Amsterdam                                     June 2012Accuracy and cost-effectiveness     in diagnosis of CRBSI          ...
General introductionAccuracy of CRBSI diagnosis:What is accurate?Best possible sensitivity, specificity, PPV NPV, reproduc...
General introductionAccuracy of CRBSI diagnosis:We should look for an optimal balance between:-  Avoidance of delayed cath...
Topics of today on diagnosis:1.  Maki versus sonication2.  The ins, outs and problems of D T T P3.  Surface Cultures Surve...
To roll or to sonicate?                          5
To roll or to sonicate?Roll plate (Maki):Sonication:                                        6                             ...
n=1000 tip cultures in random order (33% positive)   Gold standard: Positive culture in at least 1 of the 3 techniques=> S...
“Long-term CVC” in this study >6 days in situ“Long-term CVC” Roll-plate as good as sonication (100cfu cut-off) But what in...
313 Hickman catheters  Dwell time 55 days  25% of tips were positive  40 patients with CRBSI (DTTP or tip + peripheral BC)...
Guembe M et al. J Clin Microb 2012                                     11                                     11
To roll or to sonicate?35 years after Maki’s publication:Maki DG et al. A semiquantitative culture method for identifyingi...
Topics of today on diagnosis:1.  Maki versus sonication2.  The ins, outs and problems of D T T P3.  Surveillance surface c...
In vivo diagnosis of CRBSIi.      Catheter brush: Don’t try this at home!ii.     Acridine orange leucocyte cytospin: Labou...
15
DTTP =             Time needed for the peripheral BC to become positive                                                   ...
Raad I et al. Ann Intern Med. 2004; 140: 18-25.   17
Raad I et al. Ann Intern Med. 2004; 140: 18-25.                                                  18
Raad I et al. Ann Intern Med. 2004; 140: 18-25.                                                  19
“Although the test seems to have excellent sensitivity and specificity, theauthors do not discuss the consequences of the ...
A Randomized and Prospective Study of 3 Procedures for the Diagnosis ofCatheter-Related Bloodstream Infection without Cath...
A Randomized and Prospective Study of 3 Procedures for the Diagnosis ofCatheter-Related Bloodstream Infection without Cath...
A Randomized and Prospective Study of 3 Procedures for the Diagnosis ofCatheter-Related Bloodstream Infection without Cath...
What about the arterial line ?All   studies     in     English         literature        that   prospectivelyexamined the ...
What about the arterial line ?                                                  2.7/1000    2.0/1000                      ...
1.                   What about the arterial line ? ed am                         201                                     ...
BUT:⇒  Do we have to sample all lumina all the time?  171 CRBSI, all lumina sampled + peripheral BC, DTTP >2hrs as gold st...
BUT:Sampling all lumina => Optimal sensitivitySampling all lumina => much more false positive/contamination               ...
Topics of today on diagnosis:1.  Maki versus sonication2.  The ins, outs and problems of D T T P3.  Surveillance surface c...
The challenge of anticipating catheter tip colonization in major heart surgery patients in the intensive care unit: Are su...
130 patients studied: 15 CRBSI episodes                                         6 secundary BSI                           ...
Topics of today on diagnosis:1.  Maki versus sonication2.  The ins, outs and problems of D T T P3.  Surveillance surface c...
100 consecutive ICU patients in which the physician had decided toremove the catheters for “suspected” catheter-related in...
= 63 with all negativeblood cultures                         34
In every study that includes ICU patients with suspected CRI,the diagnosis can be confirmed during follow up in onlysmall ...
80-90% of catheter removed in vain …                                       36
Is systematic catheter removal beneficial for every “suspected” catheter   related infection ?      Watchful waiting or Im...
38
Methods:Measurements:  During the 10 days after inclusion : T, CRP, SOFA score  WBC count, AB use was registered.  All cat...
Results:Study team was contacted for 144 patients64 of 144 pts (44.5%) could be included.Reasons for excluding 80 of 144 e...
Pts with suspec-         ted CRI (n=144)                                 80 excluded                                 (92 C...
Pts with suspec-         ted CRI (n=144)                                  80 excluded                                  (92...
SOC     WWCVC changes          38/38   16/42   p<0.01CRBSI                2       3       p>0.2Duration of Hosp.    42    ...
SOC     WWCVC changes          38/38   16/42   p<0.01CRBSI                2       3       p>0.2Duration of Hosp.    42    ...
DefinitionsCatheter-related sepsis:= Fever disappeared after catheter-removal (+/- positive tip)In many patients fever wou...
