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Epidemiology and Prevention of Catheter-Related Bloodstream Infections in Outpatient Settings Alice Guh, MD, MPH
Division of Healthcare Quality Promotion Centers for Disease Control and Prevention November 3, 2012
National Center for Emerging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion
Overview
Epidemiology of catheter-related bloodstream infections (CRBSI) in outpatient settings
Core and supplemental measures for CRBSI prevention with focus on outpatient settings
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.
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)
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.
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.
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.
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.
Polymicrobial BSIs among Pediatric Outpatients with CVCs
Downes KJ et al. Clin Infect Dis. 2008;46:387-394
General Risk Factors for Outpatient CRBSIs
Prospective study: 827 patients receiving home infusions
Tokars J et al. Ann Intern Med. 1999;131:340-347.
CRBSI PREVENTION IN OUTPATIENT SETTINGS
Limitations of Current Recommendations
Based on studies conducted in ICU settings
Prevention of outpatient CRBSIs largely focused on hemodialysis patients
Surveillance
Outbreak detection
Staff feedback to improve performance
Collection of outcome and/or process measures
CRBSI rates Adherence to hand hygiene
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
Antimicrobial Starts
George A et al. BMJ 2006; 332:1435-1439 Slide courtesy of Dr. Priti Patel
Access-Related Bacteremia
George A et al. BMJ 2006; 332:1435-1439 Slide courtesy of Dr. Priti Patel
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
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
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.
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.
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.
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
Skin Antisepsis for Cleansing Catheter SIte
Prospective, randomized trial (n=668 catheters: CVC, arterial catheters)
Maki D et al. Lancet 1991;388:339-343.
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.
Meta-analysis: Results 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])
Chaiyakunapruk N et al. Ann Intern Med 2002;136:792-801.
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.
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.
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
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) Bouza E et al. J Hosp Infect 2003;54:279-87.
Yebenes JC et al. Am J Infect Control 2004;32:291-5.
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.
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.
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)
Mechanical Valves in Long-Term Acute Care Setting CRBSI increased from 1.79 to 5.9 / 1000 catheter days
Salgado CD et al. Infect Control Hosp Epidemiol 2007;28:684-688.
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
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
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.
Cohort Study Results
Wiersma P et al. Infect Control Hosp Epidemiol 2010;31:522-27.
Cohort Study Results
Wiersma P et al. Infect Control Hosp Epidemiol 2010;31:522-27.
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.
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)
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
SUPPLEMENTAL CRBSI PREVENTION MEASURES
Supplemental Measures
Chlorhexidine-impregnated sponge dressings
Antimicrobial / antiseptic impregnated catheters
Antimicrobial / antiseptic catheter locks
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)
Timsit JF et al. JAMA 2009;301:1231-41.
rates, catheter colonization
Results of CHGIS vs Standard Dressings: Cumulative Risk of Catheter-Related Infections 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
Timsit JF et al. JAMA 2009;301:1231-41.
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.
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.
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.
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
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
Meta-Analysis Results CVCs impregnated with chlorhexidine/silver sulfadizine effective in reducing catheter colonization and CRBSI 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.
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.
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 M-R catheter: 0.25/1000 catheter days Uncoated catheters: 1.28/1000 catheter days Hanna H et al. J Clin Oncol. 2004;22:3163-71.
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 • • M-R catheters 12 times less likely to have CRBSI 3 times less likely to be colonized Darouiche RO et al. N Engl J Med 1999;340:1-8.
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.
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
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
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.
Use of 70% Ethanol Lock
Prospective, randomized trial of patients with hematological disease (long-term CVC):
70% ethanol lock vs heparinized saline 0.6 CRBSI/1000 days 3.11/1000 CVC days Sanders J et al. J Antimicrob Chemother 2008;62:809-15.
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
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
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
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
Thank you 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: [email protected] 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