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Treatment of catheter-related infections. Jean-François TIMSIT CHU Albert Michallon Université Joseph Fourrier, INSERM U578, Grenoble France. Slides available on http://www.outcomerea.org. Epidemiology of catheter-related bacteremia in HD patients Allon M – Am J Kidney Dis – 2004; 44:779.

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Treatment of catheter related infections l.jpg

Treatment of catheter-related infections

Jean-François TIMSIT

CHU Albert Michallon

Université Joseph Fourrier, INSERM U578, Grenoble France

Slides available on http://www.outcomerea.org


Epidemiology of catheter related bacteremia in hd patients allon m am j kidney dis 2004 44 779 l.jpg

Epidemiology of catheter-related bacteremia in HD patientsAllon M – Am J Kidney Dis – 2004; 44:779


Slide3 l.jpg

Epidemiology of catheter-related bacteremia in HD patientsAllon M – Am J Kidney Dis – 2004; 44:779

  • 25% of the 300,000 US HD patients

  • 2-fold: infection-related hospitalization and death

  • 2.5 to 5.5 cases/1000 pts days = 0.9 to 2 episodes/patient-year

     67,500 to 150,000 episodes/year

     10%= 7,000 to 15,000 with serious complications


Cr infection in hd patients l.jpg

CR- Infection in HD patients

  • 11.7% of septicemia in HD pts

  • Temporary uncuffed cath. 1.6 to 7.7 bacteremias / 1000 catheter-days

  • Tunneled or cuffed cath. 0.2 to 0.5 bacteremias / 1000 catheter-days

  • Staphylococci coag neg. 40-77%, methicillin resistant 40-75%

  • Enterococci, gram neg rod.

  • Metastatic complications: 8.7 to 50% (med 25%)

    • Studies

    • Microbes

    •  cuffed cath.

Peleman et al – Nephrol dial transplant 2000; 15:1281


Complications associated with cuffed hd cath nephrol dial transplant 2001 16 2194 l.jpg

Complications associated with cuffed HD Cath. Nephrol Dial transplant 2001; 16:2194

1 episode of CRS per 25.6 Pts months

24% in the first insertion week


Slide6 l.jpg

CR- Infection in HD patients


Slide7 l.jpg

Contamination

From the hub

Cross contamination

Cutaneous flora

Extraluminal cutaneous Colonization

SKIN

VEIN

Hematogeneous Colonisation

Mechanisms of colonization

From Maki DG et coll., in "Hospital Infections", Bennett JE & Brachman PS, 1992, 849-98.


Slide8 l.jpg

Extraluminal Colonization

Short term CVCs

Colonisation

Of the endoluminal surface

Long term CVCs

Slime


Predisposing factors l.jpg

Predisposing factors


Spectrum of crbsi associated bacterial flora l.jpg

Spectrum of CRBSI associated bacterial flora

Saxena AK et al – Swiss Med Wkly 2005; 135:127


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Spectrum of CRBSI associated bacterial flora


Crs the treatment is depending on the l.jpg

CRS : The treatment is depending on the

  • Severity of the sepsis

  • Underlying illness (immunosuppression, prothesis).

  • Micro-organisms identified or suspected

  • Results of the blood cultures (positive or not).

  • Need and easiness of a central venous access


Crs what should be the questions l.jpg

CRS: What should be the questions?

  • What should be done with the CVC?

  • Should we prescribe systemic antimicrobials ?

  • If Yes, which one?

  • What should be done in case of failure ?

  • What should be the duration of treatment ?


Slide15 l.jpg

  • What should be done with the CVC?

  • Should we prescribe systemic antimicrobials ?

  • If Yes, which one?

  • What should be done in case of failure ?

  • What should be the duration of treatment ?


What should be done with the catheter l.jpg

What should be done with the catheter ?

Two constraints :

To avoid useless removal of CVCs (75% cases) and further risks of catheter insertion

 To save patients and avoid complications of infection


Crb diagnosis in hd patients l.jpg

CRB diagnosis in HD patients

  • 59-81% of HD patients with fever or chills have positive BC

  • ¾ related to CRI (pneumonia, foot infections)

  • Use DTP methods (???)