1366 patients, 2101 catheters, 66 CRBSICNS CRBSI:             Mortality with early (6/21) = late removal (3/9) P = 0.9Othe...
Topics of today on diagnosis:1.  Maki versus sonication2.  The ins, outs and problems of D T T P3.  Surveillance surface c...
Cost-effectiveness catheter diagnosis infectionSearch in pubmed                  109English                           -919...
General issues:Too sensitive/aspecific testing       => Costs of unnecessary treatment       => Complications of unnecessa...
Cost-effectiveness of CRBSI diagnosis:JCM 1998: Blood Cultures Positive for Coagulase-Negative Staphylo-cocci: Antisepsis,...
QUESTIONS ?              51
16.30 17.00 bart rijnders - publiceren
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16.30 17.00 bart rijnders - publiceren

  1. 1. Amsterdam June 2012Accuracy and cost-effectiveness in diagnosis of CRBSI BJ Rijnders, MD, PhD Internal Medicine Section Infectious Dis. Erasmus MC Rotterdam The Netherlands B.Rijnders@erasmusmc.nl
  2. 2. General introductionAccuracy of CRBSI diagnosis:What is accurate?Best possible sensitivity, specificity, PPV NPV, reproducibility  But inevitably: very high sensitivity ≈ decrease in specificity / PPVAccuracy of in vitro culture methods: Maki vs sonication vs other ?Accuracy of in vivo culture methods: DTTP / surface cultures / other ? 2
  3. 3. General introductionAccuracy of CRBSI diagnosis:We should look for an optimal balance between:-  Avoidance of delayed catheter removal in patients with CRBSI and severe sepsis: S. aureus, Candida-  Avoidance of unnecessary catheter removal/reinsertion * In particular in pts with long-term CVC * In particular in pts at risk for CVC insertion complications 3
  4. 4. Topics of today on diagnosis:1.  Maki versus sonication2.  The ins, outs and problems of D T T P3.  Surface Cultures Surveillance4.  When (not)to pull the trigger/CVC? 4
  5. 5. To roll or to sonicate? 5
  6. 6. To roll or to sonicate?Roll plate (Maki):Sonication: 6 6
  7. 7. n=1000 tip cultures in random order (33% positive) Gold standard: Positive culture in at least 1 of the 3 techniques=> Short-term CVC: Roll-plate preferred (sonication with100cfu cut-off) Bouza E et al. Clin Inf Dis 2005
  8. 8. “Long-term CVC” in this study >6 days in situ“Long-term CVC” Roll-plate as good as sonication (100cfu cut-off) But what in truly long term CVC? Bouza E et al. Clin Inf Dis 2005
  9. 9. 313 Hickman catheters Dwell time 55 days 25% of tips were positive 40 patients with CRBSI (DTTP or tip + peripheral BC) Often treated with vancomycine before catheter was removedSlobbe L et al. J Clin Microb 2009 10 10
  10. 10. Guembe M et al. J Clin Microb 2012 11 11
  11. 11. To roll or to sonicate?35 years after Maki’s publication:Maki DG et al. A semiquantitative culture method for identifyingintravenous catheter–related infection. N Engl J Med 1977; 296:1305–9.Let’s keep on rolling !
