Percutaneous Bone Biopsy for Diabetic Foot Osteomyelitis: A Systematic Review and Meta-Analysis

Abstract Background Diabetes is the leading cause of lower extremity nontraumatic amputation globally, and diabetic foot osteomyelitis (DFO) is usually the terminal event before limb loss. Although guidelines recommend percutaneous bone biopsy (PBB) for microbiological diagnosis of DFO in several common scenarios, it is unclear how frequently PBBs yield positive cultures and whether they cause harm or improve outcomes. Methods We searched the PubMed, EMBASE, and Cochrane Trials databases for articles in any language published up to December 31, 2019, reporting the frequency of culture-positive PBBs. We calculated the pooled proportion of culture-positive PBBs using a random-effects meta-analysis model and reported on PBB-related adverse events, DFO outcomes, and antibiotic adjustment based on PBB culture results where available. Results Among 861 articles, 11 studies met inclusion criteria and included 780 patients with 837 PBBs. Mean age ranged between 56.6 and 71.0 years old. The proportion of males ranged from 62% to 86%. All studies were longitudinal observational cohorts, and 10 were from Europe. The range of culture-positive PBBs was 56%–99%, and the pooled proportion of PBBs with a positive culture was 84% (95% confidence interval, 73%–91%). There was heterogeneity between studies and no consistency in definitions used to define adverse events. Impact of PBB on DFO outcomes or antibiotic management were seldom reported. Conclusions This meta-analysis suggests PBBs have a high yield of culture-positive results. However, this is an understudied topic, especially in low- and middle-income countries, and the current literature provides very limited data regarding procedure safety and impact on clinical outcomes or antibiotic management.

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A Bayesian meta-analytic approach for safety signal detection in randomized clinical trials

Clinical Trials ◽

10.1177/1740774516683920 ◽

2017 ◽

Vol 14 (2) ◽

pp. 192-200 ◽

Cited By ~ 2

Author(s):

Motoi Odani ◽

Satoru Fukimbara ◽

Tosiya Sato

Keyword(s):

Clinical Trials ◽

Adverse Event ◽

Adverse Events ◽

Hierarchical Structure ◽

Meta Analysis ◽

Event Data ◽

Analysis Model ◽

Exact Test ◽

Adverse Event Data ◽

Fisher’S Exact Test

Background/Aim: Meta-analyses are frequently performed on adverse event data and are primarily used for improving statistical power to detect safety signals. However, in the evaluation of drug safety for New Drug Applications, simple pooling of adverse event data from multiple clinical trials is still commonly used. We sought to propose a new Bayesian hierarchical meta-analytic approach based on consideration of a hierarchical structure of reported individual adverse event data from multiple randomized clinical trials. Methods: To develop our meta-analysis model, we extended an existing three-stage Bayesian hierarchical model by including an additional stage of the clinical trial level in the hierarchical model; this generated a four-stage Bayesian hierarchical model. We applied the proposed Bayesian meta-analysis models to published adverse event data from three premarketing randomized clinical trials of tadalafil and to a simulation study motivated by the case example to evaluate the characteristics of three alternative models. Results: Comparison of the results from the Bayesian meta-analysis model with those from Fisher’s exact test after simple pooling showed that 6 out of 10 adverse events were the same within a top 10 ranking of individual adverse events with regard to association with treatment. However, more individual adverse events were detected in the Bayesian meta-analysis model than in Fisher’s exact test under the body system “Musculoskeletal and connective tissue disorders.” Moreover, comparison of the overall trend of estimates between the Bayesian model and the standard approach (odds ratios after simple pooling methods) revealed that the posterior median odds ratios for the Bayesian model for most adverse events shrank toward values for no association. Based on the simulation results, the Bayesian meta-analysis model could balance the false detection rate and power to a better extent than Fisher’s exact test. For example, when the threshold value of the posterior probability for signal detection was set to 0.8, the false detection rate was 41% and power was 88% in the Bayesian meta-analysis model, whereas the false detection rate was 56% and power was 86% in Fisher’s exact test. Limitations: Adverse events under the same body system were not necessarily positively related when we used “system organ class” and “preferred term” in the Medical Dictionary for Regulatory Activities as a hierarchical structure of adverse events. For the Bayesian meta-analysis models to be effective, the validity of the hierarchical structure of adverse events and the grouping of adverse events are critical. Conclusion: Our proposed meta-analysis models considered trial effects to avoid confounding by trial and borrowed strength from both within and across body systems to obtain reasonable and stable estimates of an effect measure by considering a hierarchical structure of adverse events.

