Antibody responses in patients with invasive Staphylococcus aureus infections.

Correlation between antibody response and clinical outcome in Staphylococcus aureus bacteremia has yielded conflicting results. Immunization schedules have failed in clinical trials. Is the humoral response toward S. aureus of protective nature? A prospective study was performed in patients with invasive S. aureus (ISA) infections during the period 2003-2005. The antibody levels were determined at the beginning and at the end of treatment and one month later (n = 96, n = 71, and n = 51, respectively). As controls, 115 healthy individuals were used. A quantitative enzyme-linked immunosorbent assay (ELISA) against eight purified antigens was performed. Bacterial isolates were grouped as to the production of alpha-toxin, agr type, and pulsed-field gel electrophoresis (PFGE) type. Large variations were seen in the antibody levels. The levels in the second sample were the highest. A correlation between agr group, PFGE group, alpha-toxin production, and initial antibody levels was observed. Patients with fatal outcome displayed lower initial antibody levels to all antigens and significantly so in regard to teichoic acid, lipase, enterotoxin A, and scalded skin syndrome toxin. In episodes with complicated bacteremia, initial significantly low levels to teichoic acid and lipase were registered. Low initial antibody levels against several antigens were associated with increased mortality and complicated bacteremia in invasive S. aureus infections. Bacterial properties, strain, and toxin production affected the antibody response.

Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement.

The aims of this study were to evaluate the serological response to treatment with staphylococcal vaccine in fibromyalgia/chronic fatigue syndrome patients and to explore the relationship between serological response and clinical effect. Twenty-eight patients, half of whom served as controls, were recruited from a 6-month randomised trial in which repeated administration of the staphylococcal toxoid vaccine Staphypan Berna (Berna Biotech, Switzerland) was tested against placebo. Antibody status against extracellular toxins/enzymes, cell-wall components, and enterotoxins was evaluated at baseline and at endpoint. The clinical response to treatment was recorded in rating scales. In the group receiving active treatment, significant serological changes were recorded, whereas no significant changes were found in controls. Treatment led to a significantly increased capacity of serum to neutralise alpha-toxin and a significant increase in serum IgG to alpha-toxin and lipase. Furthermore, the increase in these parameters combined paralleled the improvement in clinical outcome. Thus, the greater the serological response, the greater was the clinical effect. In conclusion, this explorative study has shown that repeated administration of the Staphypan Berna vaccine in patients with fibromyalgia/chronic fatigue syndrome causes a serological response to several staphylococcal antigens, particularly to certain extracellular toxins and enzymes. The results further show that this response is related to the clinical outcome of treatment.

Fenotipos bioquímicos y fagotipos de cepas de Salmonella enteritidis aisladas en Antofagasta, 1997-2000 / Biochemical phenotypes and phage types of Salmonella enteriditis strains isolated in Antofagasta during the period 1997-2000

BACKGROUND: PhP-S48 (Phene Plate Techniques AB), a method based on biochemical phenotypes has been developed and used successfully to typify S enteritidis strains in epidemiological studies. AIM: To identify phenotypes of S enteritidis isolated from eggs, chicken meat and infected humans in Antofagasta during the period 1997-2000. MATERIAL AND METHODS: PhP-S48 and phage typing were used to identify phenotypes of 33 S enteritidis strains, sixteen isolated from poultry and 17 from clinical sources. S enteritidis ATCC17036 was used as control strain. RESULTS: Twelve biochemical phenotypes (BTs) including 4 common (C) and 8 single (S) were identified. BTs C1 y C3 containing 16 and 5 strains, respectively, accounted for 63.6 per cent of the isolates. BT C1 was found in poultry and human sources in the period 1997-2000, and BT C3 was isolated from humans, in the period 1999-2000. Using phage typing, 5 phage types (PT) and 3 strains could be not typed (NTs). PT1 and PT21 were the dominant phage types, with 14 and 13 strains respectively. Strains of PT1 were isolated from poultry and human sources in the period 1997-2000. PT21 was found in poultry samples in the period 1997-1998 and in clinical samples, in the period 1997-1998. Combination of biochemical phenotypes and phage typing divided the strains into 5 phenotypes (BT:PT). Two phenotypes were the most frequently isolated, phenotype C1:1 with 8 isolates found in eggs and humans in 1999, and phenotype C1:21 with 5 strains isolated in 1997-1999. CONCLUSIONS: These results indicate the presence of one persistent and one recently emerged phenotype among S enteritidis in Antofagasta, Chile. PhP-S48 also provided information about a relationship among the strains.

Role of staphylococcal enterotoxin A in a fatal case of endocarditis.

A young female with no identifiable risk factors developed rapid, overwhelming Staphylococcus aureus endocarditis. Despite rapid sterilization of the blood and the mitral valve with optimal antimicrobials, she had persistent septic shock. In order to investigate this, the toxin-producing capacity of the infecting strain and the patient's ability to produce antibodies were determined. The strain produced high levels of both alpha-toxin and staphylococcal enterotoxin A (SEA), whilst the patient responded with modestly high levels of antibodies to alpha-toxin and low-normal levels to SEA. The patient was most probably susceptible to the actions of SEA and developed a toxic-shock-syndrome-like disease that further aggravated her valvular dysfunction. This case illustrates that optimal antimicrobial therapy alone is not sufficient treatment in patients with persistent toxic shock and that there is a need to evaluate immunomodulatory strategies in such patients.

