Osteomyelitis: Procalcitonin to Diagnose and Monitor Osteomyelitis (PCT)
Condition: Osteomyelitis
MeSH terms: Osteomyelitis
Study type: Observational

Summary: 
      We plan a cohort study of 40 diabetic patients admitted to Parkland hospital with a foot
      infection. We will enroll a representative cross section of subjects with diabetic foot
      infection. Patient will be consented and will receive therapy based on standard protocols.
      Currently patients with suspected osteomyelitis have bone biopsies to identify bacterial
      pathogens and verify MRI diagnosis. Repeat bone biopsies are performed at the end of therapy
      to verify that osteomyelitis has been successfully treated. Serum to measure procalcitonin
      will be obtained at baseline, week 3 and week 6.
    

Detailed description: 
      Infection: will be defined as a patient with three of six clinical signs of infection
      (erythema, heat, edema, pain, loss of function, purulence) or leukocytosis. We will use the
      Infectious Diseases Society of America's Diabetic Foot Infection guidelines to stratify the
      severity of infection. This guideline stratifies infections into three categories (mild,
      moderate, and severe) based on practical clinical and laboratory findings. Our group has
      shown this system to be predictive of morbidity.

      Osteomyelitis Diagnosis: We will evaluate suspected cases of osteomyelitis with bone biopsy
      for histology and culture and sensitivity. Bone biopsy to diagnose osteomyelitis is part of
      the standards of care established from the "diabetic foot infection guidelines" in our
      institution. We expect 1/4 of patients will have negative bone biopsy results. We will define
      a positive case of osteomyelitis as bone with positive bacterial cultures or histologic
      finding of acute osteomyelitis or chronic osteomyelitis. Acute osteomyelitis will be defined
      as the presence of acute inflammatory cells, congestion or thrombosis of medullary or
      periosteal small vessels, and necrotic bone. Chronic osteomyelitis will demonstrate areas of
      woven bone and fibrosis with large numbers of lymphocytes, histiocytes, and plasma cells.

      Outcome Measures: Our primary endpoints will be resolution of osteomyelitis based on
      percutaneous bone biopsy six weeks after initiation of therapy. We will evaluate patients for
      six months for signs of recurrent osteomyelitis and other clinical outcomes (wounds, Charcot
      fracture, and infection). Clinical outcomes will include (1.) wound healing, (2.) limb
      salvage, (3.) hospitalizations for recurrent diabetic foot infection (4.) surgical
      procedures, and (5.) recurrent ulcers.

      Confounding Variables: Most imaging studies of diabetic foot osteomyelitis do not assess
      potential confounding variables such as wound severity, diabetes severity, diabetes
      co-morbidities, and perfusion to the extremity. Outcomes such as wound healing and resolution
      of infection are clearly affected by current medical problems, social history, peripheral
      arterial disease, wound severity, and treatment factors such as type of antibiotics,
      off-loading, debridement and vascular surgery interventions. We will include the following
      variables in the study and in the analysis plan.

        1. Medical History: The diagnosis of diabetes will be based on American Diabetes
           Association criteria. We will evaluate glycated hemoglobin at baseline and quarterly per
           our standard of care. In addition, we will document: duration and type of diabetes, type
           of diabetes medication (insulin, oral, combination therapy, diet), previous history of
           foot ulcers, amputation (toe, foot), lower extremity bypass, lower extremity
           angioplasty, Coronary artery bypass surgery, cardiac angioplasty, arthritis, liver
           disease, osteoporosis, malignancy, and bone tumors. We will use the Kaplan co-morbidity
           index to record disease severity. We will use the New York Heart Association criteria to
           classify congestive heart failure, and the National Kidney Foundation Disease Outcomes
           Quality Initiative Clinical Practice Guidelines for chronic kidney disease to stage
           kidney disease. We will measure height and weight to determine body mass index (BMI). We
           will document all prescription and over-the-counter medications as well as the type,
           route and duration of antibiotic therapy.

        2. Social Factors: We will evaluate the following factors: marital status, years of
           education, type of work, tobacco history (pack years, current smoker, current use of
           chewing tobacco, previous smoker, no tobacco history), drug history (current, previous
           history, no drug history), and alcohol history.

        3. Vascular Assessment: We will assess perfusion of the macro-circulation with arterial
           Doppler studies and micro-circulation with Skin Perfusion Pressure measurements.

        4. Wound Assessment: We will use the University of Texas Diabetic Ulcer Classification to
           grade ulcer severity. We use acetate tracings, clinical measurements of length, width
           and depth and digital photos to measure wound area and volume before and after
           debridement. These technique has been shown to be highly reproducible. A wound will be
           considered "healed" when it is fully epithelialized with no drainage.

        5. Offloading and Debridement: For wounds on the weight-bearing surface of the foot, the
           most feasible offloading modality will be provided based on postural stability, wound
           location, and patient acceptance. Modalities available will be total contact cast,
           removable boot, healing sandal, and therapeutic shoes. Debridement will be performed as
           needed during the study.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Potential subjects will be identified from the investigator's inpatient and outpatient
        populations. This is not a treatment study, so subjects participating in other protocols
        will also be eligible to participate.
      
Biospecimen description: 
      Blood and tissue samples
    
Keywords: osteomyelitis, diabetic foot infection