1. Central Line Infection: Pull or Leave it in
David Nguyen PGY 2
5/1/12

2. Objective Determine catheter related blood stream infection (CRBSI)
Key Factors to consider when removing cathether:
Patient-related factors
Organism
Catheter

3. Case 1
65 y/o pmhsx DMII, HTN, CAD presents with severe sepsis likely source PNA into ICU, had right IJ central line placed and all the right abx and pressors started. Several days later, noticed that the patient had developed fever and leukocytosis, which had been trending down to normal. Site of IJ is slightly erythematous, not too tender, no pus drainage. Patient’s MAP > 65, not tachycardic, has been off of pressors for 1 day. How do you proceed?

4. Clinical Evaluation Local inflammation Hemodynamic stability Sepsis
Blood culture
Catheter dysfunction
Rapid improvement following catheter removal
Typically we begin to suspect that the patient may have a catheter related blood stream infection when there is fever that has been unaccounted for and that they may have had a catheter in place for some time or it may be unclear whether pt may have a CRBSI and thus it is left in. Therefore, will first talk about the diagnosis of catheter related blood stream infection through blood cultures as opposed to diagnosing after the catheter has been pulled and that the tip is cultured.

5. Diagnosis
Blood cultures from catheter AND peripheral vein at ~ same time. (A-II)
If cannot get peripheral vein, get 2 or more blood samples through different catheter lumens (C-III)
Differential time to positivity (DTP)
Quantitative blood culture (not used by our micro lab)*
Some important points about diagnosis of CRBSI:
Clinical findings are unreliable  poor sensitivity and specificity
Most sensitive is fever, but has poor specificity
Inflammation or pururlence around insertion site has greater specificity but poor sensitivity
In general blood cultures positive for the following species should make you more suspicious of CRBSI:
S. aureus
Coag-neg staph
Candida species
Recently inserted catheter (i.e. one that had ben indwelling < 14 days) is commonly colonized from skin microorganisms along the external surface of the catheter.
Antimicrdobial coatings may lead to fal-negative culture results, but can use silver sulfadizine or chlorhexidine coated catheters specific inhibitors to abrogate this effect.
* More info on quantitative blood culture at the end of the presentation.

6. Dx: Differential time to positivity
Catheter microbial growth detected 2 hours before peripheral vein
Sens: 85% and spec 91% (1)
More cost-effective than quantitative method and can be done here at UCI
Definition of positive CRBSI via Differential time to positivity is comparing the catheter to the peripheral vein to see which sample grows out first.
Monitoring for growth is based on radiometric methods
So the theory is that the greater the inoculum of microbes inoculated into blood cultures bottles, the shorter the incubation required to detect microbial growth, one would expect the catheter to have the greater inoculum.
85-89% sensitivity and 81-83% specificity in meta-analysis of 8 studies

7. Case 1 revisited… Next steps
Obtain blood culture from peripheral vein and from the central line.
If the blood culture from the central line becomes positive at least two hours before that of the peripheral line, then diagnosis of CRBSI.
How do you proceed if positive CRBSI?
Obtain blood culture from peripheral vein and from the central line.
If the blood culture from the central line becomes positive at least two hours before that of the peripheral line, then diagnosis of CRBSI.
How do you proceed from here if positive CRBSI?

8. Treatment What to do with the catheter?
Remove vs
Salvage vs
Exchange
Type of device: short vs long term (excluding HD)
Infecting pathogens
Presence of alternative venous access sites
Duration of anticipated need for access
Systemic antibiotics
Other treatment modalities not discussed:
Salvage
Exchange
Antibiotic lock therapy

9. Catheter removal indications
Severe sepsis
Hemodynamic instability
Endocarditis or evidence of metastatic infection
Erythema due to suppurative thrombophlebitis
Persistent bacteremia after 72 hrs abx to which organism is susceptible
Main point of this slide is to say that these are “COMPLICATED” infection scenarios that require catheter removal. You’ll see this reiterated in the flow diagram towards the end of this presentation. Anything that falls under “complicated” means you need to remove the catheter.

