Download Infectious complications during dialysis

Infectious complications
during dialysis
Scope


Infectious disease in dialysis

Epidemiology and importance

Diagnosis and management

Prevention
Conclusions
Infectious disease in dialysis
 Mortality:
 General

population perspective,
Mortality rates attributable to bacterial
infection have declined in many countries
• E.g. overall unadjusted death rate was 841.9 per
100 000 in the United States in 2003


Cardiac diseases (28.0%), malignancy (22.7%), and
cerebrovascular disease (6.4%)
Influenza/pneumonia (7th rank, 2.7% ) and septicemia
(10th rank, 1.4% of mortality events)
Natl Vital Stat Rep 2006; 54:1–120
Infectious disease in dialysis (Contd)
 Mortality:
 Infectious

causes have consistently
Ranked second to cardiovascular disease in
reported causes of death in dialysis
populations
• E.g. during the years 2002–2004, mortality rates in
dialysis populations were 19.8 times those in the
general population, and
• Mortality was attributed to septicemia in 9.7% and
2.5% of all deaths respectively
Perit Dial Int 2008; 28(S3):S167–S171
Infectious disease in dialysis (Contd)
 Infectious

complications
continue to be among the foremost causes of
morbidity and mortality in hemodialysis (HD)
patients
• The USRDS:1991-92, infection accounted for 12%
of all deaths among HD patients
• In a subsequent report for the 1993-95, USRDS
infection accounted for 15.5% of adult end-stage
renal disease (ESRD) causes of death
USRDS: United States Renal Data System
Infectious disease in dialysis (Contd)
Kidney International 2001 (60):1–13
Adjusted admissions for infection in the first
year of hemodialysis, by month & age
Figure 1.8 (Volume 2)
Incident hemodialysis patients age 20 and older; followed from the day of onset of ESRD; adjusted for gender, race, &
primary diagnosis. Incident hemodialysis patients alive at day 90 after initiation, 2005, used as reference.
USRDS 2009 ADR
Infectious disease in dialysis (Contd)
 A noteworthy

study*
Compared mortality attributed to sepsis in
dialysis patients with corresponding rates in
the general population for the years 1994
through 1996
• Even when disparities in age, sex, race, and
diabetes mellitus were taken into account,
 Mortality rates in dialysis patients were higher
by a factor of 100 to 300
*Kidney Int 2000; 58:1758–64
Trends in CVD and Infectious
Hospitalization rates in the first month
Rate per 1,000 Pt Yrs
Adjusted for age, gender, race and cause of ESRD
Infectious hospitalizations now
approach CVD for the 1st time!
750
700
650
600
550
500
450
400
350
300
All CV 0<1
All Infect 0<1
All CV 1<2
All Infect 1<2
2005
2004
Incident Cohort Year
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
USRDS 2008 ADR
Mortality Risk in Facilities that have
Greater Use of Catheters or AV Grafts versus low use
RR of death
Fac. Catheter Use
1.5
(R2=0.95)
1.45
1.31
1.26
1.24
1.25
1.14
1
1
1.07
1.38
Fac. Graft Use
(R2=0.966)
1.14
1
Quintiles for Graft
and Catheter Use
0.75
0.5
0
20
40
60
% Adjusted Facility Access Use
80
Infectious disease in dialysis (Contd)

Trends
 Infection hospitalizations substantially
increasing over past 10 years, largely due to
catheters
 Infection hospitalizations increasing at a rate
greater than cardiovascular hospitalizations
 Much higher costs in patients with catheters
 There is even likely a linkage between one
access infection and associated ongoing risk
of death
 Higher mortality in catheter patients and
facilities with more catheters (and grafts)
Infectious disease in dialysis (Contd)
 Thus,

Mortality from infectious diseases is much
more prominent than might otherwise be
expected in chronic dialysis patients
Infectious disease in dialysis (Contd)
 Even
though dialysis populations generally
have pessimistic survival expectations,
and infectious mortality is more prominent
than in the general population,

