Health Technology Assessment 2006; Vol 10: number 12
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EA Nelson,1* S O’Meara,1 D Craig,2 C Iglesias,1 S Golder,2 J Dalton,1 K Claxton,3 SEM Bell-Syer,1 E Jude,4 C Dowson,5 R Gadsby,6 P O’Hare7 and J Powell8
1 Department of Health Sciences, University of York, UK
2 Centre for Reviews and Dissemination, University of York, UK
3 Department of Economics and Centre for Health Economics, University of York, UK
4 Tameside General Hospital, Ashton-under-Lyne, UK
5 Department of Biological Sciences, University of Warwick, UK
6 Warwick Diabetes Care, University of Warwick, UK
7 Warwick Medical School, University of Warwick, UK
8 Faculty of Medicine, Imperial College, London, UK
* Corresponding author
Around 6% of people with diabetes have a foot ulcer or have a history of one. Diabetic foot ulcers (DFUs) are associated with increased mortality, illness and reduced quality of life. Diagnosing infection in DFU accurately and administering antibiotics may be important as infection can lead to amputation. However, using antimicrobial agents inappropriately could be costly, and lead to increased bacterial resistance. This review concentrates on the diagnosis of infection and the management of DFUs with antimicrobial agents.
The objectives of this study were:
Electronic searches were made of 19 databases covering the period from inception of each database to November 2002. In addition, handsearches of book chapters, conference proceedings, a journal and bibliographies of retrieved studies were carried out. Internet searches were also made.
Studies that dealt with the following areas were selected.
Studies of the diagnosis of infection in people with DFUs or venous leg ulceration where a reference standard was compared with an alternative assessment.
Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of the effect of microbiological analysis or antimicrobial agents in people with DFUs.
Economic evaluations of eligible interventions studied in which costs and effectiveness were synthesised.
Economic or decision analytic models in which the progress of patients with DFUs was described in sufficient detail to allow replication of the model.
Quality checklists and data extraction forms for each study design were completed by one reviewer and checked by a second. Interviews were held with experts to inform gaps in the evidence.
Studies were described in a narrative review. The structure of a decision analytic model was derived for two groups of patients in whom diagnostic tests were likely to be used.
Three studies investigated the performance of diagnostic tests for infection on populations including people with diabetic foot ulcers. One study investigated the performance of clinical assessment, another investigated the performance of punch biopsy versus wound swab and quantitative analysis and the third compared quantitative and semi-quantitative wound swabs in people with chronic wounds, including DFUs, for the identification of infection. These studies, all of which looked at identifying infection in chronic wounds, found that:
For the three diagnostic studies few people with DFUs were included, so it was not possible to tell whether diagnostic performance differs for DFUs relative to wounds of other aetiologies.
Twenty-three studies investigated the effectiveness (n = 23) or cost-effectiveness (n = 2) of antimicrobial agents for DFU. Eight studied intravenous antibiotics, five oral antibiotics, four different topical agents such as dressings, four subcutaneous granulocyte colony stimulating factor (G-CSF), one evaluated oral and topical Ayurvedic preparations and one compared topical sugar versus antibiotics versus standard care.
The majority of trials were underpowered and were too dissimilar to be pooled. There was no strong evidence for recommending any particular antimicrobial agent for the prevention of amputation, resolution of infection or ulcer healing. Topical pexiganan cream may be as effective as oral antibiotic treatment with ofloxacin for the resolution of local infection.
Ampicillin and sulbactam were less costly than imipenem and cilastatin, a growth factor (G-CSF) was less costly than standard care and cadexomer iodine dressings may be less costly than daily dressings.
A decision analytic model was derived for two groups of people, those for whom diagnostic testing would inform treatment people with ulcers which do not appear infected but whose ulcer is not progressing despite optimal concurrent treatment and those in whom a first course of antibiotics (prescribed empirically) have failed. There was insufficient information from the systematic reviews or interviews with experts to populate the model with transition probabilities for the sensitivity and specificity of diagnosis of infection in DFUs. Similarly, there was insufficient information on the probabilities of healing, amputation or death in the intervention studies for the two populations of interest. Therefore, we were unable to run the model to inform the most effective diagnostic and treatment strategy.
The available evidence was too weak to be able to draw reliable implications for practice. This means that, in terms of diagnosis, infection in DFUs cannot be reliably identified using clinical assessment. This also has implications for determining which patients need formal diagnostic testing for infection, whether empirical treatment with antibiotics (before the results of diagnostic tests are available) leads to better outcomes, and identifying the optimal methods of diagnostic testing. With respect to treatment, we do not know whether treatment with systemic or local antibiotics leads to better outcomes or whether any particular agent is more effective. Limited evidence suggests that both G-CSF and cadexomer iodine dressings may be less expensive than ‘standard’ care, that ampicillin/sulbactam may be less costly than imipenem/cilastatin, and also that an unlicensed cream (pexiganan) may be as effective as oral ofloxacin.
Questions to be answered are:
Nelson EA, O’Meara S, Craig D, Iglesias C, Golder S, Dalton J, et al. A series of systematic reviews to inform a decision analysis for sampling and treating infected diabetic foot ulcers. Health Technol Assess 2006;10(12).
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