Clinical trial NCT04041739: Fungal Infection in Patients With Diabetic Foot Osteomyelitis
Official title: The Effect of Fungal Infection on the Outcome Among Diabetic Patients With Foot Osteomyelitis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diabetic Foot Osteomyelitis
Keywords: fungal infection
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2019-08-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: prospective cohort study, The study included 100 patients with diabetic foot osteomyelitis.

They all had long-standing recurrent foot ulceration in which healing had failed despite intensive foot care .

Ulcer material and bone fragments taken for mycological examination. All ulcers had multiple swabs taken for microbial culture and were examined under direct microscopy .

Tissue specimens were obtained from the depth of the wound (taking aseptic precautions) after debridement.

- Venous blood will be withdrawn to do the following laboratory tests :

* HbA1c
* erythrocyte sedimentation rate
* C reactive protein
* Complete blood culture
* Serum urea and creatinine 4-culture and sensitivity test 5-Bone fragments and tissue biopsy from infected ulcers 6-Fundus examination

Brief summary: estimate the percentage of fungal infection in the pathogenesis of diabetic foot osteomyelitis and assess the outcome of patients with fungal diabetic foot osteomyelitis

Detailed description: Approximately 60% of diabetic foot ulcers (DFUs) are complicated by infection. In more than two-thirds of the cases, infection is the main cause for major lower limb amputation in diabetic patients with foot ulceration. Infections may complicate DFUs in both neuropathic and ischemic ulcers.

However, the simultaneous presence of peripheral arterial disease (PAD) and infection influence the evolution of DFUs, increasing the risk of non-healing and major amputation.

Osteomyelitis is usually due to non-healing ulcers and it is associated with high risk of major amputation.

Osteomyelitis can affect any bone but most frequently the forefoot (90%), followed by the midfoot (5%) and the hindfoot (5%). Forefoot have a better prognosis than midfoot and hindfoot osteomyelitis. Above the ankle amputation risk is significantly higher for hindfoot (50%), than midfoot (18.5%) and forefoot (0.33%).

The diagnosis of osteomyelitis should be first based on clinical signs of infection supported by laboratory, microbiological and radiological evaluation. However, the diagnosis remains a challenge and DFO is often not recognized easily in its initial phase.

Infected wounds usually show purulent secretions or at least two signs of inflammation (swelling, erythema, blood serum secretion or simply blood with or without bone fragments). However, DFO can occur without any local sign of inflammation. Systemic symptoms such as fever and malaise are rare, especially in case of chronic osteomyelitis.

Various clinical findings can help clinicians in detecting bone infection. Two specific clinical signs are predictive of osteomyelitis. The first is the width and depth of the foot ulcer. An ulcer larger than 2 cm2 has a sensitivity of 56% and a specificity of 92%. Deep ulcers (\> 3 mm) are more easily associated with an underlying osteomyelitis than superficial ulcers (82% vs 33%).

A second diagnostic criterion to detect DFO is the "probe-to-bone test" (PTB). PBT is performed probing the ulcer area with a sterile blunt probe. If the probe reaches the bone surface the PTB is considered positive. In a study involving 75 diabetic patients, PTB showed a sensitivity of 66%, a specificity of 85% and a positive predictive value of 89%. The same test, evaluated in a subsequent prospective study of 1666 diabetic patients and compared with the culture of infected bones, was found to have a sensitivity of 87%, a specificity of 91%, a positive predictive value of only 57% and a negative predictive value of 98%.

Therefore, in the presence of infected ulcers, a positive PTB test is highly suggestive of osteomyelitis, but a negative test does not exclude it. Instead, in presence of an ulcer without clinical signs of infection, a positive test may be not specific for osteomyelitis while a negative PBT test should exclude a bone infection.

The combination of the PTB test with X-ray improve the sensitivity and specificity in the diagnosis of DFO. Bone infection is also considered in case of visible or exposed bone or discharge of bone fragments.

Diabetic foot osteomyelitis (DFO) is mostly the consequence of a soft tissue infection that spreads into the bone, involving the cortex first and then the marrow. The possible bone involvement should be suspected in all DFUs patients with infection clinical findings, in chronic wounds and in case of ulcer recurrence.The bacterial flora involved has been characterized in much detail and highlights a contemporaneous role for many organisms, both aerobic and anaerobic, in the infective process at a single ulcer site, the metabolic deregulation following DFO may lead to hyperglycemia and a degree of immunocompromise, factors allowing fungi to thrive. In addition, many patients with chronic DFU receive multiple courses of broad-spectrum antibiotics, altering the within wound milieu, suppressing normal flora, and thereby allowing the proliferation of opportunistic pathogens..

Fungal osteomyelitis (OM) is relatively rare. There is scarce literature discussing fungal OM in diabetic foot infections (DFIs).

A role for fungal infection in the pathogenesis of diabetic foot lesions has been suggested previously but remains unstudied

Eligibility criteria: Inclusion Criteria:

* All diabetic foot ulcers with osteomyelitis

Exclusion Criteria:

* Patients on corticosteroid therapy.
* Patients on long term antibiotic therapy.

Primary outcomes:
measure: detect magnitude of fungal infection as an etiology causing persistent non healed diabetic foot osteomyelitis
timeFrame: "through study completion, an average of 2 year".
Secondary outcomes:
measure: detect response of healing of resistant infected osteomyelitis to antifungal therapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Assiut,71511
country: Egypt
facility: Assuit University,71511
Study officials:
affiliation: Assiut University
name: Mostafa Haridy
role: STUDY_DIRECTOR
References:
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