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Antimicrobial Resistance in the Maintenance Hemodialysis Unit

Antimicrobial Resistance in the Maintenance Hemodialysis Unit. Matthew J. Arduino, MS, Dr.P.H. Division of Healthcare Quality Promotion Centers for Disease Control and Prevention matthew.arduino@cdc.hhs.gov.

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Antimicrobial Resistance in the Maintenance Hemodialysis Unit

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  1. Antimicrobial Resistance in the Maintenance Hemodialysis Unit Matthew J. Arduino, MS, Dr.P.H. Division of Healthcare Quality Promotion Centers for Disease Control and Prevention matthew.arduino@cdc.hhs.gov The findings and conclusions in this presentation are those of the author(s) and do not necessarily represent the views of the Centers for Disease Control and Prevention

  2. Overview • Background on susceptible population • Emergence of antimicrobial resistance • Methicillin-resistant Staphylococcus aureus • Vancomycin Resistant Enterococci • Surveillance • Dialysis Surveillance Network/National Healthcare Safety Network • Active Bacterial Core Surveillance • Preventing Antimicobial Resistance • CDC/HICPAC MDRO Guideline • CDC Infection Control Precautions for Dialysis Patients

  3. Transmission of Antimicrobial Resistance in the Dialysis Unit • Transmission of MRSA or VRE have no been demonstrated in the dialysis setting • MDROs are acquired in the acute care setting • Arise from patients own flora

  4. Chronic Kidney Disease in the United States • An estimated 20 million Americans have significantly reduced kidney function1 • End Stage Renal Disease (ESRD) was reported in over 470,000 Americans in 2004 and predicted to rise to 700,000 by 20101,2 • Nearly 336,000 Americans on dialysis in 2004, triple the number from 1988, up 16% since 20002 • ESRD patients are especially vulnerable to infections, including methicillin-resistant Staphylococcus aureus (MRSA)

  5. Infections and Mortality in ESRD Patients • Infections are 2nd leading cause of mortality in ESRD patients, accounting for 14% of deaths • Infections associated with vascular access are common • ESRD patients often at high risk for infection due to immunocompromised state and frequent puncture of vascular-access site • Antibiotic-resistant pathogens (including MRSA) are increasingly seen due to frequent hospitalizations and antibiotic exposure3

  6. XX Emergence of Antimicrobial Resistance Susceptible Bacteria Resistant Bacteria Mutations Resistance Gene Transfer New Resistant Bacteria

  7. x x Resistant StrainsRare Antimicrobial Exposure Resistant Strains Dominant x x x x x x x x x x Selection for Antimicrobial-Resistant Strains

  8. Evolution of Drug Resistance in S. aureus Penicillin Methicillin Methicillin-resistant S. aureus (MRSA) Penicillin-resistant S. aureus [1950s] S. aureus [1970s] Vancomycin [1997] [1990s] Vancomycin intermediate- resistant S. aureus (VISA) Vancomycin- resistant S. aureus Vancomycin-resistant enterococci (VRE) [ 2002 ] CDC MMWR 2002;51(26):565-67

  9. Summary CDC Data, 2002

  10. Percent of Facilities Reporting >1 Patient with Either MRSA or VRE

  11. Antibiotic Utilization% of Antibiotics Ordered that are Vancomycin or GentamicinJan - Apr, 2002 Slide provided by Dr. Ray Hakim/RCG

  12. Antibiotic UtilizationVials Per 100 PatientsJan - Apr, 2002 Slide provided by Dr. Ray Hakim

  13. Colonization With VRE Among Dialysis Patients Who Received Vancomycin p<0.001 Atta et al. Kidney Int 2001;59:718-24

  14. Access Associated Bacteremia Infection by Access Type Dialysis Surveillance Network September 1999-March 2005 Klevens M, et al. NNI;June 2005:37-8,43

  15. Microorganisms Isolated From Blood Cultures DSN September 1999-March 2005

  16. Epidemiology of Catheter Associated Infections • Estimated attributable mortality for catheter-associated bloodstream infections (BSI) ranges from 0% to 35%, depending on study design. • Estimated attributable cost per BSI ranges from $34,508 to $56,000. • Use of catheters for hemodialysis is the most common factor contributing to bacteremia in dialysis patients. • Primary risk factor for access infection is access type.

