1. Intravascular Catheter-Related Infection: Clinical Practice Guideline 감염 내과 박 기 호

2. Intravascular Catheters

3. Risk of Catheter infection Maki DG, et al. Mayo Clin Proc 2006;81:1159-71 Type of Intravascular Catheters CR-BSI, no./1000 catheter-days Peripheral inserted midline catheters (Ix. central venous thrombus and endocarditis) 0.2 (95% CI 0.0-0.5) Peripheral venous catheters0.5 (95% CI 0.2-0.7) Peripheral inserted central catheters (PICC)1.1 (95% CI 0.9-1.3) Cuffed and tunneled CVCs (e.g. Hickman catheter)1.6 (95% CI 1.5-1.7) Arterial catheters for hemodynamic monitoring1.7 (95% CI 1.2-2.3) Non-cuffed and non-tunneled CVCs2.7 (95% CI 2.6-2.9) Pulmonary artery catheters (e.g. Swan-ganz catheter)3.7 (95% CI 2.4-5.0)

4. PICC and Midline catheter Peripheral inserted midline catheters (PICC) Midline catheters (Ix. central venous thrombus and endocarditis)

6. Pathogenesis 1) Extraluminal spread 2) Intraluminal spread ex) Long-term catheter 3) Hematogenous spread → Endogenous (GI tract) → Catheter tip colonization ex) Candidemia

7. Cather tip culture Catheter tip culture ≥15 colony forming unit Semi-quantitative methods Maki’s methods Maki DG, et al. N Engl J Med 1977;296:1305-9.

8. Biofilm and catheter colonization Raad I, et al. J Infect Dis 1993;168:400-7 Organisms associated with biofilm formation 1) S. aureus 2) CoNS 3) Candida species → Typical organism of catheter-related infection

9. Intraluminal vs. Extraluminal Raad I, et al. J Infect Dis 1993;168:400-7 1.False negative catheter tip culture in long- term CRBSI 2. Antibiotic lock therapy may be ineffective for short-term CRBSI

10. Clinical Diagnosis  Fever: most sensitivity, poor specificity  External signs of infections: greater specificity, poor sensitivity 1) Exit site infection 2) Tunnel infection  Tunnel infection → High failure rate of attempted catheter salvage!! → Should remove CVC !! Tunnel infection Exit site infection 2 cm Mermel LA, et al. Clin Infect Dis 2009;49:1-45

11. Clinical Diagnosis  Blood cultures that are positive for S. aureus, CoNS, Candida in the absence of identifiable sources of infection → Suspicion for CRBSI !!!  G+cocci (clusters), budding yeast in preliminary blood culture reports → Suspicion for CRBSI !!! Mermel LA, et al. Clin Infect Dis 2009;49:1-45

12. Laboratory Diagnosis  For suspected CRBSI, paired blood samples drawn from the catheter and a peripheral vein.  Bottles should be appropriately marked to reflect the site.  Enough (≥5-7mL) and equal volumes !!  If a blood sample for culture cannot be drawn from a peripheral vein, it is recommended that 2 blood samples should be obtained through different catheter lumens (B-III). Mermel LA, et al. Clin Infect Dis 2009;49:1-45

13. Definite catheter-related BSI i) Catheter tip culture ≥ 15 CFU ii) Positive percutaneous BC results i) Positive catheter BC + percutaneous BC results ii) DTP > 2hr (e.g. percutaneous BC 5 hr – catheter BC 1 hr = 4 hr) i) Positive catheter-drawn BC + percutaneous BC results ii) Colony count of catheter BC / colony count of percutaneous BC > 3 1) Semiquantitative catheter tip cultures 2) Differential Time to Positivity (DTP) **long-term catheters 3) Quantiative paired blood cultures Mermel LA, et al. Clin Infect Dis 2009;49:1-45

14. DTP: clinical practice Example 1) Day 1: catheter drawn BCx: G(+) cocci, clusters percutaneous drawn BCx: no growth Day 2: catheter drawn BCx: G(+) cocci, clusters percutaneous drawn BCx: G(+) cocci, clusters → Catheter-related bacteremia!! Example 2) Day 1: catheter drawn BCx: no growth percutaneous drawn BCx: G(+) cocci, clusters → Non-catheter related bacteremia or contamination !!

