1. Alice Guh, MD, MPH Division of Healthcare Quality Promotion Centers for Disease Control and Prevention November 3, 2012 Epidemiology and Prevention of Catheter-Related Bloodstream Infections in Outpatient Settings National Center for Emerging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion

2. Overview  Epidemiology of catheter-related bloodstream infections (CRBSI) in outpatient settings  Core and supplemental measures for CRBSI prevention with focus on outpatient settings

3. Burden of Central Venous Catheter Use  >5 million CVCs inserted in US annually  93% of patients receiving home infusion therapy, compared to 13% of hospitalized patients  Approximately 25-30% of all hemodialysis patients  80% initiate hemodialysis with CVC  Estimated 2/3 of cancer patients use long-term CVC Moureau N et al. J Vasc Interv Radiol 2002;13:1009-1016. Herbst S et al. Infusion 1998;4(suppl):S1-132. Kallen A et al. Clin Infect Dis 2010;51(3):335-341. Van de Wetering MD et al. Cochrane Database Syst Rev 2007.

4. Outpatient Central Venous Catheter Use  Diverse indications  Hemodialysis  Chemotherapy administration  Intravenous antimicrobial therapy  Parenteral nutrition, intravenous fluids  Treatment of pulmonary hypertension  Various outpatient settings  Physician offices, clinics, infusion centers, home settings (self- care, home healthcare agencies)

5. Overall Burden of Catheter-Related Bloodstream Infections (CRBSI)  ~250,000 BSI cases in US annually  Majority associated with central venous catheter  Higher costs, crude mortality rates, and number of hospital-days  Acute care settings (2009 NHSN data)  Medical-surgical wards: 1.2 cases / 1000 catheter-days  Medical-surgical ICU: 1.5-2.1 cases / 1000 catheter-days  Outpatient settings  Variable rates  Multiple factors: patient comorbidities, catheter type, CVC indication Klevens RM et al. Public Health Rep 2007;122:160-166. Edwards JR et al. Am J Infect Control 2009;37:783-805.

6. Outpatient CRBSI Rates  >50,000 patients receiving home infusion  Retrospectively collected data from 37 US states  0.19 cases per 1000 catheter-days Highest in tunneled (0.34) and nontunneled (0.22) catheters Lowest in midline catheters (0.09) and PICCs (0.11) Ports and midline had lowest combined local and BSI rates (0.3)  827 patients receiving outpatient/home infusion  Two study sites, prospective evaluation  0.99 cases per 1000 catheter-days Nonsignificantly higher risk in centrally inserted catheter versus ports Moureau et al. J Vasc Interv Radiol 2002;13:1009-1016. Tokars J et al. Ann Intern Med. 1999;131:340-347.

7. Outpatient CRBSI Rates by Population Type  Outpatient hemodialysis facilities (NHSN data)  4.2 BSI cases per 100 pt-months (1.4 cases per 1000 catheter- days)  Cancer patients  Studies of mostly adults: 1.0 to 2.1 per 1000 catheter-days  Outpatient pediatric studies: 0.1 to 7.4 per 1000 catheter-days  One study: home parenteral nutrition (n=53)  2.5 cases of “line sepsis” per 1000 catheter-days Adults 0.8 /1000 catheter-days vs children 6.9 / 1000 catheter-days Klevens RM et al. Semin Dial 2008;21:24-28. Howell PB et al. Cancer 1995;75:1367-75. Groeger Js et al. Ann Inter Med 1993;119:1168-1174. Barrell C et al. AJIC 2012;40:434-439. Gillanders L et al. Clin Nutr. 2012;31:30-34.

8. Pathogens Associated with Outpatient CRBSIs  Varies by patient population type  Gram-positive organisms most common  Coagulase-negative Staphylococci – 28-60%  Increasing infections by gram-negative organisms  Pediatric oncology and HSCT patients Nonendogenous organisms during summer months  Higher risk for Candida infections in long-term parental nutrition population  20-37% polymicrobial infections Tokars J et al. Ann Intern Med. 1999;131:340-347. Opilla M. AJIC. 2008;36(10):S173.e5-8. Smith T et al. Infect Control Hosp Epidmiol 2002;23:239-243. Barrell C et al. AJIC 2012:40:434-439.