Remarkably few studies have examined the
clinical epidemiology of septicemia in
maintenance dialysis patients
Perit Dial Int 2008; 28(S3):S167–S171
Infectious disease in dialysis (Contd)
 Widely

believed that
Central venous catheters are primarily
responsible for excessive rates of septicemia
in HD populations
Relationships
between factors
associated with
hemodialysis
central
venous catheterrelated blood
stream infections
Nature Clinical Practice Nephrology 2007; 3(5): 256-266
Catheters are the major source
of dialysis access infections
Complications:
Endocarditis
Osteomyelitis
Epidural abscess
Septic shock
Septic arthritis
Septic
thrombophlebitis
Death
Infectious disease in dialysis (Contd)
 Prospective

study from France reported
Catheter use was associated with a covariateadjusted hazard ratio for septicemia 7.6 times
that of native arteriovenous fistulae
J Am Soc Nephrol 1998; 9:869–76.
Infectious disease in dialysis (Contd)
 US

group study
Using HD patients with fistulae as reference
group, rates of septicemia were shown to be
similar in those patients, in PD patients, and
in HD patients with synthetic grafts
• In contrast, septicemia rates in patients with
central venous catheters were approximately twice
as high as expected, a disparity that remained
after extensive adjustment was made for baseline
comorbidity patterns
Perit Dial Int 2008; 28(S3):S167–S171
Consequences of Catheters





22% infectious complications, with septic
arthritis, endocarditis and osteomyelitis
43% higher cardiovascular related death rate
than fistulas in some studies
AVF after 90 days with 29% reduction in allcause mortality compared to catheters
Greater all cause and infection related
hospitalizations
Reduced dialysis adequacy, poorer quality of life
and greater costs
Infectious disease in dialysis (Contd)
Kidney International 2001 (60):1–13
Time to first CRB in patients
with tunneled HD catheters
Lee, AJKD, 2005
Infectious disease in dialysis (Contd)
 Because
the risk of serious bacterial
infection and mortality is strongly related to
mode of arteriovenous access,

intensive efforts at creating native
arteriovenous fistulas have been
recommended
U.S. National Kidney Foundation (NKF). Home > Professionals
>KDOQI > Clinical Practice Guidelines > Vascular Access’
Fistula First” as a CMS breakthrough initiative: improving vascular
access through collaboration. Nephrol Nurs J 2005; 32:686–7.
Infectious disease in dialysis (Contd)
 It

seems unlikely that
Catheters can be avoided in all HD patients
even with well-organized, fully-integrated
systems
• Developing strategies to minimize infection risk in
patients with catheters therefore remains important
Perit Dial Int 2008; 28(S3):S167–S171
Diagnosis and management
 The
acute onset of fever and chills in a
patient with a HD catheter and no
localizing signs is easily recognized and is
generally considered to be a CRB until
proven otherwise

Such an explosive presentation is often
observed during the hemodialytic procedure,
but could occur at any time during the
interdialytic period
Kidney International 2001 (60):1–13
Diagnosis and management (Contd)
 Less
acute presentations of CRB are also
frequent,


Especially in the older population and the
immunocompromised
May include any of the following
• the insidious onset of low-grade fever,
hypothermia, lethargy, confusion, hypotension,
hypoglycemia, or diabetic ketoacidosis
Kidney International 2001 (60):1–13
Diagnosis and management (Contd)
Main diagnostic approaches for Gram-positive
bacteremia in dialysis patients
UTI = Urinary tract infection
Nephrol Dial Transplant 2008;23: 27–32
Diagnosis and management (Contd)
 HD
patients with suspicion of CRB must
have blood cultures done immediately and
should be promptly initiated on empiric
antimicrobial therapy
Kidney International 2001 (60):1–13
Nature Clinical Practice Nephrology 2007; 3(5): 256-266
Diagnosis and management (Contd)
 Management
of CRB in the HD patient has
two aspects:
 1. Antimicrobial therapy
 2. Removal of the HD catheter, which is
the source of the bacteremia
Kidney International 2001 (60):1–13
Diagnosis and management (Contd)