15. Example 3) Day 0: catheter drawn BCx: S. epidermidis percutaneous drawn BCx: S. epidermidis Day 1-3: antibiotic treatment of S. epidermidis bacteremia Day 3: catheter drawn BCx: S. epidermidis percutaneous drawn BCx: no growth → Catheter-related S. epidermidis bacteremia!! → Consider catheter retention rather than catheter removal DTP: clinical practice

16. Diagnostic work-up Blood cultures should be repeated at the intervals of 2-3 days until negative blood culture results obtained Diagnostic workup and treatment duration depend on duration of bloodstream infections Candidemia → dilated funduscopic examination (endopthalmitis) S. aureus bacteremia → TTE/TEE at 5-7 days after onset of catheter-related S. aureus bacteremia (endocarditis) Mermel LA, et al. Clin Infect Dis 2009;49:1-45

17. Persistent catheter-related Bacteremia Complicated infection (63%) 1) Central vein thrombus (30%) 2) Metastatic infection (35%) (e.g. Vertebral osteomyelitis) 3) Infective endocarditis (14%) Infection-related death (23%) Relapse (5%) Park KH, et al. PloS One 2012;7:e46389 Persistent Catheter-related S. aureus bacteremia (≥ 3days) after catheter removal and initiation of antibiotic therapy

18. Persistent S. aureus catheter-related Bacteremia Persistent CRSAB (≥ 3 days) → High rate of complications (>70%) → Aggressive diagnostic and therapy approach !! Aggressive diagnostic approach !! 1) Suppurrative thrombophlebitis: Neck vein US or CT 2) Infective endocarditis: TTE or TEE 3) Vertebral osteomyelitis: Spine MR or bone scan Aggressive therapeutic approach !! → Prolonged antibiotic therapy for at least 4 weeks (Occult metastatic infection or occult endocarditis) Mermel LA, et al. Clin Infect Dis 2009;49:1-45

19. W/u for candidemia 55 patients with venous catheter-associated candidemia 20 died during fungemia 35 patients: catheter removal + no antifungal therapy 1) Death from candidemia 2) Persistent candidemia 3) Resolved Rose HD. Am J Med Sci 1978;275:265-9 → None → 9 pts.→ antifungal therapy → 26 pts. → 4/26 pts. endophthalmitis !! → 3/4 pts. vision loss !!

20. Empiric treatment  CoNS, S. aureus → Vancomycin or Teicoplanin !!  Gram-negative : neutropenia, femoral catheter, neutropenia  Candida spp.: TPN, hematologic malignancy, femoral catheter Mermel LA, et al. Clin Infect Dis 2009;49:1-45

21. Catheter removal vs. Salvage S. aureus > MDR gram (-) > (Candida spp.) > Enterococcus > CoNS Removal Salvage  Absolute indication of catheter removal !! ‒ Hemodynamic stability !! ‒ Suppurrative thrombophlebitis ‒ Infective endocarditis ‒ BSIs persisted for ≥3 days despite antimicrobial therapy P. aeruginosa, A. baummanni, S. maltophilia Mermel LA, et al. Clin Infect Dis 2009;49:1-45

22. Attempted Catheter Salvage in S. aureus catheter-related bacteremia 41 Cases of Hickman catheter-associated S. aureus bacteremia Success rate of attempted catheter salvage: only 18% !! Cases with exit site infections: only10% !! Dugdale DC, et al. Am J Med 1990;89:137-141

23. Park KH, et al. Ann Hematol 2010;89(11):1163-9 Hickman catheter salvage in neutropenic cancer patients with S. aureus bacteremia Success rate of attempted catheter salvage: 60% !! Attempted Catheter Salvage in S. aureus catheter-related bacteremia

24. Park KH, et al. Ann Hematol 2010;89(11):1163-9 Attempted Catheter Salvage in S. aureus catheter-related bacteremia Higher success rate 1) β-lactam antibiotics other than ceftazidime 2) Fluoroquinolone combination: biofilm penetration!! Suggested regimen!! 1) β-lactam or vancomycin 2) Antibiotic locking 3) Rifampin+fuoroquinolone 4) Muprocin oint

25.  Attempted catheter salvage - 80%:success !! - 20%: recurrence Raad I, et al. Infect Control Hosp Epidemiol 1992;13:215-221 Attempted Catheter Salvage in CoNS catheter-related bacteremia