9. Polymicrobial BSIs among Pediatric Outpatients with CVCs Downes KJ et al. Clin Infect Dis. 2008;46:387-394

10. General Risk Factors for Outpatient CRBSIs  Prospective study: 827 patients receiving home infusions Tokars J et al. Ann Intern Med. 1999;131:340-347.

11. CRBSI PREVENTION IN OUTPATIENT SETTINGS

12. Limitations of Current Recommendations  Based on studies conducted in ICU settings  Prevention of outpatient CRBSIs largely focused on hemodialysis patients

13. Surveillance  Outbreak detection  Staff feedback to improve performance  Collection of outcome and/or process measures  CRBSI rates  Adherence to hand hygiene

14. Value of Surveillance  Busy London dialysis unit: 112 patients  Implemented CDC dialysis surveillance; described their experience over 18 months  After initial set up, required 2 hours per month  Outcomes: Reductions in  Access-related bacteremia  Antibiotic usage  Hospital admissions George A et al. BMJ 2006; 332:1435-1439 Slide courtesy of Dr. Priti Patel

15. Antimicrobial Starts George A et al. BMJ 2006; 332:1435-1439 Slide courtesy of Dr. Priti Patel

16. Access-Related Bacteremia George A et al. BMJ 2006; 332:1435-1439 Slide courtesy of Dr. Priti Patel

17. Observations  “Surveillance raised awareness and provided a cornerstone for improved infection control and line care involving all staff of the dialysis unit.”  “The data feedback generated unit led programmes of risk reduction and infection control.” George A et al. BMJ 2006; 332:1435-1439 Slide courtesy of Dr. Priti Patel

18. Challenges Related to Surveillance  Challenges of measuring outpatient CRBSI rates  No established surveillance system for all outpatient settings  Determining infections originating in outpatient facility or related to home infusion  Collecting appropriate denominator data, e.g., catheter days

19. Considerations for CRBSI Surveillance in Certain Outpatient Settings  Hematology/oncology patients with long-term CVC  Tracking positive blood culture results: laboratory notification, ask patients at visits  Denominator data: total number of line days/month  Building line days database  Determine list of patients with CVCs  Designate personnel to build and maintain database  Collect initial and subsequent data Nurses reporting, monthly surgery list of lines placed/removed Children’s Hospital Association Heme-Onc Collaborative for Prevention of CLABSI.

20. Pathogenesis: Mechanism for Colonization of Longer-term CVC  Intraluminal pathway most common for CVC >1 week  Contamination of the hub, catheter, or other administration device  Presence of biofilm greater on luminal surface in CVC >30 days  Emphasis on appropriate CVC maintenance and access practices Raad I et al. J Infect Dis 1993;168:400-407. Safdar N et al. Intensive Care med 2004; 30:62-67.

21. Removal of Unnecessary CVC  Important component of interventions to decrease CRBSIs  Multisite studies of ICU settings  Implementation of multifaceted interventions led to significant decrease in CRBSI rates  Interventions included: asking providers daily whether catheters can be removed Added to rounding form: “daily goals form” Brenholz SM et al. Crit Care Med 2004;32:2014-2020. Pronovost P et al. N Engl J Med 2006;355:2725-2732.

22. Hand Hygiene  Perform hand hygiene before and after:  Palpating catheter insertion sites  Changing dressing of catheter site  Accessing catheter  Outpatient facilities  Ensure easy access to alcohol-based hand rub and/or soap and water  Observation of practices and “just in time” feedback as needed

23. Skin Antisepsis for Cleansing Catheter SIte  Prospective, randomized trial (n=668 catheters: CVC, arterial catheters) Maki D et al. Lancet 1991;388:339-343.

24. Meta-analysis: Comparison of Chlorhexidine and Povidone-Iodine Solution  Vascular catheter-site care  4143 catheters (various types)  All hospital settings Chaiyakunapruk N et al. Ann Intern Med 2002;136:792-801.

