Background: Diabetic foot osteomyelitis (DFO) poses a major disease burden. It can generally be treated with long-term antibacterial therapy. International guidelines recommend to base antibacterial therapy choices on percutaneous bone biopsy culture, while in practice, therapy is frequently based on (less invasive) ulcer bed cultures. It is currently unknown if treatment outcomes of DFO differ depending on the chosen diagnostic strategy.Methods: The BeBoP trial is a multicentre; randomised controlled; physician-, researcher- and subject-blinded; clinical trial comparing two diagnostic strategies in persons with DFO. Culture-directed antibacterial therapy will be based on either percutaneous bone biopsy culture results (intervention group) or ulcer bed biopsy culture results (comparison group). We will enrol 80 subjects with diabetes mellitus (≥ 18 years) and DFO, and we will use block randomisation stratified per centre to randomise them in a 1:1 allocation. The primary outcome is remission of DFO 12 months after enrolment. The secondary outcomes are the time to remission, signs of inflammation or ulceration at the primary location of infection at 6 and 12 months, microbiological and molecular profiles of culture outcomes, surgical interventions including amputation, total antibacterial therapy duration, infection-free survival days, adverse events, quality of life and survival. We will compare the outcomes by intention-to-treat and per-protocol analysis.Discussion: We aim to compare clinical remission in persons with DFO treated with antibacterial therapy based on either percutaneous bone biopsy culture results or ulcer bed biopsy culture results.Trial registration: Netherlands Trial RegisterNL 7582. Registered on 05 March 2019

Background: Antibiotic use prior to biopsy acquisition in people with diabetes and osteomyelitis of the foot (DFO) might influence bacterial yield in cultures or induce bacterial resistance. Obtaining reliable culture results is pivotal to guide antibiotics for conservative treatment of DFO. Methods: We prospectively analysed cultures of ulcer bed and percutaneous bone biopsies of people with DFO and investigated if antibiotics administered prior to (<2 months up to 7 days) biopsy acquisition led to more negative cultures or increased resistance in virulent bacteria. We calculated relative risks (RR) and 95% confidence intervals (CIs). We stratified analyses according to biopsy type (ulcer bed or bone). Results: We analysed bone and ulcer bed biopsies of 64 people, of whom 29 received prior antibiotics, and found that prior antibiotics did not lead to a higher risk of at least one negative culture (RR 1.3, (CI 0.8–2.0), nor did prior treatment increase the risk of a specific type of negative culture (RR for bone cultures 1.15, (CI 0.75–1.7), RR for ulcer bed cultures 0.92 (CI 0.33–2.6)) or both cultures (RR 1.3 (CI 0.35–4.7), and neither did it increase the risk of antibiotic resistance in the combined bacterial results of ulcer bed and bone cultures (RR 0.64, (CI 0.23–1.8)). Conclusions: Antibiotics administered up to 7 days before obtaining biopsies in people with DFO do not influence culture yield regardless of biopsy type, nor are they associated with more antibiotic resistance.

Background: In clinical practice the diagnosis of diabetic foot osteomyelitis (DFO) relies on cultures of bone or ulcer bed (UB) biopsies, of which bone biopsy is reference standard. The slow growth or fastidious nature of some bacteria, hamper expeditious detection and identification. Rapid molecular techniques may solve both issues, but their additional value for everyday practice is unknown. We investigated the concordance between conventional culture, the molecular techniques Molecular Culture (MC), and illumina 16S rRNA gene amplicon (16S) sequencing in people with DFO. Methods: In the BeBoP trial, bone and UB biopsies were obtained from people with DFO who visited Amsterdam UMC. These biopsies were analysed using 1) conventional culture, 2)MC, a rapid broad range PCR analysing the 16S-23S ribosomal-interspace-region, and 3) 16S sequencing, and evaluated concordance among these techniques. Results: We analysed 20 samples (11 bone and 9 UB) of 18 people. A total of 84 infectious agents were identified, 45 (54%) by all techniques, an additional 22 (26.5%, overall 80.5%) by both MC and 16S, and the remaining 16 species by culture and MC or 16S, or by a single method only. MC and 16S identified anaerobes not detected by culturing in 5 samples, and the presence of bacteria in 7 of 8 culture-negative (6 bone, 2 UB) samples. Conclusion: The high level of concordance between MC and 16S and the additional ability of molecular techniques to detect various bacteria not detected by culturing opens up prospects for routine use of fast molecular techniques, in clinical settings including DFO. Trial registration: The BeBoP trial is retrospectively registered on 05–03-2019 in Netherlands Trial Register: NL 7582.

