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P.Acnes Colony Count Following Subdermal Cefazolin

Primary Purpose

Surgical Site Infection, Microbial Colonization

Status
Unknown status
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Cefazolin
Sponsored by
University of British Columbia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Surgical Site Infection

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • age greater than or equal to 18
  • patients requiring deltopectoral approach and opening of joint capsule for primary shoulder surgery

Exclusion Criteria:

  • allergy to cefazolin or cephalosporins
  • tattoos over operative site
  • previous surgical site infections in either shoulder
  • revision surgical procedure
  • immunocompromised patients

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Subcutaneous cefazolin arm

    Arm Description

    A patient receiving a standard deltopectoral approach will have the planned incision site divided into thirds. This will produce 6 segments. Each segment will be biopsied using a commercially available dermatology punch and sent for colony count prior to local antibiotic infiltration. Cefazolin will be administered to one half of the incision only, into three segments. Following 60 minutes of operative time, the biopsies will be repeated and sent for colony count for comparison. Cefazolin administered will be 100mg/mL in 3 aliquots for 3 site administrations leading to a total subcutaneous injection of approximately 900mg. There will be a one time administration of the antibiotics in a subcutaneous route.

    Outcomes

    Primary Outcome Measures

    Change in P.acnes colony count
    Colony count before and 60 minutes after subcutaneous cefazolin administration

    Secondary Outcome Measures

    Full Information

    First Posted
    February 20, 2019
    Last Updated
    February 21, 2019
    Sponsor
    University of British Columbia
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03853096
    Brief Title
    P.Acnes Colony Count Following Subdermal Cefazolin
    Official Title
    Do Intra-incisional Subdermal Antibiotics Alter the Colony Count of P. Acnes
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2019
    Overall Recruitment Status
    Unknown status
    Study Start Date
    April 1, 2019 (Anticipated)
    Primary Completion Date
    April 1, 2020 (Anticipated)
    Study Completion Date
    April 1, 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of British Columbia