    • When? before dialysis session, during the session?

    • BC via peripheral vein often difficult (39%)

  • Significance of a positive BC via the cath. Lumen?

  • Bacteriologic evaluation in freestanding HD units?

    Classification system:

    Definite: C/P quantitative BC> 10

    Probable: Positive BC and no evidence of other infectious site

    Possible: neg BC and resolution of fever at CVC removal


2 situations l.jpg

Severe sepsis of unknown origin

Catheter removal

(or Guidewire exchange)

Which antimicrobials?

How to diagnose complications?

Fever, chills without severe sepsis

Positive blood culture

Is it possible to keep the CVC without risks?

2 situations


Slide19 l.jpg

Type et incidence of severe complications (n = 102)

Shock Sepsis Thrmb. Sept. Other Total (%)*

CNS3 1 1 1 6/33 (18)

S. aureus3 3 4 812/32 (38)

Enterococci0 0 0 0 0/3

GNB2 0 0 0 2/10 (20)

P.aeruginosa1 0 1 0 2/4 (50)

Candida spp.0 7 0 0 7/11 (64)

Polymicrob.2 1 1 0 4/9 (44)

* Nb Complications/Nb of events

Arnow PM et al. 1993 Clin Infect Dis


Is catheter removal associated with a higher cure rate and with an improved outcome l.jpg

Is catheter removal associated with a higher cure rate and with an improved outcome?


Slime production scn 24h cellulose x 5000 l.jpg

The Slime…

Slime production (SCN) 24h cellulose (x 5000)

SCN culture


Cns carsenti etesse 2000 l.jpg

MICs (107 cfu/ml) (mg/l)

MHSlime

1.566.254

6.25>100>32

0.1912.564

1.562516

0.79>100>126

0.792532

CNS-Carsenti-Etesse 2000

Oxacillin

Vancomycin

Clindamycin

Ciprofloxacin

Gentamicin

Netilmicin

MBC of attached bacterias increased by 128-256 fold

1- Bacterias with slime production have an increased MICs and MBCs to ABt

2- The Biofilm increase the resistance of bacteria to ABt


Slide23 l.jpg

Catheter removal and duration of candidemia

Rex et al

-Decrease of the duration of the candidemia

New site 5.6 days vs Other 2.6 days

- Bias:

APACHE II 14.5 vs 16.9 p=0.03

Other catheter: 1.2 vs 1.8,p<0.001

- GWX: 6.3 + 1.8 j

Catheter removal should be prefered


Slide24 l.jpg

Candidemia: CVC Removal and mortality

Nguyen et al - Arch Intern Med 1995;155:2429

427 consecutive patients with candidemia

Multicentric prospective study

MortalityKT removed: 21% vs KT in place: 41%

p<0.001

Microbio failure (multivariate analysis)

Neutropenia0.002

Intra-abdo0.02

KT left in place0.05

Mortality (multivariate analysis)

ICU patients<0.001

Age > 60 y0.004

Steroïds0.02

Candidal pulmonary metastasis<0.001

KT left in place<0.001


Candidemia cvc removal and mortality meta analysis l.jpg

Candidemia: CVC removal and mortality: meta-analysis

  • 4 studies with severity scores adjustment

    Anaissie 1998 (n=491) Retroadjusted OR: 2 (1.4-2.9, p=0.06)

    Nucci 1998 (n=54) Proadjusted OR:

    Nucci (2) 1998 (n=145) Proadjusted OR: 4.22 (2-11.6)

    Luzzatti 2000 (n=189) retroadjusted OR: 1.61 (1.01-2.63, p=0.047)

    Analyses are biased because CVCs removal is associated with severity…

Nucci – Clin Infect dis 2002; 34:591


Management of cvcs in patients with cancer and candidemia raad i et al clin infect dis 2004 38 1119 l.jpg

Management of CVCs in patients with cancer and candidemia Raad I et al – Clin Infect Dis 2004; 38:1119

  • 1993-1998:

  • 404 episodes of candidemia (50% ICU) with 1 CVCs for more than 1 days

    • 3 categories

      • Primary candidemia : 241 (60%)

      • Secondary candidemia: 52 (13%)