  17. Biofilm on Intravenous Catheter Connector 24 Hours after Insertion Scanning Electron Micrograph Photo: Janice Carr DHQP

  18. Vancomycin Intermediate-Resistant S. aureus (VISA) State, YearSitePD/HD* Michigan, 1997 Peritonitis Chronic PD New Jersey, 1997 Blood Recent PD New York, 1998 Blood Chronic HD Illinois, 1999 Endocarditis Chronic HD Minnesota, 2000 Bone Chronic HD Nevada, 2000 Liver ----- Maryland Blood ----- PD=peritoneal dialysis HD=hemodialysis Fridkin Clin Infect Diseases 2001

  19. VISA • Definition based on MIC break points has changed • Prior to 2006 breakpoints were 8-16 µg/L • After 2006 4-8 µg/L • Prior to change 16 isolates were confirmed as VISA • CDC still provides confirmatory susceptibility testing, but we no longer actively request VISAs to be sent for confirmation. • laboratories don’t always send VISAs to CDC for confirmation • many VISAs get sent to reference laboratories and not CDC. As of October 2007 • We have confirmed only 19 with an MIC=8 and near 80-100 with MIC=4. So about 80-100 VISAs (1997-2007), if you use the current definition

  20. First Case of Vancomycin - Resistant S. aureus (VRSA) • First fully vancomycin resistant clinical isolate of S. aureus • Michigan, June 2002 • 40-year old black female with diabetes mellitus, peripheral vascular disease,on chronic hemodialysis • VRSA from foot ulcer and catheter exit site • During the 6 months preceding VRSA: • patient experienced 6 hospitalizations, totaling 18 days • patient received multiple antimicrobial therapy, including • 5.5 weeks of vancomycin Chang S et al, New England J of Med 2003; 348:14,1342-3447

  21. VRSA • 9 cases of VRSA since 2002 (7 in Michigan, 1 PA, 1 NY) • Two were dialysis dependent (Including index case) • Most patients diabetics • Infected wounds • MIC vancomycin > 16µg/mL • Acquisition of VanA gene: many cases shown to VRE donor and MRSA recipient ZhuW, et al. Vancomycin-Resistant Staphylococcus aureus Isolates Associated with Inc18-Like vanA Plasmids in Michigan. Antimicrob Agents Chemother 2008;52(2):452-7.

  22. Staphylococcus aureus and ESRD Patients • S. aureus causes a sizable proportion of severe infections in ESRD patients • 29% of catheter-related bacteremias and 50% of fistula or graft-related bacteremias3 • S. aureus bacteremia leads to costly and lengthy hospitalizations, frequent complications and readmissions4 Image from CDC/DHQP/Janice Carr

  23. CDC’s Active Bacterial Core Surveillance (ABCs) System • Surveillance data obtained from • Population-based surveillance for invasive pathogens, including MRSA, covering 23 counties in 8 states (CA, CO, GA, MD, MN, NY, OR and TN) and the entire state of Connecticut • Case Definition: Positive MRSA culture from a normally sterile site (e.g. blood, cerebrospinal fluid, joint fluid) • Demographic and clinical data from patient records were collected for each case • USRDS to obtain denominator data

  24. Staphylococcus aureus Isolates • Isolates from 126 Dialysis Patients and 72 Renal insufficiency patients were tested by pulsed-field gel electrophoresis (PFGE) • PFGE Types USA300, USA400, USA1000, USA1100 considered community origin; • PFGE Types USA100, USA200 and USA500 considered health-care origin6 • Antibiotic susceptibility testing was performed on 113 Dialysis Patient isolates and 88 Renal Insufficiency patient isolates

