Clinical practice recommendations for infectious disease management of diabetic foot infection (DFI) - 2023 SPILF.

In march 2020, the International Working Group on the Diabetic Foot (IWGDF) published an update of the 2015 guidelines on the diagnosis and management of diabetic foot infection (DFI). While we (the French ID society, SPILF) endorsed some of these recommendations, we wanted to update our own 2006 guidelines and specifically provide informative elements on modalities of microbiological diagnosis and antibiotic treatment (especially first- and second-line regiments, oral switch and duration). The recommendations put forward in the present guidelines are addressed to healthcare professionals managing patients with DFI and more specifically focused on infectious disease management of this type of infection, which clearly needs a multidisciplinary approach. Staging of the severity of the infection is mandatory using the classification drawn up by the IWGDF. Microbiological samples should be taken only in the event of clinical signs suggesting infection in accordance with a strict preliminarily established protocol. Empirical antibiotic therapy should be chosen according to the IWGDF grade of infection and duration of the wound, but must always cover methicillin-sensitive Staphylococcus aureus. Early reevaluation of the patient is a fundamental step, and duration of antibiotic therapy can be shortened in many situations. When osteomyelitis is suspected, standard foot radiograph is the first-line imagery examination and a bone biopsy should be performed for microbiological documentation. Histological analysis of the bone sample is no longer recommended. High dosages of antibiotics are recommended in cases of confirmed osteomyelitis.

Treatment of acute Charcot foot with bisphosphonates: a systematic review of the literature.

AIM/HYPOTHESIS: We undertook a systematic review of the literature concerning the efficacy and safety of bisphosphonates in acute Charcot neuropathic osteoarthropathy. METHODS: MEDLINE, PubMed, the Cochrane Database of Systematic Reviews, and abstracts presented during the meetings of the American Diabetes Association and the European Association of Diabetes were searched for relevant publications from the period January 1990 to September 2011. RESULTS: A total of ten studies on the treatment of acute Charcot osteoarthropathy with bisphosphonates were identified and included in the analysis. Only four clinical trials were published, three of which were randomised. Bisphosphonates appeared to induce significant reductions in skin temperature and bone turnover markers compared with placebo, without serious adverse events. Nevertheless, bisphosphonates did not shorten the immobilisation time. Moreover, no data were available regarding their long-term effects. CONCLUSIONS/INTERPRETATIONS: Bisphosphonates have been shown to be effective for reducing bone turnover markers and skin temperature in some studies. Nevertheless, the long-term efficacy, specifically that regarding the occurrence of deformities and ulcerations, remains to be demonstrated as no follow-up studies have been published. Moreover, some studies have suggested that bisphosphonates may lengthen the resolution phase of the disease. In our opinion, the data are too weak to support the use of bisphosphonates as a routine treatment for acute Charcot neuroarthropathy.

Management of diabetic foot ulcers with a TLC-NOSF wound dressing.

OBJECTIVE: To evaluate the efficacy, tolerance and acceptability of UrgoStart Contact (Laboratoires Urgo), a new wound dressing impregnated with NOSF, as an MMP regulator in the management of neuropathic diabetic foot ulcers. METHOD: A multicentre, pilot, prospective, non-controlled open-label clinical trial. Adult patients with type 1 or 2 diabetes mellitus, who had a grade 1A (Texas classification), uninfected, neuropathic foot ulcer, 1-15cm2 in size and of 1-20 months' duration (mean 6.7 ± 5.2 months) were included in the study. The primary endpoint was the relative reduction of the wound surface area (%) at the end of the study. Secondary endpoints included rate of complete healing, and tolerability and acceptability of the dressing. The wound dressing was changed regularly at the investigator's discretion, in accordance with the wound status and exudate level. Patients were followed up every 2 weeks for a 12-week period. At each visit, patients underwent clinical assessments, and ulcer surface area was measured by planimetry and photographs. RESULTS: Thirty-four diabetic patients with a neuropathic foot ulcer were included but only 33 cases were analysed, as data were completely lost for one patient. At baseline, mean surface area was 2.7±2.4cm2. At the 12-week follow-up, the median surface area reduction was 82.7% (mean reduction 62.7 ± 49.9%) and in 10 of the 33 analysed patients (30%) the wound was healed. Only two of the seven documented local adverse events were deemed to be dressing related. According to the nursing staff, acceptability was considered very satisfactory, particularly in term of conformability and ease of use. CONCLUSION: This pilot study indicates that use of the new UrgoStart Contact dressing, combined with offloading and debridement,may help promote the healing process of the neuropathic diabetic foot ulcers, and was well tolerated and accepted.

Beneficial effects of implementing guidelines on microbiology and costs of infected diabetic foot ulcers.

