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The 23 Greatest Research Priorities in Musculoskeletal Infection

By Dr. Edward Schwarz

Musculoskeletal infections (MSKI) remain the bane of orthopaedic surgery, resulting in grievous illness and inordinate costs that threaten healthcare systems. As prevention, diagnosis and treatment remain largely unchanged over the last fifty years, a 2nd International Consensus Meeting on MSKI (ICM 2018) was completed on July 25-27, 2018 in Philadelphia, PA, USA. This 2-year long process derived the final set of 652 consensus questions, which were discussed and voted on by 658 scientists, internists and orthopaedic surgeons representing 92 countries. As critical outcomes of ICM 2018 include determining the current incidence and costs of MSKI, establishing what is currently known about the basic science of MSKI and effective standards of care, and deriving the greatest research priorities, two ICM 2018 research workgroups (RW) were assembled to accomplish these tasks. The findings appear in the May 2019 issue of the Journal of Orthopaedic Research.

The Consensus Article by Saeed et al (DOI: 10.1002/jor.24229) reports the findings of the 28-member Biofilm RW, which highlights 13 cutting-edge areas of MSKI and fundamental knowledge gaps in this field. The RW’s consensus spans conclusions on the molecular nature and function of biofilm, the mechanism by which biofilms resist antibiotics and host immunity, microbial synergizes in polymicrobial infections, diagnostics for biofilm on implants, definitions for minimum biofilm eradication concentration (MBEC) of anti-infective agents, and the potential of bacteriophage therapy. The Consensus Article by Schwarz et al (DOI:10.1002/jor.24293) presents the results of the 29-member General RW and has two salient features: up-to-date data on the current and projected incidences of infection, and costs per patient for all orthopaedic subspecialties, which range from 0.1%-30%, and $17,000-$150,000. The RW also reviewed all of the questions from ICM 2018 and determined that 23 of them are high priorities for research funding. These questions fall within six thematic categories: Acute vs. Chronic Infection, Host Immunity, Antibiotics, Diagnosis, Research Caveats, and Modifiable Factors.

To disseminate this information, the Journal of Orthopaedic Research established a new category of publication: Consensus Articles. These invited peer-reviewed manuscripts are submitted by a large group of recognized thought leaders who utilize an established methodology (e.g. the Delphi method) to derive a consensus on important issues based on established literature, non-peer reviewed information, and expert opinion. The resulting summary is intended to provide a broad audience guidance on the controversies and major unmet needs in the field, and to define the clinical and economic significance of the problems by providing consensus data on the incidences of the clinical problem, and costs. The Orthopaedic Research Society is supporting this effort by hosting free downloadable PDFs of the consensus questions, response, and rationale: Biofilm RW’s PDFs and General Assembly RW’s PDFs.  These high-impact Consensus Articles can positively influence multidisciplinary investigative teams with the will to solve these problems and private foundations, governmental agencies and commercial funding mechanisms who need to provide the medical community the resources necessary to establish best practices with scientific evidence.

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Paper of the week: Large variations in clinical antibiotic activity against Staphylococcus aureus biofilms of periprosthetic joint infection isolates.

Paper of the week: Large variations in clinical antibiotic activity against Staphylococcus aureus biofilms of periprosthetic joint infection isolates. Mandell JB, Orr S, Koch J, Nourie B, Ma D, Bonar DD, Shah N, Urish KL. J Orthop Res. 2019 Mar 27. doi: 10.1002/jor.24291

Summary by Dr Sreeram Penna

In this study researchers assessed the efficacy of various antibiotics against staphylococcal aureus bacterial isolates in both planktonic and biofilm stages. They have measured minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for isolates in planktonic state and minimum biofilm inhibitory concentration (MBIC) and minimum biofilm bactericidal concentration (MBBC) for bacteria isolates grown in biofilm state. They have tested two lab strains USA300 and SH1000 and 10 Methicillin resistant Staphylococcus aureus (MRSA) clinical isolates and 8 Methicillin sensitive Staphylococcus aureus (MSSA) clinical isolates. They have tested these isolates against various dilutions of vancomycin, rifampin, gentamycin, trimethoprim/sulphamethoxazole, doxycycline and daptomycin. In addition to above MSSA isolates were tested with cefazolin and nafcillin and MRSA isolates were tested with clindamycin and linezolid.

