Embed Size (px)
Citation preview
Accuracy and cost-effectiveness in diagnosis of CRBSI
BJ Rijnders, MD, PhD
Internal Medicine
Section Infectious Dis.
Erasmus MC
Rotterdam
The Netherlands
Amsterdam
June 2012
2
Accuracy of CRBSI diagnosis:
What is accurate?
Best possible sensitivity, specificity, PPV NPV, reproducibility But inevitably: very high sensitivity ≈ decrease in specificity / PPV
Accuracy of in vitro culture methods: Maki vs sonication vs other ?
Accuracy of in vivo culture methods: DTTP / surface cultures / other ?
General introduction
3
Accuracy 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
General introduction
4
Topics of today on diagnosis:
1. Maki versus sonication
2. The ins, outs and problems of D T T P
3. Surface Cultures Surveillance
4. When (not)to pull the trigger/CVC?
5
To roll or to sonicate?
6
6
Roll plate (Maki):
Sonication:
To roll or to sonicate?
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
Bouza E et al. Clin Inf Dis 2005
“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?
10
10
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 removed
Slobbe L et al. J Clin Microb 2009
11
11
Guembe M et al. J Clin Microb 2012
35 years after Maki’s publication: Maki DG et al. A semiquantitative culture method for identifying
intravenous catheter–related infection. N Engl J Med 1977; 296:1305–9.
Let’s keep on rolling !
To roll or to sonicate?
13
Topics of today on diagnosis:
1. Maki versus sonication
2. The ins, outs and problems of D T T P
3. Surveillance surface cultures
4. When (not)to pull the trigger/CVC?
14
In vivo diagnosis of CRBSI
i. Catheter brush: Don’t try this at home!
ii. Acridine orange leucocyte cytospin: Labour intensive
iii. Quantitive BC: Not available/labour intensive/expensive
iv. DTTP: Differential time to positivity
Qualitative BC with continuous CO2 measurement
- BacTalert - BacTec - …
B Rijnders et al. Crit Care Med 2001
15
16
e.g. 13.3 hrs - 8.3 hrs = DTTP 5.0
e.g. 13.3 hrs - 11.9 hrs = DTTP 1.4
In 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
DTTP = Time needed for the peripheral BC to become positive Minus
Time needed for the “catheter BC” to become positive
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 Raad I et al. Ann Intern Med. 2004; 140: 18-25.
20 (1) T Barton et al. Ann Intern Med 2004 (2) Desjardin JA et al. Ann Intern Med. 1999
“Although the test seems to have excellent sensitivity and specificity, the authors do not discuss the consequences of the sample collection strategy required 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
21 Bouza E Clin Inf Dis 2007
ICU 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
A Randomized and Prospective Study of 3 Procedures for the Diagnosis of Catheter-Related Bloodstream Infection without Catheter Withdrawal
22 Bouza E Clin Inf Dis 2007
A Randomized and Prospective Study of 3 Procedures for the Diagnosis of Catheter-Related Bloodstream Infection without Catheter Withdrawal
CONCLUSION: CR-BSI can be assessed without CVC withdrawal in ICU pts who have catheters inserted for a short time
Convenience, use of resources, and expertise should determine choice
Because of ease of performance, low cost, and wide availability, we recommend combining superficial cultures and peripheral BC to screen for CR-BSI, leaving DTTP as a confirmatory and more specific technique.
23 Bouza E Clin Inf Dis 2007 Rijnders BJ Clin Inf Dis 2007
BUT:
⇒ 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
A Randomized and Prospective Study of 3 Procedures for the Diagnosis of Catheter-Related Bloodstream Infection without Catheter Withdrawal
24
All studies in English literature that prospectively examined the risk of BSI associated with arterial catheters and provide sufficient data to calculate a rate of infection per 100 catheters and 1000 days.
What about the arterial line ?
Data from Safdar N, Maki DG et al unpublished
25
2.0/1000
catheterdays
2.7/1000
catheterdays
for CVC
Versus
Data from Safdar N, Maki DG et al unpublished
What about the arterial line ?
J Infect. 2011 Aug;63(2):139-43. Esteve F et al. 26
What about the arterial line ?
Traore O et al. Crit Care Med 2005.
Prospective study of arterial and central
venous catheter colonization and of
arterial- and central venous catheter-
related bacteremia in intensive care units.
Rijnders BJ. Crit Care Med 2005. Catheter
related infection can be prevented? If we
take the arterial line seriously too!
Rupp ME. Crit Care Med 2011. Arterial
catheters: “They don’t get no respect” Pirracchio R et al. Crit C
are Med 2011.
Arterial catheter-related bloodstream
infections: results of an 8-year survey in
a surgical intensive care unit.
Most recent large study on incidence of arterial catheter related BSI:
Barcelona, Spain
A total of 1543 AC were inserted for 14,437 catheter days.
The incidence of AC-related bloodstream infections (ACR-BSI) was 3.53 episodes per 1000 catheter days.
