Sue E. Gardner

The validity of the clinical signs and symptoms used to identify localized chronic wound infection

It is uncertain how accurately classic signs of acute infection identify infection in chronic wounds, or if the signs of infection specific to secondary wounds are better indicators of infection in these wounds. The purpose of this study was to examine the validity of the “classic” signs (i.e., pain, erythema, edema, heat, and purulence) and the signs specific to secondary wounds (i.e., serous exudate, delayed healing, discoloration of granulation tissue, friable granulation tissue, pocketing at the base of the wound, foul odor, and wound breakdown). Thirty‐six chronic wounds were assessed for these signs and symptoms of infection with interobserver reliability ranging from 0.53 to 1.00. The wounds were then quantitatively cultured, and 11 (31%) were found to be infected. Increasing pain, friable granulation tissue, foul odor, and wound breakdown showed validity based on sensitivity, specificity, discriminatory power, and positive predictive values. The signs specific to secondary wounds were better indicators of chronic wound infection than the classic signs with a mean sensitivity of 0.62 and 0.38, respectively. None of the signs or symptoms was a necessary indicator of infection, but increasing pain and wound breakdown were both sufficient indicators with specificity of 100%.

Effect of electrical stimulation on chronic wound healing: a meta-analysis

The purpose of this meta‐analysis was to quantify the effect of electrical stimulation on chronic wound healing. Fifteen studies, which included 24 electrical stimulation samples and 15 control samples, were analyzed. The average rate of healing per week was calculated for the electrical stimulation and control samples. Ninety‐five percentage confidence intervals were also calculated. The samples were then grouped by type of electrical stimulation device and chronic wound and reanalyzed. Rate of healing per week was 22% for electrical stimulation samples and 9% for control samples. The net effect of electrical stimulation was 13% per week, an increase of 144% over the control rate. The 95% confidence intervals of the electrical stimulation (18–26%) and control samples (3.8–14%) did not overlap. Electrical stimulation was most effective on pressure ulcers (net effect = 13%). Findings regarding the relative effectiveness of different types of electrical stimulation device were inconclusive. Although electrical stimulation produces a substantial improvement in the healing of chronic wounds, further research is needed to identify which electrical stimulation devices are most effective and which wounds respond best to this treatment.

The Neuropathic Diabetic Foot Ulcer Microbiome Is Associated With Clinical Factors

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.

Diagnostic validity of three swab techniques for identifying chronic wound infection

This study examined the diagnostic validity of three different swab techniques in identifying chronic wound infection. Concurrent swab specimens of chronic wounds were obtained using wound exudate, the Z‐technique, and the Levine technique, along with a specimen of viable wound tissue. Swab and tissue specimens were cultured using quantitative and qualitative laboratory procedures. Infected wounds were defined as those containing 1 × 106 or more organisms per gram of tissue. Accuracy was determined by associating the quantitative cultures of swab specimens with the cultures from tissue specimens using receiver operating characteristic curves. Of the 83 study wounds, 30 (36%) were infected. Accuracy was the highest for swab specimens obtained using Levines technique at 0.80. Based on Levines technique, a critical threshold of 37,000 organisms per swab provided a sensitivity of 90% and a specificity of 57%. The mean concordance between swab specimens obtained using Levines technique and tissue specimens was 78%. The findings suggest that swab specimens collected using Levines technique provide a reasonably accurate measure of wound bioburden, given that they are more widely applicable than tissue cultures. The diagnostic validity of Levines technique needs further study using an alternative reference standard, such as the development of infection‐related complications.