AIMS/HYPOTHESIS: In 2003, guidelines for management of diabetic foot infection (DFI) were written by the authors' team according to the guidelines of the International Working Group on the Diabetic Foot. The effects of implementing these guidelines on the microbiology and costs of infected diabetic foot ulcers were assessed. METHODS: From 2003 to 2007, potential beneficial effects of implementing these guidelines were assessed by comparison over time of bacteriological data (number of bacterial samples, number of microorganisms isolated in cultures, prevalence of multidrug-resistant organisms [MDRO] and colonising flora), and costs related to use of antimicrobial agents and microbiology laboratory workload. RESULTS: The study included 405 consecutive diabetic patients referred to the Diabetic Foot Unit for a suspected DFI. From 2003 to 2007, a significant decrease was observed in the median number of bacteria species per sample (from 4.1 to 1.6), prevalence of MDRO (35.2% vs 16.3%) and methicillin-resistant Staphylococcus aureus (52.2% vs 18.9%) (p < 0.001). Moreover, prevalence of pathogens considered as colonisers dramatically fell from 23.1% to 5.8% of all isolates (p < 0.001). In parallel, implementation of guidelines was associated with a saving of euro14,914 (US$20,046) related to a reduced microbiology laboratory workload and euro109,305 (US$147,536) due to reduced prescription of extended-spectrum antibiotic agents. CONCLUSIONS/INTERPRETATION: Implementation of guidelines for obtaining specimens for culture from patients with DFI is cost-saving and provides interesting quality indicators in the global management of DFI.

[Epidemiology of diabetic foot problems]. / Epidémiologie du pied diabétique.

Since diabetes mellitus is growing at epidemic proportions worldwide, the prevalence of diabetes-related complications is bound to increase. Diabetic foot disorders, a major source of disability and morbidity, are a significant burden for the community and a true public health problem. Many epidemiological data have been published on the diabetic foot but they are difficult to interpret because of variability in the methodology and in the definitions used in these studies. Moreover, there is a lack of consistency in population characteristics (ethnicity, social level, accessibility to care) and how results are expressed. In westernized countries, two of 100 diabetic patients are estimated to suffer from a foot ulcer every year. Amputation rates vary considerably: incidence ranges from 1 per thousand in the Madrid area and in Japan to up to 20 per thousand in some Indian tribes in North America. In metropolitan France, the incidence of lower-limb amputation is approximately 2 per thousand but with marked regional differences, and in French overseas territories, the incidence rate is much higher. Nevertheless, the risk for ulceration and amputation is much higher in diabetics compared to the nondiabetic population: the lifetime risk of a diabetic individual developing an ulcer is as high as 25% and it is estimated that every 30s an amputation is performed for a diabetic somewhere in the world. As reviewed in this paper, peripheral neuropathy, arterial disease, and foot deformities are the main factors accounting for this increased risk. Age and sex as well as social and cultural status are contributing factors. Knowing these factors is essential to classify every diabetic using a risk grading system and to take preventive measures accordingly.

The Internet and the diabetic foot: quality of online information in French language.

UNLABELLED: The Internet has become a major source of health information for consumers. Nevertheless the quality of medical information varies widely and is generally poor. AIM: This study aimed to evaluate the quality of information delivered on French-speaking Internet about the diabetic foot. METHODS: Websites were selected using three popular search engines and introducing "foot+diabetes" and "foot+diabetic" as keywords. Two diabetologists independently evaluated the quality of information using a specially created scoring grid (range 0-52) based on acknowledged and published criteria with items relevant to general characteristics of the site and to information content. One hundred and twenty websites were selected but only 27 were included for analysis. RESULTS: Agreement between the two raters was close for global score and site content but lower for site characteristics. Averaged global score ranged from 8 to 44. Only five sites were assessed as very advisable with a score higher than 39; in contrast 18 sites were judged as not advisable at all (score lower than 26). CONCLUSION: This study, the first to be devoted to information about the diabetic foot on the Internet, clearly shows the variability and the general poor quality of information delivered by the great majority of French-speaking websites. Regulation organisms are urgently needed for checking and labelling public oriented health information in order to make the Internet a performing tool for patient information.

Link between nasal carriage of Staphylococcus aureus and infected diabetic foot ulcers.