26. Catheter removal vs. Salvage S. aureus > MDR gram (-) > (Candida spp.) > Enterococcus > CoNS Removal Salvage  Absolute indication of catheter removal !! ‒ Hemodynamic stability !! ‒ Suppurrative thrombophlebitis ‒ Infective endocarditis ‒ BSIs persisted for ≥3 days despite antimicrobial therapy P. aeruginosa, A. baummanni, S. maltophilia Mermel LA, et al. Clin Infect Dis 2009;49:1-45

27. Duration of therapy S. aureus: removal (4-6 weeks) GNR: removal (7-14 days) Candida spp.: removal (14 days), endoophthalmitis !! Enterococcus: removal / salvage (7-14 days) CoNS: removal (5-7 days), salvage (10–14 days) Day 1 is the first day on which negative blood culture results are obtained Mermel LA, et al. Clin Infect Dis 2009;49:1-45

28. Therapy for S. aureus CRBSI Should be received four-six weeks Short course therapy (2-4 weeks) – If not diabetic – Not immunosuppressed – Infected catheter removed – No prosthetic device – No endocarditis or suppurative thrombophlebitis on TEE and US – Fever and bacteremia resolved within 72 h after initiation of appropriate antibiotics and catheter removal Mermel LA, et al. Clin Infect Dis 2009;49:1-45

29. Vertebral osteomyelitis Hematogenous vertebral osteomyelitis has increased in recent years – longer life expectancy, increasing prevalence of chronic disease, better diagnosis, and more frequent use of indwelling intravascular catheters IV catheter-related infections were responsible for – 47% of MRSA vertebral osteomyelitis – 23% of MSSA vertebral osteomyelitis Park KH, et al. J Infect 2013;67:556-64

30. Routine CVC tip cultures? CVC tip cultures (+) / blood cultures (-) 312 patients with a positive catheter culture and a negative blood culture Only eight patients (2.6%) subsequently developed CRBSI Park KH, et al. Clin Microbiol Infect 2010;16:742-746

31. Routine CVC tip cultures? Catheter cultures should not be obtained routinely (A-II) a ERBP raises questions about the relevance of this labour-intensive and costly approach in view of the low yield b a Mermel LA, et al. Clin Infect Dis 2009;49:1-45 b Vanholder R, et al. Nephrol Dial Transplant 2010;25:1753-6

32. CVC tip cultures+ / BC- Hetem DJ, et al. Medicine 2011;90:284-8 Park KH, et al. Clin Microbiol Infect 2010;16(6):742-6 Antimicrobial therapy after removal of S. aureus colonized catheter prevented the subsequent S. aureus bacteremia

33. When to perform catheter tip culture? When to treat the patients? Symptom or signs of catheter infection Yes No No catheter tip cultures No blood cultures Catheter tip cultures Blood cultures CRBSI S. aureus tip culture (+) Blood culture (-) Treat Treat (Updated guideline)

34. Catheter BC+/ percutaneous BC- Probably because of – Intraluminal colonization – False negative peripheral blood cultures – Contamination There were 112 episodes with positive CBC and negative PBC. Subsequent BSI developed in 6 of 31 episodes (19%) where empiric antibiotics were inappropriate but in 3 of 81 episodes (4%) where empiric antibiotics were appropriate (P = 0.01). Candida, S. aureus, gram-negative rods > CoNS, Enterococcus !! Park KH, et al. Diagn Microbiol Infect Dis 2011;70:31-36

35. Summary 1 1. PICC or midline catheter: the lowest risk of catheter infection 2. Definite CRBSI: peripheral blood cultures (+) plus catheter tip cultures (+) 3. Probable CRBSI: S. aureus, CoNS, Candida BSIs without other foci of infection 4. Blood cultures should be repeated at the intervals of 2-3 days

36. Summary 2 5. S. aureus CRBSI → TTE/TEE at 5-7 days 6. Candidemia → Dilated funduscopic exam 7. Persistent CRBSI despite initiation of treatment → 1) thrombosis, 2) endocarditis, 3) vertebral OM 9. S. aureus, Candida, GNB → Catheter removal !! 10. CoNS, Enterococcus → Catheter retention

37. Summary 3 A. Positive catheter tip cultures plus Negative Blood cultures → Treat for S. aureus B. Catheter-drawn blood cultures (+) Percutaneous blood cultures (-) → Treat for S. aureus, Candida, GNB

38. Thank you for your kind attention!! Q & A