Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT

Background Management of bone and joint infection commonly includes 4–6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. Objective To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. Design Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. Setting Twenty-six NHS hospitals. Participants Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). Interventions Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. Main outcome measure The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. Results Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was –1.38% (90% confidence interval –4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. Limitations The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. Conclusions PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. Future work Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics. Trial registration Current Controlled Trials ISRCTN91566927. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 38. See the NIHR Journals Library website for further project information

Diagnosing diabetic foot infection : the role of imaging and a proposed flow chart for assessment

Diabetes mellitus, a major current epidemic, is frequently complicated by foot infections that are associated with high morbidity. Diagnosing these infections, especially whether or not underlying bone is involved, poses clinical challenges, but is crucial to making proper decisions regarding therapeutic strategies. The most effective means of managing patients with a diabetic foot infection is within the framework of a multidisciplinary team. Present diagnostic efforts are aimed at developing better methods to differentiate uninfected from infected soft tissue wounds, to determine when bone infection is present, and to more clearly define when infection has resolved with treatment. Imaging studies play a major role in diagnosis. This usually begins with plain radiographs, but when advanced imaging is needed, magnetic resonance imaging (MRI) is considered the modality of choice. Newer techniques, such as molecular hybrid imaging, positron emission tomography (PET)/computed tomography (CT) and single photon emission (SPECT)/CT using various radiotracers, play an increasing role. These tests may redefine the non-invasive diagnostic work-up of diabetic foot wounds, potentially leading to substantial improvements in patient management. As experts in infectious diseases, radiology and nuclear medicine, we reviewed the available literature on diagnosing diabetic foot infections, especially the currently available imaging techniques, and developed a proposed diagnostic flow chart, for evaluating patients with a diabetic foot wound

Prevention and management of foot problems in diabetes: A summary guidance for daily practice 2015, based on the IWGDF Guidance Documents

In this 'Summary Guidance for Daily Practice', we describe the basic principles of prevention and management of foot problems in persons with diabetes. This summary is based on the International Working Group on the Diabetic Foot (IWGDF) Guidance 2015. There are five key elements that underpin prevention of foot problems: \ud \ud (1) identification of the at-risk foot; \ud \ud (2) regular inspection and examination of the at-risk foot; \ud \ud (3) education of patient, family and healthcare providers; \ud \ud (4) routine wearing of appropriate footwear, and; \ud \ud (5) treatment of pre-ulcerative signs. \ud \ud Healthcare providers should follow a standardized and consistent strategy for evaluating a foot wound, as this will guide further evaluation and therapy. The following items must be addressed: type, cause, site and depth, and signs of infection. There are seven key elements that underpin ulcer treatment: \ud \ud (1) relief of pressure and protection of the ulcer; \ud \ud (2) restoration of skin perfusion; \ud \ud (3) treatment of infection; \ud \ud (4) metabolic control and treatment of co-morbidity; \ud \ud (5) local wound care; \ud \ud (6) education for patient and relatives, and; \ud \ud (7) prevention of recurrence. \ud \ud Finally, successful efforts to prevent and manage foot problems in diabetes depend upon a well-organized team, using a holistic approach in which the ulcer is seen as a sign of multi-organ disease, and integrating the various disciplines involved

The 2015 IWGDF guidance documents on prevention and management of foot problems in diabetes: development of an evidence-based global consensus

Foot problems complicating diabetes are a source of major patient suffering and societal costs. Investing in evidence-based, internationally appropriate diabetic foot care guidance is likely among the most cost-effective forms of healthcare expenditure, provided it is goal-focused and properly implemented. The International Working Group on the Diabetic Foot (IWGDF) has been publishing and updating international Practical Guidelines since 1999. The 2015 updates are based on systematic reviews of the literature, and recommendations are formulated using the Grading of Recommendations Assessment Development and Evaluation system. As such, we changed the name from Practical Guidelines' to Guidance'. In this article we describe the development of the 2015 IWGDF Guidance documents on prevention and management of foot problems in diabetes. This Guidance consists of five documents, prepared by five working groups of international experts. These documents provide guidance related to foot complications in persons with diabetes on: prevention; footwear and offloading; peripheral artery disease; infections; and, wound healing interventions. Based on these five documents, the IWGDF Editorial Board produced a summary guidance for daily practice. The resultant of this process, after reviewed by the Editorial Board and by international IWGDF members of all documents, is an evidence-based global consensus on prevention and management of foot problems in diabetes. Plans are already under way to implement this Guidance. We believe that following the recommendations of the 2015 IWGDF Guidance will almost certainly result in improved management of foot problems in persons with diabetes and a subsequent worldwide reduction in the tragedies caused by these foot problems

Septic Tenosynovitis of the Hand: Factors Predicting Need for Subsequent Débridement.

BACKGROUND: Treatment of septic hand tenosynovitis is complex, and often requires multiple débridements and prolonged antibiotic therapy. The authors undertook this study to identify factors that might be associated with the need for subsequent débridement (after the initial one) because of persistence or secondary worsening of infection. METHODS: In this retrospective single-center study, the authors included all adult patients who presented to their emergency department from 2007 to 2010 with septic tenosynovitis of the hand. RESULTS: The authors identified 126 adult patients (55 men; median age, 45 years), nine of whom were immunosuppressed. All had community-acquired infection; 34 (27 percent) had a subcutaneous abscess and eight (6 percent) were febrile. All underwent at least one surgical débridement and had concomitant antibiotic therapy (median, 15 days; range, 7 to 82 days). At least one additional surgical intervention was required in 18 cases (median, 1.13 interventions; range, one to five interventions). All but four episodes (97 percent) were cured of infection on the first attempt after a median follow-up of 27 months. By multivariate analysis, only two factors were significantly associated with the outcome "subsequent surgical débridement": abscess (OR, 4.6; 95 percent CI, 1.5 to 14.0) and longer duration of antibiotic therapy (OR, 1.2; 95 percent CI, 1.1 to 1.2). CONCLUSION: In septic tenosynovitis of the hand, the only presenting factor that was statistically predictive of an increased risk of needing a second débridement was the presence of a subcutaneous abscess. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III