  25. Results-Summary • From July 2004-June 2006, 2130 cases of invasive MRSA in dialysis patients and 1189 cases in renal insufficiency patients were reported • Almost all cases were hospitalized • > 50% of the patients in each group had diabetes • Renal insufficiency patients had higher in-hospital mortality (25 vs. 17%, p<.01) • Dialysis Patients: • more likely to have recurrent invasive MRSA infection (27 vs. 13%, p<.01) • more likely to have any history of MRSA infection or colonization (35 vs. 24%, p<.01) • more likely to have an invasive device (86 vs. 38%, p<.01), including central venous catheters (70 vs. 19%, p<.01)

  26. Study findings

  27. Characteristics of selected patients with invasive MRSA *p<0.01

  28. Additional Characteristics Of Selected Patients With Invasive MRSA *p<0.01, †previously documented in ABCs system

  29. Healthcare Risk Factors Among Selected Patients With Invasive MRSA *p=0.024, p<.01, ‡in place at the time of admission/evaluation, †infection or colonization

  30. Clinical Syndromes Associated With Invasive MRSA Disease Among Selected Patients *more than one infection could be listed, 3% or fewer in each group had meningitis, bursitis, pericarditis, peritonitis, pressure ulcer, otitis media, empyema, internal abscess, internal surgical site, surgical incision or traumatic wound infection

  31. Type of Invasive MRSA Infection Among Selected Patients †bacteremia alone without other type of MRSA infection, ‡out of 1831 DP and 915 RI patients where type of MRSA infection was known, *culture of same sterile site was positive between 7 and 30 days after initial culture

  32. MRSA Isolates By Strain Type Among Dialysis And Renal Insufficiency Patients Active Bacterial Core Surveillance, 2004-2006, US

  33. Antibiotic Susceptibility Results For MRSA Isolates Among Dialysis And Renal Insufficiency Patients†

  34. Number and Incidence rate of invasive MRSA cases among dialysis patients Active Bacterial Core surveillance system*, 2005 *Surveillance areas include the entire state of Connecticut and 23 counties in eight other states. †Number of dialysis patients in the selected surveillance area, based on USRDS Dialysis population count as of Dec. 31, 2004.

  35. Limitations • ABCs case report form does not distinguish between peritoneal and hemodialysis and does not ask about access type (i.e. catheter vs. graft vs. fistula) so comparisons between these groups cannot be made • Denominator data not available for patients with renal insufficiency so incidence rate could not be calculated for this group • Surveillance areas comprise a diverse set of geographic regions, may not be representative of the rates in other U.S. cities and counties • Laboratory analysis was conducted on a convenience sample of voluntarily submitted isolates

  36. ABCs Conclusions • Dialysis patients have an extremely high incidence of invasive MRSA, more than 100-fold greater than the general U.S. population, where the rate is 32/100,000 • Dialysis patients more often present with uncomplicated bacteremia compared to patients with renal insufficiency not on dialysis • Heightened vigilance and prevention strategies to decrease invasive MRSA in the chronic kidney disease population are essential • Studies are needed to further characterize risk factors and incidence of invasive MRSA in all chronic kidney disease patients, including those not on dialysis

  37. Preventing Infections Implement CDC 12 Step Program to Prevent Antimicrobial Resistancein Dialysis Patients Follow recommended infection control recommendations Partner with your patients

  38. 12 Partner with your patients 11 Practice hand hygiene 10 Follow infection control precautions 9 Stop antimicrobial treatment 8 Treat infection not contamination or colonization 7 Know when to say “No” to Vanco 6Use local data 5 Access the experts 4 Target the pathogen 3 Optimize access care 2 Get the catheters out 1Vaccinate staff and patients Prevent Transmission Use Antimicrobials Wisely Diagnose & Treat Effectively Prevent Infection 12 Steps to Prevent Antimicrobial Resistance:Dialysis Patients

  39. Prevent Infection Step 2: Get the catheters out Fact:Indwelling catheters are the single most important factor contributing to bacteremia in hemodialysis patients. Actions: Hemodialysis: • Use catheters only when essential • Maximize use of fistulas/grafts • Remove catheters when they are no longer essential Peritoneal Dialysis: • Remove/replace infected catheters