1. Antimicrobial therapy

Initial empiric antibiotic therapy should take into
consideration the frequency of the bacterial isolates in
such settings
• Staphylococcal species have repeatedly been demonstrated
to be the most prevalent (60 to 100%) bacterial isolates in
HD patients with CRB
• The prevalence of S. aureus and coagulase negative
staphylococci bacteremia is similar in most series
• Enterococci have been found in 11 to 19% of CRB
• Gram-negative rods are reported in up to 33% of cases
Kidney International 2001 (60):1–13
Diagnosis and management (Contd)
 1. Antimicrobial



therapy
Some patients both gram-positive and gramnegative organisms have been isolated from
the blood stream, indicating mixed bacteremia
These data mandate that empiric antibiotic
therapy should target both gram-positive and
gram-negative organisms
Specific antimicrobial therapy should replace
empiric therapy as soon as the identity of the
bacterial isolate is determined
Kidney International 2001 (60):1–13
Nature Clinical Practice Nephrology 2007; 3(5): 256-266
Nature Clinical Practice Nephrology 2007; 3(5): 256-266
Kidney International 2001 (60):1–13
Rx of catheter-related bacteremia:
Principles and practice
Allon, AJKD, 2004
Nephrol Dial Transplant 2008;23: 27–32
Treatment of CRB:
What to do with the catheter?
 2.
Removal of the HD catheter, which is
the source of the bacteremia

Scientifically the most correct, it poses certain
practical problems, especially in HD patients
whose vascular access sites have been
exhausted
Kidney International 2001 (60):1–13
Strategies for treatment of
catheter-related bacteremia
 Systemic
antibiotics alone (low rate of
catheter salvage ~25%)--Ignore
 Catheter removal with delayed placement
of new catheter
 Catheter exchange over guidewire
Can antibiotic locks kill bacteria
in catheter biofilm?
 New
catheter
Catheter with biofilm
Rationale for antibiotic lock
 Bacterial
biofilm develops within 24 hours
in all indwelling catheters, and is the major
source of catheter-related bacteremia
 IV antibiotics do not treat the biofilm.
 If antibiotic lock can kill bacteria in catheter
biofilm, management of CRB would be
simplified (no need to replace catheter)
Antibiotic lock protocol:
Definition of outcomes
 Failure:



Persistent fever
OR
Positive surveillance cultures
 Success:



Resolution of symptoms at 48 hours
AND
Negative surveillance cultures one week after
completing antibiotics
Poole, NDT, 2004
Antibiotic lock for treatment
of CRB (summary)
 Use
of an antibiotic lock, in conjunction
with systemic antibiotics, can eradicate
catheter related bacteremia while
salvaging the catheter in about 2/3 of
cases
 In 9 studies, 307/405 of CRB episodes
(76%) were cured with an antibiotic lock
Success of antibiotic lock
depends on the organism
Poole, NDT, 2004
Prevention of CRB
Rate of catheter related bloodstream
infections with antimicrobial lock solution
versus heparin: Randomized studies
CRB 7.7
times
less likely with
anti-microbial
lock than with
heparin lock.
Jaffer, AJKD, 51:
233-241, 2008
Allon, AJKD 2008;51:165-168
70% ethanol lock prevents CRB




Randomized study (64 pts) with Hickman catheters
locked with 70% ethanol or heparin.
CRB was lower in ethanol lock group (0.6 vs 3.1 per
1000 catheter-days, p=0.008).
Sanders, J Antimicrob Chemother, 2008
Randomized study of 92 Greek patients (103 uncuffed
HD catheters) receiving 70% ethanol vs heparin locks.
CRB was lower in ethanol lock group (2.5 vs 6.7 per
1000 catheter-days (p=0.04).
Sofroniadou et al, 2009 ASN abstract (F-FC300)
Methylene blue prevents CRB

Randomized study of 407 pts with tunneled HD
catheters receiving a lock containing citrate +
methylene blue + parabens (C-MB-P) vs heparin
lock

Frequency of CRB was lower with C-MB-P vs
heparin (0.24 vs 0.82 per 1000 catheter-days
(p=0.005)
Ash et al, 2009 ASN abstract (F-FC299).
Can lock solutions select for
antibiotic-resistant infections?
 No
known resistance to ethanol, 30%
citrate,m or taurolidine.
 The 5 studies evaluating Abx locks used
them for short periods of time (<6 months),
and did not observe Abx resistance
 A recent abstract raised serious concerns
about the risk with long-term Abx lock
prophylaxis
Can lock solutions select for
antibiotic-resistant infections?