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The specific outcome is to determine whether the colony count of Propionibacterium acnes, one of the commonest causes of shoulder infection and not eradicated by conventional forms of surgical preparatory solutions and antibiotics, in a shoulder surgical wound will be altered by the use of subdermal cefazolin.
    Detailed Description
    Purpose The purpose of the study is to review if the subdermal injection of antibiotics intraoperatively reduces the bacterial load in the subcutaneous tissue during the course of an open shoulder operation. Null Hypothesis There will be no change in the colony count of P.acnes following administration of subdermal antibiotics. Justification. P. Acnes is the most common cause of shoulder infection. The incidence of post-operative shoulder joint infection varies from 4-18%. The P.acnes organism is a Gram positive, largely anaerobic but aerotolerant commensal of the deep skin follicles and standard skin preparation may inadequately penetrate the pilosebaceous follicles. It has also been shown in a study by Levy et al that 41.8% of patients had a positive biopsy or aspirate result for P.acnes prior to implantation of components. This study will determine whether intraoperative subdermal antibiotic administration reduces the bacterial load and in turn reduce the incidence of shoulder joint infection. Cefazolin has been chosen because cephalosporins and penicillins have the lowest minimum inhibitory concentration (MIC) against P.acnes. There is a lower incidence of allergy to cephalosporins than penicillins. This study has the potential to change clinical practice world wide. Objectives The specific outcome is to compare the bacterial cell count on either side of a surgical wound and determine if subcutaneous antibiotics on a single side reduces subcutaneous cell counts over various time courses throughout the operation. Research Method. Targeted recruitment is 20 patients in this pilot study. This figure has been arrived at after determining the power of the study, significance levels and the anticipated drop in P.acnes count colonisation after the use of local antibiotics. It is also a number that can be achieved rapidly, enabling us to assess whether there is an observed difference between the groups and thereby gauge the feasibility of a larger trial. The patients will receive the standard of care pre-operative antibiotics 30 minutes prior to incision and surgical intervention. The skin will also be prepped using a chlorhexidine alcohol based solution as is standard at the investigator's institution. The investigators will divide the normal surgical incision into three even sections on either side of the incision, thus forming six segments. One side of the wound will be injected with three aliquots of 3 mLs using a concentration 100mg/mL of cefazolin. This equates to 900mg of subcutaneous cefazolin antibiotic. There are no specific efficacy criteria for agents in this setting that have been standardised and approved by an official oversight agency. We have selected this quantity based upon safe and wide-spread use of this concentration in a systemic manner as well as being mindful of the readily available concentrations. There is no known study describing any harm on introduction of antibiotics into the soft tissue, e.g. vancomycin used topically in prosthetic joints as a prophylaxis against infection, and the widespread use of intra-muscular (IM) penicillin products. Subcutaneous cefazolin has been demonstrated as safe in a porcine model while delivering higher cutaneous concentrations than with comparative systemic administration. Subcutaneous ceftriaxone is approved for use in France and is of increasing use for geriatric populations as well as by infectious disease practitioners. There is published evidence of safe administration of cefazolin in tumescent anesthesia antibiotic delivery mixed with lidocaine, epinephrine, and sodium bicarbonate. Standardized samples from all six sections will be sampled using a disposable 6mm Mitex biopsy punch before inoculation and this process will be repeated at the 60 minute mark. The samples will be sent to the microbiology lab where colony count will be obtained and long term cultures i.e. 3 weeks will be performed. It is routine in surgery to inject subcutaneous substances and not infrequently biopsies are taken. The only potential side effect is allergy to cephalosporins, which would have been determined preoperatively and is part of the exclusion criteria. There will be no expected increased incidence of infection or bleeding. Collection, Handling and Storage Specimens will be labeled with appropriate patient identifiers and clearly labeled as to the site of collection, and sent to the laboratory immediately for processing as soon as possible. Tissue biopsies will be sent either in anaerobic transport media or in a sterile container with a piece of sterile gauze moistened with non-bacteriostatic saline, or if piece is large enough, just a few drops of non-bacteriostatic in the container to prevent the tissue from desiccation. Tissue Processing All specimen manipulations will be carried out in the Biological Safety Cabinet and processed as soon as possible. Tissues will be inoculated to media to maximize the recovery of Propionibacterium acnes which will include a 5% sheep's blood agar and chocolate agar plates and thioglycollate (THIO) broth incubated under 5% carbon dioxide (CO2) at 35 Celsius. Brucella and Columbia Naladixic acid (CNA) agars will be incubated in an anaerobic conditions at 35 Celsius. With sterile forceps, the tissue will be transferred to a sterile Petri plate. Using a disposable sterile scalpel the tissue will be chopped into enough small pieces to inoculate all the media required. Several pieces of tissue will be added to THIO broth. The remaining media will be inoculated if order of least selective to the most selective: the blood agar plate, chocolate agar plate, Brucella and CNA agar. Lastly "touch preps" for the gram smears will be performed by gently touching a fresh piece of tissue onto the microscope slides. This piece of tissue will be discarded as it now is potentially contaminated. Tissue Investigation All media will be incubated for 5 days and read daily. The broth will be held for 21 days and examined at 7, 14 and 21 days after the initial 5 day reads. There is no need to follow the patients up for 2 years as we are only looking to determine change in intra operative colony counts which can be determined within 21 days and may be linked to a reduction in infection. All bacterial growth will be investigated per usual laboratory procedures for identification and antimicrobial susceptibility testing. Results will be reported to the study investigators in a timely fashion Statistical Analysis. Samples will be compared with either side of the wound over the respective time periods. Count averages will be obtained and analysised using a paired t-test.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Surgical Site Infection, Microbial Colonization

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Early Phase 1
    Interventional Study Model
    Single Group Assignment
    Model Description
    20 patient pilot study, single arm prospectively collected with no blinding or randomization. Consenting patients will receive at time of surgery an additional subcutaneous cefazolin injection at the surgical site as well as timed tissue biopsies for colony count of P.acnes
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Subcutaneous cefazolin arm
    Arm Type
    Experimental
    Arm Description
    A patient receiving a standard deltopectoral approach will have the planned incision site divided into thirds. This will produce 6 segments. Each segment will be biopsied using a commercially available dermatology punch and sent for colony count prior to local antibiotic infiltration. Cefazolin will be administered to one half of the incision only, into three segments. Following 60 minutes of operative time, the biopsies will be repeated and sent for colony count for comparison. Cefazolin administered will be 100mg/mL in 3 aliquots for 3 site administrations leading to a total subcutaneous injection of approximately 900mg. There will be a one time administration of the antibiotics in a subcutaneous route.
    Intervention Type
    Drug
    Intervention Name(s)
    Cefazolin
    Intervention Description
    Cefazolin 100mg/mL, 3mL in three locations will be administered around a surgical incision on the anterior shoulder in a standard deltopectoral approach interval. This will be a one time administration. Administration and route will be subcutaneous.
    Primary Outcome Measure Information:
    Title
    Change in P.acnes colony count
    Description
    Colony count before and 60 minutes after subcutaneous cefazolin administration
    Time Frame
    Baseline tissue sampling prior to subcutaneous antibiotic administration, and tissue sampling 60 minutes after