  12. 12. Topics of today on diagnosis:1.  Maki versus sonication2.  The ins, outs and problems of D T T P3.  Surveillance surface cultures4.  When (not)to pull the trigger/CVC? 13
  13. 13. In vivo diagnosis of CRBSIi.  Catheter brush: Don’t try this at home!ii.  Acridine orange leucocyte cytospin: Labour intensiveiii.  Quantitive BC: Not available/labour intensive/expensiveiv.  DTTP: Differential time to positivity Qualitative BC with continuous CO2 measurement -  BacTalert -  BacTec -  … B Rijnders et al. Crit Care Med 2001 14
  14. 14. 15
  15. 15. DTTP = Time needed for the peripheral BC to become positive Minus Time needed for the “catheter BC” to become positive e.g. 13.3 hrs - 8.3 hrs = DTTP 5.0 e.g. 13.3 hrs - 11.9 hrs = DTTP 1.4In oncology patients DTTP > 2 hrs accurately predicts CBSI- Lancet 1999. Vol 354. Sept 25. 1071--1077. Blot F et al. 94 % PPV 91 % NPV-  J Clin Microbiology. Jan. 2003, p. 118–123. Seifert H et al. 88 % PPV 75 % NPV-  Ann Intern Med. 2004; 140: 18-25. Raad I et al. 87 % PPV 85 % NPV 16
  16. 16. Raad I et al. Ann Intern Med. 2004; 140: 18-25. 17
  17. 17. Raad I et al. Ann Intern Med. 2004; 140: 18-25. 18
  18. 18. Raad I et al. Ann Intern Med. 2004; 140: 18-25. 19
  19. 19. “Although the test seems to have excellent sensitivity and specificity, theauthors do not discuss the consequences of the sample collection strategyrequired to measure differential time to positivity (1)“! 216 (3.5%) of the 6138 paired cultures were both positive! In 603 (9.8%) only the CVC blood culture was positive ==> Catheter-drawn blood cultures more likely false positive than cultures obtained through venipuncture (2) => Inappropriate AB use => Inappropriate CVC removal => Delay in diagnosis of other origin of fever/sepsis (1) T Barton et al. Ann Intern Med 2004 (2) Desjardin JA et al. Ann Intern Med. 1999 20
  20. 20. A Randomized and Prospective Study of 3 Procedures for the Diagnosis ofCatheter-Related Bloodstream Infection without Catheter WithdrawalICU setting, 3 year study•  Arterial catheters excluded•  10 ml blood culture through every lumen + peripheral for DTTP•  10 ml blood culture through every lumen + peripheral for quantitative BC•  3 cm  exit site culture + swab culture of all hubs at time of CVC removal•  5cm tip culture (roll-plate method)  DTTP > 2 hours  Quantitative CVC BC culture 5x the peripheral BC  Surface culture positive if ≥15cfu/plated  CRBSI gold standard: Tip positive + peripheral BC positive with same strain => 204 episodes of sepsis in 104 pts with CVC in place => 28 CRBSI Bouza E Clin Inf Dis 2007 21
  21. 21. A Randomized and Prospective Study of 3 Procedures for the Diagnosis ofCatheter-Related Bloodstream Infection without Catheter WithdrawalCONCLUSION: CR-BSI can be assessed without CVC withdrawal in ICU pts who havecatheters inserted for a short timeConvenience, use of resources, and expertise should determine choiceBecause of ease of performance, low cost, and wide availability, we recommendcombining superficial cultures and peripheral BC to screen for CR-BSI, leaving DTTPas a confirmatory and more specific technique.Bouza E Clin Inf Dis 2007 22
  22. 22. A Randomized and Prospective Study of 3 Procedures for the Diagnosis ofCatheter-Related Bloodstream Infection without Catheter WithdrawalBUT:⇒  Do we have to sample all lumina all the time as in this study?⇒  What to do when only CVC blood culture is positive?⇒  What did they do with the “excluded” arterial catheters? Arterial and dialysis catheters were excluded because: * To much blood would have to be taken during each sepsis episode * “ It is well known that arterial catheters are very rarely the origin of bloodstream infection, and in a study involving patients with major heart surgery, arterial catheters accounted for only 0.15% of the cases of bloodstream infection “  Several other reports Bouza E Clin Inf Dis 2007 Rijnders BJ Clin Inf Dis 2007 23
  23. 23. What about the arterial line ?All studies in English literature that prospectivelyexamined the risk of BSI associated with arterial cathetersand provide sufficient data to calculate a rate of infectionper 100 catheters and 1000 days. Data from Safdar N, Maki DG et al unpublished 24
