Prevention of Central Line-associated Bloodstream Infections and the Role of Needleless Connectors. TSICP Annual Meeting Austin, Texas March 23, 2012

Transcription

1 Prevention of Central Line-associated Bloodstream Infections and the Role of Needleless Connectors TSICP Annual Meeting Austin, Texas March 23, 2012 William R. Jarvis, M.D. Jason and Jarvis Associates, LLC

2 Objectives To discuss the CDC Draft IV Guideline recommendations. To discuss the SHEA Compendium IV recommendations. To discuss the data that led to these recommendations. To discuss the impact of implementing these recommendations.

3 Hierarchy of Medical Evidence 3

4 CDC HICPAC 2011 IV Guideline

5 CDC Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 Major areas of emphasis include: 1. Education and training healthcare personnel who insert and maintain catheters; 2. Using maximal sterile barrier precautions during central venous catheter insertion (CVC); 3. Using a >0.5% chlorhexidine (CHG) preparation with alcohol for skin antisepsis; 4. Avoiding routine replacement of CVCs as a strategy to prevent infection; 5. Using antiseptic/antibiotic impregnated short-term CVCs and chlorhexidine impregnated sponge dressings, if the rate of infection is not decreasing despite adherence to other strategies (i.e., education and training, maximum barrier precautions, and >0.5% CHG preparations with alcohol for skin antisepsis); and 6. Performance improvement by implementing bundled strategies, and documenting and reporting rates of compliance with all components of the bundle as benchmarks for quality assurance and performance improvement.

6 CDC Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 Guideline Categorization Scheme: 1. Category IA. Strongly recommended for implementation and strongly supported by well-designed experimental, clinical, or epidemiologic studies. 2. Category IB. Strongly recommended for implementation and supported by some experimental, clinical, or epidemiologic studies and a strong theoretical rationale; or an accepted practice (e.g., aseptic technique) supported by limited evidence. 3. Category IC. Required by state or federal regulations, rules, or standards. 4. Category II. Suggested for implementation and supported by suggestive clinical or epidemiologic studies or a theoretical rationale. 5. Unresolved issue. Represents an unresolved issue for which evidence is insufficient or no consensus regarding efficacy exists.

7 CDC IV Guideline: What s Added 1. Use hospital-specific or collaborative-based performance improvement initiatives in which multifaceted strategies are "bundled" together to improve compliance with evidencebased recommended practices. Category 1B 2. Use ultrasound guidance to place central venous catheters to reduce the number of cannulation attempts and mechanical complications [if this technology is available]. Category 1B 3. When needleless systems are used, the split septum valve is preferred over the mechanical valve due to increased risk of infection. Category II

8 CDC IV Guideline: What s Added 4. Do not routinely use anticoagulant therapy to reduce the risk of catheterrelated infection in general patient populations. Category II 5. Use a 2% CHG wash daily to reduce CRBSI. Category II 6. During axillary or femoral artery catheter insertion, maximal sterile barriers precautions should be used. Category II 7. Replace arterial catheters only when there is a clinical indication. Category II 8. Remove the arterial catheter as soon as it is no longer needed. Category II

9 CDC IV Guideline: What s Been Upgraded 1. Use a chlorhexidine-impregnated sponge dressing for temporary short-term catheters in patients > 2 months of age, if the CR-BSI rate is decreasing despite adherence to basic prevention measures, including education and training, appropriate use of chlorhexidine for skin antisepsis, and MSB. Category 1B (changed from unresolved issue to Category 1B) 2. Use a CHG/silver sulfadiazine or minocycline/rifampin-impregnated CVC in patients whose catheter is expected to remain in place >5 days if, after successful implementation of a comprehensive strategy to reduce rates of CLA-BSI, the CLA-BSI rate is not decreasing. The comprehensive strategy should include at least the following three components: educating persons who insert and maintain catheters, use of maximal sterile barrier precautions, and a 2% CHG preparation with alcohol for skin antisepsis during CVC insertion. Category IA (changed from a Category 1B to a 1A)