Results showed that across the bacterial isolates MIC concentrations varied largely for gentamicin, trimethoprim/sulfamethoxazole and vancomycin (approximately 1.5 log spread) and smaller variation (0.5 log spread) for rifampin, doxycycline, and daptomycin. Similarly, MBC concentrations varied significantly (2 log spread) for all antibiotics. Rifampin was superior to other antibiotics against planktonic cultures with MBC concentrations ranging from 0.13 to 8 microgram / ml. With biofilm isolates most antibiotics showed significant variability (2 to 3 log spreads) in MBIC except daptomycin. Of all the antibiotics tested only rifampin, doxycycline, and daptomycin had impact on 48-hour mature biofilms, with biofilm MBCs ranging from 80 to 2000 μg/ml. In conclusion this research shows variable impact of antibiotics on different strain isolates and also difference in susceptibilities of isolates in planktonic stages versus biofilm stages.

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Paper of the week: Modifiable Factors as Current Smoking, Hypoalbumin, and Elevated Fasting Blood Glucose Level Increased the SSI Risk Following Elderly Hip Fracture Surgery.

Paper of the week: Modifiable Factors as Current Smoking, Hypoalbumin, and Elevated Fasting Blood Glucose Level Increased the SSI Risk Following Elderly Hip Fracture Surgery. Ma T, Lu K, Song L, Wang D, Ning S, Chen Z, Wu Z. J Invest Surg. 2019 Mar 19:1-9. doi: 10.1080/08941939.2018.1556364.

Summary by Dr Sreeram Penna

Aim of this retrospective study was to find incidence of infection post hip fracture surgery in elderly population. In addition, researchers were also looking for independent risk factors associated with infection in this cohort. Infections were classified in to superficial and deep infections based on combination of clinical findings of persistent wound discharge, wound dehiscence, gangrene and abscess development, need for surgical intervention and positive cultures. 611 patients were included in the final study. Over all infection incidence was 4.4% (27/611), superficial infection was 3.1% (21/611) and deep infection was 1.3% (6/611). Multivariate analysis showed that body mass index, current smoking, surgical duration of more than 2 hours, preoperative hospital stay more than 7 days, ASA class of III and IV, albumin levels less than 35 gram per liter, and fasting blood glucose more than 110 mg/dl were know to be independent risk factors for development of infection following hip fracture surgery.

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Paper of the week: Perioperative Antibiotic Prophylaxis in Total Joint Arthroplasty: A Single Dose Is as Effective as Multiple Doses.

Paper of the week: Perioperative Antibiotic Prophylaxis in Total Joint Arthroplasty: A Single Dose Is as Effective as Multiple Doses. Tan TL, Shohat N, Rondon AJ, Foltz C, Goswami K, Ryan SP, Seyler TM, Parvizi J. J Bone Joint Surg Am. 2019 Mar 6;101(5):429-437. doi: 10.2106/JBJS.18.00336.

Summary by Dr. Sreeram Penna

This study is a retrospective study comparing the incidence of periprosthetic joint infection (PJI) in primary joint arthroplasty who had a single dose of prophylactic antibiotic versus multiple doses at the time of surgery. A total of 20,682 patients were included in the study. Of these 4523 had a single dose and 16159 had multiple doses. All patients who had an infection within 1 year were identified and confirmed with MSIS criteria. In addition, researchers calculated and recorded the patient’s preoperative infection risk score.

The results showed that overall rates of PJI were 0.60% (27/4523) in patients receiving a single dose and 0.88% (142/16159) in patients receiving multiple prophylactic antibiotic doses. Researchers also noted that both patient groups were significantly different in various demographics (age, sex, BMI, comorbidities, ASA score, length of stay). Researchers then performed multivariate analysis after controlling for potential confounders and found no significant difference between the PJI rate between both groups. They have also used propensity score matching with preoperative risk score and found no increase in PJI rate in patients with a single dose of prophylactic antibiotic at the primary procedure.

Although this study has limitations of being retrospective study and statistically significant differences between two groups, it provides the necessary evidence to support the use of single-dose prophylactic antibiotic during primary joint arthroplasty.

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ICM document update: Spanish translation completed

ICM document Spanish translation is completed. It is available online at the following link.