Dataset Information

Anti-glucosaminidase IgG in sera as a biomarker of host immunity against Staphylococcus aureus in orthopaedic surgery patients.

ABSTRACT:

Background

Staphylococcus aureus infections remain a major complication of orthopaedic surgery. Although serum C-reactive protein is useful for diagnosis, there are no specific tests for host immunity that can assess a patient's risk for serious infection. On the basis of the identification of glucosaminidase as a potentially protective antigen in animal models, we tested the hypotheses that anti-glucosaminidase IgG (immunoglobulin G) levels vary in sera of mice and orthopaedic patients with Staphylococcus aureus infections and that physical and neutralizing titers correlate.

Methods

In vitro ELISAs (enzyme-linked immunosorbent assays) were developed to quantify binding (physical) and enzyme-neutralizing (functional) anti-glucosaminidase IgG titers. The assays were validated with use of sera from naive, Staphylococcus aureus-challenged, and glucosaminidase-immunized mice. The physical, functional, and isotype titers of anti-glucosaminidase IgG were measured in sera from twenty-four patients with a confirmed Staphylococcus aureus infection following orthopaedic surgery and in sera from twenty noninfected patients. The specificity of the anti-glucosaminidase assay was evaluated by means of linear regression and receiver-operator characteristic curve analysis.

Results

In mice, the analytic range of the physical titer assay for anti-glucosaminidase IgG was determined to be 1 ng/mL to 1 ?g/mL, and physical titers correlated with functional titers (p < 0.002). Although all patients had measurable anti-glucosaminidase IgG, the physical titers in the infected patients were significantly higher by a factor of two compared with those in the healthy controls (p = 0.015). The physical titers were significantly correlated with the functional titers (p < 0.0001). Receiver-operator characteristic curve analysis demonstrated a diagnostic specificity of 0.72 (p = 0.014) for the assay. The anti-glucosaminidase titer in almost every patient was dominated by the IgG1 isotype.

Conclusions

Humoral immunity against glucosaminidase varied in mammals with Staphylococcus aureus osteomyelitis. Anti-glucosaminidase titers in sera were a potential biomarker of infection and have the potential to assess the quality of host immunity against Staphylococcus aureus.

Clinical relevance

Staphylococcus aureus infections can be challenging to diagnose, and there is no diagnostic test for host immunity. We demonstrated a cost-effective assay for determining the anti-glucosaminidase titer, which can be readily combined with conventional serology to improve diagnosis and to assess host immunity against Staphylococcus aureus.

SUBMITTER: Gedbjerg N

PROVIDER: S-EPMC3821157 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Anti-glucosaminidase IgG in sera as a biomarker of host immunity against Staphylococcus aureus in orthopaedic surgery patients.

Gedbjerg Nina N LaRosa Rachel R Hunter Joshua G JG Varrone John J JJ Kates Stephen L SL Schwarz Edward M EM Daiss John L JL

The Journal of bone and joint surgery. American volume 20131101 22

<h4>Background</h4>Staphylococcus aureus infections remain a major complication of orthopaedic surgery. Although serum C-reactive protein is useful for diagnosis, there are no specific tests for host immunity that can assess a patient's risk for serious infection. On the basis of the identification of glucosaminidase as a potentially protective antigen in animal models, we tested the hypotheses that anti-glucosaminidase IgG (immunoglobulin G) levels vary in sera of mice and orthopaedic patients ...[more]