  40. Prevent Infection Step 3: Optimize access care Fact:Careful infection control prevents peritoneal dialysis-related infections. Actions: • Follow established guidelines for access care • Use proper insertion and catheter-care protocols • Remove access device when infected • Use the correct catheter HICPAC, CDC. Guidelines for the Prevention of Intravascular Catheter-Related Infections. MMWR 2002;51(RR10):1-26. (http://www.cdc.gov/mmwr/PDF/rr/rr5110.pdf) NKF. K/DOQI clinical practice guidelines for vascular access: update 2000 (http://www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_uptoc.html#va) NKF. K/DOQI clinical practice guidelines for vascular access, update 2006 (http://www.kidney.org/professionals/Kdoqi/guideline_upHD_PD_VA/index.htm)

  41. Diagnose & Treat EffectivelyStep 4:Target the pathogen Fact:Identifying the pathogen using microbiologic cultures and antimicrobial susceptibility testing allows for targeted antimicrobial therapy. Actions: • Obtain appropriate cultures • Target empiric therapy to likely pathogens • Target definitive therapy to known pathogens • Optimize timing,regimen,dose,route and duration

  42. Use Antimicrobials WiselyStep 6: Use local data Fact: The prevalence of resistance varies by locale. Actions: • Know your local antibiogram • Get previous microbiology results when patients transfer to your facility

  43. Use Antimicrobials WiselyStep 7: Know when to say “No” to vanco Fact:Reduction of vancomycin use is one of the most important strategies to limit the emergence, selection, and spread of vancomycin resistant bacteria. Action: • Follow CDC guidelines for vancomycin use • Consider 1st generation cephalosporins instead of vancomycin

  44. Guidelines for Appropriate Vancomycin Use (HICPAC/CDC) • Selected situations in which the use of vancomycin is appropriate or acceptable: • For treatment of serious infections caused by beta-lactam-resistant gram-positive microorganisms. • For treatment of infections caused by gram-positive microorganisms in patients who have serious allergies to beta-lactam agents. • When antibiotic-associated colitis fails to respond to metronidazole therapy or is severe and potentially life-threatening. CDC, MMWR 1995;44(RR12):1-13

  45. Guidelines for Appropriate Vancomycin Use (HICPAC/CDC) • Selected situations in which the use of vancomycin should be discouraged: • Treatment in response to a single blood culture positive for CNS, if other cultures taken during the same time frame are negative. • Continued empiric use for presumed infections in patients whose cultures are negative for ß-lactam resistant gram + organisms. • Eradication of MRSA colonization. • Systemic or local prophylaxis for infection or colonization of indwelling central or peripheral intravascular catheters. • Primary treatment of antibiotic-associated colitis. • Routine prophylaxis for patients on CAPD or HD. • Treatment (chosen for dosing convenience) of infections caused by ß-lactam-sensitive gram + organisms in patients who have renal failure.

  46. Use Antimicrobials WiselyStep 8: Treat infection, not contamination or colonization Fact:A major cause of antimicrobial overuse is treatment of contamination or colonization. Actions: • Use proper antisepsis for drawing blood cultures • Get one peripheral vein blood culture, if possible • Avoid culturing vascular catheter tips • Treat bacteremia, not the catheter tip • Culture the blood, not the skin or catheter hub

  47. Use Antimicrobials WiselyStep 9: Stop antimicrobial treatment Fact:Stopping empiric therapy when cultures are negative can significantly reduce antimicrobial use. Actions: • Stop when infection is treated • Stop when clinical and laboratory data rule out infection

  48. Prevent TransmissionStep 10: Follow infection control procedures Fact: Following recommendedinfection control precautions for hemodialysis patients can prevent transmission of infections from patient to patient. Actions: • Use standard infection control precautions for dialysis centers • Consult local infection control experts

  49. http://www.cdc.gov/mmwr/PDF/rr/rr5005.pdf

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