Antibody responses in patients with staphylococcal septicemia against two Staphylococcus aureus fibrinogen binding proteins: clumping factor and an extracellular fibrinogen binding protein.

We analyzed the serum antibody responses against two Staphylococcus aureus fibrinogen binding proteins, the cell-bound clumping factor (Clf) and an extracellular fibrinogen binding protein (Efb). The material consisted of 105 consecutive serum samples from 41 patients suffering from S. aureus septicemia and 72 serum samples from healthy individuals. An enzyme-linked immunosorbent assay (ELISA) was developed. Healthy individuals showed variable levels of antibodies against the studied antigens, and cutoff levels (upper 95th percentile) against these antigens were determined. No correlation was seen between serum antibody levels against Clf and Efb. In acute-phase samples 27% of patients showed positive antibody levels against Clf and 10% showed positive levels against Efb, while in convalescent-phase samples 63% (26 of 41) showed a positive serology against Clf and 49% (20 of 41) showed a positive serology against Efb. Antibody levels against Efb were significantly lower in the acute-phase sera than in sera from healthy individuals (P = 0. 002). An antibody response against Clf was most frequent in patients suffering from osteitis plus septic arthritis and from endocarditis (80% positive). The antibody response against Efb appeared to develop later in the course of disease. A possible biological effect of measured antibodies was demonstrated with the help of an inhibition ELISA, in which both high-titer and low-titer sera inhibited the binding of bacteria to fibrinogen. In conclusion, we have demonstrated in vivo production of S. aureus fibrinogen binding proteins during deep S. aureus infections and a possible diagnostic and prophylactic role of the corresponding serum antibodies in such infections.

Virulence factors of Staphylococcus aureus in the pathogenesis of endocarditis. A comparative study of clinical isolates.

It is now generally accepted that adherence of microorganisms to various components of cardiac valve surfaces or vegetation lodging on the heart valves is an important early event in the pathogenesis of infective endocarditis. 120 clinical isolates of S. aureus obtained from patients with endocarditis and wound infections and from nasopharyngeal carriers were quantitatively analysed in vitro for their ability to bind to fibronectin and to produce protein A and alpha-toxin. Both cell-bound and extracellular protein A were measured and alpha-toxin was determined as antigen and as haemolytic activity. The highest fibronectin binding ability was found in carrier strains while no significant differences between strains were observed regarding the production of protein A. Strains isolated from patients with endocarditis produced significantly lower amounts of alpha-toxin than did strains from the other two groups. An inverse relationship between the production of protein A and of alpha-toxin was noticed in the material. Animal passage of five strains in an experimental endocarditis model showed a good reproducibility of the test systems and one strain was upregulated in its fibronectin binding ability and in alpha-toxin production. These in vitro results indicate that the fibronectin binding ability is not the decisive adherence factor and question the role of alpha-toxin as a virulence factor in endocarditis.

Antibody response in Staphylococcus aureus septicaemia--a prospective study.

Formation of serum antibodies against alpha-toxin, teichoic acid and lipase was followed in 63 patients with Staphylococcus aureus septicaemia in 240 consecutive serum samples. Control subjects comprised 23 patients with septicaemia due to other causes and 21 febrile patients without septicaemia. An antibody response against alpha-toxin, measured by ELISA, was most common (40%) in the initial serum, but antibody to teichoic acid was present in the highest number of positive patients (60%) when samples were drawn between 0 and 30 days: 74% of the patients showed a positive antibody response to at least one of the three antigens. When complicated versus uncomplicated septicaemia was compared (samples taken 8-14 days), 14 (45%) of 31 patients had a positive response against alpha-toxin versus 12 (75%) of 16, against teichoic acid 16 (51%) of 31 versus 12 (75%) of 16 and against lipase 15 (48%) of 31 versus 8 (50%) of 16. Patients with low initial antibody levels displayed a poorer antibody response than those with higher initial antibody levels. This phenomenon was observed with all three antigens, but was most pronounced with alpha-toxin. The initial antibody levels may predict the antibody response during the course of the disease. ELISA titres against alpha-toxin correlated (r=0.87) with biological neutralising activity of the antisera. The results may indicate a biological role of serum antibodies in staphylococcal septicaemia.

Antibody response in patients with osteomyelitis of the mandible.

Patients with mandibular osteomyelitis had quantification of 10 antibodies against certain bacterial proteins and polysaccharides. Sera from 31 patients with acute or chronic osteomyelitis of the mandible and from 17 healthy controls were analyzed. Some patients showed low levels of investigated antibodies in general and a lack of specific antiteichoic acid antibodies, as well as of different antipneumococcal antibodies particularly. Two patients with therapy-resistant osteomyelitis showed IgG2 and IgG3 subclass deficiency. They had replacement therapy with intravenous 10 or 15 gm immunoglobulin every 3 weeks for 6 months. Both patients showed considerable improvement in their clinical symptoms after treatment with immunoglobulin. This study indicates that impaired humoral immune response may be of importance in subgroups of patients with osteomyelitis of the mandible.

Lipase versus teichoic acid and alpha-toxin as antigen in an enzyme immunoassay for serological diagnosis of Staphylococcus aureus infections.

Titres of IgG antibodies to Staphylococcus aureus lipase were analysed in 448 sera from patients suspected of having Staphylococcus aureus infections and the results compared to those for the routinely used staphylococcal antigens teichoic acid and alpha-toxin. The results indicated that determination of serum antibodies to lipase is a sensitive assay for serological diagnosis of staphylococcal infections and increased sensitivity may be achieved by selection of optimal antigen combinations.