It is difficult to identify diabetic foot ulcers (DFU) destined for infection-related complications. The objective of this application is to develop strategies to accurately identify DFUs that are likely to proceed to develop infection-related complications.
The aims are to 1) determine the prognostic efficacy of a) high microbial load, b) microbial diversity, and c) Staphylococcus aureus and anaerobes based on swab cultures obtained using Levine's technique in predicting infection-related complications among diabetic foot ulcers without signs of clinical infection;and 2) Determine the extent to which combining microbiological dimensions will improve the predictive ability above any single dimension. A prospective research design will be used to observe infection-related complications among DFUs before wound closure. A sample of 150 subjects with DFUs but without signs of clinical infection will be assessed for wound bioburden and followed for infection-related complications every two weeks until 1) wound closure, 2) DFU-related amputation, 3) loss to follow-up or 4) the end of six months of data collection. Wound bioburden has three dimensions: microbial load, microbial diversity, and presence of virulent organisms. Each dimension will be measured by quantitatively culturing swab specimens obtained using Levine's technique. Levine's technique samples fluid from deep tissue layers and has been shown to be a valid measure of wound bioburden when compared to cultures of wound tissue. Repeat measures of wound bioburden will be collected during each follow-up. In addition, the outcomes of wound deterioration, osteomyelitis, or amputation will be assessed during follow-up. ROC analysis will be used to evaluate the prognostic efficacy in terms of area under the ROC curve (AUC). Two outcomes will be considered: (a) the development of wound deterioration and/or osteomyelitis before wound closure, and (b) amputation before wound closure. A composite predictor will be developed using multivariable logistic regression. The findings from this research will improve the discrimination of DFUs at-risk from those not-at-risk for developing complications. In this way, resources can be more cost efficiently directed toward patients for whom more vigorous interventions can prevent undesirable outcomes.

National Institute of Health (NIH)
National Institute of Nursing Research (NINR)
Research Project (R01)
Project #
Application #
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Jett, Kathleen
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Schools of Nursing
Iowa City
United States
Zip Code
Loesche, Michael; Gardner, Sue E; Kalan, Lindsay et al. (2017) Temporal Stability in Chronic Wound Microbiota Is Associated With Poor Healing. J Invest Dermatol 137:237-244
Kalan, Lindsay; Loesche, Michael; Hodkinson, Brendan P et al. (2016) Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing. MBio 7:
Haleem, Ambar; Schultz, Jonathan S; Heilmann, Kristopher P et al. (2014) Concordance of nasal and diabetic foot ulcer staphylococcal colonization. Diagn Microbiol Infect Dis 79:85-9
Misic, Ana M; Gardner, Sue E; Grice, Elizabeth A (2014) The Wound Microbiome: Modern Approaches to Examining the Role of Microorganisms in Impaired Chronic Wound Healing. Adv Wound Care (New Rochelle) 3:502-510
Vu, Bao G; Stach, Christopher S; Salgado-Pabón, Wilmara et al. (2014) Superantigens of Staphylococcus aureus from patients with diabetic foot ulcers. J Infect Dis 210:1920-7
Gardner, Sue E; Haleem, Ambar; Jao, Ying-Ling et al. (2014) Cultures of diabetic foot ulcers without clinical signs of infection do not predict outcomes. Diabetes Care 37:2693-701
Gardner, Sue E; Hillis, Stephen L; Heilmann, Kris et al. (2013) The neuropathic diabetic foot ulcer microbiome is associated with clinical factors. Diabetes 62:923-30
Gardner, Sue E; Frantz, Rita A; Hillis, Stephen L et al. (2012) Volume Measures Using a Digital Image Analysis System are Reliable in Diabetic Foot Ulcers. Wounds 24:146-51
Gardner, Sue E; Frantz, Rita A (2008) Wound bioburden and infection-related complications in diabetic foot ulcers. Biol Res Nurs 10:44-53