10 CDC IV Guideline: What s Been Upgraded 3. Minimize contamination risk by scrubbing the access port with an appropriate antiseptic (CHG, povidone iodine, an iodophor, or 70% alcohol) and accessing the port only with sterile devices. Category IA (upgraded from a Category 1B to a 1A) 4. Replace dressings used on short-term CVC sites every 2 days for transparent dressings, except in those pediatric patients in which the risk for dislodging the catheter may outweigh the benefit of changing the dressing. Category IB (changed from 11 to 1B) 5. Use a fistula or graft in patients with chronic renal failure instead of a CVC for permanent access for dialysis. Category IA (changed from a 1B to a 1A) 6. When adherence to aseptic technique cannot be ensured (i.e., catheters inserted during a medical emergency), replace the catheter as soon as possible, i.e., within 48 hours. Category 1B (changed from a II to 1B)

11 CDC IV Guideline: What s Been Upgraded 7. Use povidone iodine antiseptic ointment or bacitracin/gramicidin/polymyxin B ointment at the hemodialysis catheter exit site after catheter insertion and at the end of each dialysis session only if this ointment does not interact with the material of the hemodialysis catheter per manufacturer's recommendation. Category IB (changed from a Category II to 1B) 8. Use a sutureless securement device to reduce the risk of infection for intravascular catheter. Category II (changed from unresolved issue to Category II) 9. Use prophylactic antimicrobial lock solution in patients with long-term catheters who have a history of multiple CR-BSI despite optimal maximal adherence to aseptic technique. Category II (changed from do not use to use ; both Category II)

12 Strategies to Prevent Central Line-Associated Bloodstream Infections (CLA-BSIs) in Acute Care Hospitals. Marschall J, et al. Infect Control Hosp Epidemiology 2008;29:S22-30.

13 SHEA Recommended Basic and Special Approaches for the Prevention of CLA-BSIs Basic Practices Catheter Checklist Hand Hygiene Insertion site-femoral Cart Kit Maximal Barrier Precautions Chlorhexidine (CHG) Skin Prep Special Approaches CHG Baths (ICU patients) Impregnated Catheters BioPatch Disk Antimicrobial Locks B- II B- II A- I B- II A- I A- I B- II A- I B- I A- I Catheter Insertion Bundle Catheter Maintenance Bundle Marschall J, et al. ICHE 2008;29:S22-30.

14 Enhancing Patient Safety Through Implementing These Recommendations

15 Microbial Source of CLA-BSI EXTRALUMINAL COLONIZATION INTRALUMINAL COLONIZATION Hub Catheter Vein Skin Skin Extraluminal biofilm is the major source of CLA-BSI within the first week of catheterization in short-term catheters. Extraluminal biofilm is the major source of tunnel infections in long-term catheters. Intraluminal biofilm is the major source of CLA-BSI after 1 week in both shortand long-term catheters. 1. Ryder, MA. Catheter-Related Infections: It's All About Biofilm. Topics in Advanced Practice Nursing ejournal. 2005;5(3) 2005 Medscape. Posted 08/18/

16 Contaminated Catheter Hub 2 Endogenous Skin flora Extrinsic Contaminated Infusate HCW hands Extrinsic Fluid Medication Skin Organisms Endogenous Skin flora Intrinsic 1 Manufacturer Extrinsic HCW hands Contaminated disinfectant 3 1 = 60% Fibrin Sheath, Thrombus Skin 2 = 12% 3 = <1% Vein 1. Safdar N, Maki DG. The pathogenesis of catheter-related bloodstream infection with noncuffed short-term central venous catheters. Int Care Med. 2004;30: Unk = 28%

17 SHEA Recommended Basic and Special Approaches for the Prevention of CLA-BSIs Basic Practices Catheter Checklist Hand Hygiene Insertion site-femoral Cart Kit Maximal Barrier Precautions Chlorhexidine (CHG) Skin Prep B- II B- II A- I B- II A- I A- I Catheter Insertion Bundle Special Approaches CHG Baths (ICU patients) Impregnated Catheters BioPatch Disk Antimicrobial Locks B- II A- I B- I A- I Catheter Maintenance Bundle Marschall J., et al. ICHE 008;29:S22-30.

