Current health and economic burden of chronic diabetic osteomyelitis

Geraghty, Terese; LaPorta, Guido A.

doi:10.1080/14737167.2019.1567337

Cited by 62 publications

(44 citation statements)

References 55 publications

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“…Diabetic patients have a 15-25% lifetime risk of developing diabetic foot ulcers, of which 40-80% become so severely infected it involves the bone, leading to osteomyelitis [4]. Global epidemiological studies suggest a higher prevalence in North America [5].…”

Section: The Problem Of Wound Healing and Its Incidence In Diabetesmentioning

confidence: 99%

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

et al. 2020

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Chronic wounds often occur in patients with diabetes mellitus due to the impairment of wound healing. This has negative consequences for both the patient and the medical system and considering the growing prevalence of diabetes, it will be a significant medical, social, and economic burden in the near future. Hence, the need for therapeutic alternatives to the current available treatments that, although various, do not guarantee a rapid and definite reparative process, appears necessary. We here analyzed current treatments for wound healing, but mainly focused the attention on few classes of drugs that are already in the market with different indications, but that have shown in preclinical and few clinical trials the potentiality to be used in the treatment of impaired wound healing. In particular, repurposing of the antiglycemic agents dipeptidylpeptidase 4 (DPP4) inhibitors and metformin, but also, statins and phenyotin have been analyzed. All show encouraging results in the treatment of chronic wounds, but additional, well designed studies are needed to allow these drugs access to the clinics in the therapy of impaired wound healing.

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Section: The Problem Of Wound Healing and Its Incidence In Diabetesmentioning

confidence: 99%

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

et al. 2020

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“…aureus strains, which are the most common cause of bone infection[6]. Of diabetic foot ulcers, which occur in 25% of diabetic patients, approximately 20% will spread to nearby bone tissues and result in osteomyelitis[7]. As diabetic diagnoses continue to increase in the United States with an expected 55 million to be afflicted by 2030, osteomyelitis infections will be an ongoing challenge for the healthcare community[8].…”

Section: Introductionmentioning

confidence: 99%

CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection

et al. 2019

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Osteomyelitis, or bone infection, is often induced by antibiotic resistant Staphylococcus aureus strains of bacteria. Although debridement and long-term administration of antibiotics are the gold standard for osteomyelitis treatment, the increase in prevalence of antibiotic resistant bacterial strains limits the ability of clinicians to effectively treat infection. Bacteriophages (phages), viruses that in a lytic state can effectively kill bacteria, have gained recent attention for their high specificity, abundance in nature, and minimal risk of host toxicity. Previously, we have shown that CRISPR-Cas9 genomic editing techniques could be utilized to expand temperate bacteriophage host range and enhance bactericidal activity through modification of the tail fiber protein. In a dermal infection study, these CRISPR-Cas9 phages reduced bacterial load relative to unmodified phage. Thus we hypothesized this temperate bacteriophage, equipped with the CRISPR-Cas9 bactericidal machinery, would be effective at mitigating infection from a biofilm forming S. aureus strain in vitro and in vivo. In vitro, qualitative fluorescent imaging demonstrated superiority of phage to conventional vancomycin and fosfomycin antibiotics against S. aureus biofilm. Quantitative antibiofilm effects increased over time, at least partially, for all fosfomycin, phage, and fosfomycin-phage (dual) therapeutics delivered via alginate hydrogel. We developed an in vivo rat model of osteomyelitis and soft tissue infection that was reproducible and challenging and enabled longitudinal monitoring of infection progression. Using this model, phage (with and without fosfomycin) delivered via alginate hydrogel were successful in reducing soft tissue infection but not bone infection, based on bacteriological, histological, and scanning electron microscopy analyses. Notably, the efficacy of phage at mitigating soft tissue infection was equal to that of high dose fosfomycin. Future research may utilize this model as a platform for evaluation of therapeutic type and dose, and alternate delivery vehicles for osteomyelitis mitigation.

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“…Acute osteomyelitis begins with high fever and local pain, and when it turns to chronic osteomyelitis, there will be rupture, pus, dead bone or cavity formation. Severe patients are often in danger of life, which have to take emergency measures of amputation, resulting in lifelong physical disability [5] . Thorough debridement, opening cancellous bone graft and repeated irrigation are the most commonly method of clinical treatment of osteomyelitis so far [6] .…”

Section: Introductionmentioning

confidence: 99%

Establishment of an animal model of chronic osteomyelitis with Staphylococcus aureus by ligating the femoral artery of rats

Feng

Yang

Wang

et al. 2020

Preprint

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Background Osteomyelitis caused by Staphylococcus aureus (S. aureus) is an important post-operation complication, especially after fracture internal fixation and artificial joint replacement. Animal models play an indispensable role in exploring the pathogenesis of osteomyelitis. Most models use internal fixation, bacterial suspension and vascular sclerosing agent to destroy blood vessels. Vascular sclerosing agents not only damage blood vessels but also lead to local inflammatory immune disorders, which is different from simple vascular disease and osteomyelitis caused by ischemia in clinical practice. Methods The experimental animals were randomly divided into three groups: femoral artery ligation group, vascular sclerosing agent group and non-infection aseptic operation group. In the femoral artery ligation group, the femoral artery was ligated to reduce the blood flow of the affected limb to simulate the clinical ischemic state and increase the susceptibility, then the Kirschner needle with S. aureus biofilm was implanted into the tibia of rats, and the bone defect was sealed with aseptic paraffin. The non-infection aseptic operation group and the infection model group caused by vascular sclerosing agent have been used as the blank and positive control group. After operation, survival rate, body temperature and incision healing were monitored. Four weeks later, radiological and pathological changes of all animals were evaluated, and the secretions from osteomyelitis experienced etiological separation and cultivation. Results The chronic osteomyelitis model was established successfully by ligating femoral artery and implanting Kirschner needle covered with S. aureus biofilm. Signs of chronic osteomyelitis were observed in all rats of femoral artery ligation infection group and positive control group. No signs of infection and chronic osteomyelitis were found in the non-infection aseptic operation control group. Conclusion The method of ligating the femoral artery and implanting Kirschner needle with S. aureus biofilm into the tibia of rats can effectively establish a stable and reproducible chronic osteomyelitis model which is closer to the clinical pathogenesis and natural route of infection. This model could be useful for the study of pathogenesis and therapeutics of chronic osteomyelitis with S. aureus.

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Current health and economic burden of chronic diabetic osteomyelitis

Cited by 62 publications

References 55 publications

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection

Establishment of an animal model of chronic osteomyelitis with Staphylococcus aureus by ligating the femoral artery of rats

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