1. Approach to Catheter-related Bloodstream Infections in Patients on Haemodialysis Nephrology discussion Registrar: Dr. Coetser Consultants: Prof. Van Rensburg Dr. Rossouw

2. INTRAVASCULAR INTRACUTANEOUS INTRALUMINAL AND/OR HUB TUBING INFUSATE

3. Prevention of CRBSI  5 principles strongly recommended by CDC: Hand washing Full barrier precautions during insertion of central venous catheters Chlorhexidine for skin disinfection Avoidance of the femoral insertion site Removal of catheters when no longer indicated  If these principles are adhered to, showed a 12% sustainable reduction in incidence of CRBSI in intensive care units Pronovost, PJ et al. Sustaining reductions in catheter related bloodstream infections in Michigan intensive care units: observational study. BMJ 2010; 340

4. Unique features in the haemodialysis patient applicable in our setting  Usually outpatients  Hospitalization only indicated for severe sepsis or metastatic infection  Parenteral antibiotics can be given during dialysis sessions  Preference given to antibiotics that can be delivered during dialysis  Peripheral venous access unavailable or should be avoided  Catheter removal often requires urgent placement of a new dialysis catheter  Quantitative blood culture and/or determining differential time to positivity frequently unable to be done

5. Risk of infection vs. location in dialysis catheters  Subclavian catheters have least risk of infection, but high incidence of venous stenosis  Femoral catheters have highest risk of infection due to microbial load and should be avoided if possible  Internal jugular catheters have an intermediate risk of infection, but is the most appropriate site for acute haemodialysis access

6. Unique aspects in haemodialysis: Obtaining blood cultures  Peripheral blood samples should spare veins for potential fistula creation (A-III)  If no sample can be obtained, blood culture can be taken from bloodlines connected to the catheter during haemodialysis (B- II)  If no sample can be obtained from peripheral site, no other catheter is in situ and no drainage from exit site that can be cultured, accept positive culture from dialysis catheter as evidence of a CRBSI (B-II)

7. Category, grade Definition Strength of recommendation A Good evidence to support a recommendation for or against use B Moderate evidence to support a recommendation for or against use C Poor evidence to support a recommendation Quality of evidence I Evidence from more than 1 properly randomized, controlled trial II Evidence from more than 1 well-designed clinical trial, without randomization; from cohort or case-controlled analytic studies; from multiple time series; or from dramatic results from uncontrolled experiments III Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

8. Unique aspects in haemodialysis: Removal of infected catheter  Always remove catheter when these organisms are cultured (A-II) S. aureus Pseudomonas spp Candida spp  If no alternative sites for catheter placement, exchange infected catheter over a guidewire (B-II)  Place longterm catheter again when blood cultures become negative (B-III)

9. Unique aspects in haemodialysis: Removal of infected catheter  For other pathogens (gram-negative bacilli other than Pseudomonas or coagulase-negative staph) catheter need not be removed immediately. Start empiric antibiotics (B-II)  3 options remain: If symptoms resolve within 2-3 days, exchange infected catheter over guidewire (B-II) or Leave catheter in place and treat with antibiotic lock for 10-14 days (B-II) If symptoms persist, or signs of metastatic infection present, remove line

10. Unique aspects in haemodialysis: Removal of infected catheter  Treating with antibiotics alone and not removing the infected catheter is not satisfactory: Bloodstream infection returns in majority after therapy is stopped Treatment failure risk is 5x higher  Catheter should be inserted at a new sight or at least be exchanged over a guidewire

11. Unique aspects in haemodialysis: Empiric antibiotic coverage  Include vancomycin and coverage for gram-negative bacilli (e.g. 3 rd generation cephalosporin, carbapenem or beta- lactam/beta-lactamase combination) (A-II)  Aminoglycosides, e.g. gentamycin, can be used, but risk of irreversible ototoxicity  If found to have methicillin-susceptible S.aureus, switch to cefazolin (20mg/kg) after each dialysis session

12. Unique aspects in haemodialysis: Empiric antibiotic coverage

13. Unique aspects in haemodialysis: Duration of antibiotic treatment  Uncomplicated infection and no evidence of metastatic infection: Coagulase negative staph  5-7 days if catheter removed (B-III)  10-14 days if catheter retained, in combination with antibiotic lock (B- III) S. aureus  4-6 weeks  Shorter duration (minimum 14 days) can be considered in: - non-diabetics - non-immunosuppressed - catheter removed - no prosthetic intravascular device - no evidence of endocarditis - fever and bacteraemia resolve within 72h on TEE (5-7 days after onset) - no evidence of metastatic infection

14. Unique aspects in haemodialysis: Duration of antibiotic treatment  4-6 weeks if complicated infection, i.e.: Persistent bacteraemia or fungaemia (>72h) after infected catheter was removed If infective endocarditis or suppurative thrombophlebitis present  6-8 weeks for osteomyelitis  Surveillance blood culture to be taken 1 week after completion of antibiotic course. If culture postive, remove catheter and only place new longterm catheter when blood culture becomes negative

15. Antibiotic lock  Definition A solution of antibiotic and heparin instilled into a catheter lumen. Solution is then left in place for a certain time period.  Mechanism of action Bacteria form a biofilm on the endoluminal side of a long-term placed catheter Bacteria are sequestered here from systemic levels of antibiotics Antibiotic lock delivers supratherapeutic levels of antibiotics to the biofilm

16. Antibiotic lock therapy  Indications (B-II): CRBSI in patients with long-term (>2 weeks) catheters in which salvage is desirable No signs of exit site or tunnel infection must be present  Success rates: Gram-negative pathogens (87-100%) Staphylococcus epidermidis (40-50%) Staphylococcus aureus (40-55%)

17. Antibiotic lock therapy: Practical aspects  Use in conjunction with systemic antibiotic therapy for 7-14 days (B-II)  Dwell times not >48h Preferably q24h in patients with femoral catheters If undergoing haemodialysis, change lock with every session  Not all antiobiotics are suitable for use in combination with heparin, as precipitation can occur  Antibiotic lock is unlikely to have effect if catheter has been in place for <2 weeks

18. Antibiotic lock therapy: Practical aspects  Do not use antibiotic lock and remove catheter for S.aureus and candida infections, unless no alternative site available  If multiple positive catheter culture results for coagulase- negative staph or gram-negative bacilli, but negative peripheral cultures, antibiotic lock can be given for 10-14 days without systemic antibiotics (B-III)

19. Antibiotic lock therapy: Practical aspects * * Insufficient data to recommend ethanol lock