10. Case 2
65 y/o with DMII, HTN p/w LLL PNA. Had L IJ line placed (difficult stick) as this was the weekend and could not get PICC. Pt’s vitals on admission only significant for fever Treating for CAP.
3 days later, pt’s bp drops to 80s/40s hr: 120s, febrile again 39.3, pt more lethargic. Blood cultures drawn from periphery and central line, UA and CXR unremarkable, WBC increased to 16, lactate 4. How do you proceed?

11. Case 2 Keep the line, transfer the patient to the ICU and broaden abx.
Change the line via guidewire as patient is difficult stick and broaden abx.
Transfer pt to ICU (IVF and pressors) and broaden abx. Obtain another access site, pull the line.
Keep the line, keep pt on floor, fluid boluses and follow up on cultures in the morning.

12. Case 2 Keep the line, transfer the patient to the ICU and broaden abx.
Change the line via guidewire as patient is difficult stick and broaden abx.
Transfer pt to ICU (IVF and pressors) and broaden abx. Obtain another access site, pull the line.
Keep the line, keep pt on floor, fluid boluses and follow up on cultures in the morning.
This patient has criteria for severe sepsis. He/She needs to have fluid boluses and likely pressors to be given as well. The issue here is to obtain another access site and pull the line as this is short term catheter and patient is hemodynamically unstable with the likely source as the catheter since he/she has been doing ok up until this point with current abx for CAP.
Keeping the line is an option, but since this is the likely source of infection better to take it out in light of new hemodynamic instability requiring pressors, and broadening of abx coverage. In addition, treating through the infection is indicated in cases where cultures for the following bugs are not found: s. aureus, pseudomonas, fungi or mycobacteria.
Changing the line via guidewire is not indicated in this case if you can obtain another line else where. Guidewire exchange is for circumstances in which catheter removal is necessary for suspected catheter-related infection and the risk for mechanical complications or bleeding during catheter reinsertion is high, guidewire exchange of the catheter is acceptable (except in the setting of sepsis). Clinical scenarios: liver disease, coagulopathy, medication induced.
D) D is not an option as patient has criteria for severe sepsis and hemodynamically unstable, pt needs closer monitoring.

13. Case 3
65 y/o woman with DMII, HTN p/w sepsis 2/2 UTI. PICC line was placed on previous admission so pt can get home IV abx. You obtain blood cultures from that line and periphery and blood culture from line grew out s. aureus 1 day prior to periphery which also grew out same organism. Pt currently hemodynamically stable, afebrile on ceftriaxone for UTI. Leukocytosis has improved to normal range now. How should you proceed?

14. Case 3 Treat with vancomycin and await sensitivities.
Obtain another set of blood cultures from PICC and peripheral. Start vancomycin thereafter.
Obtain another set of blood cultures from PICC and periphery, pull the line and start vancomycin.
Pull the line, that things been in there for way too long.

15. Catheter removal indications
Short term catheters (< 14 days)
S. aureus, enterococci, gram neg bacilli, fungi, and mycobacteria
Erythema or purulence at insertion site
Low virulence but difficult to eradicate (eg, Bacillus spp, Micrococcus spp, or Propionibacteria)
No evidence for catheter exchange i.e. salvage
Essentially this slide is further breaking down other reasons why you should remove the catheter into the organisms associated with short term and long term catheters (does not apply to hemodialysis catheters).
Removal of long term catheters is a management challenge, particularly in the setting of surgically implantable intravascular devices. Therefore, it is important to establish true CRBSI.
In the setting of CRBSI due to organisms of relatively low virulence that are difficult to eradicate (eg, Bacillus spp, Micrococcus spp, or Propionibacteria), removal of both short and long term catheters is appropriate if blood culture contamination has been ruled out (eg, based on multiple positive culture results with at least one sample drawn from a peripheral vein) There is no evidence to support routine catheter exchange.
Basically don’t remove catheter in patient with negative blood cultures and hemodynamically stable but you have unexplained fever, unless patient has endovascular prosthetic material (such as a prosthetic valve, pacemaker, or vascular graft).

