcal exfoliatin. Only one of seven contacts and 0/3 older children with other febrile exanthematous illness grew a similar phage group I staphylococcus. The toxic shock syndrome appears to be a dramatic new clinical entity possibly related to toxin production by certain staphylococci.