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The neuropathic diabetic foot ulcer microbiome is associated with clinical factors.

ABSTRACT: Nonhealing diabetic foot ulcers (DFUs) are a common and costly complication of diabetes. Microbial burden, or "bioburden," is believed to underlie delayed healing, although little is known of those clinical factors that may influence microbial load, diversity, and/or pathogenicity. We profiled the microbiomes of neuropathic nonischemic DFUs without clinical evidence of infection in 52 individuals using high-throughput sequencing of the bacterial 16S ribosomal RNA gene. Comparatively, wound cultures, the standard diagnostic in the clinic, vastly underrepresent microbial load, microbial diversity, and the presence of potential pathogens. DFU microbiomes were heterogeneous, even in our tightly restricted study population, but partitioned into three clusters distinguished primarily by dominant bacteria and diversity. Ulcer depth was associated with ulcer cluster, positively correlated with abundance of anaerobic bacteria, and negatively correlated with abundance of Staphylococcus. Ulcer duration was positively correlated with bacterial diversity, species richness, and relative abundance of Proteobacteria, but was negatively correlated with relative abundance of Staphylococcus. Finally, poor glycemic control was associated with ulcer cluster, with poorest median glycemic control concentrating to Staphylococcus-rich and Streptococcus-rich ulcer clusters. Analyses of microbial community membership and structure may provide the most useful metrics in prospective studies to delineate problematic bioburden from benign colonization that can then be used to drive clinical treatment.

SUBMITTER: Gardner SE

PROVIDER: S-EPMC3581190 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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The neuropathic diabetic foot ulcer microbiome is associated with clinical factors.

Gardner Sue E SE Hillis Stephen L SL Heilmann Kris K Segre Julia A JA Grice Elizabeth A EA

Diabetes 20121108 3

Nonhealing diabetic foot ulcers (DFUs) are a common and costly complication of diabetes. Microbial burden, or "bioburden," is believed to underlie delayed healing, although little is known of those clinical factors that may influence microbial load, diversity, and/or pathogenicity. We profiled the microbiomes of neuropathic nonischemic DFUs without clinical evidence of infection in 52 individuals using high-throughput sequencing of the bacterial 16S ribosomal RNA gene. Comparatively, wound cultu ...[more]

PMID: 23139351

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Project description:PurposeWe aimed to investigate the prevalence of diabetic retinopathy (DR) in patients with diabetic foot ulcer (DFU) and elucidate the association between DR and DFU severities and their shared risk factors.MethodsA retrospective review was conducted on DFU patients who underwent ophthalmic and vascular examinations within 6 months; 100 type 2 diabetic patients with DFU were included. The medical records of 2496 type 2 diabetic patients without DFU served as control data. DR prevalence and severity were assessed in DFU patients. DFU patients were compared with the control group regarding each clinical variable. Additionally, DFU patients were divided into two groups according to DR severity and compared.ResultsOut of 100 DFU patients, 90 patients (90%) had DR and 55 (55%) had proliferative DR (PDR). There was no significant association between DR and DFU severities (R = 0.034, p = 0.734). A multivariable analysis comparing type 2 diabetic patients with and without DFUs showed that the presence of DR [OR, 226.12; 95% confidence interval (CI), 58.07-880.49; p < 0.001] and proliferative DR [OR, 306.27; 95% CI, 64.35-1457.80; p < 0.001), higher HbA1c (%, OR, 1.97, 95% CI, 1.46-2.67; p < 0.001), higher serum creatinine (mg/dL, OR, 1.62, 95% CI, 1.06-2.50; p = 0.027), older age (years, OR, 1.12; 95% CI, 1.06-1.17; p < 0.001), higher pulse pressure (mmHg, OR, 1.03; 95% CI, 1.00-1.06; p = 0.025), lower cholesterol (mg/dL, OR, 0.94; 95% CI, 0.92-0.97; p < 0.001), lower BMI (kg/m2, OR, 0.87, 95% CI, 0.75-1.00; p = 0.044) and lower hematocrit (%, OR, 0.80, 95% CI, 0.74-0.87; p < 0.001) were associated with DFUs. In a subgroup analysis of DFU patients, the PDR group had a longer duration of diabetes mellitus, higher serum BUN, and higher serum creatinine than the non-PDR group. In the multivariable analysis, only higher serum creatinine was associated with PDR in DFU patients (OR, 1.37; 95% CI, 1.05-1.78; p = 0.021).ConclusionsDiabetic retinopathy is prevalent in patients with DFU and about half of DFU patients had PDR. No significant association was found in terms of the severity of these two diabetic complications. To prevent blindness, patients with DFU, and especially those with high serum creatinine, should undergo retinal examinations for timely PDR diagnosis and management.