  24. 24. What about the arterial line ? 2.7/1000 2.0/1000 Versus catheterdays catheterdays for CVC Data from Safdar N, Maki DG et al unpublished 25
  25. 25. 1. What about the arterial line ? ed am 201 M C are odstre in l. Crit d blo survey R et a relate -year hio eter- 8 cc ath f an unit. Pirra ial c o sults e care l Most recent large study onte r :r incidence siv e of arterial catheter related BSI:Arteria ” Ar ions inten 1. t ct infe gical 201 respec r e Med et no Barcelona, Spain a su rit Car n’t g M E. C hey do A total of 1543 AC were inserted for 14,437 p ters: “T days. R upcatheter he cat 5. 200 entral The incidence of AC-related bloodstream infections nd c f was ed are M l a(ACR-BSI) o 3.53 episodes per 1000 catheter days.Cr i t C rteria and ter- l. a n et a udy of nizatio athe unit s. eO t lo c e Tr aor ctive s ter co enous ive car e e lv s P rosp s cath entra in inten u c v eno l- and remia a rteri d bact e er a thet e te 5. Ca ? If w rela 200 nted ed ar e M preve o! .C rit C an be usly to c d e rs BJ ction e serio Rijn ed infe erial lin t t rela the arJ Infect. 2011 Aug;63(2):139-43. Esteve F et al. take 26
  26. 26. BUT:⇒  Do we have to sample all lumina all the time? 171 CRBSI, all lumina sampled + peripheral BC, DTTP >2hrs as gold standard Eliminating 1 lumen in triple lumen CVC led to missed diagnosis in 16% Eliminating 2 lumina in triple lumen CVC led to missed diagnosis in 32% Eliminating 1 lumen in double lumen CVC led to missed diagnosis in 27% M Guembe et al. Clin Inf Dis 2010 27
  27. 27. BUT:Sampling all lumina => Optimal sensitivitySampling all lumina => much more false positive/contamination => decrease in specificity / PPVIn low incidence setting: PPV even lower M Guembe et al. Clin Inf Dis 2010 28
  28. 28. Topics of today on diagnosis:1.  Maki versus sonication2.  The ins, outs and problems of D T T P3.  Surveillance surface cultures -  Previous study: Surface cultures taken at time of new episode of sepsis has good NPV -  But is physician able to standby for 48 hours in pnt with sepsis? Surveillance surface cultures may help 29
  29. 29. The challenge of anticipating catheter tip colonization in major heart surgery patients in the intensive care unit: Are surface cultures useful? Prospective study in 131 cardiosurgical ICU pts admitted for >4 days From day 5 on: Surveillance hub and insertion site skin cultures/3 days 561 catheters (CVC + AC + Sw-Ganz): 3712 surface cultures 133 positive tips, 15 CRBSIBouza E et al. Crit Care Med 2005; 33:1953–1960. 30
  30. 30. 130 patients studied: 15 CRBSI episodes 6 secundary BSI 10 primary BSI All CRBSI occurred with positive previous surface cultures 9 (60%) extraluminal, 3 (20%) endoluminal, 3 both Considering all previous skin and hub cultures as a single test: Se 100% (skin cultures only: 80%) Sp 64.7% PPV 7.2% NPV 100% (skin only: 98%)Bouza E et al. Crit Care Med 2005; 33:1953–1960. 31
  31. 31. Topics of today on diagnosis:1.  Maki versus sonication2.  The ins, outs and problems of D T T P3.  Surveillance surface cultures4.  When (not)to pull the trigger/CVC? Are there other ways to assist the ICU physician to standby for 48 hours at bedside of a patient with new episode of sepsis? 32
  32. 32. 100 consecutive ICU patients in which the physician had decided toremove the catheters for “suspected” catheter-related infection - Blood cultures through every line in place - Periferal blood culture - All catheters were removed (166 catheters) and cultured 3 (…) pnts with CRBSI (positive tip + positive peripheral blood cult.) 9 patients with non-CRBSI (negative tip + positive blood culture)Rijnders BJ et al. Crit Care Med 2001;29:1399-1403 33
  33. 33. = 63 with all negativeblood cultures 34
  34. 34. In every study that includes ICU patients with suspected CRI,the diagnosis can be confirmed during follow up in onlysmall minority e.g. 28 of 204 patients Clin Inf Dis feb. 2007. E. Bouza et al. 6 of 68 patients JAMA 2001;286(6):700-7. Merrer, J et al. 3 of 100 patients ! Crit Care Med 2001 Rijnders BJ et al. The art of removing catheters when suspicion is high The art of leaving catheters in place for FUO in a “stable” ICU patient
  35. 35. 80-90% of catheter removed in vain … 36