PMID: 24257671

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Project description:BackgroundGlucosaminidase (Gmd) is known to be a protective antigen in animal models of Staphylococcus aureus osteomyelitis. We compared the endogenous anti-Gmd antibody levels in sera of patients with culture-confirmed S. aureus bone infections to their sera at 1 year after operative treatment of the infection.MethodsA novel global biospecimen registry of 297 patients with deep-wound culture-confirmed S. aureus osteomyelitis was analyzed to assess relationships between baseline anti-Gmd serum titers (via custom Luminex assay), known host risk factors for infection, and 1-year postoperative clinical outcomes (e.g., infection control, inconclusive, refracture, persistent infection, septic nonunion, amputation, and septic death).ResultsAll patients had measurable humoral immunity against some S. aureus antigens, but only 20 patients (6.7%; p < 0.0001) had high levels of anti-Gmd antibodies (>10 ng/mL) in serum at baseline. A subset of 194 patients (65.3%) who completed 1 year of follow-up was divided into groups based on anti-Gmd level: low (<1 ng/mL, 54 patients; 27.8%), intermediate (<10 ng/mL, 122 patients; 62.9%), and high (>10 ng/mL, 18 patients; 9.3%), and infection control rates were 40.7%, 50.0%, and 66.7%, respectively. The incidence of adverse outcomes in these groups was 33.3%, 16.4%, and 11.1%, respectively. Assessing anti-Gmd level as a continuous variable showed a 60% reduction in adverse-event odds (p = 0.04) for every tenfold increase in concentration. No differences in patient demographics, body mass index of >40 kg/m, diabetes status, age of ≥70 years, male sex, Charlson Comorbidity Index of >1, or Cierny-Mader host type were observed between groups, and these risk factors were not associated with adverse events. Patients with low anti-Gmd titer demonstrated a significant 2.68-fold increased odds of adverse outcomes (p = 0.008).ConclusionsDeficiency in circulating anti-Gmd antibodies was associated serious adverse outcomes following operative treatment of S. aureus osteomyelitis. At 1 year, high levels of anti-Gmd antibodies were associated with a nearly 3-fold increase in infection-control odds. Additional prospective studies clarifying Gmd immunization for osteomyelitis are needed.Level of evidencePrognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Project description:BackgroundA multi centre double-blind randomised-controlled trial (M-RCT), carried out in the Netherlands in 2005-2007, showed that hospitalised patients with S. aureus nasal carriage who were treated prophylactically with mupirocin nasal ointment and chlorhexidine gluconate medicated soap (MUP-CHX), had a significantly lower risk of health-care associated S. aureus infections than patients receiving placebo (3.4% vs. 7.7%, RR 0.42, 95% CI 0.23-0.75). The objective of the present study was to determine whether treatment of patients undergoing elective cardiothoracic or orthopaedic surgery with MUP-CHX (screen-and-treat strategy) affected the costs of patient care.MethodsWe compared hospital costs of patients undergoing cardiothoracic or orthopaedic surgery (n=415) in one of the participating centres of the M-RCT. Data from the 'Planning and Control' department were used to calculate total hospital costs of the patients. Total costs were calculated including nursing days, costs of surgery, costs for laboratory and radiological tests, functional assessments and other costs. Costs for personnel, materials and overhead were also included. Mean costs in the two treatment arms were compared using the t-test for equality of means (two-tailed). Subgroup analysis was performed for cardiothoracic and orthopaedic patients.ResultsAn investigator-blinded analysis revealed that costs of care in the treatment arm (MUP-CHX, n=210) were on average €1911 lower per patient than costs of care in the placebo arm (n=205) (€8602 vs. €10513, p=0.01). Subgroup analysis showed that MUP-CHX treated cardiothoracic patients cost €2841 less (n=280, €9628 vs €12469, p=0.006) and orthopaedic patients €955 less than non-treated patients (n=135, €6097 vs €7052, p=0.05).ConclusionsIn conclusion, in patients undergoing cardiothoracic or orthopaedic surgery, screening for S. aureus nasal carriage and treating carriers with MUP-CHX results in a substantial reduction of hospital costs.

Dataset Information

Anti-glucosaminidase IgG in sera as a biomarker of host immunity against Staphylococcus aureus in orthopaedic surgery patients.

Background

Methods

Results

Conclusions

Clinical relevance

Publications

Anti-glucosaminidase IgG in sera as a biomarker of host immunity against Staphylococcus aureus in orthopaedic surgery patients.

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