27 M Guembe et al. Clin Inf Dis 2010
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 1 lumen in double lumen CVC led to missed diagnosis in 27%
Eliminating 2 lumina in triple lumen CVC led to missed diagnosis in 32%
28 M Guembe et al. Clin Inf Dis 2010
BUT:
Sampling all lumina => Optimal sensitivity
Sampling all lumina => much more false positive/contamination
=> decrease in specificity / PPV
In low incidence setting: PPV even lower
29
Topics of today on diagnosis:
1. Maki versus sonication
2. The ins, outs and problems of D T T P
3. 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
30
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 CRBSI
Bouza E et al. Crit Care Med 2005; 33:1953–1960.
31
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.
32
Topics of today on diagnosis:
1. Maki versus sonication
2. The ins, outs and problems of D T T P
3. Surveillance surface cultures
4. 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?
33 Rijnders BJ et al. Crit Care Med 2001;29:1399-1403
100 consecutive ICU patients in which the physician had decided to
remove 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)
34
= 63 with all negative blood cultures
In every study that includes ICU patients with suspected CRI,
the diagnosis can be confirmed during follow up in only
small 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
36
80-90% of catheter removed in vain …
37
Is systematic catheter removal beneficial for every “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 FB
Watchful waiting or Immediate catheter removal
in ICU patients with suspected catheter-related infection ?
B Rijnders et al. Intensive Care Med 2004. Vol 30. p1073-80. C Brun-Buisson. Intensive Care Med 2004. Vol 30. p1005-7.
38
39
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 ?
40
Results:
Study team was contacted for 144 patients
64 of 144 pts (44.5%) could be included.
Reasons for excluding 80 of 144 evaluated patients:
(n=) Bloodstream infection 36 HD unstable 31 Inflamed/purulent ins. site 18 High risk patient 12 Other 4
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)
42
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 - 2 CRBSI
- 16/42 CVC removed - 3 CRBSI
43
SOC WW
CVC changes 38/38 16/42 p<0.01 CRBSI 2 3 p>0.2 Duration of Hosp. 42 34 p>0.2 ICU Mortality 10/32 8/32 p>0.2 T (°C) d 1 37.9 38.4 p=0.02 d 5 37.6 37.6 p>0.2 d 10 37.5 37.4 p>0.2 CRP (mg/l) d 1 128 155 p>0.2
d 5 100 134 p>0.2 d 10 85 104 p=0.15 SOFA score d 1 6.1 6.9 p>0.2 d 5 5.4 6.2 p>0.2 d 10 5.3 5.8 p>0.2
44
SOC WW
CVC changes 38/38 16/42 p<0.01 CRBSI 2 3 p>0.2 Duration of Hosp. 42 34 p>0.2 ICU Mortality 10/32 8/32 p>0.2 T (°C) d 1 37.9 38.4 p=0.02 d 5 37.6 37.6 p>0.2 d 10 37.5 37.4 p>0.2 CRP (mg/l) d 1 128 155 p>0.2
d 5 100 134 p>0.2 d 10 85 104 p=0.15 SOFA score d 1 6.1 6.9 p>0.2 d 5 5.4 6.2 p>0.2 d 10 5.3 5.8 p>0.2
45
Catheter-related sepsis:
= Fever disappeared after catheter-removal (+/- positive tip)
In many patients fever would have disappeared without catheter
removal anyway !
Disappearance of fever does not prove that the catheter was the cause !
= ASPECIFIC DEFINITION
Watchfull waiting is a valid option
Definitions
46 Garnacho-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.
1366 patients, 2101 catheters, 66 CRBSI
CNS CRBSI: Mortality with early (6/21) = late removal (3/9) P = 0.9
Other CRBSI: Mortality with late (6/9) > early removal (7/27) P = 0.05
Mortality not different in pts without septic shock: 18.2 vs. 25%; P = 0.450
47
Topics of today on diagnosis:
1. Maki versus sonication
2. The ins, outs and problems of D T T P
3. Surveillance surface cultures
4. When (not)to pull the trigger/CVC?
48
Cost-effectiveness catheter diagnosis infection
Search in pubmed 109
English -9
1992-2012 -15
Not on urinary, intracranial, peritoneal dialysis catheters -40
Only on specifically on cost-E -39 of CVC infection diagnosis
= 1
49
General issues:
Too sensitive/aspecific testing
=> Costs of unnecessary treatment
=> Complications of unnecessary treatment
Too insensitive testing
=> Cost of longer hospital stay
=> Cost of missed diagnosis (S. aureus)
50
Cost-effectiveness of CRBSI diagnosis:
JCM 1998: Blood Cultures Positive for Coagulase-Negative Staphylo-cocci: Antisepsis, Pseudobacteremia, and Therapy of Patients
1000 USD additional treatment costs for pt with contaminated BC
JAMA 1991: contaminant blood cultures and resource utilisation: The true consequences of false pos. results
4500 USD additional treatment costs for pt with contaminated BC
⇒ Attention to sterile technique !
Non-tunneled CVC replacement (1995): 700USD
Blood / tip / surface culture = 35 euro
51
QUESTIONS ?