Purpose: Different bacteria lead to divers diabetic foot infections (DFIs), and some bacteria probably lead to higher amputation and mortality risks. We assessed mortality and amputation risk in relation to bacterial profiles in people DFI and investigated the role of sampling method. Methods: We included people (> 18 years) with DFI in this retrospective study (2011–2020) at a Dutch tertiary care hospital. We retrieved cultures according to best sampling method: (1) bone biopsy; (2) ulcer bed biopsy; and (3) swab. We aggregated data into a composite determinant, consisting of unrepeated bacteria of one episode of infection, clustered into 5 profiles: (1) Streptococcus and Staphylococcus aureus; (2) coagulase-negative Staphylococcus, Cutibacterium, Corynebacterium and Enterococcus; (3) gram-negative; (4) Anaerobic; and (5) less common gram-positive bacteria. We calculated Hazard Ratio’s (HR’s) using time-dependent-Cox regression for the analyses and investigated effect modification by sampling method. Results: We included 139 people, with 447 person-years follow-up and 459 episodes of infection. Sampling method modified the association between bacterial profiles and amputation for profile 2. HR’s (95% CI’s) for amputation for bacterial profiles 1–5: 0.7 (0.39–1.1); stratified analysis for profile 2: bone biopsy 0.84 (0.26–2.7), ulcer bed biopsy 0.89 (0.34–2.3), swab 5.9*(2.9–11.8); 1.3 (0.78–2.1); 1.6 (0.91–2.6); 1.6 (0.58–4.5). HR’s (95% CI’s) for mortality for bacterial profiles 1–5: 0.89 (0.49–1.6); 0.73 (0.38–1.4); 2.6*(1.4–4.8); 1.1(0.58–2.2); 0.80(0.19–3.3). Conclusions: In people with DFI, there was no association between bacterial profiles in ulcer bed and bone biopsies and amputation. Only in swab cultures, low-pathogenic bacteria (profile 2), were associated with a higher amputation risk. Infection with gram-negative bacteria was associated with a higher mortality risk. This study underlined the possible negative outcome of DFI treatment based on swabs cultures.

Background: The optimal antimicrobial treatment duration for diabetes-related foot osteomyelitis (DFO) currently needs to be determined. We systematically reviewed the effects of short and long treatment durations on outcomes of DFO. Methods: We performed a systematic review searching Cochrane, CENTRAL, MEDLINE, Embase, and CINAHL Plus from inception up to 19 January 2024. Two independent reviewers screened the titles and abstracts of the studies. Studies comparing short (6 weeks) treatment durations for DFO were included. The primary outcome was amputation; the secondary outcomes were remission, mortality, costs, quality of life, and adverse events. Risk of bias and GRADE were assessed. Results: We identified 2708 references, of which 2173 remained after removing duplicates. Two studies were included. Differences in methodology precluded a meta-analysis. The primary outcome, major amputation, was reported in one study, with a rate of 10% in both the intervention and comparison groups (p = 1.00), regardless of treatment duration. For the secondary outcome, remission rates, the first study reported 60% in the intervention group versus 70% in the comparison group (p = 0.50). In the second study, remission rates were 84% in the intervention group versus 78% in the comparison group (p = 0.55). Data for the outcomes mortality, costs, and quality of life were not available. Short treatment duration may lead to fewer adverse events. The risk of bias was assessed as low to moderate, and the level of evidence ranged from very low to moderate. Conclusions: Our findings suggest that for DFO, there is no difference between a shorter and more prolonged duration of antimicrobial treatment regarding amputation and remission, with potentially fewer adverse events with shorter treatment durations. However, the uncertainty stems from limited, heterogeneous studies and generally low-quality evidence marred by moderate biases, imprecision, and indirectness. More high-quality studies are needed to substantiate these findings.

Additional file 3:. Reporting checklist for protocol of a clinical trial.