Targeted treatment of invasive fungal infections accelerates healing of foot wounds in patients with Type 2 diabetes

Chellan, Gopi; Neethu, K.a; Varma, Ajit; Mangalanandan, Thacho S; Shashikala, S.; Dinesh, K.R.b; Sundaram, K. R.; Varma, Narendra; Jayakumar, RV; Bal, Antonin; Kumar, Harish

doi:10.1111/j.1464-5491.2012.03574.x

Cited by 19 publications

(21 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of pathogenic fungi in wounds is correlated to poorer wound healing outcomes and can complicate treatment [26][27][28]. A major component of the chronic wound microbiome is community stability, or the lack of, as being a key factor for predicting wound outcomes [6,14].…”

Section: Discussionmentioning

confidence: 99%

Priority effects dictate community structure and alter virulence of fungal-bacterial biofilms

et al. 2021

View full text Add to dashboard Cite

Polymicrobial biofilms are a hallmark of chronic wound infection. The forces governing assembly and maturation of these microbial ecosystems are largely unexplored but the consequences on host response and clinical outcome can be significant. In the context of wound healing, formation of a biofilm and a stable microbial community structure is associated with impaired tissue repair resulting in a non-healing chronic wound. These types of wounds can persist for years simmering below the threshold of classically defined clinical infection (which includes heat, pain, redness, and swelling) and cycling through phases of recurrent infection. In the most severe outcome, amputation of lower extremities may occur if spreading infection ensues. Here we take an ecological perspective to study priority effects and competitive exclusion on overall biofilm community structure in a three-membered community comprised of strains of Staphylococcus aureus, Citrobacter freundii, and Candida albicans derived from a chronic wound. We show that both priority effects and inter-bacterial competition for binding to C. albicans biofilms significantly shape community structure on both abiotic and biotic substrates, such as ex vivo human skin wounds. We further show attachment of C. freundii to C. albicans is mediated by mannose-binding lectins. Co-cultures of C. freundii and C. albicans trigger the yeast-to-hyphae transition, resulting in a significant increase in neutrophil death and inflammation compared to either species alone. Collectively, the results presented here facilitate our understanding of fungal-bacterial interactions and their effects on host-microbe interactions, pathogenesis, and ultimately, wound healing.

show abstract

Section: Discussionmentioning

confidence: 99%

Priority effects dictate community structure and alter virulence of fungal-bacterial biofilms

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Fluconazole, an antifungal drug, has been shown to significantly reduce the mean healing time of DFUs when compared to the standard of care in a randomized control study. 42 More recently, it was demonstrated that treatment of a tripartite bacterial-fungal biofilm with antibiotics alone resulted in a threefold increase of viable fungal cells, whereas only a combination treatment with antibiotics (ciprofloxacin and flucloxacillin) and fluconazole resulted in decreased viable cells of both bacteria and fungi. 40 Current literature, while limited, suggest that wound care strategies could benefit from inclusion of antifungal drugs such as fluconazole, amphotericin B, or caspofungin 43 concurrent with antibacterial therapy, or application of a broad-spectrum topical antimicrobial that targets both.…”

Section: Discussionmentioning

confidence: 99%

Fungi in the Wound Microbiome

Kalan

Grice

2018

Advances in Wound Care

View full text Add to dashboard Cite

Culture-independent methods have revealed the diverse and dynamic bacterial communities that colonize chronic wounds. Only recently have studies begun to examine fungal colonization and interactions with the bacterial component of the microbiome, their relationship with the host, and influence on wound outcomes. Studies using culture-independent sequencing methods reveal that fungi often go undetected in wounds. spp. and spp. are the most commonly identified fungi in wounds. The wound environment may promote multispecies biofilm formation between bacteria and fungi in wounds, with implications for pathogenicity, treatment, and outcomes. Identifying microorganisms that are problematic for healing will require a comprehensive understanding of all members of the polymicrobial wound community, including fungi and bacteria. Improved reference databases and bioinformatics tools for studying fungal communities will stimulate further research into the fungal microbiome. Continued study of polymicrobial wound communities using culture-independent methods will further our understanding of the relationships between microbial bioburden, the host response, and impact on healing, complications, and patient outcomes. Future studies should encompass all types of microbiota, including fungi, and focus on potential multi-kingdom interactions that contribute to pathogenicity, biofilm formation, and poor outcomes.

show abstract

“…Indeed, fungal infection in DFUs is underrecognized, although recently some studies have begun to shed light on the significant involvement of the wound mycobiome (9). While antifungal treatments have been shown to improve DFU outcome, they are only used routinely to treat superficial fungal infections in diabetics, such as onychomycosis (10,11). Therefore, it is not a great leap to suspect fungal components as a key contributor to pathogenic DFU biofilms.…”

mentioning

confidence: 99%

Implications of Antimicrobial Combinations in Complex Wound Biofilms Containing Fungi

Townsend

Sherry

Kean

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Diabetic foot ulcer treatment currently focuses on targeting bacterial biofilms, while dismissing fungi. To investigate this, we used an biofilm model containing bacteria and fungi, reflective of the wound environment, to test the impact of antimicrobials. Here we showed that while monotreatment approaches influenced biofilm composition, this had no discernible effect on overall quantity. Only by combining bacterium- and fungus-specific antibiotics were we able to decrease the biofilm bioburden, irrespective of composition.

show abstract

Targeted treatment of invasive fungal infections accelerates healing of foot wounds in patients with Type 2 diabetes

Cited by 19 publications

References 27 publications

Priority effects dictate community structure and alter virulence of fungal-bacterial biofilms

Priority effects dictate community structure and alter virulence of fungal-bacterial biofilms

Fungi in the Wound Microbiome

Implications of Antimicrobial Combinations in Complex Wound Biofilms Containing Fungi

Contact Info

Product

Resources

About