      • CVC related candidemia : 111 (27%)

        • + tip cult (66) or quantitative BC > 5:1 (45)

%


Is candidemia catheter related raad i et al clin infect dis 2004 38 1119 l.jpg

Is candidemia catheter-related? Raad I et al – Clin Infect Dis 2004; 38:1119

  • 111 catheter-related candidemia and 52 secondary candidemia

    No CS within 1 month: OR 3.5 (1.3-9.4), p=0.02

    No chemotherapy within 1 month: OR 4.3 (1.5-13.3), p<0.01

    Non disseminated infection *OR 9.7 (3.5-26.3), p<0.01

    Good response to antifungal therapy*OR 2.9 (2.2-7.2), p=0.03

(*) Dissemination to non contiguous sites

Resolution of fever and chills, BC neg.


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Outcome of candidemia: time of catheter removal after the first positive culture Raad I et al – Clin Infect Dis 2004; 38:1119


Predictors of failure to respond to antifungal therapy raad i et al clin infect dis 2004 38 1119 l.jpg

Predictors of failure to respond to antifungal therapy Raad I et al – Clin Infect Dis 2004; 38:1119


Proposed algorythm for candidemia raad i et al clin infect dis 2004 38 1119 l.jpg

Proposed algorythm for candidemia Raad I et al – Clin Infect Dis 2004; 38:1119


Biofilm production and antifungal effects l.jpg

Biofilm production and antifungal effects

  • In the biofilm (C. albicans and C. glabrata):

    • AMPHO B > Voriconazole > fluconazole

  • Regrowth was noted in the biofilm

    Lewis et al – Antimicrob Agent Chemother 2002; 3499

  • Killing of the biofilm cells better with eichinocandins (caspofungin)

    Kuhn DM - Antimicrob Agent Chemother 2002; 1773

    Ramage R - Antimicrob Agent Chemother 2002; 3634

    Bachmann SP- Antimicrob Agent Chemother 2002;3591


Fungal biofilm and drug resistance l.jpg

Fungal biofilm and drug resistance

  • Mechanism not completely understood

  • Biofilm cells resist > planktonic cells?

  • Role of few persisters cells

    • Grew slowly in the presence of antimicrobials,

    • A particular resistance to program cell death (apoptosis) induced by antimicrobials?


S aureus bacteremia catheter removal l.jpg

S. aureus bacteremia: Catheter removal?

  • 50 CRB (retrospective)

  • Long-term (16) or short-term (34) CVCs

%

P=0.01

Malanovski GJ - Arch Intern Med 1995;155:1161


65 s aureus bacteremia in hd patients l.jpg

65 S. aureus bacteremia in HD patients

Marr et al – Kidney Int 1998; 54:1684


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Absence of catheter removal is an independent predictor of treatment failure in Catheter-related-S aureus bacteremia Fowler et al – Clin Infect Dis 1998; 27:478

244 patients

  • Advices by the infectious diseases department

  • 12-month follow up

  • Advice followed: 112 pts (49.5%)

    Perform TEE, removed infected intravascular devices, perform surveillance BC, use beta-lactam as often as possible (MSSA)


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HD is significantly associated with hematogeneous complications (multivariate analysis) Fowler et al – Clin Infect Dis 2005; 40:695


In vivo biofilm bacterial killing wilcox mh et al j antimicrob chemother 2001 47 171 l.jpg

In vivo biofilm-bacterial killingWilcox MH et al – J antimicrob Chemother 2001; 47:171

  • 50 µl blood: acridine orange Gram pos HD biofilm + quantitative colony count (100 µl of blood)

  • HD cath removed : VAN 1g 2 hours and then 10 ml flush of 0.9% saline

  • Endoluminal biofilm recovered using special brushes

    Eradication failed+++

    Uge variation of biofilm VAN level (0.2-89 mg/g!!)

