Optimization of the antibiotic management of diabetic foot infections: protocol for two randomized controlled trials

Abstract

Background: Few studies have addressed the appropriate duration of antibiotic therapy for diabetic foot infections (DFI) with or without amputation. We will perform two randomized clinical trials (RCTs) to reduce the antibiotic use and associated adverse events in DFI. Methods: We hypothesize that shorter durations of postdebridement systemic antibiotic therapy are noninferior (10% margin, 80% power, alpha 5%) to existing (long) durations and we will perform two unblinded RCTs with a total of 400 DFI episodes (randomization 1:1) from 2019 to 2022. The primary outcome for both RCTs is remission of infection after a minimal follow-up of 2 months. The secondary outcomes for both RCTs are the incidence of adverse events and the overall treatment costs. The first RCT will allocate the total therapeutic amputations in two arms of 50 patients each: 1 versus 3 weeks of antibiotic therapy for residual osteomyelitis (positive microbiological samples of the residual bone stump); or 1 versus 4 days for remaining soft tissue infection. The second RCT will randomize the conservative approach (only surgical debridement without in toto amputation) in two arms with 50 patients each: 10 versus 20 days of antibiotic therapy for soft tissue infections; and 3 versus 6 weeks for osteomyelitis. All participants will have professional wound debridement, adequate off-loading, angiology evaluation, and a concomitant surgical, re-educational, podiatric, internist and infectiology care. During the surgeries, we will collect tissues for BioBanking and future laboratory studies. Discussion: Both parallel RCTs will respond to frequent questions regarding the duration of antibiotic use in the both major subsets of DFIs, to ensure the quality of care, and to avoid unnecessary excesses in terms of surgery and antibiotic use. Trial registration: ClinicalTrials.gov, NCT04081792. Registered on 4 September 2019.

Treating Diabetic Foot Osteomyelitis: A Practical State-of-the-Art Update

“…Among 93 enrolled patients, remission of infection was noted in 84% of patients in the three-week arm compared to 73% in the six-week arm, and the rates of adverse events were similar. The same group of Swiss investigators is currently conducting a larger trial (with a planned enrollment of 400 diabetic patients with soft tissue or bone infection of the foot) to see if they can confirm the results of this pilot study [ 53 ]. Based on currently available evidence, we think it is DFO usually does not need to be treated for more than six weeks, and even shorter durations may soon be proven to be sufficient.…”

“…In a report from Saltoğlu et al from Turkey, who treated a series of DFI patients with a total excision of infected bone, administering just five days of post-surgical antibiotic therapy was largely sufficient, although their study was not specifically aimed at the question of post-amputation antibiotic continuation [ 59 ]. The first interim analysis of an ongoing prospective trial of DFI patients in Zurich, in which the post-amputation antibiotic therapy for residual DFO is randomized to 1 versus 3 weeks [ 53 ], shows there are no apparent differences between the groups. Based on the evidence available to date, we encourage clinicians to sample the post-resection residual bone stump and administer prolonged antibiotic therapy to patients whose sample demonstrates evidence of osteomyelitis, especially when they were sampled through the operative site [ 60 ].…”

“…Based on the evidence available to date, we encourage clinicians to sample the post-resection residual bone stump and administer prolonged antibiotic therapy to patients whose sample demonstrates evidence of osteomyelitis, especially when they were sampled through the operative site [ 60 ]. In addition to limiting this prolonged antibiotic treatment to just those who have evidence of residual infection, this protocol also enhances the likelihood of identifying the true bone pathogens and their current antibiotic susceptibilities [ 13 , 53 ].…”

How good are clinicians in predicting the presence ofPseudomonasspp. in diabetic foot infections? A prospective clinical evaluation

“…The Balgrist University Hospital in Zurich is affiliated with the University of Zurich and is a tertiary referral centre for patients with DFIs. For these patients, it employs a multidisciplinary team composed of four diabetic foot surgeons, three internists, a hospital pharmacist, five specialized wound nurses, radiologist experts in musculoskeletal disorders, a diabetes nurse, three nutritionists, an orthopaedic shoe factory, prosthesis specialists and an infectious diseases physician specialized in orthopaedic infections 10 …”

“…This evaluation was conducted as part of the larger “DF‐MANAG” study conglomerate that evaluates clinical, laboratory and radiological variables associated with various outcomes in the management of the diabetic foot syndrome (Ethical Committee Zurich, BASEC number 2019‐01994). Many of the patients whose results were used in this study also participated in one or both of two randomized controlled DFI trials on the duration of antibiotic therapy (http://ClinicalTrial.gov NCT04081792; BASEC number 2019‐00778) 10 …”