18 Evidence-Based Measures to Decrease the Risk of Infection During Insertion of the Intravascular Catheter: INSERTION BUNDLE Insert a catheter only when clinically essential. Use a catheter insertion check-list. Use a catheter insertion cart or kit. Hand hygiene. Chlorhexidine-alcohol skin antisepsis. Maximum barrier precautions. Select the correct catheter and insert in the correct location (Vessel Preservation; avoid femoral).

19 Basic Practices: Use a Checklist 1 1.Marschall J. et al., Strategies to prevent Central Line Associated Bloodstream Infections in Acute Care Hospitals. Infect Control Hospital Epidemiol 2008;29:S22-30

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21 Basic Practices: Use Catheter Cart or Kit 1 1. Marschall J. et al., Strategies to prevent Central Line Associated Bloodstream Infections in Acute Care Hospitals. ICHE 2008;29:S22-30.

22 Effect of Hand Hygiene on Resistant Organisms* Year Author Setting Impact on organisms 1982 Maki adult ICU decreased 1984 Massanari adult ICU decreased 1990 Simmons adult ICU no effect 1992 Doebbeling adult ICU decreased with one versus another hand hygiene product 1994 Webster NICU MRSA eliminated 1999 Pittet Hospital-wide MRSA decreased 2009 Rupp Adult ICU No effect ICU = intensive care unit; NICU = neonatal ICU MRSA = methicillin-resistant Staphylococcus aureus *All interventions included multifaceted intervention programs; Most quasi-experimental or observational, not randomized trials. No randomized trial of hand hygiene vs. no hand hygiene has been conducted.

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24 Basic Practices: Use CHG Skin Prep 1 Apply 30 seconds with friction Allow 30 seconds to dry Marschall J. et al., Strategies to prevent Central Line Associated Bloodstream Infections in Acute Care Hospitals. Infect Control Hospital Epidemiol 2008;29:S22-30

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26 Effect of Maximal Barrier Precautions during Insertion on CVC Infections Raad et al, Infect Control Hosp Epidemiol, 1994 p=0.03 p=0.01

27 Evidence-Based Measures to Decrease the Risk of Infection During Maintenance of the Intravascular Catheter Minimize catheter site skin bioburden (BioPatch). Device selection (Catheter and connector) Aseptic manipulation of catheter connectors--scrub the hub (15-30 secs)! Antibiotic/antiseptic lock Antimicrobial/antiseptic-impregnatedcatheters

28 Microbiology of the Skin 80% of the resident bacteria exist within the first 5 layers of the stratum corneum 20% are found in biofilms within hair follicles and sebaceous glands Complete recolonization of the epidermis can occur within 18 hours of antiseptic application ETHICON, Inc 2005 Ryder, MA. Catheter-Related Infections: It's All About Biofilm. Topics in Advanced Practice Nursing ejournal. 2005;5(3) Posted 08/18/

29 Skin Microbial Density Catheter Entry Site Matters Skin surface microbial density varies at different body sites and between genders Normal microbial colony counts at the antecubital space are CFU per cm 2 ANTECUBITAL SPACE cfu/cm Ryder M. Evidence-based practice in the management of vascular access devices for home parenteral nutrition therapy.jpen. 2006;30(1):S Photo contributed by Marcia Ryder PhD MS RN

30 Skin Microbial Density Catheter Entry Site Matters Skin surface microbial density is highest on the skin at the femoral, jugular, and subclavian sites Normal microbial colony counts at the subclavicular space are CFU per cm 2 SUBCLAVICULAR SPACE Ryder M. Evidence-based practice in the management of vascular access devices for home parenteral nutrition therapy.jpen. 2006;30(1):S82-93 Photo contributed by Marcia Ryder, PhD, MS, RN cfu/cm 2

31 Timsit s Randomized Controlled Trial:

32 Results Timsit et al. JAMA. 2009;301:

33 Meta-analysis of CA-BSI Rates with Antiseptic Catheters Tennenberg Maki Hannan Bach Heard Collin Ciresi Pemberton Ramsay Trazzera George Summary Odds Ratio OR 0.56, 95% CI ( ) (Veenstra, Saint, Saha, et al. JAMA 1999)