Prospective follow-up of 1488 catheterdependent patients in Massachusetts receiving
prophylactic gentamicin locks over a 4-year
period.
 Overall, CRB rate decreased from 17 to 3.7 per
1000 catheter-days (78% reduction).
 Within 8 months of starting the protocol, they
began to observe gent-resistant bacteremias.
Landry et al, 2009 ASN abstract (F-FC301)
Can lock solutions select for
antibiotic resistant infections?

(cont)
Over the next 40 months, they observed 31
gentresistant bacteremias (including 19 Staph
epi and 8 Enterococcus).
 No episodes of gent-resistant S. epi CRB
observed in 25 HD patients without catheters.
 Among pts with gent-resistant Gram-positive
CRB, 4 had endocarditis, 14 were hospitalized, 2
required ICU stays, and 6 died within 60 days.
Landry et al, 2009 ASN abstract (F-FC301)
Are lock solutions safe?



Gentamicin lock produced median pre-HD gentamicin
conc of 2.8 mg/L in one study
4 /42 pts (10%) c/o of intermittent dizziness (?mild
aminoglycoside ototoxicity)
No toxicity with 30%citrate in one randomized study
(Weijmer, JASN, 2005)

In a recent randomized study, 15% of pts receiving
46.7% citrate were withdrawn due to metallic taste or
facial and digital paresthesias (Power, AJKD, 2009)

USFDA withdrew 46.7%citrate after one pt death
Are lock solutions safe?
 Taurolidine
(cont)
is safe even when large
volumes are deliberately given IV.
 70% ethanol locks have been used in 2
randomized studies without systemic
toxicity
Sanders, J Antimicrob Chemother, 2008
Sofroniadou et al, 2009 ASN abstract (F-FC300)
Potential antimicrobial solutions
None of these are US FDA approved!
Kidney International 2001 (60):1–13
Kidney International 2001 (60):1–13
Septicemia in dialysis
 General

guidelines
(not specific to dialysis patients and based largely on common
sense rather than on randomized trials)



include
Sterile barrier precautions,
Antiseptic solutions, and
Education of health care personnel, patients,
caregivers, and family members
• Additional interventions may be useful in catheterdependent dialysis patients
Perit Dial Int 2008; 28(S3):S167–S171
Preventive care for infectious
complications
•
•
•
•
•
The variation is vaccination rates for influenza and
pneumococcal pneumonia are considerable and
unexplained.
These vaccinations are very inexpensive compared to the
cost of a single hospitalization for pneumonia yet universal
adoption is lacking.
In fact, there has been no progress in influenza vaccination
rates for the last 5 years!
Pneumococcal pneumonia vaccinations have increase to a
greater degree in some providers!
Providers need to be held accountable for the lack of
performance is this area.
USRDS 2008 ADR
Boston Meeting Recommendations #1:
Infection and Access


Acknowledge: The catheter problem is IATROGENIC
Hospitals, health plans, nephrologists, providers and
vascular surgeons (currently, 50% primary failure
rate) must be accountable for reducing catheter
placement
 CMS might consider moving catheters, as a CPM, to
the very highest level of scrutiny and surveys and
place less emphasis on CPMs that make little
difference in outcomes


They just concluded a TEP to make just such
recommendations, which are now being considered
Vaccination, as a CPM, needs to be an important
aspect of facility practice and accountability
Conclusions

Central venous catheter-related blood stream infection
(CRBSI)—most often with Staphylococcus aureus or S.
epidermis—is a common complication and cause of
death among maintenance hemodialysis patients

Diagnosis of CRBSI is confirmed by isolation of the
same microorganism from quantitative cultures of both
the catheter and the peripheral blood of a patient that
has clinical features of infection without any other
apparent source
Conclusions

Choice of antibiotics for initial empirical
treatment of CRBSIs is a major management
decision, as is determining whether catheter
removal is appropriate

Topical antibiotics and catheter-lock solutions
are the primary means of preventing CRBSIs,
but risk of antibiotic-resistant organism
emergence should be considered