    Reduction of 84-100% bacterial count (med 95%) with VAN and

    Reduction of 0-98% (med 91%) with LNZ


Slide38 l.jpg

LNZ, VAN, GEN, eperezolid in vitro S. epidermidis catheter-related biofilm infectionsCurtin J et al – Antimicrob Agent Chemother 2003; 47:3145

  • Biofilm: modified rubbins device 12 sampling ports of 50 mm2 + SE ATCC 35984 + continuous flow of MH broth 24 hours + 24 hours of sterile MH broth feeding

  • AB lock of VAN (10mg/ml),LNZ (4),GEN (10),EPZ (2mg/ml) 24, 72, 168 and 240 hours


149 patients with bacteremia pseudomonas spp et xanthomonas elting et al medicine 1990 69 296 l.jpg

149 Patients with bacteremia (Pseudomonas spp et Xanthomonas)Elting et al - Medicine 1990;69:296

%

P<0.00001

49/49

4/4

32/62

2/6


Coagulase negative staphylococci raad et al iche 1992 l.jpg

Coagulase negative staphylococciRaad et al ICHE 1992

70 patients

Cath. removed

n=36

Catheter not removed

n=34

4 Deaths due to sepsis

4 Deaths due to sepsis

6 bacteremia recurrences after 3 months

1 bacteremia recurrence after 3 months


Enterococcal cr bsi sandoe ja jac 2002 50 577 l.jpg

Enterococcal CR-BSISandoe JA –JAC 2002; 50:577

  • 3-year cohort (n=268)  61 CRBSIs

Cured

4

2

100

1

27

76

0

11

65

45

Failed

0

0

0

1

4

13

0

2

10

7

Recurred

0

0

0

3

1

11

4

1

25

9

Appropriate cell wall agent + aminoglycoside

Catheter maintained (n=4)

Catheter removed (n=2)

%

Appropriate cell wall agent alone

Catheter maintained (n=5)

Catheter removed (n=30)

%

Inappropriate or no antimicrobial

Catheter maintained (n=4)

Catheter removed (n=16)

%

Total


Crb and dialysis catheter removal l.jpg

CRB and dialysis: catheter removal?

102 patients

41 pts/62 bacteremias

  • 102 patients/16081 days tunneled cath.

  • 62 bacteremias (30% MRSA, 33 % other Gram+, 24% GNB, 5% P. aeruginosa)

38 without removal

24 removal< 3 days

12 success

9/41 (22%) complications

always Gram+ (4 IE, 6 osteomyelitis, 1 arthritis)

26 failures

6 catheter removed without infection

6 cath still in place (3 months)

Maar KA Ann. Intern Med 1997;127:275


Crb and cvc removal l.jpg

CRB and CVC removal

  • The CVC maintained

  • Success: Gram + 6/26 (23%) vs Gram- 6/12 (50%) (NS)

  • NOT associated with more secondary infections/deaths

    RR:0,8, IC95%, 0,2-2,7

  • BUT with more relapses:

    68% vs 17% (RR:4,1, IC95%, 1,6-10,3)

  • Marr et al - Ann. Intern Med 1997;127:275


Tunnelitis antimicrobials alone l.jpg

Tunnelitis Antimicrobials alone

Microorganisms Cured Failures

(n=5) (n=15)

S. aureus11

P. aeruginosa0 7

polymicrobial1 5*

Negative culture3 2

* 4 with P. aeruginosa et 1 with P. maltophilia

Benezra et al, Am. J. Med., 1988, 85, 495


Catheter removal yes vs no l.jpg

Catheter removal: Yes vs No

  • S. aureus: 50 CRB (retrospective)

    • Persistent BC:11 vs 56% (p=0.01), Deaths: 5 vs 20%

      Malanovski GJ - Arch Intern Med 1995;155:1161

  • X. maltophilia:

    • % cured: 49/49 vs 32/62 (p<0.0001)

      Elting et al - Medicine 1990;69:296

  • Gram negative bacili

    • % relapse: 1/67 vs 5/5 (p<0.001)

      Hanna et al – ICHE 2004; 25:646

  • Enterococci (n=61)

    • % cured: 5/13 vs 40/47 (p<0.01)

    • especially if aminoglycosides are not associated with cell-wall agent

      Sandoe JA –JAC 2002; 50:577

  • CNS:

    • Deaths: 4/36 vs 4/34, recurrence after 3 months: 1/36 vs 6/34

      Raad et al ICHE 1992


Crb cvc removal or not l.jpg

CRB:CVC removal or not

Situation/microorganism CVC maintained

Severe Sepsis No

Local signs No

Thrombosis (Doppler)No

S. aureus No

Pseudomonas No

Candida sp No

CNS and no severe sepsis Yes

Other Gram neg. ???