25. Meta-analysis: Results Chaiyakunapruk N et al. Ann Intern Med 2002;136:792-801. Chlorhexidine gluconate reduced catheter-related BSI by approximately 50% (summary risk ratio 0.49 [95% CI, 0.28-0.88]) Similar findings when only CVCs were included in the analysis (summary risk ratio, 0.51 [95% CI, 0.27-0.97])

26. Why Chlorhexidine Gluconate May be Better Antisepsis Than Povidone-Iodine  Microbicidal effect might not be affected by protein- rich biomaterials (e.g., blood, serum)  Prolonged residual effect (at least 6 hours)  Superior bactericidal effect against coagulase- negative staphylococci  Disinfection of peritoneal dialysis catheter sites Chaiyakunapruk N et al. Ann Intern Med 2002;136:792-801. Shelton DM. Adv Perit Dial. 1991;7:120-4.

27. Catheter Site Dressing: Gauze and Tape vs Transparent Polyurethane Dressing  Study of peripheral catheters (n=2000 catheters)  No difference in rate of catheter colonization or phlebitis  Systematic review and meta-analysis:  8 of 23 studies included; data available from only 6 studies No difference in incidence of infectious complications (catheter- related sepsis, exit site infection)  Updated review in 2011 higher CRBSI rate with polyurethane dressing, but small sample size with low quality evidence  Use either sterile gauze or sterile, transparent, semipermeable dressing to cover catheter site Maki DG et al. JAMA 1987;258:2396-403. Gillies D et al. J Adv Nurs 2003;44:623-32. Gillies D et al. Cochrane Database Syst Rev 2011;9:CD003827.

28. Catheter Site Dressing Changes  Wear clean or sterile gloves  Replace dressing if becomes damp, loosened, or visibly soiled  Remove dressing to allow examination if:  Tenderness at insertion site  Other symptoms suggestion of local infection or BSI  Do not use topical antibiotic ointment or creams on insertion site (except for dialysis catheters)  Potential for fungal infections  Antimicrobial resistance

29. Needleless Connectors  Catheter hub is important portal of entry  Needleless connectors evolved from split septum to mechanical valves  Potential decreased microbial contamination rate compared to stopcocks/caps  Randomized controlled trial in ICU  243 patients, mean CVC duration 9.9 days  CVC with needleless connectors vs 3-way stopcock/cap  CRBSI incidence significantly reduced with needleless connectors (0.7 / 1000 catheter days vs 5.0 / 1000 catheter days) Caeey AL et al. J Hosp Infect 2003l54:288-93. Bouza E et al. J Hosp Infect 2003;54:279-87. Yebenes JC et al. Am J Infect Control 2004;32:291-5.

30. Importance of Access Port / Connector Disinfection  Appropriate disinfection must be performed  Experimental model evaluating barrier effect of 3 different needleless connectors  Peripheral catheter with connector inserted in blood culture bottle  Contaminated external surfaces of connectors with different concentrations of S. epidermidis  Assigned to “correct cleaning group” (70% alcohol before handling) vs. control group (no disinfection before handling)  Incorrect handling reduced sterility from 94.4 to 66.7% (p=0.001) Yebenes JC et al. Crit Care Med 2008;36:2558-61.

31. Disinfection Procedure for Connectors  Mixed findings regarding alcohol vs chlorhexidine disinfectants  Earlier study showing ethanol-based disinfectants most effective  Recent studies: higher microbial contamination following alcohol (69%) than chlorhexidine (30.8%) or povidone-iodine (25%)  Role of antimicrobial impregnated connector  Wiping with 70% alcohol for 3-5 sec not effective  No difference when vigorously scrubbing 15 sec with alcohol or chlorhexidine  In vitro study of various mechanical valves Salzman MB et al. J Clin Microbil 1993;31:475. Casey AL et al. J Hosp Infect 2003;54:288-293 Menyhay SZ et al. Infect Control Hosp Epidemiol 2006;27:23-7. Kaler W et al.JAVA 2007;12:3-9.

