first year preseatheter Related Bloodstream Infection (CRBSI)atheter Related Bloodstream Infection (CRBSI)vatheter Related Bloodstream Infection (CRBSI)ntation .pptx

atheter Related Bloodstream Infection (CRBSI)atheter Related Bloodstream Infection (CRBSI)atheter Related Bloodstream Infection (CRBSI)vatheter Related Bloodstream Infection (CRBSI)

1. Bacterial infection of tunneled hemodialysis catheter Dr. Muhamed Al Rohani, MD Consultant nephrologist

2. To remember In 1980s permanent catheters Despite the Fistula First Initiative, nearly 80% of patients initiate hemodialysis with a central venous catheter Recent USRDS report observed high 1 st and 2 nd month death rates after HD initiation, coincident with the increase in CVC placement rates. The mortality rate from infection is now 2.4 times greater than in 198. Hospitalizations is more than doubled between 1993 and 2005. A tunneled central venous catheter have a 15-fold increased risk of catheter-related bloodstream infection (CRBSI) and an all-cause mortality rate ranging from 12% to 25%. Ten percent to 20% of CRBSIs are associated with metastatic complications Catheter-related infections: Exit site infections, Tunnel infections, Bacteremia The risk of sepsis with a CVC is 2 – 5 fold higher than that with AVG and AVF After an episode of sepsis, the rate of adverse cardiovascular events increases by up to 2fold, these include: Myocardial infarction, Congestive heart failure, Peripheral vascular disease, Cerebral vascular accident events.

3. Hemodialysis Catheters Tunneled, cuffed catheters Non-tunneled, non-cuffed catheters

4. Summary of bloodstream infection data AJKD, 2002; 39 (3): 549-555

5. Risk factors for catheter-related bacteremia AJKD 2004, 44(5): 779 AJKD 2005, 46(3): 501 KI, 2000; 57(5): 2151 Duration of catheterization Conditions for insertion Catheter site and catheter site care Repeated catheterization Increased catheter maniplation Tunneled vs nontunnelled catheters Immunosuppressive therapy Hypoalbuminemia AJKD, 2005; 46 (3): 501. Lee T. Et all, «Tunneled catheters in hemodialysis patients: Reasons and Subsequent Outcomes» The most important risk factor for tunneled catheter-related bacteremia is prolonged duratiom of usage

6. Catheter Exit Site infection Photo provided by Stephanie Booth, used with permission Catheter Tunnel infection New catheter Catheter with biofilm

7. Biofilm: The critical adherence of the organism to the catheter surface initiates the common pathway of biofilm production. A mature biofilm is a unique self-sustaining community of microorganisms protected by an exopolysaccharide matrix that is stimulated and secreted by the microorganisms. Common microorganisms found in biofilms include Staphylococcus, Candida, Pseudomonas, and other. ‘fibrin sheath’ or ‘adherent biological material’: universal endoluminal coverage of material consistent with biofilm but without universal colonization by bacteria (electron microscopy scanning) super resistant barrier to antibiotic penetration and action

8. Evaluation, diagnosis and differential diagnosis CRB suspect threshold should be low. Two blood cultures should be drawn; Peripheral vein and catheter Separate peripheral veins Differential diagnosis includes pneumonia, foot infection and other infections UpToDate, 2014 The def i n i t i ve diagnosis of CRB requires one of the following Concurrent positive blood cultures of the same organism from the catheter and a peripheral vein. Culture of the same organism from both the catheter tip and at least one percutaneous blood culture. Cultures of the same organism from two peripherally drawn blood cultures and an absence of alternate focus of infection.

9. JASN , 1999 : 10(5): 1045 Gerald A. Beathard Table 2: Bacterial isolates from 18 blood cultures. Count % Gram-positive organisms     Coagulase-negative Staphylococcus (CONS) 3 (14.3)   Bacillus sp. 3 (14.3)  Methicillin sensitive Staphylococcus aureus (MSSA) 2 (9.52)  Methicillin resistant Staphylococcus aureus (MRSA) 1 (4.76)   Enterococcus sp. 1 (4.76) Gram-negative organisms     Stenotrophomonas sp. 3 (14.3)   Pseudomonas sp. 2 (9.52)   Enterobacter sp. 2 (9.52)   Citrobacter sp. 1 (4.76)   Flavobacterium sp. 1 (4.76)   Morganella sp. 1 (4.76)   Serratia sp. 1 (4.76) International Journal of Nephrology Volume 2014 (2014), Article ID 629459, 6 pages

10. Staphylococcus Aureus: Annual incidence bacteremia in HD patients is between 6 and 27%. CRB is associated with more than 3-fold higher rate of infectious complications, and 4-fold greater risk of recurrent bacteremia or septic death in 3 months, The mortality rate associated with S. aureus access infections has been reported to be as high as 30%. Pseudomonas Aragenosa : Sepsis Death Gram-negative species are isolated in 27–36% of episodes. The high mortality rates reported in Pseudomonas sepsis associated with visceral nosocomial infections (non-CRB),