Recommendations l.jpg

Recommendations

  • Catheter removal

    • Exit site or tunnel infections

      Preferentially catheter change

  • If impossible

    • Catheter salvage attempted

      • With BC (peripheral and via the catheter)

      • 2-day AB trial

      • If fever>2 days or hemodynamic unstability: catheter removal

  • If persistent fever or positive BC after catheter removal: metastatic complications

Peleman et al – Nephrol dial transplant 2000; 15:1281


The cvc l.jpg

The CVC…

1. CVC removal

2. Diagnosis catheter in place

3. Guidewire exchange (GWX)


Slide49 l.jpg

Watchful waiting vs immediate CVC removal in the ICU - Rijnders BJ et al – Intens Care Med 2004; 30: 1073-80

Exclusion:

Neutropenia, foreign body, transplantation

BSI (positive BC)

Erythema, induration or purulence

HD instability

Previous DNR


Slide50 l.jpg

Watchful waiting vs immediate CVC removal in the ICU - Rijnders BJ et al – Intens Care Med 2004; 30: 1073-80 (2)


Limitations l.jpg

limitations

  • Weak and subjective exclusion criterias

  • Low power

  • Rate of non bacteremic sepsis not reported

  • Decrease in the rate of suspicion of CR-BSI during the study:

  • First half 85/704 vs 2nd half 59 / 790 p=0.003

Rijnders BJ et al – Intens Care Med 2004; 30: 1073-80


The cvc52 l.jpg

The CVC ?

  • 1. CVC removal

  • Diagnosis catheter in placeCutaneous swabsBC with quantitative cult. or differential time to positivity

  • 3. Guidewire exchange (GWX)


The cvc53 l.jpg

The CVC ?

1. CVC removal

2. Diagnosis catheter in place

3. Guidewire exchange (GWX)


New site vs guidewire exchange complications l.jpg

New site vs Guidewire exchangecomplications

New

(n=76 Pts)

3

2

3

1

11

2

GWX

(n=84 Pts)

3

2

0

0

15

6

Pneumothorax

Arythmia

Suspected thrombosis

Bleeding

Colonization

BSI

Cobb N. Eng J Med 1992; 327:1062


New site vs guidewire exchange metaanalysis 8 trials l.jpg

New site vs Guidewire exchange(metaanalysis: 8 trials)

Catheter colonization 1.26 [0.87-1.84]

Catheter exit site infection1.52 [0.34-6.73]

Catheter- related bacteremia1.72 [0.89-3.33]

Cook DJ Crit Care Med 1997;25:1417


Guidewire exchange gwx l.jpg

Guidewire exchange (GWX)

1. When to start antimicrobials?

 Before the guidewire exchange

2. Attitude with the second CVC

 Keep it if culture neg.

 Remove ot if culture pos.

 It might be possible to keep the 2nd CVC in case of CNS or Enterobacteriaceae????


Gwx vs ab plus delayed replacement hd tanriover b et al kidney international 2000 57 2151 l.jpg

GWX vs AB plus delayed replacement (HD)Tanriover B et al – Kidney International 2000; 57:2151

  • Retrospective

  • Birmingham, Alabama

  • Removal if: severe sepsis, exit site infection

  • GWX plus a creation of a new tunnel

  • AB 3 wks

  • Femoral HD cath in the interim

GWX

Del. repl


Slide58 l.jpg

Cost effectiveness of 3 strategies of managing tunnelled cuffed HD cath with mild or asymptomatic bacteremiasMokrzycki et al – Nephrol Dial Transplant 2002; 17:2196

Cost/effectiveness

Salvage: 11579 $/ 89% 3month surv

GWX 6338 $/ 93.2%

Removal 7088 $ / 93%


Crs what should be the questions59 l.jpg

CRS: What should be the questions?

  • What to do with the catheter?

  • Should we always prescribe systemic antimicrobials ?