  36. 36. Is systematic catheter removal beneficial for every “suspected” catheter related infection ? Watchful waiting or Immediate catheter removal in ICU patients with suspected catheter-related infection ? Included: All consecutive ICU pts in which CVC change for suspected CR-infection was planned by the treating physician. Excluded:1. Haemodynamically unstable patient 2. Confirmed bacteremia 3. Suppuration or frank erythema at insertion site 4. <500/mm3 neutrophils, intravascular FBB Rijnders et al. Intensive Care Med 2004. Vol 30. p1073-80.C Brun-Buisson. Intensive Care Med 2004. Vol 30. p1005-7. 37
  37. 37. 38
  38. 38. Methods:Measurements: During the 10 days after inclusion : T, CRP, SOFA score WBC count, AB use was registered. All catheters were cultured when removed.Endpoints:•  Evolution of fever/SOFA score/CRP in SOC versus WW group ?•  Duration of ICU stay in WW versus SOC group ?•  Number of CVCs removed in WW versus SOC group ?•  Are exclusion criteria selecting for pts with CRBSI ? 39
  39. 39. Results:Study team was contacted for 144 patients64 of 144 pts (44.5%) could be included.Reasons for excluding 80 of 144 evaluated patients: (n=)Bloodstream infection 36HD unstable 31Inflamed/purulent ins. site 18High risk patient 12Other 4 40
  40. 40. Pts with suspec- ted CRI (n=144) 80 excluded (92 CVCs) No BSI (n=33) BSI (n=47) No CRBSI (n=27) CRBSI (n=20) 64 included (80 CVCs)SOC (n=32, 38 CVC) WW (n=32, 42 CVC) 41
  41. 41. Pts with suspec- ted CRI (n=144) 80 excluded (92 CVCs) No BSI (n=33) BSI (n=47) No CRBSI (n=27) CRBSI (n=20) 64 included (80 CVCs)SOC (n=32, 38 CVC) WW (n=32, 42 CVC)- 38/38 CVC removed - 16/42 CVC removed- 2 CRBSI - 3 CRBSI 42
  42. 42. SOC WWCVC changes 38/38 16/42 p<0.01CRBSI 2 3 p>0.2Duration of Hosp. 42 34 p>0.2ICU Mortality 10/32 8/32 p>0.2T (°C) d1 37.9 38.4 p=0.02 d5 37.6 37.6 p>0.2 d 10 37.5 37.4 p>0.2CRP (mg/l) d 1 128 155 p>0.2 d5 100 134 p>0.2 d 10 85 104 p=0.15SOFA score d 1 6.1 6.9 p>0.2 d5 5.4 6.2 p>0.2 d 10 5.3 5.8 p>0.2 43
  43. 43. SOC WWCVC changes 38/38 16/42 p<0.01CRBSI 2 3 p>0.2Duration of Hosp. 42 34 p>0.2ICU Mortality 10/32 8/32 p>0.2T (°C) d1 37.9 38.4 p=0.02 d5 37.6 37.6 p>0.2 d 10 37.5 37.4 p>0.2CRP (mg/l) d 1 128 155 p>0.2 d5 100 134 p>0.2 d 10 85 104 p=0.15SOFA score d 1 6.1 6.9 p>0.2 d5 5.4 6.2 p>0.2 d 10 5.3 5.8 p>0.2 44
  44. 44. DefinitionsCatheter-related sepsis:= Fever disappeared after catheter-removal (+/- positive tip)In many patients fever would have disappeared without catheterremoval anyway !Disappearance of fever does not prove that the catheter was the cause != ASPECIFIC DEFINITIONWatchfull waiting is a valid option 45
  45. 45. 1366 patients, 2101 catheters, 66 CRBSICNS CRBSI: Mortality with early (6/21) = late removal (3/9) P = 0.9Other CRBSI: Mortality with late (6/9) > early removal (7/27) P = 0.05Mortality not different in pts without septic shock: 18.2 vs. 25%; P = 0.450Garnacho-Montero J et al. Risk factors and prognosis of catheter-related bloodstream infection in critically ill patients:a multicenter study. Intensive Care Med. 2008 Dec;34(12):2185-93. 46
  46. 46. Topics of today on diagnosis:1.  Maki versus sonication2.  The ins, outs and problems of D T T P3.  Surveillance surface cultures4.  When (not)to pull the trigger/CVC? 47
  47. 47. Cost-effectiveness catheter diagnosis infectionSearch in pubmed 109English -91992-2012 -15Not on urinary, intracranial,peritoneal dialysis catheters -40Only on specifically on cost-E -39of CVC infection diagnosis =1 48
  48. 48. General issues:Too sensitive/aspecific testing => Costs of unnecessary treatment => Complications of unnecessary treatmentToo insensitive testing => Cost of longer hospital stay => Cost of missed diagnosis (S. aureus) 49
  49. 49. Cost-effectiveness of CRBSI diagnosis:JCM 1998: Blood Cultures Positive for Coagulase-Negative Staphylo-cocci: Antisepsis, Pseudobacteremia, and Therapy of Patients1000 USD additional treatment costs for pt with contaminated BCJAMA 1991: contaminant blood cultures and resource utilisation: Thetrue consequences of false pos. results4500 USD additional treatment costs for pt with contaminated BC ⇒  Attention to sterile technique !Non-tunneled CVC replacement (1995): 700USDBlood / tip / surface culture = 35 euro 50
  50. 50. QUESTIONS ? 51

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