11. Clinical manifestations of hemodialysis catheter infections Fever and/or chills Purulence at the catheter insertion site Hemodynamic instability Catheter dysfunction Hypothermia Acidosis Hypotension Man i festat i ons of metastatic i nfect i o n s UpToDate, 2014 Complications Endocarditis Osteomyelitis Epidural abscess Septic shock Septic arthritis Septic thrombophlebitis Death

12. Transesophageal echocardiogram image of the mitral valve (MV), anterior MV leaflet (m), and posterior MV leaflet (mm) with a vegetation (*) attached by a stalk to the left atrial (LA) side of the posterior MV leaflet, near its tip. LV, left ventricle Autopsy image of a large cardiac valvular vegetation

13. Prevention of infection Catheter insertion and position Catheters should be inserted under strict aseptic conditions. The right internal jugular vein position is the preferred location for insertion, followed by the left internal jugular vein position. The use of the femoral vein position is discouraged. The use of the subclavian vein position is discouraged for reasons not related to infection (frequent stenosis). Nurse care Universal precautions, a sterile environment and aseptic technique should be applied at any occasion when a venous catheter is manipulated, connected or disconnected. Preventive antimicrobial catheter locks and catheter surface treatment: Vancomycin/ceftazidime/heparin Vancomycin/heparin Ceftazidime/heparin Cefazolin/heparin Gentamycine/heparin Taurolidine 4% and 30 % citrate 70 % ethanol Acceptable exit site cleaning solutions: chlorhexidine 2% alcohol 70% povidone-iodine 10% solution The use of chlorhexidine skin antisepsis at the catheter exit site, catheter hub disinfection, The application of triple antibiotic (or povidone iodine) ointment to catheter exit sites during dressing changes. Similar “bundled” care efforts in intensive care units have shown dramatic decreases in nondialysis CRBSI rates. 54% reduction ( P <0.001) in CRBSI during the 15-month intervention period.

14. Different Locking Solutions Prevent thrombosis Risk of bleeding Prevent Infection Systemic effect Bacteria resistance Heparin yes yes no yes no Citrate 30% yes no yes yes no Gentamicin + Citrate yes no yes yes yes Taurolidine + Citrate yes no yes no no Isopropyl alcohol 70 % yes no yes no no The success rate of an antibiotic lock: Gram-negative infections 87 to 100% , S. epidermidis infections 75 to 84%, S. aureus infections 40 to 55% Potential risks: Arrhythmias, Toxicity, Allergic reactions, Development of resistance to antibiotics

15. Recent studies: Abbas et al : using bundled care without antimicrobial locks have achieved CRBSI rates of ≤1 per 1000 catheter-days, can the use of antimicrobial locks further reduce CRBSI? Maki et al: Performed an observational study of gentamicin-heparin versus heparin catheter locks, Moran and their colleagues performed randomized controlled trials with gentamicin- trisodium citrate (citrate) and citrate–methylene blue– methylparaben – propylparaben , respectively. Conclusions: All three studies achieved CRBSI rates of <1 per 1000 catheter-days in their control groups and yet still showed a significant decrease in infection rates with their interventions (Abbas, Moran, and Maki et al. reported rates of 0.62, 0.28, and 0.24 events per 1000 catheter-days, respectively). However, two major unanswered questions remain: Does the routine use of antimicrobial locks in dialysis patients with tunneled central venous catheters lead to a mortality benefit? Is there risk of antibiotic resistance in patients using antibiotic-based lock solutions?

16. To answer the mortality Moore et al: conducted a prospective, multicenter, observational cohort study to compare the effectiveness of a gentamicin-citrate lock versus heparin. They included the use of a triple antibiotic ointment (bacitracin, neomycin, and polymyxin B) on the exit site. The dose of gentamicin (0.32 mg/ml) used with 4% citrate. The authors report a reduced rate of CRBSI in the antibiotic lock period of 0.45 per 1000 catheter-days compared with 1.68 events during the heparin period ( P =0.001). The use of gentamicin-citrate lock was also associated with a significant reduction in all-cause mortality (0.32; 95% confidence interval, 0.14 to 0.75 after multivariate adjustment). CJASN , 2014 The issue of the antibiotic resistance in hemodialysis catheter remains discussable The CDC and the Infectious Diseases Society of America do not recommend the routine use of antimicrobial lock in hemodialysis patients dialyzed with a central venous catheter. They suggest reserving this treatment for patients with a history of multiple CRBSIs, citing concerns for the potential emergence of antibiotic resistance. In contrast, the European Best Practices Report has concluded that the effectiveness of antimicrobial lock to reduce CRBSI outweighs any potential risk and recommends prophylactic antimicrobial lock use in all patients with ESRD who have tunneled central venous catheters.