Wound Bioburden and Infection-Related Complications in Diabetic Foot Ulcers

The identification and diagnosis of diabetic foot ulcer (DFU) infections remains a complex problem. Because inflammatory responses to microbial invasion may be diminished in persons with diabetes, clinical signs of infection are often absent in persons with DFUs when infection is limited to localized tissue. In the absence of these clinical signs, microbial load is believed to be the best indicator of infection. Some researchers, however, believe microbial load to be insignificant and type of organism growing in the ulcer to be most important. Previous studies on the microbiology of DFUs have not provided enough evidence to determine the microbiological parameters of importance. Infection-related complications of DFUs include wound deterioration, osteomyelitis, and amputation. Risk factors for amputation include age, peripheral vascular disease, low transcutaneous oxygen, smoking, and poor glycemic control. These risk factors are best measured directly with physiological measures of arterial perfusion, glycemic control, sensory neuropathy, plantar pressures, and activity level and by controlling off-loading. DFU bioburden has not been examined as a risk factor for infection-related complications. To address the relationship between wound bioburden and the development of infection-related complications in DFUs, tightly controlled prospective studies based on clearly defined, valid measures of wound bioburden and wound outcomes are needed. This article reviews the literature and proposes a model of hypothesized relationships between wound bioburden—including microbial load, microbial diversity, and pathogenicity of organisms—and the development of infection-related complications.

Clinical signs of infection in diabetic foot ulcers with high microbial load.

Aims. One proposed method to diagnose diabetic foot ulcers (DFUs) for infection is clinical examination. Twelve different signs of infection have been reported. The purpose of this study was to examine diagnostic validity of each individual clinical sign, a combination of signs recommended by the Infectious Disease Society of America (IDSA), and a composite predictor based on all signs of localized wound infection in identifying DFU infection, among a sample of DFUs. Methods. A cross-sectional research design was used. Sixty-four individuals with DFUs were recruited from a Department of Veterans Affairs Medical Center and an academic-affiliated hospital. Each DFU was independently assessed by 2 research team members using the clinical signs and symptoms checklist. Tissue specimens were then obtained via wound biopsy and quantitatively processed. Ulcers with more than 106 organisms per gram of tissue were defined as having high microbial load. Individual signs and the IDSA combination were assessed for validity by calculating sensitivity, specificity, and concordance probability. The composite predictor was analyzed using c-index and receiver operating curves. Results. Twenty-five (39%) of the DFUs had high microbial loads. No individual sign was a significant predictor of high microbial load. The IDSA combination was not a significant predictor either. The c-index of the composite predictor was .645 with a 95% confidence interval of .559-.732. Conclusions. Individual signs of infection do not perform well nor does the IDSA combination of signs. However, a composite predictor based on all signs provides a moderate level of discrimination, suggesting clinical use. Larger sample sizes and alternate reference standards are recommended.

Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing

ABSTRACT Chronic nonhealing wounds have been heralded as a silent epidemic, causing significant morbidity and mortality especially in elderly, diabetic, and obese populations. Polymicrobial biofilms in the wound bed are hypothesized to disrupt the highly coordinated and sequential events of cutaneous healing. Both culture-dependent and -independent studies of the chronic-wound microbiome have almost exclusively focused on bacteria, omitting what we hypothesize are important fungal contributions to impaired healing and the development of complications. Here we show for the first time that fungal communities (the mycobiome) in chronic wounds are predictive of healing time, associated with poor outcomes, and form mixed fungal-bacterial biofilms. We longitudinally profiled 100, nonhealing diabetic-foot ulcers with high-throughput sequencing of the pan-fungal internal transcribed spacer 1 (ITS1) locus, estimating that up to 80% of wounds contain fungi, whereas cultures performed in parallel captured only 5% of colonized wounds. The “mycobiome” was highly heterogeneous over time and between subjects. Fungal diversity increased with antibiotic administration and onset of a clinical complication. The proportions of the phylum Ascomycota were significantly greater (P = 0.015) at the beginning of the study in wounds that took >8 weeks to heal. Wound necrosis was distinctly associated with pathogenic fungal species, while taxa identified as allergenic filamentous fungi were associated with low levels of systemic inflammation. Directed culturing of wounds stably colonized by pathogens revealed that interkingdom biofilms formed between yeasts and coisolated bacteria. Combined, our analyses provide enhanced resolution of the mycobiome during impaired wound healing, its role in chronic disease, and impact on clinical outcomes. IMPORTANCE Wounds are an underappreciated but serious complication for a diverse spectrum of diseases. High-risk groups, such as persons with diabetes, have a 25% lifetime risk of developing a wound that can become chronic. The majority of microbiome research related to chronic wounds is focused on bacteria, but the association of fungi with clinical outcomes remains to be elucidated. Here we describe the dynamic fungal communities in 100 diabetic patients with foot ulcers. We found that communities are unstable over time, but at the first clinical presentation, the relative proportions of different phyla predict healing times. Pathogenic fungi not identified by culture reside in necrotic wounds and are associated with a poor prognosis. In wounds stably colonized by fungi, we identified yeasts capable of forming biofilms in concert with bacteria. Our findings illuminate the associations of the fungal mycobiome with wound prognosis and healing. Wounds are an underappreciated but serious complication for a diverse spectrum of diseases. High-risk groups, such as persons with diabetes, have a 25% lifetime risk of developing a wound that can become chronic. The majority of microbiome research related to chronic wounds is focused on bacteria, but the association of fungi with clinical outcomes remains to be elucidated. Here we describe the dynamic fungal communities in 100 diabetic patients with foot ulcers. We found that communities are unstable over time, but at the first clinical presentation, the relative proportions of different phyla predict healing times. Pathogenic fungi not identified by culture reside in necrotic wounds and are associated with a poor prognosis. In wounds stably colonized by fungi, we identified yeasts capable of forming biofilms in concert with bacteria. Our findings illuminate the associations of the fungal mycobiome with wound prognosis and healing.