16. Case 3 Treat with vancomycin and await sensitivities.
Obtain another set of blood cultures from PICC and peripheral. Start vancomycin thereafter.
Obtain another set of blood cultures from PICC and periphery, pull the line and start vancomycin.
Pull the line, that things been in there for way too long.
S. aureus, enterococci, gram neg bacilli, fungi, and mycobacteria
Low virulence but difficult to eradicate (eg, Bacillus spp, Micrococcus spp, or Propionibacteria)

17. Case 3 Treat with vancomycin and await sensitivities.
Obtain another set of blood cultures from PICC and peripheral. Start vancomycin thereafter.
Obtain another set of blood cultures from PICC and periphery, pull the line and start vancomycin.
Pull the line, that thing has been in there for way too long.
S. aureus, enterococci, gram neg bacilli, fungi, and mycobacteria
Low virulence but difficult to eradicate (eg, Bacillus spp, Micrococcus spp, or Propionibacteria)

18. Essentially a summarized approach to the above discussion/slides
Ares to emphasize/reiterate to the audience:
Complicated = indications to remove the catheter
But also take note that in this setting coag neg staph, s. aureus, enterococcus, gram neg bacilli and candida ALL require removal of catheter
Approach to the management of patients with short-term central venous catheter–related or arterial catheter–related bloodstream infection. CFU, colony-forming units; S. aureus, Staphylococcus aureus.

19. Case 4
62 y/o w/hsx of liver mets has a Port-a-cath presents with altered mental status. Not receiving chemotherapy currently. Family says that after discharge, pt has become more confused, no fever, cough, dysuria or hematuria, diarrhea. PE: no erythema or tenderness at site or port-a-cath. UA Blood cultures grew out E.coli from portacath site. Repeat cultures demonstrated same organism from catheter and peripheral site. What should be done next?
Remove it!!!

20. Catheter removal indications
Long term catheters (> 14 days)
S. aureus, Gram negative bacilli, P. aeruginosa, fungi, or mycobacteria
Tunnel infection, port abscess
Essentially this slide is further breaking down other reasons why you should remove the catheter into the organisms associated with short term and long term catheters (does not apply to hemodialysis catheters).
Removal of long term catheters is a management challenge, particularly in the setting of surgically implantable intravascular devices. Therefore, it is important to establish true CRBSI.
In the setting of CRBSI due to organisms of relatively low virulence that are difficult to eradicate (eg, Bacillus spp, Micrococcus spp, or Propionibacteria), removal of both short and long term catheters is appropriate if blood culture contamination has been ruled out (eg, based on multiple positive culture results with at least one sample drawn from a peripheral vein) There is no evidence to support routine catheter exchange.
Basically don’t remove catheter in patient with negative blood cultures and hemodynamically stable but you have unexplained fever, unless patient has endovascular prosthetic material (such as a prosthetic valve, pacemaker, or vascular graft).
Port-A-Cath
Hickman catheter, tunneled

21. Approach to the treatment of a patient with a long-term central venous catheter (CVC) or a port (P)-related bloodstream infection.
Points to highlight:
“Complicated infections”  take out the catheter
Staph aureus  take out catheter mortality is high if try to treat through the infection
Gram negative bacilli  take out catheter
Candida  take out
May retain and try to treat through: coag neg staph, enterococcus, but if no clinical improvement take it out.
Approach to the treatment of a patient with a long-term central venous catheter (CVC) or a port (P)-related bloodstream infection.