17. Prevention of catheter related infection General measures : Every dialysis unit must develop written protocol for maniplation of hemodialysis catheters and exit -site dressing technique , Hand hygiene before and after patient contact , Wear nonsterile gloves and masks during catheter procedures, Other methods : Elimination of S. Aureus nasal carriage , Topical application of different substances , Utilize antibiotic-lock technique , U s age of different catheters ( Are there catheters with a lower infection rate?) impregnated with antimicrobial agents , with subcutaneos port, Usage of Tego needlefree hemodialysis connector

18. TREATMENT Management of diaysis-catheter induced bacteremia Antibiotic therapy Empiric systemic antimicrobial therapy Tailored systemic antimicrobial therapy Removal or exchange of catheter UpToDate, 2014

19. Approach to the management of a patient with a tunneled central venous catheter (CVC)— or a surgically implanted device (ID)—related bloodstream infection. Leonard A. Mermel et al. Clin Infect Dis. 2001;32:1249-1272 © 2001 by the Infectious Diseases Society of America

20. Em piric systemic antimicrobial therapy for hemodialysis catheter infection AJKD, 2009: 54(1): 13. Treatment guidelines for dialysis catheter-related bacteremia

21. Methicillin-resistant Staphylococcus   With the isolation of a methicillin-resistant Staphylococcus, Continue to administer vancomycin if the organism has a low-minimal inhibitory concentration. Patients with vancomycin allergy can be treated with daptomycin. UpToDate, 2014 Methicillin- sensitive Staphylococcus   With the isolation of a methicillin-sensitive Staphylococcus, Vancomycin should be substituted with cephazolin. 20 mg/kg cephazolin, IV, after each hemodialysis session. Vancomycin is the preferred treatment for patients who are penisillin allergic. Cephazolin as empiric therapy in hemodialysis-related infections. AJKD 1998, 32(3):410. Use of vancomyin or cephazolin for treatment of hemodialysis-dependent patients with methicillin-susceptible staphyloccocus aureus bacteremia. Clin Infect Dis 2007, 44(2): 190. Vancomycin-resistant Enterococcus Can be treated with daptomycin, 6 mg/kg, following a dialysis session in inpatients, 7 mg/kg (low- flux dialyzers), during the last 30 minutes of each dialysis session, 9 mg/kg (high-flux dialyzers) , during the last 30 minutes of each dialysis session Intradialytic administration of daptomycin in end stage renal disease patients on hemodialysis CJASN 2009, 4(7):1190

22. Gram-negative organisms U p to 95 % of Gram-negative bacteria isolated in dialysis catheter-related bacteremia are presently sensitive to both aminoglycosides and third-generation cephalosporins . prefer  ceftazidime  for longer-term treatment, rather than gentamycin , given the risk of aminoglycoside ototoxicity . I n regions or institutions in which resistance to ceftazidime is more common, aminoglycosides o r carbepenems  may be alternate choices . UpToDate, 2014 Candidemia catheter removal treatment with an appropriate antimicrobial agent Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic lock solution . K I 2002;61(3):1136

23. Duration of antimicrobial therapy for CRB Uncertain. It depends on clinical, microbiologic features and whether the catheter is removed Treat uncomplicated CRB for two or three weeks. Treat uncomplicated CRB due to S. Aureus for four weeks. If there is evidence of metastatic infection, use of antibiotics at least six weeks. When blood cultures remain positive after three or more days of appropriate therapy, use antibiotics at least six weeks. Among patients with osteomyelitis, experts advise treatment for six to eight weeks. UpToDate, 2014 Catheter management in case of CRB Immediate catheter removal, followed by placement of a temporary non-tunneled catheter for short-term dialysis access. After bacteremia has resolved, a new tunneled dialysis catheter can be inserted. Replacement of the infected catheter via exchange over a guidewire. Use an antibiotic lock in the infected catheter. Leave the infected catheter in place (no replacing, no an antibiotic lock)

24. Conditions for i mmed iate removal of infected hemodialysis catheters Severe sepsis, Hemodynamic instability, Evidence of metastatic infection, Signs of accompanying exit-site or tunnel infection, If fever and /or bacteremia persist 48 to 72 hours after initiation of antibiotics to which the organism is susceptible, When infection is due to difficult-to-culture pathogens, such as S. Aureus, Pseudomonas, Candida, other fungi, or multiply-resistant bacterial pathogens. UpToDate, 2014

25. Gu idewire catheter exchange «If there is no conditions of immediate catheter removal, delayed exchange of the infected cuffed catheter over a guidewire with a new catheter two or three days after institution of effective antimicrobial therapy is a reasonable option.» K I 2000;57(5):2151 . Bacteremia associated with tunneled dialysis catheters: comparison of two treatment strategies. A JKD 1995;25(4):593 . Catheter-related sepsis complicating long-term, tunnelled central venous dialysis catheters: management by guidewire exchange. K I 1998;53(6):1792 . Treatment of infected tunneled venous access hemodialysis catheters with guidewire exchange. Conditions for guidewire replacement of the catheter Afebrile after 48 hours of antibiotic therapy Clinically stable patient No evidence of tunnel tract involvement C JASN 2009, 4: 1102– 1105. Catheter exchange over a guidewire in conjunction with antifungal therapy is an effective and safe treatment regimen also in catheter-related candidemia cases.

26. Leaving the catheter in place without intervention Only systemic antibiotics, Without replacing the infected catheter, Without instilling an antibiotic lock, Clinical cure rate, 22-37 % Eradication of bacteria imbedded in biofilms ? UpToDate, 2014