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.


  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.

Paper of the week: Stopping antibiotics after surgical amputation in diabetic foot and ankle infections-A daily practice cohort.

Paper of the week: Stopping antibiotics after surgical amputation in diabetic foot and ankle infections-A daily practice cohort. Rossel A, Lebowitz D, Gariani K, Abbas M, Kressmann B, Assal M, Tscholl P, Stafylakis D, Uçkay I. Endocrinol Diabetes Metab. 2019 Feb 6;2(2): e00059. doi: 10.1002/edm2.59. eCollection 2019 Apr.

Summary by Dr. Sreeram Penna

This is a retrospective cohort study included adult diabetic foot and ankle infection patients who underwent amputation. Researchers studied benefits of continuing antibiotics after amputation. Overall 482 episodes in 258 patients were included in the study. Osteomyelitis was diagnosed in 239 cases. Median duration of antibiotics post amputation was 7 days. In 109 episodes antibiotic was discontinued immediately after surgery. Using multivariate analysis researchers concluded that neither duration of post-operative antibiotics (Hazards ratio: 1.0; CI 0.99 – 1.01) nor immediate discontinuation (Hazards ratio: 0.9; CI 0.5 -1.5) altered overall failure rate. Researchers also stressed importance of amputation with clear margins.


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.