22. Case 4
Essentially you need to remove this catheter as you cannot treat through this in light of cultures growing out E.coli.
Remember the other organisms that require removal:
S. aureus, Gram negative bacilli, P. aeruginosa, fungi, or mycobacteria
Other scenarios that necessitate removal:
Tunnel infection, port abscess

23. Factors Affecting Abx Choice
severity of illness
risk factors for infection
likely pathogens a/w specific catheter
Start with Vancomycin
Coag negative staph are most common and usually resistant to methicillin.
Be careful with Vanc resistance  daptomycin
Neutropenia, sepsis  empiric coverage for gram negative
Essentially going over some scenarios and how these will affect empiric antibiotic choice.
Initial choice of antibiotics for catheter-related blood stream infection (CRBSI) depends on the clinical circumstances, including the severity of illness, the risk factors for infection, and the likely pathogens associated with the specific intravascular device.
In general, coagulase negative staphylococci are the most common cause of catheter-related infection; most isolates are resistant to methicillin. Therefore empiric therapy of CRBSI in health care settings should consist of vancomycin.
In institutions with high rates of infection due to MRSA isolates with vancomycin MIC ≥2 mcg/mL, an alternative agent such as daptomycin should be used. 
Linezolid is not an appropriate agent for empiric therapy of CRBSI.
Addition of empiric coverage for gram negative organisms depends on individual circumstances and the severity of disease.
In the setting of suspected CRBSI among patients with neutropenia or sepsis, empiric antibiotic therapy for gram negative bacilli (including Pseudomonas) is appropriate.
Patients known to be colonized with drug resistant organisms should receive empiric antibiotic therapy selected accordingly

24. Empiric Antibiotic Cover for candidemia when (B-II):
TPN
Prolonged use of broad-spectrum abx
Hematologic malignancy
Bone marrow or solid organ transplant
Femoral catherization
Colonization due to Candida species at multiple sites
Ex: caspo, micafungin, fluconazole (if organism is susceptible) (A-II)
Essentially going over some scenarios to keep in mind.
Empiric therapy for suspected catheter-related candidemia should be administered for septic patients with the above risk factors.
Empiric treatment include echinocandin or azole drugs.
Fluconazole if no azole exposure in previous 3 months and in settings where the risk of C. krusei or C. glabrata is very low.
If catheter removal is not possible, antibiotics should be administered through the colonized catheter, although recurrent bacteremia is more likely if therapy is administered through a retained catheter than if the catheter is removed

25. Antibiotic Duration
Typically 10 to 14 days (day one is the first day on which negative blood cultures are obtained)
4 to 6 weeks in patients with recent prosthetic valve placement placed prosthetic valves, even if investigation fails to demonstrate evidence of IE.
Patients with persistent bacteremia >72 hours following catheter removal should generally receive tx for at least 4 to 6 weeks
Complications related to bacteremia (such as suppurative thrombophlebitis, endocarditis, osteomyelitis, metastatic infection) the duration of therapy should be tailored accordingly depending on the nature of infection.
10 to 14 days (day one is the first day on which negative blood cultures are obtained)
The duration of therapy may be extended to 4 to 6 weeks in patients with recent prosthetic valve placement placed prosthetic valves, even if investigation fails to demonstrate evidence of IE.
Patients with persistent bacteremia >72 hours following catheter removal should generally receive treatment for at least 4 to 6 weeks. For patients with complications related to bacteremia (such as suppurative thrombophlebitis, endocarditis, osteomyelitis, metastatic infection) the duration of therapy should be tailored accordingly depending on the nature of infection.

26. Take home points
Time to positivity dx: catheter site culture should have growth at least 2 hrs before peripheral site
Catheter removal:
“complicated” infection,
short term CVC: S. aureus, enterococci, gram neg bacilli, fungi, and mycobacteria
Long term CVC: S. aureus, P. aeruginosa, fungi, or mycobacteria
Abx choice: depends on severity of illness, risk factors (neutropenia, candida coverage)

27. Reference
Meta-analysis: methods for diagnosing intravascular device-related bloodstream infection. Safdar N, Fine JP, Maki DG. Ann Intern Med. 2005 Mar 15; 142(6) :
Clinical Practice Guidelines for Dx and Management of Intravascular Catheter-Related Infection: IDSA 2009 guidelines
UpToDate: Intravascular catheter device dx and management