  • If Yes, Which one?

  • What should be done in case of failure ?

  • What should be the duration of treatment ?


Crb due to xanthomonas ou pseudomonas spp elting et al medicine 1990 69 296 l.jpg

CRB due to Xanthomonas ou Pseudomonas sppElting et al - Medicine 1990;69:296

AB appropriate

% cured

AB inappropriate

33/33

6/6

45/52

7/16

CVC removed

CVC left in place


Antimicrobials l.jpg

Antimicrobials

  • Always if severe sepsis or septic shock

  • Positive blood cultures

  • - Yes, always

    • For CNS (2 positive BC)

    • In case of negative BC ????


Antimicrobials bc neg l.jpg

Antimicrobials (BC neg)

SituationAntimicrobials

Candida spp, S. aureus or P. aeruginosa

Sepsis after CVC removalYes

No fever after CVC removalNo ?

Other micro-organisms

 Fever after CVC removalNo*

If GWX or CVC in placeYes

__________________________________________________

* Except immunosuppression


Antibiotic lock in icu l.jpg

Antibiotic lock in ICU?

  • Antimicrobial concentration high (X 50 to 100)

  • Volume 2 ml (+ héparine if vanco, cipro, teico)

  • Anticrobials stable: (even with heparine)

    • vanco, cefazolin, ticar-clavu,cipro (Anthony et al, AAC 1999;2074)

  • CVC use is impossible during the lock…

  • Injection 2 fold a day, for 2 to 3 weeks

  • Associated IV antimicrobialsContra-indications: fungal infections, neutropenia, thrombophlebitis, tunnelitis, septic shock

    Very rarely in ICU


Slide64 l.jpg

AB heparin lock solution: in vitro biofilm model 2 ABx better than only oneVercaigne LM et al – J antimicrob Chemother 2002; 49:693

  • 2.5 106 cfu of 4 MRSE strains: 24 hours 37°C, MH broth

  • Heparine 5000 IU/ml, GEN 5 mg/ml, VAN 10mg/ml, CEF 10 mg/ml

    Monotherapy less effective:

    H863: VH and CH  >97% kill

    H900: VH and CH  >96% kill


Antibiotic lock for cvcs l.jpg

Antibiotic lock for CVCs

Antibio

Vanco,AMK,Minocycline/12h

Teico /j

AMK, AmphoB, Amoxi-genta

Results

cured 92%

Relapse: 7%

Cured 100%

Relapse 36%

Cured 83%

I. V. AB

18/49

2days

If leucopenia (2)

Messing 91

N=49

Mc Carty 95

N=11

Johnson 94

N=12

Patients with severe sepsis were excluded

CNS or Enterobacteriaceae,

Contra-indications: yeast, S. aureus, Pseudomonas

immunosuppression, tunnelitis, severe sepsis


Maintien du cath ter l.jpg

Maintien du cathéter

Alimentation parentérale


Abx lock in hd patients krishnasami et al kidney intern 2002 1136 l.jpg

Abx lock in HD patientsKrishnasami et al – Kidney Intern 2002;1136

Success= absence of recurrent fever and negative surveillance culture

Overall complications: 11/62 (18%)

septic shock 5

arthtritis 2

endocarditis 3

spinal osteomyelitis 1

Cath exchange

+ ABx

1 candida arthritis

1 death:

fungal endocarditis


Abx lock in hd patients krishnasami et al kidney intern 2002 113668 l.jpg

Abx lock in HD patientsKrishnasami et al – Kidney Intern 2002;1136

Further infection-free cath survival compared to historical controls

P=0.54

Further overall cath survival compared to historical controls

P=0.24


Antibiotic lock in hd patients poole cv et al nephrol dial transplant 2004 19 1237 l.jpg

Antibiotic lock in HD patientsPoole CV et al – Nephrol Dial Transplant 2004; 19:1237

  • Vanco+cefta IV (3wks) + AB lock

  • Failure: fever or BP instablility >48h, + BC> 1wk

  • 141 CRB suspected: 83 + BC,

  • 97 pathogens (72% Gram pos.)

