Proposal for Additional Intended Uses and Performance Criteria for the TFM: Topical Antimicrobials for Skin Site Preparation Prior to the Placement of Percutaneous Medical Devices Intended to Remain Indwelling

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Proposal for Additional Intended Uses and
Performance Criteria for the TFM Topical
Antimicrobials for Skin Site Preparation Prior to
the Placement of Percutaneous Medical Devices
Intended to Remain Indwelling
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Presented by

• Steven C. Felton, Ph.D., SM(ASCP)
• Staff Scientist
• BD (Becton Dickinson and Company)

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Current Performance Criteria and Intended Uses

• Surgical Hand Scrub
• Patient Preoperative Skin Prep
• Preinjection
• And
• Health Care Personnel Handwash

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ProposedSkin Antisepsis Prior to Indwelling
Percutaneous Medical Device Placement

• Performance criterion that is no worse
  (non-inferiority) than current standard of
  practice with regard to the risk for indwelling
  device-related infections.

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Examples of Indwelling Percutaneous Medical
Devices

• Short-term peripheral vascular catheters (PIV)
• Central Venous Catheters (CVC)
• Peripherally Inserted Central Catheters (PICC
  Lines)
• Surgical pins
• Intraosseous Infusion Devices
• Continuous Ambulatory Peritoneal Dialysis (CAPD)
• Others

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Indwelling Percutaneous Medical Devices

• Through-the-skin break in skin barrier is held
  open by the device
• Intended to remain in place hours, days, months,
  or longer
• Have significant risk of infection
• Studies have demonstrated that the effectiveness
  of the topical antimicrobial used for placement
  can reduce the risk of infection (Maki, 1991
  Sheehan, 1993 Chalyakunapruk meta-analysis,
  2002)

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Catheter-Related Bloodstream Infection (CRBSI)

• Special case
• Administer meds, fluid replacement, monitoring,
  collect blood samples
• Significant risk in Central Venous Catheters
  (3-10) Maki (1994)
• Estimated costs up to 2.3 Billion and 5-20,000
  deaths/year (Mermel, 2000 Widmer, 1997)

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CRBSI (Contd)

• The major cause of infection during the first
  weeks of indwelling time is from skin
  microorganisms.
• Rannem, et. al., 1990
• Maki, et. al., 1991
• Maki (review), 1994 20 references
• Widmer (review), 1997 10 references

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CRBSI (Contd)

• These microorganisms initiate an infection
  cascade that progresses
• from microbes on the skin,
• to colonization of the invasive portions of the
  device
• to local signs of infection (inflammation,
  phlebitis)
• to a CRBSI
• significant morbidity, mortality (5-20) and
  added healthcare expense (5,000 to 40,000 per
  occurrence for survivors) (Maki, 1987 Pittet,
  1994).

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CRBSI (Contd)

• CRBSI has been well studied and methods to
  diagnose CRBSI have been developed and validated.
  
• Maki - Semi-quantitative tip culture matched to
  positive blood cultures
• Sherertz - Sonication method to quantitate
  microorganisms on catheter SQ and tip segments
  matched to positive blood cultures

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Topical Antimicrobials and CRBSI

• Studies have shown that the efficacy of topical
  antimicrobials is inversely related to the rate
  of infection.
• Maki, 1991
• Sheehan, 1993
• Chalyakunapruk, meta-analysis 2002

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Summary

• The intended uses of topical antimicrobials for
  placement of other indwelling percutaneous
  medical devices are the same as for vascular
  access catheters.
• Unlike current performance criteria in the TFM,
  reduction of the incidence of device-related
  infections can be demonstrated in clinical trials
  in the intended use population.
• The TFM should identify the need for and
  establish performance criteria for the clinical
  evaluation of topical antimicrobials prior to the
  placement of indwelling percutaneous medical
  devices.

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Design of these Clinical Trials

• Maki (1994), echoed by Widmer (1997) proposed
  clinical trials to evaluate infection associated
  with vascular access catheters contain
• Skin cultures before topical antisepsis
• Study design would require an active comparator
  control as a placebo design would be considered
  to be unethical.
• Blood cultures for all suspected CRBSI at a
  minimum
• Recovery and culture of the device SQ and tip
  segments
• Skin cultures at the time the device is
  discontinued
• Correlation of all culture results with a minimum
  concordance by molecular methods between a
  catheter culture and a blood culture drawn from a
  different site.

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Design Continued

• However, such trials are complex
• Patients are not homogeneous for admitting
  diagnoses, underlying disease states, etc.
• Up to 38 Risk Factors have been identified to be
  covariates with CRBSI.
• Nursing requirements are 24/7 for the duration.
• Requires a competent microbiology laboratory with
  molecular subtyping technology.
• Samples sizes are large several hundred per
  treatment group.

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Risk Factors for CRBSI

• Other Active Infection
• Diabetes
• CAD
• PVD
• COPD
• APACHE II
• Renal Failure
• Aspiration
• Steroids

• HIV
• Neoplastic Disease
• Neutropenia
• Malnutrition
• CHF
• Hypertension
• AODA
• Transplant Recipient
• Trauma

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Risk Factors for CRBSI

• Obesity
• Burn
• Hypotension
• ICU Days
• TPN/TNA
• Ventilatory Support
• ICP Monitor
• Abdominal Drains
• ASA Score

• Other Vascular Catheters
• Open Surgical Wound
• Hemodialysis
• T.I. Coma
• Immunosuppressives
• Balloon Pump/LVAD
• Antibiotics
• Chest Tube