34 Prevention: Impact of Coated Catheters Meta-analysis of published studies N of studies RR (95% CI) NNT 18 colonization 0.60 ( ) 8 16 bloodstream infections 0.64 ( ) 55 6 >1 week 0.35 ( ) 28 9 <1 week 0.82 ( ) 122 Walder, Pittet, Tramer CCM 02

35 Does the BioPatch Enhance CVC-BSI Prevention in Patients with Impregnated Catheters? Study design: Prospective, randomized, open, controlled study in cancer chemotherapy patients requiring central venous catheters (CVC) for >5 days between January 2004 and January All patients had a chlorhexidine and silver sulfadiazine-impregnated triple lumen CVC. Randomized to CHG-sponge vs. standard dressing. Independent observation of site. Results: 601 patients with 9,731 CVC-days. Mean CVC duration: 16.6 days (treatment) vs days (control). Mean neutropenia: 7.5 days (treatment) vs. 6.9 days (control). CVC-related infections: 34/301 (11.3%) in control vs. 19/300 (6.3%) in CHG-sponge group (p=0.016, RR=0.54). CVC-related infections significantly reduced at internal jugular vein-inserted CVCs (P=0.018). Summary: The use of the CHG-sponge (BioPatch) reduced CVCrelated infections by 44% even when CHG-silver impregnated catheters were used. Reschulte H et al. Ann Hematol 2009;88;

36 Types of Needleless Connectors Negative Pressure Positive Pressure Neutral Pressure

37 Increased Bloodstream Infection (BSI) Rates Associated with Needleless Author SS Used SS-BSI Rate* Connectors MV Used MV-BSI Rate* P- value Salgado 1 Interlink 1.79 Smartsite 5.41 <0.001 Rupp 2 Interlink 3.87 SmartSite Plus <0.001 Fields 3 Interlink 2.60 Clave/CLC Toscano 4 Needles 0.70 Clave SS=Split Septum; MV=Mechanical Valve; Rate=BSI/1000 catheter days. References: 1. ICHE 2007;35:648-8; 2. CID 2007;44: ; 3. ICHE 2007;28:610-13; 4. AJIC 2009;37:327

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42 How May the Mechanical Valves Lead to BSIs? Location: Wake Forest University School of Medicine. Study Design: Quantitative cultures of blood from ICU patients drawn through MV ND from December 12, 2004 to January 21, 2005 (initial syringe pull back of morning blood draw). Results: 226 discards obtained from 83 patients. 39/226 (17%; range 8% to 50%, by unit) culture positive. Colony forming units (CFU/ml): median=0.3, range 0.1->100. Pathogens: 25 CNS, 5 yeast, 2 S. aureus, 2 each Serratia or Enterococcus spp., 1 each S. maltophilia or Acinetobacter spp.; 31% would be considered pathogens in a blood culture. 31% of nurses did not disinfect the MV before accessing system. Karchmer TB et al. SHEA 2005, Abstract #307

43 Disinfection of Needleless Catheter Connectors Study design: In vitro study. 3 luer-activated valved connectors (Clearlink [Baxter Healthcare], PosiFlow [Becton-Dickinson], and Micro CLAVE [ICU Medical]) were studied. One device as control, the rest inoculated by immersing the membranous surface in a suspension of E. faecalis containing >10 8 colony forming units (CFUs) per ml. Septum allowed to dry for 24 hours (final inoculum 10 5 CFU/ml). Accessed by sterile syringe containing 3ml of sterile tryptocase soy broth and flushed with broth. Vigorous 3-5 second swabbing. Menyhay and Maki ICHE 2006;27:23-27.

