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Postsurgical deep musculoskeletal infections are a major clinical problem in Orthopaedic Surgery. A serum-based nomogram, which can objectively risk-stratify patients, and aid surgeons in delineating infection risk associated with orthopedic surgical interventions, would be immensely helpful. Here, we constructed a multi-parametric nomogram based on serum anti-Staphylococcus aureus antibody responses, patient characteristics including demographics and standard clinical tests. This nomogram was formally tested in a prospective cohort study comparing 303 hospitalized patients with culture-confirmed S. aureus infection compared with a cohort of 223 healthy screened preoperative patients. Serum anti-S. aureus antibody responses, standard of care clinical tests, and patient demographic data were utilized to perform multivariate logistic regression analysis to quantify the presence of infection and adverse outcome using odds ratios (OR) and to assess predictive ability via area under the ROC curve (AUC). At enrollment, high anti-S. aureus IgG titers were predictive of infection. Remarkably, low serum albumin was found to be significantly associated with infection (OR = 479.963, 95% CI 61.59 - 3740.33, p 0.0001) and this finding was surprisingly higher than BMI or HbA1c-associations. Combining all risk factors in the nomogram yielded a diagnostic AUC of 0.949 for predicting S. aureus infection. Our results indicate that a serum-based multi-parametric nomogram can be useful in diagnosing S. aureus infections, and importantly, malnourishment is significantly associated with these infections.

Bone infection represents a serious complication of orthopedic surgery and Staphylococcus aureus is the most common pathogen. To improve the understanding of host-pathogen interaction, we developed a biospecimen registry (AO Trauma CPP Bone Infection Registry) to collect clinical data, bacterial isolates, and serum from patients with S. aureus bone infection. A prospective multinational registry with a 12-month follow-up was created to include adult patients (18 years or older) with culture-confirmed S. aureus infection in long bones after fracture fixation or arthroplasty. Baseline patient attributes and details on infections and treatments were recorded. Blood and serum samples were obtained at baseline, 6, and 12 months. Patient-reported outcomes were collected at 1, 6, and 12 months. Clinical outcomes were recorded. Two hundred and ninety-two patients with fracture-related infection (n = 157, 53.8%), prosthetic joint infection (n = 86, 29.5%), and osteomyelitis (n = 49, 16.8%) were enrolled. Methicillin-resistant S. aureus was detected in 82 patients (28.4%), with the highest proportion found among patients from North American sites (n = 39, 48.8%) and the lowest from Central European sites (n = 18, 12.2%). Patient outcomes improved at 6 and 12 months in comparison to baseline. The SF-36 physical component summary mean (95% confidence interval) score, however, did not reach 50 at 12 months. The cure rate at the end of the study period was 62.1%. Although patients improved with treatment, less than two-thirds were cured in 1 year. At 12-month follow-up, patient-reported outcome scores were worse for patients with methicillin-resistant S. aureus infections. ispartof: JOURNAL OF ORTHOPAEDIC RESEARCH vol:39 issue:1 pages:136-146 ispartof: location:United States status: published

While it is well known that Staphylococcus aureus establishes chronic implant-associated osteomyelitis by generating and persisting in biofilm, research to elucidate pathogen, and host specific factors controlling this process has been limited due to the absence of a quantitative in vivo model. To address this, we developed a murine tibia implant model with ex vivo region of interest (ROI) imaging analysis by scanning electron microscopy (SEM). Implants were coated with Staphylococcus aureus strains (SH1000, UAMS-1, USA300LAC) with distinct in vitro biofilm phenotypes, were used to infect C57BL/6 or Balb/c mice. In contrast to their in vitro biofilm phenotype, results from all bacteria strains in vivo were similar, and demonstrated that biofilm on the implant is established within the first day, followed by a robust proliferation phase peaking on Day 3 in Balb/c mice, and persisting until Day 7 in C57BL/6 mice, as detected by SEM and bioluminescent imaging. Biofilm formation peaked at Day 14, covering ∼40% of the ROI coincident with massive agr-dependent bacterial emigration, as evidenced by large numbers of empty lacunae with few residual bacteria, which were largely culture negative (80%) and PCR positive (87.5%), supporting the clinical relevance of this implant model. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1311–1319, 2015.

Towards the development of a methicillin-resistant Staphylococcus aureus (MRSA) vaccine we evaluated a neutralizing anti-glucosaminidase (Gmd) monoclonal antibody (1C11) in a murine model of implant-associated osteomyelitis, and compared its effects on LAC USA300 MRSA versus a placebo and a Gmd-deficient isogenic strain (ΔGmd). 1C11 significantly reduced infection severity, as determined by bioluminescent imaging of bacteria, micro-CT assessment of osteolysis, and histomorphometry of abscess numbers (p

New healthcare demands for quality measures of elective procedures, such as anterior cruciate ligament (ACL) reconstructive surgery, warrant the establishment of high throughput outcomes for high volume clinics. To this end, we evaluated the PROMIS and GAITRite as physical function outcome measures to quantify early healing and post-operative complications in 106 patients at pre-operative and 3, 10, 20 and 52 weeks post-ACL reconstruction with bone-tendon-bone autograft, and compared the results to the current IKDC validated outcome measure. The results showed that both PROMIS and GAITRite were significantly quicker to administer versus IKDC (p