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Blood cultures after bone biopsy in diabetic foot osteomyelitis

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2017.02.011 ◽

2017 ◽

Vol 89 (1) ◽

pp. 78-79 ◽

Cited By ~ 3

Author(s):

Paule Letertre-Gibert ◽

Françoise Desbiez ◽

Magali Vidal ◽

Natacha Mrozek ◽

Pereira Bruno ◽

...

Keyword(s):

Diabetic Foot ◽

Bone Biopsy ◽

Blood Cultures ◽

Diabetic Foot Osteomyelitis

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Are surrogate markers for diabetic foot osteomyelitis remission reliable?

Journal of the American Podiatric Medical Association ◽

10.7547/20-147 ◽

2020 ◽

Author(s):

Peter A Crisologo ◽

Matthew Malone ◽

Javier La Fontaine ◽

Orhan Oz ◽

Kavita Bhavan ◽

...

Keyword(s):

Soft Tissue ◽

Diabetic Foot ◽

Bone Biopsy ◽

Surrogate Marker ◽

Surrogate Markers ◽

Bone Culture ◽

Soft Tissue Infections ◽

Diabetic Foot Infections ◽

Index Site ◽

Diabetic Foot Osteomyelitis

Background: The aim of this study was to evaluate surrogate markers commonly used in the literature for diabetic foot osteomyelitis remission after initial treatment for diabetic foot infections. Methods: Thirty-five patients with diabetic foot infections were prospectively enrolled and followed for 12 months. Osteomyelitis was determined from bone culture and histology initially and for recurrence. Chi square and Fischer's exact test were used for dichotomous variables and the student's t-test and Mann-Whitney U test for continuous variables with an alpha of 0.05. Results: Twenty-four patients were diagnosed with osteomyelitis and eleven patients with soft-tissue infections. 16.7% (n=) of patients with osteomyelitis had a re-infection based on bone biopsy. The success of osteomyelitis treatment varied based on the surrogate marker used to define remission: osteomyelitis infection (16.7%), failed wound healing (8.3%), re-ulceration (20.8%), re-admission (16.7%), amputation (12.5%). There was no difference in outcomes among patients who were initially diagnosed with osteomyelitis and soft tissue infections. There were no differences in osteomyelitis re-infection (16.7% vs 45.5%, p=0.07), wounds that failed to heal (8.3% vs 9.1%, p=0.94), re-ulceration (20.8% vs 27.3%, p=0.67), re-admission for diabetic foot infections at the same site (16.7% vs 36.4%, p=0.20), amputation at the same site after discharge (12.5% vs 36.4%, p=0.10). Osteomyelitis at the index site based on bone biopsy indicated that failed therapy was 16.7%. Indirect markers demonstrated a failure rate ranging from 8.3-20.8%. Conclusions: Most osteomyelitis markers were similar to markers in soft tissue infection subjects. Commonly reported surrogate markers were not shown to be specific to identify patients that failed osteomyelitis treatment when compared with patients that had soft tissue infections. Given this, these surrogate markers are not reliable for use in practice to identify osteomyelitis treatment failure.

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Optimization of the antibiotic management of diabetic foot infections - Protocol for two randomized controlled trials

10.21203/rs.2.15844/v2 ◽

2019 ◽

Author(s):

Felix WA Waibel ◽

Martin Berli ◽

Sabrina Catanzaro ◽

Kati Sairanen ◽

Madlaina Schöni ◽

...