44 Menyhay and Maki ICHE 2006;27:23-27.

45 Disinfection of Mechanical Valves Study design: 300 MVs (4 types from 3 manufacturers) were tested. Each septum inoculated with 10 5 CFUs/ml of S. epidermidis, S. aureus, P. aeruginosa, and/or C. albicans. Membranous septum disinfected for 15 seconds with friction, using 70% alcohol or 3.15% chlorhexidine/70% alcohol (Chlorascrub ). 0.9% non-bacteriostatic saline flush solutions were collected downstream and quantitatively cultured. Results: Disinfection of the membranous septum for 15 seconds with friction, using either 70% alcohol alone or 3.15% chlorhexidine/70% alcohol (Chlorascrub ) was equally effective in preventing the transfer from the membranous septum downstream in the process of accessing the ports. Kaler W et al. JAVA 2007;12:

46 Letter to Infection Control Practitioners Regarding Positive Displacement Needleless Connectors: Dear Infection Control Professional: The Food and Drug Administration is requiring nine companies to conduct a postmarket surveillance study on positive displacement needleless connectors to assess whether they may be associated with a higher rate of device-associated bloodstream infections (BSI) than other types of needleless connectors, and to assess the factors that may contribute to a possible increased risk. Summary of the Problem: FDA has become aware of information that raises concerns about the safety of positive displacement needleless connectors. These devices are intended for use as an accessory to an intravascular administration set to allow delivery of a wide range of fluids to a patient's vascular system through a cannula inserted into a vein or artery. Needleless connectors may also be referred to as valves or accesses. Positive displacement refers to the positive pressure of fluid movement from a reservoir into the lumen of the catheter upon disconnection of an administration set or syringe. FDA has received three reports of death associated with BSI and positive displacement needleless connectors. Infection control authorities are also concerned about positive displacement connectors and the device s association with BSI...Because there is presently insufficient information to determine if positive displacement connectors increase the risk of BSI compared with other needleless connectors, FDA is requiring the companies to conduct postmarket surveillance studies to provide an assessment of the risk associated with positive displacement needleless connectors. The Postmarket Studies> Manufacturers must answer the following two public health questions about positive displacement needleless connectors with their postmarket surveillance studies: 1. What is the rate of bloodstream infections for subjects receiving your positive displacement connector for central line access and is it statistically non-inferior to the rates seen in subjects receiving other needleless connectors (e.g. negative, neutral, or split-septum connectors) for central line access, given comparable patient populations? 2. Are there patient demographics, comorbidities/severity of illness, or device cleaning practices for which placement of your positive displacement connector for central line access increases subjects risk of bloodstream infections compared with other needleless connectors? These studies may take up to three years to complete. At the end of the study period, FDA will assess whether regulatory or other actions need to be taken. References: Field K, McFarlane C, Cheng AC, Hughes AJ, Jacobs E, Styles K, Low J, Stow P, Campbell P, Athan E. Infect Control Hosp Epidemiol May;28(5):610-3.; Jarvis WR, Murphy C, Hall KK, Fogle PJ, Karchmer TB, Harrington G, Salgado C, Giannetta ET, Cameron C, Sherertz RJ. Clin Infect Dis Dec 15;49(12):1821-7; Maragakis LL, Bradley KL, Song X, Beers C, Miller MR, Cosgrove SE, Perl TM. InfectControl Hosp Epidemiol Jan;27(1):67-70; Rupp ME, Sholtz LA, Jourdan DR, Marion ND, Tyner LK, Fe; PD, Iwen PC, Anderson JR. Clin Infect Dis Jun 1;44(11): ; Salgado CD, Chinnes L, Paczesny TH, Cantey JR. Infect Control Hosp Epidemiol Jun;28(6):684-8.

47 Companies FDA is Requiring to Perform Positive Displacement Needleless Connector Post-market Surveillance Study Amsino International, Inc.: Cortez Needle Free IV Connector. Baxter Healthcare Corporation: IV/Catheter Extension Set with NAC Plus Needleless Access Connector and NAC Plus Needleless Access Connector. Becton Dickinson Infusion Therapy Systems Inc.: BD posiflow TM Positive Displacement Valve. B. Braun Medical Inc.: Ultrasite Valve. Cardinal Health 200, LLC: IVAC Needle Free Administration Sets. Carefusion 303, Inc.: SmartSite Needle Free Valve Administration Sets. Critical Device Corporation: NIMA Needleless Injection site Master Adapter with PosiFlow Positive Displacement Feature, and IV Sets. ICU Medical, Inc: CLC 2000, CLC2000 Catheter Patency Device, and TEGO. Medegen Medical Manufacturing Services/System: Maxplus/MaxPlus Tru-Swab Positive Displacement Connector.