  • 19 (23%) concurrent exit site infection

  • Exclusion: Enterococcus sp (15), Candida (0)

  • Success rate:

    • Gram neg: 13/15 (87%)

    • SE: 12/16 (75%)

    • S. aureus: 4/10 (40%)


Slide70 l.jpg

Antibiotic lock in HD patientsPoole CV et al – Nephrol Dial Transplant 2004; 19:1237

AB lock

CVC replac. (Historical ctrl)


Ab lock when it should not be done l.jpg

AB lock: when it should not be done?

  • Severe local infection

  • Rods: fungus, S. aureus, GNB?.

  • Fever > 48 hours

  • Relapse

  • When alternative is easy

It is not to date a routine treatment modality…


Slide72 l.jpg

AB lock : what is possible?Berrington et al – J Antimicrob Chemother 2001; 48:597Droste et al - J Antimicrob Chemother 2003; 51:849

  • Have been tried:

    • Vancomycin (50 mg/ml), teicoplanin (133 mg/ml)

    • Gentamicin (40 mg/ml), amikacin (250 mg/ml)

    • Ampicillin, nafcillin, mezlocillin, cefotaxime, ceftazidime, ceftriaxone

    • Erythromicin, clindamycin

  • Know biocompatibility with heparin

    • vancomycin, cefazolin, ceftazidime, gentamicin (<4mg/ml).

  • Known precipitates (depends on the heparin concentration)

    • ciprofloxacin + heparin

  • Fibrinolytic:

    • no data


Catheter strategies in hd patients summary uncontroled studies allon m am j kidney dis 2004 44 779 l.jpg

Catheter strategies in HD patients: summary (uncontroled studies) Allon M – Am J Kidney Dis – 2004; 44:779


A more pragmatic approach beathard ga j am soc neprol 1999 1045 l.jpg

A more pragmatic approach Beathard GA – J Am Soc Neprol 1999;1045

+

4 complications (2 arthritis or abscess, delay), (2 endocarditis, delay)


Crs what should be the questions75 l.jpg

CRS: What should be the questions?

  • What to do with the catheter?

  • Should we always prescribe systemic antimicrobials ?

  • If YES, which one?

  • What should be done in case of failure ?

  • What should be the duration of treatment ?


Choice of the molecules l.jpg

Choice of the molecules

Situations

active on CNS

If severe, consider immediately GNB and yeast

Molecules

Glycopeptide + gentamicin

If GNB suspected: activity against P. aeruginosa

Candida: Fluconazole (or amphotéricine B)

Antimicrobials shoud be adapted to blood and catheter cultures


Vancomycin in s aureus cr bsi in hd patients l.jpg

Vancomycin in S. aureus CR-BSI in HD patients

  • Vancomycin alone may be less effective than when combined with another antistaphylococcal drug

  • Slow bactericidal activity, less active than methicillin on methicillin susceptible S. aureus

  • Emergence of GISA


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Epidemiology is varying according to years…

From U.H.L.I.N Bichat: I Lolom, JC Lucet


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Causes varies according to outbreaks…

from U.H.L.I.N Bichat: I Lolom, JC Lucet


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Fluconazole vs Ampho B for the treatment of Candidemia in non-neutropenic patients

  • FluconazoleAmpho B

  • n = 103 n = 103

  • Efficacy 70 % 79 % p = 0.22

  • Uncleared 14.5 % 12 %

  • bloodstream ( 15 pts )( 12 pts )

  • infection

  • Mortality 33 % 40 % p = 0.20

    • NOTES : - 64 % of infections were due to Candida albicans

      • - IV catheters were reponsible for 72 % of all episodes of candidemia

    • Rex et al N Engl J Med 1994 ;331:1325


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    Fluconazole or Ampho B

    Patient is stable

    • Ampho B 0.5 - 0.7 mg/kg/day or Fluconazole 400 mg/day

      Patient is unstable

    • Ampho B 0.7 - 1.0 mg/kg/day or/andFluconazole 600 - 800 mg/day

  • (+ flucytosine 100 - 150 mg/kg/day ?)

    C. krusei, C. glabrata, C. lusitaniae infections

    • Ampho B 0.5 - 1.0 mg/kg/day (+ flucytosine ?)