Chronic wound repair and healing in older adults: Current status and future research

The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound healing slows with age. However, the basic biology underlying chronic wounds and the influence of age‐associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The impact of age and accompanying multi‐morbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables, lack of standardization in data collection, and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age‐associated changes in chronic wound healing.

Temporal Stability in Chronic Wound Microbiota Is Associated With Poor Healing

Microbial burden of chronic wounds is believed to play an important role in impaired healing and the development of infection-related complications. However, clinical cultures have little predictive value of wound outcomes, and culture-independent studies have been limited by cross-sectional design and small cohort size. We systematically evaluated the temporal dynamics of the microbiota colonizing diabetic foot ulcers, a common and costly complication of diabetes, and its association with healing and clinical complications. Dirichlet multinomial mixture modeling, Markov chain analysis, and mixed-effect models were used to investigate shifts in the microbiota over time and their associations with healing. Here we show, to our knowledge, previously unreported temporal dynamics of the chronic wound microbiome. Microbiota community instability was associated with faster healing and improved outcomes. Diabetic foot ulcer microbiota were found to exist in one of four community types that experienced frequent and nonrandom transitions. Transition patterns and frequencies were associated with healing time. Exposure to systemic antibiotics destabilized the wound microbiota, rather than altering overall diversity or relative abundance of specific taxa. This study provides evidence that the dynamic wound microbiome is indicative of clinical outcomes and may be a valuable guide for personalized management and treatment of chronic wounds.

Nursing assessment: Impact on type and cost of interventions to prevent pressure ulcers

Objective To describe pressure ulcer preventive interventions and their cost, and to compare the preventive intervention use and cost with level of risk. Design Comparative, descriptive design. Setting and Subjects A large midwestern Veterans Affairs Medical Center with 260 long‐term care beds. Thirty‐one chair‐ or bed‐bound residents from 1 long‐term care unit comprised the study sample. Main Outcome Measures The outcome variables included demographic information (patient record), Braden Risk Assessment score, institutional risk assessment score (Pressure Ulcer Risk Tool), type and frequency of preventive interventions, and the related costs. Methods Subjects were assessed on a weekly basis for type and frequency of preventive intervention and for the development of a pressure ulcer. Each subject was observed until death, discharge, pressure ulcer formation, or the end of the 3‐month study period. Results The 3‐month pressure ulcer incidence rate was 13%. All subjects were at risk for pressure ulcer development according to Braden scores; whereas only 74% were assessed at risk with use of the facilitys risk assessment tool. Preventive measures included regular repositioning (87%); 67% were placed on mattress support surfaces. There was no relationship between level of risk (facility risk tool score) and type of prevention used. The total cost of pressure ulcer prevention to the nursing unit was