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Paper of the Week: Four versus six weeks of antibiotic therapy for osteoarticular infections after implant removal: a randomized trial.

Four versus six weeks of antibiotic therapy for osteoarticular infections after implant removal: a randomized trial. Benkabouche M, Racloz G, Spenchbach H, Lipsky BA, Gaspoz JM, Uçkay I. J Antimicrob Chemother 2019 May 18. Doi: 10.1093/jac/dkz202.

Summary and editorial by Dr. Marjan Wouthuyzen-Bakker

For several decades, osteoarticular infections after implant removal have been treated with antibiotics for a duration of six weeks. In this single-centre, unblinded, randomized trial, 123 patients were randomized to 4 or 6 weeks of systemic antibiotic treatment after infected hardware was removed (i.e. prosthetic joints, orthopaedic plates or nail implants). Most patients received intravenous antibiotics for 4 days before switching to oral. Intraoperative cultures were taken after a minimum antibiotic holiday of 2 weeks before re-implantation of hardware. Microbiological recurrence during reimplantation was observed in 2 of 62 patients in the 4-week arm (3.2%) versus 1 of 61 patients in the 6-week arm (1.6%) (P=0.57). Recurrence of clinical infection occurred in 4 out of 62 patients in the 4-week arm (6.5%) and in 3 out of 61 patients in the 6-week arm (4.9%) (P=0.74) during a minimum follow-up of 6 months (median follow-up of 2.2 years).

Based on these results, the authors demonstrate non-inferiority of a 4-week antibiotic treatment course compared to 6-weeks for osteoarticular infections after implant removal. It should be noted that a large proportion of included infections were acute and thus, its non-inferiority can probably not be extrapolated one on one to chronic infections with the presence of mature biofilm.

The study conducted by Benkabouche et al. again demonstrates that the habit of prescribing long courses of antibiotics can be questioned. Nowadays, several studies suggest that antibiotic duration can be shortened for indications that traditionally have been treated for longer periods, in particular prosthetic joint infections, provided that proper surgical debridement has been performed [1]. In addition, in agreement with the OVIVA trial [2], early switch to oral antibiotics can be safely performed if antibiotics are chosen with adequate oral bioavailability.

References

  1. Lora-Tamayo J, Euba G, Cobo J et al. Short- versus long-duration levofloxacin plus rifampicin for acute staphylococcal prosthetic joint infection managed with implant retention: a randomised clinical trial. Int J Antimicrob Agents. 2016 Sep;48(3):310-6.
  2. Li HK, Rombach I, Zambellas R et al. Oral versus Intravenous Antibiotics for Bone and Joint Infection. N Engl J Med. 2019 Jan 31;380(5):425-436.
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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: Risk factors associated with periprosthetic joint infection after total elbow arthroplasty

Paper of the week: Risk factors associated with periprosthetic joint infection after total elbow arthroplasty. Somerson JS, Boylan MR, Hug KT, Naziri Q, Paulino CB, Huang JI. Shoulder Elbow. 2019 Apr;11(2):116-120. doi: 10.1177/1758573217741318.

Summary by Dr Sreeram Penna

This is a retrospective registry study of patients who had total elbow arthroplasty (TEA). Data was obtained from New York SPARCS database. Study included 1452 patients who had TEA in New York state between 1st Jan 2003 to 30th September 2012. Overall rate of infection was 3.72% (54/1452). There were 30 early infections (2.1%), 17 delayed infections (1.2%) and seven late infections (0.5%). Regression model showed that main risk factors associated with periprosthetic joint infection in TEA was rheumatoid arthritis (OR:3.31; p<0.001), tobacco use disorder (OR:3.39; p=0.003) and hypothyroidism (OR:2.04; p=0.045).

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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.