Keyword(s):

Soft Tissue ◽

Adverse Events ◽

Antibiotic Therapy ◽

Diabetic Foot ◽

Randomized Clinical Trials ◽

Antibiotic Use ◽

Wound Debridement ◽

Diabetic Foot Infections ◽

Systemic Antibiotic Therapy ◽

Antibiotic Management

Abstract Background: Few studies address the appropriate duration of antibiotic therapy for diabetic foot infections (DFI); with or without amputation. We will perform two randomized clinical trials (RCT) to reduce the antibiotic use and associated adverse events in DFI. Methods: We hypothesize that shorter durations of post-debridement systemic antibiotic therapy are non-inferior (10% margin, 80% power, ɑ 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 RCT is “remission of infection” after a minimal follow-up of two months. The secondary outcomes for both RCT 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 vs. 3 weeks of antibiotic therapy for residual osteomyelitis (positive microbiological samples of the residual bone stump); or 1 vs. 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 vs. 20 days of antibiotic therapy for soft tissue infections; and 3 vs. 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 parellel RCTs will repond to frequent questions regarding the duration of antibiotic use in the both major subsets of DFIs, to assure the quality of care, and to avoid unnecessary excesses in terms of surgery and antibiotic use. Trial registration: ClinicalTrial.gov NCT04081792. Registered on 4th September 2019. Protocol version: 2 (15th July 2019)

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Adjunctive rifampin therapy for diabetic foot osteomyelitis: a protocol for systematic review and meta-analysis

10.37766/inplasy2020.4.0084 ◽

2020 ◽

Author(s):

Yanli Zhang

Keyword(s):

Systematic Review ◽

Diabetic Foot ◽

Meta Analysis ◽

Diabetic Foot Osteomyelitis

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Time-to-Report of the Bone Culture and Microbiologic Adequacy of Empiric Antibiotics in Patient’s with Diabetic Foot Osteomyelitis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.067 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S94-S95

Author(s):

Hyun Kyung Kim ◽

Olga Vasylyeva

Keyword(s):

Diabetic Foot ◽

Bone Biopsy ◽

Anaerobic Bacteria ◽

Accurate Method ◽

Bone Culture ◽

Culture Result ◽

Gram Positive ◽

Diabetic Foot Infection ◽

Superficial Wound ◽

Diabetic Foot Osteomyelitis

Abstract Background Bone cultures in diabetic foot infection is the most accurate method to identify causative pathogen, while there is only 30% concordance between superficial wound swab and bone biopsy cultures. Diabetic foot infection is commonly polymicrobial, therefore report on the bone biopsy culture may come with several updates before it is finalized. Our study is aimed to describe how often additional pathogens were identified after patients’ discharge on antibiotics therapy for diabetic foot osteomyelitis, and evaluate microbiological appropriateness of antibiotic regimen upon discharge based on the final result of the bone culture. Methods Medical records of the patients 18 years old or older, who had inpatient bone biopsy, deep tissue debridement or amputation for diabetic foot infection, were reviewed from January 2014 through Dec 2015 in Rochester Regional Health System. Antibiotic regimens for the patients discharged before final culture result were evaluated for microbiological appropriateness by two reviewers trained in infectious diseases. Results In total, 198 procedures were screened, 158 procedures met inclusion criteria, out of which 74 patients with 80 procedures (51%) were discharged before the final culture result was available. Average time from procedure to the final culture report was 6 days, and from discharge to the final culture was 3.7 days. In most of the cases (70%, 56 out of 80) the patients were discharged on empiric regimen discordant with final culture result. Predominant organisms were Gram-positive bacteria 74%, with Gram negatives 24%, and yeast 2%. Most infections were polymicrobial (81%), mixed with anaerobic bacteria in 37%. The most frequent isolates were Staphylococcus aureus (15%), Corynebacterium (14%), anaerobic Gram-positive cocci (12%), and Staphylococcus epidermidis (8%). All negative Gram stains (31%, 25 out of 80) had positive growth on culture. Conclusion Half of the patients with diabetic foot osteomyelitis, who underwent bone biopsy, were discharged before final culture results were available. Most of them were discharged on empiric regimen discordant with final culture. This data suggests that careful outpatient follow-up on the final culture would likely result in modification of antibiotics therapy to target newly reported pathogen. Disclosures All authors: No reported disclosures.

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