48 Current SHEA or CDC Recommendations Regarding Neeleless Connectors SHEA: Do not routinely use positive-pressure needleless connectors with mechanical valves before a thorough assessment of risks, benefits, and education regarding proper use (B-II). Marschall J. et al., Infect Control Hosp Epidemiology 2008;29:S CDC: When needleless systems are used, a split septum valve may be preferred over a mechanical valve due to increased risk of infection with some mechanical valves. Category II

49 49 Not All CHG-Containing Devices Are Created Equal

50 3M Tegaderm CHG Data Publications (N=2) 1. Olson C, et al. Clinical Performance of a New Transparent Chlorhexidine Gluconate Central Venous Catheter Dressing (Ease of Use Study). JAVA 2008;13: The primary objective was to evaluate the overall satisfaction with the securement at the end of the study participation. The secondary objectives were to evaluate the overall satisfaction with the dressing. Results: There was no statistically significant difference between TegadermTM CHG and the non-antimicrobial dressing in dressing wear time, number of dressing changes, ease of application, ease of applying correctly and ease of removal. Only at the end of study evaluation, were the clinician s satisfaction with securement and overall satisfaction with dressing significantly better with TegadermTM CHG. 2. Eyberg C, et al. A Controlled Randomized Prospective Comparative Pilot Study to Evaluate the Ease of Use of a Transparent CHG Gel Dressing vs. a CHG Disk in Healthy Volunteers. JAVA 2008;13: Assessment of the ease of application and performance factors of TegadermTM CHG vs. BIOPATCH in healthy volunteers (N=12). Each clinician (total of 12 clinicians) applied and removed one TegadermTM CHG and one BIOPATCH on one simulated PICC and one simulated IJ site. Abstracts ( N=15) The majority (N=13) assessed nurse satisfaction with performance of the product, absorption of the product, cost, or in vitro antimicrobial activity. Only two even mention any CVC-BSI rates; both are small before/after studies at small hospitals. In one, the product introduction was because of a elevated CVC-BSI rate and they introduced a wide variety of measures (including changing from a positive to neutral pressure mechanical valve and expanding the PICC team [Pappas et al]). In the other (Reilly et al), a small before/after study was done over about 17 months. The CVC-BSI rate decreased initially after introduction of the CHG dressing, but the rate was increasing toward 2 (the prior baseline rate) per 1,000 CVC-days at the end of the period reported with the dressing.

51 FDA-Approved Indications BioPatch Protective Disk with CHG Indications for Use Biopatch containing Chlorhexidine Gluconate is intended for use as a hydrophilic wound dressing that is used to absorb exudates and to cover a wound caused by the use of vascular and non-vascular percutaneous medical devices such as: IV catheters, central venous lines, arterial catheters, dialysis catheters, peripherally inserted coronary catheters, mid-line catheters, drains, chest tubes, externally placed orthopedic pins and epidural catheters. It is also intended to reduce local infections, catheterrelated bloodstream infections (CRBSI), and skin colonization of microorganisms commonly related to CRBSI, in patients with central venous or arterial catheters. 3M Tegaderm CHG Dressing Indications for Use 3M Tegaderm CHG dressings Chlorhexidine Gluconate I.V. Securement Dressing), can be used to cover and protect catheter sites and to secure devices to skin. Common applications include IV catheters, other intravascular catheter percutaneous devices.