AIMS: Nasal carriage of Staphylococcus aureus in diabetic patients may be a risk factor for diabetic foot lesion infections. The aims of this study were to compare the genotypic profiles of S. aureus strains isolated from nares and diabetic foot ulcers (DFUs) using microarray technology. METHODS: Patients were included if they were admitted for diabetic foot infection (DFI) at any of three diabetology departments of Montpellier and Nîmes University Hospitals between 1 September 2010 to 30 June 2012. All S. aureus isolates were analyzed using oligonucleotides arrays; S. aureus resistance and virulence genes were determined and each isolate was affiliated to a clonal complex. RESULTS: The prevalence of S. aureus nasal carriage among the 276 included patients was 39.5% (n=109), while 36.6% (n=101) had S. aureus at both sites (nares and foot wounds) and, of these patients, 65.3% of patients harboured the same strain at both sites. In addition, the spread of the methicillin-resistant S. aureus (MRSA) ST398 clone in DFI and its tropism for bone were also further confirmed. CONCLUSION: These findings appear to provide new arguments in favour of the systematic detection of nasal S. aureus carriage to anticipate the management of DFI.

Vesicular monoamine transporters heterologously expressed in the yeast Saccharomyces cerevisiae display high-affinity tetrabenazine binding.

A mammalian vesicular neurotransmitter transporter has been expressed in the yeast Saccharomyces cerevisiae. The gene encoding the rat vesicular monoamine transporter (rVMAT(1)) was cloned in several expression plasmids. The transporter was expressed at detectable levels only when short sequences using codons favored by S. cerevisiae were fused preceding the start of translation of rVMAT(1). The scarce expression of the wild-type protein was, most likely, due to the fact that part of the N-terminus of the protein is encoded by codons not preferred in S. cerevisiae. Furthermore, low growth temperatures increased rVMAT(1) expression and altered its processing. Whereas at 30 degrees C the protein is not glycosylated, at lower temperatures ( approximately 16 degrees C) half of the expressed transporters undergo core glycosylation. In addition, under these conditions the levels of protein expression significantly increase. Using a functional chimeric protein composed by VMAT and the green fluorescent protein (GFP), it is shown that the punctate pattern of intracellular distribution remains invariable at the different temperatures. Using a similar fusion sequence, the bovine VMAT isoform 2 (bVMAT(2)) was also expressed in yeast. The yeast-expressed bVMAT(2) binds [(3)H]dihydrotetrabenazine ([(3)H]TBZOH) with the same characteristics found in the native protein from bovine chromaffin granules. Dodecyl maltoside-solubilized bVMAT(2) retains the conformation required for [(3)H]TBZOH binding. We exploited the robust binding to follow the transporter during purification assays on a Ni(2+)-chelating column. In this report we describe for the first time the heterologous expression of a neurotransmitter transporter in the yeast S. cerevisiae.

A common binding site for substrates and protons in EmrE, an ion-coupled multidrug transporter.

EmrE is an Escherichia coli 12-kDa multidrug transporter, which confers resistance to a variety of toxic cations by removing them from the cell interior in exchange with two protons. EmrE has only one membrane-embedded charged residue, Glu-14, that is conserved in more than 50 homologous proteins and it is a simple model system to study the role of carboxylic residues in ion-coupled transporters. We have used mutagenesis and chemical modification to show that Glu-14 is part of the substrate binding site. Its role in proton binding and translocation was shown by a study of the effect of pH on ligand binding, uptake, efflux and exchange reactions. We conclude that Glu-14 is an essential part of a binding site, common to substrates and protons. The occupancy of this site is mutually exclusive and provides the basis of the simplest coupling of two fluxes.

The pharmacological profile of the vesicular monoamine transporter resembles that of multidrug transporters.

Vesicular neurotransmitter transporters function in synaptic vesicles and other subcellular organelles and they were thought to be involved only in neurotransmitter storage. Several findings have led us to test novel aspects of their function. Cells expressing a c-DNA coding for one of the rat monoamine transporters (VMAT1) become resistant to the neurotoxin N-methyl-4-phenylpyridinium (MPP+) [Liu et al. (1992) Cell, 70, 539-551]. The basis of the resistance is the VMAT1-mediated transport and sequestration of the toxin into subcellular compartments. In addition, the deduced sequence of VMAT1 predicts a protein that shows a distinct homology to a class of bacterial drug resistance transporters (TEXANs) that share some substrates with mammalian multidrug resistance transporters (MDR) such as the P-glycoprotein. These findings induced us to test whether compounds that are typically transported by MDR interact also with vesicular transporters. The use of [3H]reserpine binding to determine drug interactions with VMAT allowed assessment of the ability of various drugs to bind to the substrate site of the transporter. Cytotoxic compounds such as ethidium, isometamidium, tetraphenylphosphonium, rhodamine, tacrine and doxorubicin, interact specifically with vesicular monoamine transporters. Verapamil, a calcium channel blocker, is also a competitive inhibitor of transport. In the case of rhodamine, fluorescence measurements in digitonin-permeabilized cells demonstrated ATP-dependent VMAT-mediated transport. The results imply that even though the bacterial and vesicular transporters are structurally different from the P-glycoprotein, they share a similar substrate range. These findings suggest a novel possible way of protection from the effects of toxic compounds by removal to subcellular compartments.