Bacterial Diversity, Antibiotic Resistance, and the Risk of Lower Limb Amputation in Younger and Older Individuals With Diabetic Foot Infection

Dörr, Stefan; Holland-Letz, Ann-Kathrin; Weisser, Gregor; Chatzitomaris, Apostolos; Lobmann, Ralf

doi:10.1177/1534734621992290

Cited by 10 publications

(8 citation statements)

References 34 publications

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“…Diabetic skin has been shown to have higher colonization of both S. aureus and S. epidermidis [ 74 ]. A recent analysis of German patients with DFUs identified Staphylococcus, Pseudomonas, and Enterobacteriaceae as the most common bacterial colonizers [ 76 ]. When stratifying DFUs by infection severity, a recent study identified Staphylococcus and Streptococcus as the most abundant species in mildly to moderately infected DFUs, while more severely infected DFUs had increased bacterial diversity [ 77 ].…”

Section: Pathophysiology Associated With Diabetic Wound Healingmentioning

confidence: 99%

Diabetic Wound-Healing Science

et al. 2021

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Diabetes mellitus is an increasingly prevalent chronic metabolic disease characterized by prolonged hyperglycemia that leads to long-term health consequences. It is estimated that impaired healing of diabetic wounds affects approximately 25% of all patients with diabetes mellitus, often resulting in lower limb amputation, with subsequent high economic and psychosocial costs. The hyperglycemic environment promotes the formation of biofilms and makes diabetic wounds difficult to treat. In this review, we present updates regarding recent advances in our understanding of the pathophysiology of diabetic wounds focusing on impaired angiogenesis, neuropathy, sub-optimal chronic inflammatory response, barrier disruption, and subsequent polymicrobial infection, followed by current and future treatment strategies designed to tackle the various pathologies associated with diabetic wounds. Given the alarming increase in the prevalence of diabetes, and subsequently diabetic wounds, it is imperative that future treatment strategies target multiple causes of impaired healing in diabetic wounds.

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Section: Pathophysiology Associated With Diabetic Wound Healingmentioning

confidence: 99%

Diabetic Wound-Healing Science

et al. 2021

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“…DFU is a risk factor for lower extremity amputations, especially in cases of infections caused by MDR bacteria 43,44 . Among gram‐negative bacilli, PA is the predominant causative bacterium of DFIs, 45 21% of which are MDR bacteria 6 . Additionally, PA efficiently produces strong biofilms capable of impeding wound healing and reducing the effectiveness of antimicrobial drugs 46 .…”

Section: Discussionmentioning

confidence: 99%

Autophagy ameliorates Pseudomonas aeruginosa‐infected diabetic wounds by regulating the toll‐like receptor 4/myeloid differentiation factor 88 pathway

Jin

et al. 2023

Wound Repair Regeneration

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Diabetic foot ulcers (DFUs) are among the most common complications in patients with diabetes and a leading cause of lower extremity amputation. DFUs are exacerbated by prolonged bacterial infection; therefore, there is an urgent need for effective treatments to alleviate the burden associated with this condition. Although autophagy plays a unique role in pathogen phagocytosis and inflammation, its role in diabetic foot infections (DFIs) remains unclear. Pseudomonas aeruginosa (PA) is the most frequently isolated gram‐negative bacterium from DFUs. Here, we evaluated the role of autophagy in ameliorating PA infection in wounds in a diabetic rat model and a bone marrow‐derived macrophage (BMDM) hyperglycemia model. Both models were pretreated with or without rapamycin (RAPA) and then infected with or without PA. Pretreatment of rats with RAPA significantly enhanced PA phagocytosis, suppressed wound inflammation, reduced the M1:M2 macrophage ratio, and improved wound healing. In vitro investigation of the underlying mechanisms revealed that enhanced autophagy resulted in decreased macrophage secretion of inflammatory factors such as TNF‐α, IL‐6, and IL‐1β but increased that of IL‐10 in response to PA infection. Additionally, RAPA treatment significantly enhanced autophagy in macrophages by increasing LC3 and beclin‐1 levels, which led to altered macrophage function. Furthermore, RAPA blocked the PA‐induced TLR4/MyD88 pathway to regulate macrophage polarisation and inflammatory cytokine production, which was validated by RNA interference and use of the autophagy inhibitor 3‐methyladenine (3‐MA). These findings suggest enhancing autophagy as a novel therapeutic strategy against PA infection to ultimately improve diabetic wound healing.

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“…One-half of major (above-or below-knee) lower extremity amputations in people with diabetes are due to microbial infection. 7,25 Flowchart depicting the pathophysiology of diabetic foot ulcer is given in Figure 1.…”

Section: Pathophysiology Of Diabetic Foot Ulcermentioning

confidence: 99%

Insights on MDR Mechanism of Pseudomonas aeruginosa with Emphasis on Diabetic Foot Ulcer in the Indian Subcontinent

Chatterjee,

Sivashanmugam

2024

J. Pure Appl. Microbiol.

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Diabetic foot ulcers (DFU) in patients with uncontrolled diabetes mellitus are considered a global public health menace that is highly associated with morbidity and mortality. Pathogenic microorganisms entrenched deep into diabetic foot wounds are the causative agents for delayed healing and escalation of diabetic foot wound severity. Pseudomonas aeruginosa is a common opportunistic pathogen associated with several nosocomial infections, cystic fibrosis, and one of the most critical pathogens often isolated from acute and chronic diabetic foot ulcers. The organism can exhibit resistance to a wide range of antibiotics like ciprofloxacin, cefotaxime, and meropenem, thereby causing severe damage to the host tissues, followed by amputation of the affected foot region. Due to their ability to synthesize biofilms, the wound becomes more chronic and incurable, posing a serious threat to immunocompromised diabetic patients. This review highlights on the insights of pathophysiology and microbiological profile of Diabetic foot ulcers, the resistance mechanisms, and the therapeutics available for dealing with drug-resistant Pseudomonas, which could help clinicians in treating DFUs.

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Bacterial Diversity, Antibiotic Resistance, and the Risk of Lower Limb Amputation in Younger and Older Individuals With Diabetic Foot Infection

Cited by 10 publications

References 34 publications

Diabetic Wound-Healing Science

Diabetic Wound-Healing Science

Autophagy ameliorates Pseudomonas aeruginosa‐infected diabetic wounds by regulating the toll‐like receptor 4/myeloid differentiation factor 88 pathway

Insights on MDR Mechanism of Pseudomonas aeruginosa with Emphasis on Diabetic Foot Ulcer in the Indian Subcontinent

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