52 In Vitro Comparative Analysis of a Chlorhexidine Gluconate (CHG) Sponge Dressing and a CHGcontaining Hydrogel Dressing BIOPATCH Tegaderm TM CHG CHG TRANSFER 1. CHG is transferred only where there is direct contact between the device and the skin, because CHG binds tightly to the skin 1 and does not migrate across it. This is demonstrated in tests of CHG transfer to porcine skin (Figure 1) The BIOPATCH Protective Disk with CHG design enables placement around the catheter and complete contact with the surrounding skin. In contrast, when the Tegaderm TM CHG dressing was placed over the catheter, tenting occurred and the skin immediately surrounding the insertion site and underneath the catheter was not in contact with the dressing. Figure 1 (A,B): 3 CHG is transferred from BIOPATCH circumferentially around the insertion site. Figure 1 (C,D): 3 CHG is transferred from Tegaderm TM CHG only where there is direct contact between the hydrogel pad and skin and not under the catheter or where tenting occurred. References: 1. Jackson MM. Topical antiseptics in healthcare. Clin Lab Sci. 2005;18(3): Westergom C. Ex Vivo Comparative Analysis of Chlorhexidine Gluconate (CHG) Coverage on Porcine Skin. Ethicon, Inc., Somerville, NJ, CHG Transfer Onto Porcine Skin: 2x2 pieces of porcine skin were cleaned, dried and placed on top of PBS saturated c-fold towels. Catheters were inserted through a 10 mm biopsy punch and dressed according to either product s directions for use. Samples were incubated at 30 C for 24 hours. The skin was removed, stained with Sodium Hypobromite solution and photographed. Data on file. Ethicon, Inc. 52

53 In Vitro Comparative Analysis of a Chlorhexidine Gluconate (CHG) Sponge Dressing and a CHGcontaining Hydrogel Dressing FLUID MANAGEMENT 1. BIOPATCH Protective Disk with CHG absorbs fluids rapidly, which helps avoid the potential for skin maceration. In vitro studies demonstrate that BIOPATCH fully absorbs blood within 0.5 seconds (Figure 2; A, B). 1 In contrast, Tegaderm TM CHG gel pad did not fully absorb blood even after 2 hours. This may be due to the high water content of the gel itself (70% to 90%), 1 which limits its absorption of fluids. Tegaderm TM CHG only partially absorbs blood after 2 hours (Figure 3; C) Given the fact that under normal conditions blood clots within 4 to 8 minutes, 1 this slow absorption may lead to blood clots and proteinaceous materials remaining on the skin beneath the Tegaderm TM CHG dressing. 3. Incomplete absorption of blood or bodily fluids can create an environment conducive to bacterial growth (Figure 4). 2 BIOPATCH fully absorbs blood within 0.5 seconds (Figure 2, A and B). Blood is only partially absorbed into the Tegaderm TM CHG gel pad even after 2 hours (Figure 3, A-C). 3 References: 1. Gonzalez S. Differences In Absorption Between Biopatch And Tegaderm TM CHG Part II: Rate of absorption of different fluids. Ethicon, October, Data on file. Ethicon, Inc. 2. Maki DG, Ringer M. Evaluation of dressing regimens for prevention of infection with peripheral intravenous catheters. Gauze, a transparent polyurethane dressing, and an iodophor-transparent dressing. JAMA. 1987;258(17): BIOPATCH vs. Tegaderm TM CHG Absorption pictures: Drops of citrated porcine blood were dropped onto the foam side of Biopatch or the gel side of Tegaderm TM CHG using an 18 gauge needle. The time for blood absorption was recorded. Data on file. Ethicon, Inc. 53

54 GUARDIVa TM COMPARISON In Vitro Comparative Analysis of 2 Chlorhexidine Gluconate Sponge Dressings KEY DIFFERENCE BETWEEN PRODUCTS These two CHG-impregnated sponge dressings may have a similar outward appearance, but their materials of construction and delivery characteristics are very different, and BIOPATCH is the only product clinically-proven with FDA-cleared indication for the prevention of CR-BSIs. 54

55 In Vitro Comparative Analysis of 2 Chlorhexidine Gluconate Sponge Dressings DIFFERENT FOAM CHARACTERISTICS The outside appearance of GuardIVa TM is very similar to that of BIOPATCH Protective Disk with CHG. However, on closer inspection, they are clearly different. 1 References: 1. SEM: Electron micrographs at 50 times magnification using a JEOL JSM-5900LV SEM. Data on file. Ethicon, Inc. 55