Project description:IntroductionAccurate identification of pathogens, rather than colonising bacteria, is a prerequisite for targeted antibiotic therapy to ensure optimal patient outcome in wounds, such as diabetic foot ulcers. Wound swabs are the easiest and most commonly used sampling technique but most published guidelines recommend instead removal of a tissue sample from the wound bed, which is a more complex process. The aim of this study was to assess the concordance between culture results from wound swabs and tissue samples in patients with suspected diabetic foot infection.Methods and analysisPatients with a diabetic foot ulcer that is thought to be infected are being recruited from 25 sites across England in a cross-sectional study. The coprimary endpoints for the study are agreement between the two sampling techniques for three microbiological parameters: reported presence of likely isolates identified by the UK Health Protection Agency; resistance of isolates to usual antibiotic agents; and, the number of isolates reported per specimen. Secondary endpoints include appropriateness of the empiric antibiotic therapy prescribed and adverse events. Enrolling 400 patients will provide 80% power to detect a difference of 3% in the reported presence of an organism, assuming organism prevalence of 10%, discordance of 5% and a two-sided test at the 5% level of significance. Assumed overall prevalence is based on relatively uncommon organisms such as Pseudomonas. We will define acceptable agreement as ?>0.6.Ethics and disseminationConcordance in diabetic foot ulcer infection (CODIFI) will produce robust data to evaluate the two most commonly used sampling techniques employed for patients with a diabetic foot infection. This will help determine whether or not it is important that clinicians take tissue samples rather than swabs in infected ulcers. This study has been approved by the Sheffield NRES Committee (Ref: 11/YH/0078) and all sites have obtained local approvals prior starting recruitment.Study registrationNRES Ref: 11/YH/0078, UKCRN ID: 10440, ISRCTN: 52608451.

Project description:BackgroundAt present, there is no clinical study to elucidate the correlation between vitamin D deficiency and the incidence of diabetic foot osteomyelitis (DFO).This study aims to clarify levels of 25-hydroxyvitamin D [25(OH)VD] in peripheral blood and vitamin D receptor (VDR) expression in wound margin tissues (T-VDR) of patients with type 2 diabetes mellitus (T2DM) with diabetic foot ulcer (DFU) and DFO, and to determine its correlation with treatment outcomes of DFU and DFO, and and its value as a potential biomarker for the diagnosis of DFU and DFO.Methods156 T2DM patients with DFU (DFU group), 100 T2DM patients without DFU (T2DM group), and 100 healthy controls (NC group). The DFU group patients were subdivided into DFO (n = 80) and NDFO groups (n = 76). The level of serum 25(OH)VD was measured via chemiluminescence immunoassay, and T-VDR expression level was determined by quantitative real-time PCR.ResultsThe levels of serum 25(OH)VD in the DFU group were significantly lower than the T2DM group [(10.3 (5.8, 18.7) vs 15.7 (8.6, 24.6) ng/mL, P = 0.002)]. Similarly, the levels of serum 25(OH)VD and T-VDR expression in the DFO group were statistically lower than the NDFO group [9.2 (5.2, 20.5) vs 12.8 (6.9, 22.1) ng/mL, P = 0.006)], [1.96 (0.61, 3.97) vs 3.11 (1.36, 5.11), P = 0.004)], respectively. Furthermore, the levels of serum 25(OH)VD and T-VDR expression in DFU patients were positively correlated with the ulcer healing rate of foot ulcer after 8 weeks of treatment ( P = 0.031, P = 0.016, respectively). Multivariate logistic regression analysis showed that low level of serum 25(OH)VD was an independent risk factor for DFU and DFO (ORDFU = 2.42, ORDFO = 3.05, P = 0.008, 0.001, respectively), and decreased T-VDR expression level was an independent risk factor for DFO (OR = 2.83, P = 0.004). Meanwhile, the ROC curve analysis indicated that the AUC of serum 25(OH)VD level for the diagnosis of DFU and DFO was 0.821 (95% CI, 0.754-0.886, P < 0.001) and 0.786 (95%CI, 0.643-0.867, P < 0.001), respectively. When establishing a diagnosis of DFO, the AUC of T-VDR expression level was 0.703 (95%CI: 0.618-0.853, P < 0.001).ConclusionsThe levels of serum 25(OH)VD and T-VDR expression in DFU and DFO decreased. Serum 25(OH)VD and T-VDR are potentially valuable biomarkers for diagnosis and prognosis of DFU and DFO. .

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The neuropathic diabetic foot ulcer microbiome is associated with clinical factors.

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The neuropathic diabetic foot ulcer microbiome is associated with clinical factors.

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