      Treatment duration : 10 to 14 days (at least)

  • Fluconazole switch to oral treatment after 3 - 5 days

  • Pittet, Garbino, Anaissie, Solomkin - Yearly Handbook of Emerg Crit Care Med 1996


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    CRS: What should be the questions?

    • What to do with the catheter?

    • Should we always prescribe systemic antimicrobials ?

    • If Yes, which one?

    • What should be done in case of failure ?

    • What should be the duration of treatment ?


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    CRS : failure

    Pharmacologic failure

    MRSA/glycopeptides

     Thrombophlebitis

    New CVC colonization

    Other septic foci (endocarditis+++)


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    Vancomycin

    Pharmacocinetic variable and unpredictable: Dosage+++

    Low level associated with failure

    Maintain trough > 15-20 µg/ml especially if MIC > 1 µg/ml

    Consider association: Gentamicin if possible, rifampin, linezolid?, dalfopristin-quinupristin?


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    Septic thrombophlebitis

    • Clinically silent

    • Ultrasound Doppler.

    • Ligation of the vein: very invasive, rarely indicated

    • Optimizing the antimicrobial :

      • Antibiotic dosing, 2 antimicrobials

      • Longer duration: 4-6 weeks

  • Heparin and fibrinolytic ?


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    Trans-oesophageal echography and S.aureus

    n

    26

    *

    7

    * P < 0,0005

    Adapted from Fowler et al. JACC 1997


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    TTE and TEE in HD patients with S.aureus bacteremia Marr et al - Kidney Intern. 1998: 1684

    28 TTE with normal findings 8 abnormal TEE:

    2 anatomics Abnormalities and 6 vegetations


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    CRS: What should be the questions?

    • What to do with the catheter?

    • Should we always prescribe systemic antimicrobials ?

    • If Yes, which one?

    • What should be done in case of failure ?

    • What should be the duration of treatment ?


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    Duration of treatment and complications:

    P=0.01

    S. aureus:

    Relapse increases if treatment is less than 10 days

    Malanovski GJ - Arch Intern Med 1995;155:1161


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    Jernigan et al - Ann Intern Med 1993;119:304

    S. aureus CRB : Short treatment

    • Meta-analysis 11 studies/ 132 Pts

      • Late complications after treatment < 14 days6.1% [95% CI, 2.0% - 10.2%]

      • Rare but severe:

        3 Endocarditis (1 surgery)

        2 epidural abscess (1 surgery)

        2 bacteremia (1 death)


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    Duration of treatment proposals (Positive BC)

    MicroorganismDuration (d)

    S. aureus 14 (4-6 weeks*)

    P. aeruginosa14

    Candida spp. 14 (28*)

    SCN7 (14/ 21**)

    Enterobacteriaceae7 (14/ 21**)

    ______________________________________________________

    * complications ** IfCVC left in place or immunosupression


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    Duration of treatment proposals

    (Negative BC)

    • Nothing!!

    • Probably not justified if afebrile after CVC removal?

    • S. aureus et P. aeruginosa or immunosupression

    • 1 week ??

    • If GWX and new CVC left in place

      •  ??? 2 weeks


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    Slides available on http://www.outcomerea.org


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    Slides available on http://www.outcomerea.org


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    Outcome of Hickman catheter salvage therapy in neutropenic cancer pts with S. aureus Bacteremia

    Kim SH et al – ICHE 2003; 24:897-904

    + follow up BC = 1 success/7 (14%)

    - follow up BC = 11 success/17 (65%)

    P=0.07


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    Non compliance to the IDSA CR-BSI guidelines - Effect of standardized e-mailed treatment advices

    Rijnders et al – Clin Infect Dis 2003; 37: 980

    Before:

    52 BSI

    Non compliance,

    23/52 (44%)

    (CNS excepted: 14)

    no AB (12), resistance (4), too large (5), too short (2)

    After:

    46 BSI (non ICU only)

    Non compliance

    Non ICU 7/46 (15%)

    (CNS excepted: 7)

    no AB (1), resistance (0), too large (1), too short (5)


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    Guidelines for tunneled CVCs or portsClin Infect Dis 2001; 32: 1249


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