32. CRBSI Associated with Mechanical Valves?  Several reports of increased CRBSI when switching from split septum to mechanical valves  Acute care settings  Large, multicenter study across 5 hospitals (16 ICUs, 1 entire hospital, 1 oncology unit)  Pediatric hematology/oncology patients receiving home infusion  182 patients, >75,000 catheter days  CRBSI significantly increased when mechanical valves introduced (0.8 to 1.4 / 1000 catheter days)

33. Mechanical Valves in Long-Term Acute Care Setting Salgado CD et al. Infect Control Hosp Epidemiol 2007;28:684-688. CRBSI increased from 1.79 to 5.9 / 1000 catheter days

34. Potential Explanations for Increased CRBSI with Mechanical Valves  Device-specific vs all mechanical valves?  Improper cleaning of connector surface (difficulty in adequate disinfection)  Recommendations may differ by device type  Fluid flow properties and inadequate flushing (poor visualization in opaque devices)  Exposure to blood/nutritional fluids enable biofilm formation  Presence of internal corrugations could harbor organisms

35. Recommendations for Disinfecting Access Port / Connectors  Scrub access port / connects with appropriate antiseptic  Chlorhexidine, povidione-iodine, 70% alchohol  Access port with only sterile devices  Split septum may be preferred over some mechanical valves  Must follow manufacturer recommendations for disinfection when using mechanical valves

36. Outbreak Related to Unsafe Injection Practices  Outpatient pediatric bone marrow transplant clinic  September 2007: Initially 6 patients with CVC had BSI, some polymicrobial  Surveillance blood cultures during outbreak period (n=30 patients)  13 patients with BSI, 17 without BSI  Cohort study looking at risk factors  Infection control assessment, including saline flush preparation Wiersma P et al. Infect Control Hosp Epidemiol 2010;31:522-27.

37. Cohort Study Results Wiersma P et al. Infect Control Hosp Epidemiol 2010;31:522-27.

38. Cohort Study Results Wiersma P et al. Infect Control Hosp Epidemiol 2010;31:522-27.

39. Infection Control Assessment: Saline Flush Preparation  Outside of automated medication supply  Prepared predrawn saline and heparin syringes:  Preservative-free, single-dose 50-mL saline vial  Multidose 10-mL heparin vials  Vials accessed multiple times  Predrawn syringes and vials not dated  Outbreak likely due to extrinsic contamination of saline vials Wiersma P et al. Infect Hosp Control Epidemiol 2010;31:522-27.

40. Recommendations for Safe Injection Practices  Injection safety refers to proper use and handling of supplies for administering injections and infusions  Syringes, needles, IV tubing, vials and parenteral solutions  Key injection safety recommendations include:  Dedicate single dose vials for single patient use  Always use new syringe and needle to access medication vials  Avoid prefilling and storing batch-prepared syringes (outside of pharmacy setting)  Whenever possible, use commercially manufactured or pharmacy-prepared prefilled syringes (saline, heparin)

41. Education  Education of healthcare personnel  Proper care/maintenance of catheter  Periodically assess adherence to recommended practices  Education of patients  Do not submerge catheter or catheter site in water  Report any changes in catheter site or new discomfort

42. SUPPLEMENTAL CRBSI PREVENTION MEASURES

43. Supplemental Measures  Chlorhexidine-impregnated sponge dressings  Antimicrobial / antiseptic impregnated catheters  Antimicrobial / antiseptic catheter locks

44. Chlorhexidine-Impregnated Sponge Dressings vs Standard Dressings  Largest multicenter, randomized controlled trial  7 ICUs (mix of medical and surgical) across academic and community hospitals  Included 1636 adult patients (n=3778 catheters)  Interventions included:  CHGIS dressing applied to entire insertion site under semitransparent dressing (controls: only semitransparent dressing)  Of note: Alchohol based povodone-iodine was used for antisepsis  Outcomes included catheter-related infection (BSIs) rates, catheter colonization Timsit JF et al. JAMA 2009;301:1231-41.

