INVITED ARTICLE
IMMUNOCOMPROMISED HOSTS
David R. Snydman, Section Editor
Defining Bloodstream Infections Related to
Central Venous Catheters in Patients With
Cancer: A Systematic Review
Deborah Tomlinson,1 Leonard A. Mermel,2,3 Marie-Chantal Ethier,1 Anne Matlow,4 Biljana Gillmeister,1 and
Lillian Sung1,5
1Program in Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada; 2Warren Alpert Medical School of Brown
University, Providence, Rhode Island; 3Department of Epidemiology & Infection Control, Rhode Island Hospital, Providence, Rhode Island; 4Division of
Infectious Diseases, The Hospital for Sick Children, Toronto, Ontario, Canada; and 5Division of Haematology/Oncology, The Hospital for Sick Children,
Toronto, Ontario, Canada
The objective of this review was to determine whether consistent definitions were used in published studies of
bloodstream infections due to central venous catheters in patients with cancer (ie, catheter-related or catheterassociated bloodstream infections). Review of 191 studies reporting catheter-related or catheter-associated
bloodstream infections in patients with cancer revealed a lack of uniformity in these definitions. We grouped
definitions by type, with 39 articles failing to cite or report a definition. Definitions included those of the Centers
for Disease Control and Prevention (n 5 39) and the Infectious Diseases Society of America (n 5 18). The criteria
included in the definitions in studies were also tabulated. Clinical manifestations were frequently included.
Definitions used have been highly variable; comparability of risk factors, incidence, management, and
outcomes of such infections is difficult to achieve across studies. Future research should focus on development
of a common definition of catheter-related and catheter-associated bloodstream infections for both adults and
children with cancer.
Central venous catheters (CVCs) are frequently used in
patients receiving treatment for cancer. They provide
more easily accessible, long-term venous access for
blood testing and the necessary delivery of treatment,
including chemotherapy, blood products, and occasionally, parenteral nutrition [1]. However, use of CVCs
can lead to bloodstream infection, frequently referred to
as catheter-related bloodstream infection (CRBSI) or
catheter-associated bloodstream infection (CABSI).
Such infections are associated with serious morbidity
and mortality and with increased health care costs [2–6].
Patients with cancer with CVCs are at particular risk of
Received 22 March 2011; accepted 7 June 2011.
Correspondence: Lillian Sung, MD, PhD, Division of Haematology/Oncology, The
Hospital for Sick Children, Toronto, ON M5G 1X8 ([email protected]).
Clinical Infectious Diseases 2011;53(7):697–710
Ó The Author 2011. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
[email protected].
1058-4838/2011/537-0012$14.00
DOI: 10.1093/cid/cir523
CRBSI and/or CABSI [4, 7, 8]. Signs and symptoms of
these infections may be altered in patients with cancer
due to neutropenia or steroid administration [7]. For
example, CRBSI in neutropenic patients may be unaccompanied by inflammation or purulence at the
catheter site [9].
The incidence of catheter-related infections reported
in the literature varies from 9% to 80%, depending
on catheter type and patient risk factors and on the
definition of CRBSI or CABSI that is used [10]. Also,
70%–85% of patients with suspected catheter-related
infections are proven not to have such infections after
assessment of the results of catheter tip and blood cultures [11]. An accurate diagnosis of CRBSI and/or
CABSI is important for several reasons: effective and
timely treatment may reduce further complications; the
diagnosis may influence subsequent treatment and potential catheter removal; and this outcome is an important end point for supportive care clinical trials.
The gold standard for diagnosis of CRBSI is the isolation of the same organism from a peripheral blood
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culture as that isolated from the tip of the removed CVC [12].
However, this definition is problematic, because the vast majority of patients suspected of having a bloodstream infection
associated with a long-term CVC will not have their catheter
removed. Consequently, many definitions have been proposed
for CRBSI in the absence of catheter removal. A recently published guideline for the prevention of intravascular catheter infection describes the confusion regarding the terminology used
to describe such infections because of the interchangeability of
the definitions used for CRBSI and CABSI throughout the
medical literature [13].
