Assessment of Severe Extremity Wound Bioburden and Infection Risk

1. Assessment of Severe Extremity Wound Bioburden at the Time of Definitive Wound Closure or Coverage: Correlation with Subsequent Post-Closure Deep Wound Infection (Bioburden Study) Research Coordinator Training August 11, 2011 PI: Michael Bosse (Carolinas Medical Center)

2. Introductions

3. Agenda (August 11, 2011) • Background and study rationale • Study Aims • Study Outcomes • Inclusion/Exclusion criteria • Study Procedures • Patient enrollment • Sample collection and shipping • Data collection

4. Agenda (August 18, 2011) • Review regulatory and administrative procedures • Reporting Requirements • IRB Procedures • Certification Procedures • Invoicing • Study Contacts • Study Timeline • Tissue collection during hospital readmission • Overview • Site Presentations • Discussion

5. Background • Infection is a common and significant complication following high energy fractures • Rates range from 25-40% • Typically, we close or cover the wound and provide 24 hrs of antibiotic coverage • Rarely do we know the bacterial population of sensitivity profiles • Characterizing wound bioburden at time of closure and documenting resulting infections will lead to improved primary prevention and treatment of infected wounds

6. Study Rationale • Determine microbiology profile of wound at time of wound closure • Compare PCR and routine microbiology techniques for determining microbiology profiles • Determine which pathogens at time of wound closure are associated with subsequent infection • Form the basis of an RCT that will evaluate the effect of new local wound therapies on the development of deep infection

7. Study Aims Specific Aim 1: In a subset of 60 patients, compare the bioburden, as detected by Ibis technology, from each of three sampling techniques (deep tissue; soft tissue composite; composite of tissue from the length and depth of the wound). Samples obtained using the most effective technique identified in this step will be processed using Ibis in subsequent tissue analysis. Effectiveness is defined as the ability to identify key wound infection-causing pathogens. Hypothesis 1: The composite sampling approach will be the most effective technique. Specific Aim 2: Characterize the wound bioburden at the time of definitive wound closure or coverage using the Ibis T5000 Biosensor System PCR technology as compared to standard microbiology techniques. Hypothesis 2: The Ibis technology will detect more species of pathogens than standard microbiology techniques. The percent of patients for whom Ibis will detect all species identified by standard microbiology will be greater than 95%.

8. Study Aims Specific Aim 3: Characterize the wound bioburden in the patients who develop deep infection within one year of wound closure, and determine the association between infecting pathogens with initial wound closure bioburden as measured jointly by Ibis and standard microbiology techniques. Specific Aim 4: Document the variability in antibiotic selection and duration, and examine the impact of this selection on subsequent deep infection. Hypothesis 4a: Among patients treated with antibiotic regimens that are appropriate for the pathogens identified by standard microbiology, there will be a lower probability of deep infection than among those patients who received inappropriate antibiotic regimens. Hypothesis 4b: Among patients treated with antibiotic regimens that are appropriate for the pathogens identified by Ibis, there will be a lower probability of deep infection than among those patients who received inappropriate antibiotic regimens.

9. Outcomes Primary: Infection Defined at first surgery for treatment of a deep infection. In addition we will obtain tissue samples from wounds requiring surgical treatment for a non-union, flap failure, or amputation Secondary: Classification of appropriate antibiotic care • Antimicrobial regimens will be adjudicated by an expert panel as “appropriate” or “not appropriate”

10. Main Inclusion criteria • All open Grade III tibia (plateau, shaft, pilon) fractures requiring a second procedure following fixation, or traumatic transtibial amputations requiring delayed primary closure, skin grafting and/ or flap coverage. • Ages 18 – 64 years inclusive 

11. Inclusion Criteria NOTES • Patients may have risk factors for infection including diabetes, immunosuppression from steroids or other medications, HIV, or other infections. • Patients may have a traumatic brain injury. • Patients may have other fractures including spine, upper extremity fractures, contralateral lower extremity injuries, ipsilateral pelvis, hip, femur or foot injuries. • Patients may be treated initially at an outside institution prior to transfer to the study institution, as long as the definitive fixation was not performed prior to entrance into the study. • Patients with bilateral injuries that meet inclusion criteria may be included, but only the limb rated as “more severe” by the treating surgeon will be enrolled in the study. • Patients may have co-existing non-tibial infection, with or without antibiotic treatment. • Patients may have an existing infection of the surgical wound under treatment at the time of wound closure. • Patients may be definitively fixed using any method (nail, plate, ex fix) • Patients may have a fasciotomy

12. Exclusion Criteria • Patient speaks neither English nor Spanish • Patient is a prisoner • Patient has been diagnosed with a severe psychiatric condition • Patient is intellectually challenged without adequate family support • Patient lives outside the hospital’s catchment area • Patients with planned follow-up at another medical center

13. Study Procedures

14. Screen patients for eligibility Standard aerobic and anaerobic microbiology Shipment of IBIS and Micro Samples to CGS Sample Storage IBIS Data Sample Analysis Enrollment and Baseline Data Collection Prospective tracking of readmissions (First readmission for surgical treatment of deep infection, non union, flap failure, or amputation) Final Surgical Procedure Micro Lab Reports Re-hospitalization form Antibiotic Form Follow-Up Tissue Sampling for IBIS and Study Microbiology Wound cultures to hospital lab, if surgeons typical practice Baseline Tissue Sampling for IBIS and Study Microbiology If missed prospectively At 12 months, review medical record with study surgeon to identify FIRST readmission Hospital Discharge Complete Baseline Data Collection If none identified Patient Phone Interview If readmitted Micro Lab Reports Re-hospitalization form Antibiotic Form Obtain discharge abstracts and review with study surgeon to identify FIRST readmission