45. Results of CHGIS vs Standard Dressings: Cumulative Risk of Catheter-Related Infections Timsit JF et al. JAMA 2009;301:1231-41. Major catheter-related infection rate: 1.4 / 1000 catheter-days to 0.6 / 1000 catheter-days Catheter-related BSI rate*: 1.3 / 1000 catheter-days to 0.4 / 1000 catheter-days Catheter colonization rate: 15.8 / 1000 catheter-days to 6.8 / 1000 catheter-days

46. Additional Findings From Same Study  Significant decrease in bacterial skin colonization with CHGIS dressings  Not associated with greater resistance of bacteria  Severe contact dermatitis leading to removal of CHGIS: 8 patients (10.4 / 1000 patients)  No systemic adverse reactions to chlorhexidine occurred  No difference in catheter colonization between dressing change at 3 days vs 7 days Timsit JF et al. JAMA 2009;301:1231-41.

47. Chlorhexidine-Impregnated Sponge Dressing in Cancer Patients  Randomized controlled trial at a single hopsital  601 patients receiving chemotherapy (>9000 catheter days)  Used chlorhexidine and silver sulfadiazine-impregnated CVC  CVC for ≥5 days, removed when not needed or patient discharged  Intervention: CHGIS dressing (controls: sterile transparent dressing), changed regularly after 1 wk  CRBSI was 46% less in the CHGIS dressing group  Catheter tip bacteria similar in both groups (>50% S. epidermidis) Ruschulte H et al. Ann Hematol 2009;88:267-72.

48. Other CHGIS Studies  Meta-analysis of RCTs: CHGIS vs standard dressing (7 studies) or povidone-iodine dressing (1 study)  Associated with reduction of vascular and epidural catheter exit site colonization  Trend towards reduction in CRBSI  Local cutaneous reactions in 5.6% patients in 3 studies, 96% of these in neonatal patients  Study involving 2 outpatient dialysis centers  Prospective, crossover intervention trial over 1-year period: 121 patients with tunneled catheters received CHGIS dressing  Use of CHGIS did not decrease CRBSI incidence Ho KM et al. J Antimicrob Chemother 2006;58:281-7. Camins BC et al. Infect Control Hosp Epidemiol 2010;31:1118-23.

49. Current Recommendations for Chlorhexidine- Impregnated Sponge Dressing  Limited evidence indicating CHGIS use may decrease CRBSI rates  Mainly studied short-term CVCs  May consider if CRBSI rate not decreasing despite implementation of core measures  In patients >2 months of age  ?Applicability to long-term CVC use

50. Antimicrobial / Antiseptic Impregnated Catheters  Several randomized studies in 1990s  Chlorhexidine / silver sulfadiazine coated on external luminal surface vs standard uncoated catheters  Meta-analysis:  11 studies for catheter colonization  12 studies for CRBSI  Mostly ICU patients  Median CVC duration 5.1-11.2 days

51. Meta-Analysis Results Summary OR 0.44 (95% CI, 0.36-0.54) Summary OR 0.56 (95% CI, 0.37-0.84) Veenstra DL et al. JAMA 1999;281:261-7. CVCs impregnated with chlorhexidine/silver sulfadizine effective in reducing catheter colonization and CRBSI

52. Chlorhexidine / Silver Sulfadiazine Coated Catheters  Second generation catheters  Chlorhexidine on internal surface extending to hubs  Higher concentration of chlorhexidine/silver sulfadizine on external luminal surface  Prospective, randomized studies of 2nd generation catheters vs standard uncoated catheters:  Significant reduction in catheter colonization  Underpowered to detect difference in CRBSI  Rare reports of anaphylaxis Brun-Buisson C et al. Intensive Care Med 2004;30:837-43. Ostendorf T et al. Support Care Cancer 2005;13:993-1000. Rupp ME Ann Intern Med 2005;143:570-80.