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    90 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: age greater than or equal to 18 patients requiring deltopectoral approach and opening of joint capsule for primary shoulder surgery Exclusion Criteria: allergy to cefazolin or cephalosporins tattoos over operative site previous surgical site infections in either shoulder revision surgical procedure immunocompromised patients
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    William Regan
    Phone
    1-866-737-7460
    Email
    bill.regan@ubc.ca
    First Name & Middle Initial & Last Name or Official Title & Degree
    Ryan Lohre
    Phone
    1-604-317-3275
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    William Regan
    Organizational Affiliation
    UBC clinical professor in orthopaedics
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    19947907
    Citation
    Harb G, Lebel F, Battikha J, Thackara JW. Safety and pharmacokinetics of subcutaneous ceftriaxone administered with or without recombinant human hyaluronidase (rHuPH20) versus intravenous ceftriaxone administration in adult volunteers. Curr Med Res Opin. 2010 Feb;26(2):279-88. doi: 10.1185/03007990903432900.
    Results Reference
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    PubMed Identifier
    9082104
    Citation
    Quendt J, Blank I, Seidel W. [Peritoneal and subcutaneous administration of cefazolin as perioperative antibiotic prophylaxis in colorectal operations. Prospective randomized comparative study of 200 patients]. Langenbecks Arch Chir. 1996;381(6):318-22. doi: 10.1007/BF00191311. German.
    Results Reference
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    PubMed Identifier
    24982315
    Citation
    Achermann Y, Goldstein EJ, Coenye T, Shirtliff ME. Propionibacterium acnes: from commensal to opportunistic biofilm-associated implant pathogen. Clin Microbiol Rev. 2014 Jul;27(3):419-40. doi: 10.1128/CMR.00092-13.
    Results Reference
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    PubMed Identifier
    28607871
    Citation
    Klein JA, Langman LJ. Prevention of Surgical Site Infections and Biofilms: Pharmacokinetics of Subcutaneous Cefazolin and Metronidazole in a Tumescent Lidocaine Solution. Plast Reconstr Surg Glob Open. 2017 May 30;5(5):e1351. doi: 10.1097/GOX.0000000000001351. eCollection 2017 May.
    Results Reference
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    PubMed Identifier
    25596729
    Citation
    Saper D, Capiro N, Ma R, Li X. Management of Propionibacterium acnes infection after shoulder surgery. Curr Rev Musculoskelet Med. 2015 Mar;8(1):67-74. doi: 10.1007/s12178-014-9256-5.
    Results Reference
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    PubMed Identifier
    29709392
    Citation
    Noriega OD, Yarleque Leon SN. Antibiotics by Subcutaneous Route: A Safe and Efficient Alternative. J Am Med Dir Assoc. 2018 Jun;19(6):553-554. doi: 10.1016/j.jamda.2018.03.011. Epub 2018 Apr 27. No abstract available.
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    PubMed Identifier
    29506833
    Citation
    Dubrovsky G, Huynh N, Rouch JD, Koulakis JP, Nicolau DP, Sutherland CA, Putterman S, Dunn JCY. Subcutaneous cefazolin to reduce surgical site infections in a porcine model. J Surg Res. 2018 Apr;224:156-159. doi: 10.1016/j.jss.2017.11.056. Epub 2017 Dec 28.
    Results Reference
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    PubMed Identifier
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    Citation
    Forestier E, Paccalin M, Roubaud-Baudron C, Fraisse T, Gavazzi G, Gaillat J. Subcutaneously administered antibiotics: a national survey of current practice from the French Infectious Diseases (SPILF) and Geriatric Medicine (SFGG) society networks. Clin Microbiol Infect. 2015 Apr;21(4):370.e1-3. doi: 10.1016/j.cmi.2014.11.017. Epub 2014 Nov 23.
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    PubMed Identifier
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    Citation
    Cockshott WP, Thompson GT, Howlett LJ, Seeley ET. Intramuscular or intralipomatous injections? N Engl J Med. 1982 Aug 5;307(6):356-8. doi: 10.1056/NEJM198208053070607. No abstract available.
    Results Reference
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    PubMed Identifier
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    Citation
    Levy PY, Fenollar F, Stein A, Borrione F, Cohen E, Lebail B, Raoult D. Propionibacterium acnes postoperative shoulder arthritis: an emerging clinical entity. Clin Infect Dis. 2008 Jun 15;46(12):1884-6. doi: 10.1086/588477.
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    P.Acnes Colony Count Following Subdermal Cefazolin

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