15. Patient Enrollment • Approximately 600 patients will be enrolled over a 9 month period • The following patients should be screened into the Bioburden study, and thus have a completed CRF00: all patients between the ages of 18 and 64 (inclusive) with an open Grade III fracture or traumatic amputation of the tibia, ideally, within the first day or two after initial debridement. • Consenting for those meeting study criteria should be done prior to wound closure or coverage • The study PI will be available via pager to answer any questions regarding eligibility • If allowed by local IRB, patients can be enrolled in Bioburden and another METRC or non-METRC study • CRF00 should be completed and entered into REDCap for all screened patients • At time of consent, participant should also complete and sign Authorization for Release of Health Information

16. Proxy Consent • A legally authorized representative (LAR) can consent on the patients behalf if: • The patient is unresponsive or intubated • The patient is unable to answer questions regarding what it means to participate in the study • LARs can be: • Legal guardian • Proxy (health care agent) named in an advance directive or durable power of attorney for health care • Family member or other surrogate

17. Consent for Storing Tissue • Tissue samples from patients who consent will be stored for future studies of genetic, gene expression and microbial clade analyses • Tissue samples will remain de-identified and destroyed after 10 years. • These analyses are not part of the bioburden study. This is a separate consent form- bioburden participants can refuse to have their tissues stored.

18. Labeling Samples for Tissue Storage • Indicate on the yellow card that comes in the tissue sample kits whether patients provided consent to have their tissues stored for future analysis. • If no, CGS will destroy the tissues after the study and all analyses have been completed (6 months after the study ends).

19. Tissue collection at time of hospitalization for injury 4 tissue samples should be obtained during the wound closure/coverage procedure (1) Deep tissue sample from deep fracture site for Ibis (1) Soft tissue sample from subcutaneous layers, fascia and muscle for Ibis (2) Composite tissue sample of wound region considered to be at highest risk of infection by the treating surgeon for Ibis and standard microbiology The next WebEx session, several Research Coordinators will review how they will collect tissue samples at their site.

20. Tissue Collection During Re-Admission • Tissue samples will only be collected if patient has surgery for: • Deep surgical site infection • Non-union • Flap failure • Amputation • Two composite tissue samples will be taken: • Standard microbiology • Ibis • You will receive a separate tissue sample collection kit for these samples.

21. Prospectively Tracking Re-admissions • Only the first surgery matters!! • How will you track readmissions at your site? • At night • On the weekends • How will you ensure that tissue samples are obtained during the readmission procedure? • We will review some examples during the next WebEx session.

22. Tissue Sample Collection Kits • Shipping box • Labeled sample containers (4) • Tube shuttle • Transport bag • Tape/bubble wrap • List of contents (for shipping) • Time and date card • Packaging instructions • FEDEX airbill

23. Special Notes • Anaerobic transport medium good for only 6 months • Notify the MCC when you are down to only 1 or 2 more kits and if you have a kit that will expire within 2 weeks. • Turns blue when exposed to oxygen; important to recap quickly after tissue sample is collected • Samples are good for 48 hours after collection. • Samples should be refrigerated all together if they can’t be shipped the day they are collected. • Refrigerate at 4 degrees C (38.4 degrees F) • Samples do not need to be shipped on dry ice

24. Shipping • Patient ID obtained from REDCap must be written on all sample collection tubes using a pen or permanent marker • Record the kit number on the Index Hospitalization CRF, as well as time and date sample was obtained and any refrigeration information. • Record the date and time the sample was obtained on the yellow sample card • You will be provided pre-printed FedEx air bills • Fill in the date at time of shipping • Saturday delivery • Proper positioning of air bill on package

25. Shipping Returns • Stickers with site contact information and CGS contact information will be placed on package in the event the air bill comes loose. • Re-ship to CGS even if the samples are no longer viable.

26. Data Collection Case Report Form Binder • Study related case report forms • Serious Adverse Event form • Final Status form Microbiology Reports • Lab reports will be obtained from local site labs if these analyses are done as part of the standard of care • Lab reports will be obtained for patient’s first surgical readmission to the hospital • De-identify and upload to REDCap

28. Screen patients for eligibility Standard aerobic and anaerobic microbiology Shipment of IBIS and Micro Samples to CGS Sample Storage IBIS Data Sample Analysis Enrollment and Baseline Data Collection Prospective tracking of readmissions (First readmission for surgical treatment of deep infection, non union, flap failure, or amputation) Final Surgical Procedure Micro Lab Reports Re-hospitalization form Antibiotic Form Follow-Up Tissue Sampling for IBIS and Study Microbiology Wound cultures to hospital lab, if surgeons typical practice Baseline Tissue Sampling for IBIS and Study Microbiology If missed prospectively At 12 months, review medical record with study surgeon to identify FIRST readmission Hospital Discharge Complete Baseline Data Collection If none identified Patient Phone Interview If readmitted Micro Lab Reports Re-hospitalization form Antibiotic Form Obtain discharge abstracts and review with study surgeon to identify FIRST readmission

29. Index Hospitalization Form (CRF06) • It is possible that a patient receives surgery for a deep infection, flap failure, amputation or non union during this hospitalization • If so, you will collect the initial and follow-up tissue samples • Enter information about each of these study samples separately on CRF06

30. Antibiotic Use Form (CRF07) This form should be completed for: • Each antibiotic given during the index hospitalization • Each antibiotic taken prior to first readmission (and after discharge from index hospitalization)

31. Re-Hospitalization Form (CRF09) This form should be completed for the first readmission for surgical treatment of deep infection, non-union, flap failure, or amputation: • Prospectively identified • Identified during the medical record review at the end of the study • Identified during interview with patient

32. Questions?