53. Minocycline / Rifampin Impregnated Catheters  To assess long-term catheters impregnated with minocycline/rifampin in reducing CRBSI:  Prospective, randomized trial in oncology hospital  Mean CVC duration >60 days Hanna H et al. J Clin Oncol. 2004;22:3163-71. M-R catheter: 0.25/1000 catheter days Uncoated catheters: 1.28/1000 catheter days

54. Catheters Impregnated with Minocycline / Rifampin vs Chlorhexidine / Silver Sulfadiazine  Multicenter randomized trial (n=12 hospitals):  M-R CVC vs first generation Chlorhexidine/silver sulfadizine CVC Darouiche RO et al. N Engl J Med 1999;340:1-8. M-R catheters 12 times less likely to have CRBSI 3 times less likely to be colonized

55. Additional Considerations for Minocycline/Rifampin Impregnated Catheters  No comparison with 2 nd generation chlorhexidine / silver sulfadiazine catheters  Concern for increased antimicrobial resistance but not shown in clinical settings  Prospective, 7-year follow-up study in cancer center (>500,000 catheter days) Ramos ER et al. Crit Care Med 2011;39:245-51.

56. Current Recommendations for Antimicrobial / Antiseptic Impregnated Catheters  May consider use if CRBSI rates not decreasing:  Either chlorhexidine / silver sulfadiazine or minocycline / rifampin impregnated CVC  If catheter is expected to remain in place >5 days  Additional data needed on other new catheters  Platinum/silver  Miconazole/rifampin  M-R / Chlorhexidine / silver sulfadiazine

57. Antimicrobial / Antiseptic Catheter Lock  Filling catheter lumen with antimicrobial solution when not in use  Various concentrations and combinations  Antibiotics: vancomycin, gentamicin, ciprofloxacin, minocycline, amikacin, cefazolin, cefotaxime, ceftazidime  Antiseptics: alcohol, taurolidine*, trisodium citrate*  Usually combined with anticoagulant  Heparin, EDTA *Not approved for this use in the US

58. Antimicrobial Lock Solutions in Select Patient Populations  Several studies in higher-risk patients, longer-term CVC use  Hemodialysis patients Study of 291 patients – significantly lower CRBSI rate using 30% trisodium citrate (1.1/1000 CVC days) vs heparin (4.1/1000 CVC days)  Oncology patients Study of 126 patients – median CVC days 200-247 days: o Vanc/Cipro/Heparin (0.55/1000 CVC days) vs Vanc/Heparin (0.37/1000 CVC days) vs Heparin (1.72/1000 CVC days)  Patients receiving long-term parenteral nutrition  Generally found reduction in CRBSI rates Weijmer MC et al. J Am Soc Nephrol 2005;16:2769-77. Henrickson KJ et al. J Clin Oncol 2000;18:1269-78.

59. Use of 70% Ethanol Lock  Prospective, randomized trial of patients with hematological disease (long-term CVC):  70% ethanol lock vs heparinized saline Sanders J et al. J Antimicrob Chemother 2008;62:809-15. 0.6 CRBSI/1000 days 3.11/1000 CVC days

60. Additional Considerations Regarding Catheter Locks  Need to balance benefits with potential side effects  Toxicity, allergic reactions  Emergence of antimicrobial resistance  Limitations of studies  Small sample size  Heterogeneity of patient populations  Wide variety of compounds for use  No FDA approved formulations

61. Recommendations for Catheter Locks  Not recommended for general use  May consider in patients with long-term CVC and recurrent CRBSI despite adherence to aseptic technique

62. Summary  CRBSI in outpatient settings is an emerging issue  Impacting diverse patient populations  Various outpatient settings  Limited surveillance and prevention data for outpatient settings  Additional research warranted for long-term CVC use, novel technologies

63. Summary: Key Recommendations  Similar to inpatient settings with emphasis on line care/maintenance practices:  Remove unnecessary CVC  Perform hand hygiene  Use >0.5% chlorhexidine/alcohol for skin / CVC site antisepsis  Appropriate disinfection of connectors/ports prior to access  Consideration of supplemental measures as needed

64. For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA 30333 Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 E-mail: cdcinfo@cdc.gov Web: www.cdc.gov The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion Thank you