56 GUARDIVa TM COMPARISON In Vitro Comparative Analysis of 2 Chlorhexidine Gluconate Sponge Dressings DIFFERENT INDICATIONS 1. Unlike the BIOPATCH Protective Disk with CHG, the GuardIVa TM is indicated only as an absorbent, hemostatic protective dressing and is not indicated to prevent infection. Chorhexidine gluconate (CHG) is added to the dressing as a preservative to inhibit the growth of microoganisms within the dressing. 2. According to the GuardIVa TM package insert, the CHG is added to the dressing as a preservative to prevent bacterial growth within the dressing itself 1 rather than on the skin beneath it. References: 1. GuardIVa TM [package insert]. Dublin: HemCon Medical Techologies, Europe Ltd. 56

57 Interventions That Prove That Implementation of Evidence-Based CVC-BSI Prevention Measures Can Prevent Infections, Save Lives, and Save Money

58 Keystone Project Study design: Intervention cohort study in 108 Michigan Intensive care units (ICUs) over 18 months. Comparison of CVC-BSI rates before, during, and after intervention. Results: 103 ICUs. 1,981 months of ICU data and 375,757 catheter-days. Median CVC-BSI Rates per 1,000 CVC-days Baseline 3 Months IRR Months IRR Conclusion: An evidence-based intervention resulted in a large and sustainable decrease (up to 66%) in CVC-BSI rates that was maintained for 18 months. Pronovost P. et al NEJM 2006;355:

59 Michigan s Keystone Project-Can Results Be Sustained? Pronovost P et al., BMJ. 2010;340:c309.

60 The Majority of CR-BSIs Occur Outside of the ICU Annual Central Venous CRBSIs (n=250,000) 1,2 Central Venous CRBSIs 70% 30% Non-ICU Patients ICU Patients A significant opportunity exists to reduce CR- BSI incidence in non-icu settings. 1. Mermel L, Farr B, Sheretz R. Guidelines for the management of intravascular catheter-related infections. Clinical Infectious Diseases. 2001;32: Centers for Disease Control and Prevention. Guidelines for the prevention of intravascular catheterrelated infections. Morbidity Mortality Weekly Report. 2002;51: Mermel, 2000 and CDC 2002

61 Impact Of Dedicated IV Device-Care Teams Study No. Patients IV-Related P-Value Sepsis Concurrent but non-randomized: Nehe, Ward Care % JAMA (1980) TPN Team % <.001 Randomized: Tomford et al. Ward Hos % Arch Int Med (1984) PIV Team %.02 Edlin et al. Ward HOs % Arch Int Med (1998) IV Team 412 0% <.05

62 CLA-BSI Prevention Insertion and Maintenance Bundles Insertion Bundle Catheter checklist Hand hygiene Insertion site-femoral Cart kit Maximal barrier precautions Chlorhexidine (CHG) skin prep Maintenance Bundle Select the safest needleless connector Scrub the hub (>15 secs with CHG-alcohol or alcohol) Antiseptic or antimicrobial-impregnated catheters CHG-impregnated sponge (BioPatch) Antimicrobial or antiseptic locks CHG Baths (ICU patients) Prevention Possibility: 70%-100%

63 Conclusions CVC-Related BSIs are a major cause of patient morbidity and mortality. Prevention of CVC-Related BSIs requires a multi-factorial approach, including: Implementation of SHEA and CDC CVC-BSI Prevention Guideline Recommendations (2009/2010) Implementing new prevention evidence. Implementation of insertion and maintenance bundles. Educating staff; Insuring adequate and properly trained staff Insuring that policy = practice (clinician accountability) Monitoring CVC insertion and maintenance processes and CVC-related BSI rates (outcomes). A comprehensive CVC-related BSI prevention program can dramatically reduce infection rates and improve patient safety. A rate of ZERO CVC-BSIs in ICU patients is a reality and should be our goal.

64 Thank You!