Authors: Rimke Lagrand^1,2,, Louise Sabelis^1,2,, Merel Gramberg,^2,3,, Mehtab Ahmad⁴,

Anna van den Bosch^,2,3, Wouter Brekelmans⁵, Vincent de Groot^1,2, Martin den

Heijer^2,3, Willemijn Kortmann³, Max Nieuwdorp^2,7, Edgar Peters^2,3

Affiliations: 1. Amsterdam UMC, location Vrije Universiteit Amsterdam, Rehabilitation Medicine, De Boelelaan 1117, Amsterdam, The Netherlands; 2. Amsterdam

Movement Sciences, Rehabilitation and Development, Amsterdam, the Netherlands;

3. Amsterdam UMC location Vrije Universiteit Amsterdam, Infectious Diseases, De

Boelelaan 1117, Amsterdam, The Netherlands; 4. Liverpool Hospital, Department of Vascular Surgery, Liverpool NSW 2170, Sydney, Australia; 5. Alrijne Ziekenhuis, location Leiderdorp, Division of Surgery, Simon Smitweg 1, Leiderdorp, The Netherlands; 6. Noordwest Ziekenhuisgroep, location Alkmaar, Department of

Internal Medicine, Wilhelminalaan 12, Alkmaar, The Netherlands; 7. Amsterdam

UMC, location AMC, Departments of Internal and Experimental Vascular Medicine,

Meibergdreef 9, Amsterdam, the Netherlands

Email presenting author: r.lagrand@amsterdamumc.nl

Abstract

Background: The reference method to guide antibacterial therapy in diabetes-related osteomyelitis of the foot (DFO) is culture of a percutaneous bone biopsy. In practice, treatment is often guided by ulcer bed biopsies. It is unknown whether treatment outcomes of DFO improve if treatment is based on bone biopsy instead. This study aimed to assess outcomes of DFO treated conservatively with antimicrobial therapy based on either percutaneous bone biopsy or ulcer bed biopsy 12 months.

Methods: A multicenter double-blinded randomized clinical trial was conducted. Eighty-four participants aged ≥ 18 years underwent both a percutaneous bone biopsy and an ulcer bed biopsy. They received randomly allocated treatment based on either bone biopsy cultures or ulcer bed biopsy cultures. Remission of DFO was the primary outcome determined at 12 months of follow-up. Intention to treat (ITT) as well as per protocol (PP) generalized linear model analyses were conducted.

Results: The bone biopsy group had a (non-significantly) higher risk of not achieving remission in this study in all analyses (ITT: RR = 1.13, 95% CI = [0.80;1.60], PP: RR = 1.18, 95% CI = [0.68;2.04]). In 61 cases (85.9%) all bacteria from the blinded sampling method were susceptible to the prescribed antibiotics targeted at bacteria in the unblinded sampling method.

Conclusions: No significant difference was found between remission outcomes in subjects treated based on cultures of a bone- and an ulcer bed biopsy. In most cases, the antibiotics targeted bacteria in both samples, possibly explaining results.

Future studies may determine the presence of remission at an earlier timepoint.