Definitions are used by infection control professionals for
surveillance purposes to compare the incidence density of infections in similar contexts (ie, CABSI), by clinicians caring for
patients on a day to day basis, and in clinical research studies,
such as those comparing 2 intravascular devices in which a rigorous, unambiguous definition is required (eg, for CRBSI). The
latter definition requires percutaneously obtained blood samples for culture, either catheter tip cultures or catheter-obtained
blood cultures measured quantitatively, or both compared with
regard to the differential growth rate of microbes in the percutaneously obtained and catheter-obtained blood samples for
culture. Quantitative blood cultures are not universally done in
clinical, nonstudy settings, and differential growth rates of blood
culture bottles may not be reported by the microbiology laboratory. Thus, surveillance definitions (ie, for CABSI) are used to
compare the incidence of bloodstream infections associated
with CVCs in different units or institutions. Surveillance definitions overestimate the true incidence of CRBSI [13]. Despite
the number of proposed definitions of CRBSI and CABSI [13–
18], many published studies fail to make this distinction apparent. Because many definitions are applied for CRBSI or
CABSI, comparisons between studies and interpretation of
meta-analyses are difficult [19]. Optimally, investigators should
use a common definition of CRBSI and CABSI, and a standard
definition has been recommended for hematological patients
[20].
The objectives of this study were to (1) describe the definitions
used in studies that investigate CRBSI or CABSI in patients with
cancer and (2) compare and contrast these definitions to assist in
determining an optimal definition of CRBSI and CABSI in an
oncological population.
included the available vocabulary terms and text words for
bacterial infections and catheters and study designs. Studies
focusing on renal dialysis catheters were excluded from the review with use of the Not Boolean operator. References were
limited to English language. A total of 1033 duplicates were
excluded.
Strategy for Selection of Articles for Review
Articles were included if they were clinical research studies that
reported on CRBSI or CABSI as an outcome measure in patients
with cancer. Because of the imperceptible irregularities in the use
of the 2 definitions, we considered it appropriate to include
articles that reported on either CRBSI or CABSI. All CVC types
were considered in our review, including totally implanted and
partially implanted catheters and tunneled and nontunneled
catheters. Studies were excluded if (1) they were reviews,
guidelines, commentaries, or published abstracts, or if (2) the
population was not specified to be oncological or stem cell
transplant recipients. The term ‘‘central line–associated bloodstream infection’’ was also considered. There was no restriction
by age. Figure 1 shows the flow of studies. One author (DT)
reviewed the abstracts of the remaining 1977 unique references,
and with use of the aforementioned inclusion and exclusion
criteria, a total of 218 articles were retrieved for full text review.
Of the retrieved full articles, 28 were excluded. Thus, a total of
190 studies were included for review.
METHODS
Search Strategy for Identification of Studies
We conducted literature searches with use of the OVID search
platform MEDLINE, EMBASE, and Cochrane Controlled Trial
Register from the database inception until 13 October 2010. The
search strategy is attached as Appendix 1. We retrieved a total of
3010 references from all 3 databases. The search strategy
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Figure 1. Flow diagram of study identification and selection from
literature search.
Table 1. Catheter-Related Bloodstream Infection (CRBSI) and Catheter-Associated Bloodstream Infection (CABSI) Definitions Used in
190 Studies Involving Patients With Cancer
Number
of studies
Definition/reference used or cited in study
1.
2.
Centers for Disease Control and Prevention (CDC)/National Nosocomial Infections Surveillance
(NNIS)/Healthcare Infection Control Practices Advisory Committee (HICPAC) [12, 13, 21, 22]:
539*
Study
reference
a) [8, 23–31]
b) [32–43]
c) [44–48]
d) [43, 49–54]
e) [55–60]
Catheter Associated Bloodstream Infection (CABSI) defined as:
a) Bacteremia/fungemia in a patient with an intravascular catheter with at least one positive blood
culture obtained from a peripheral vein, clinical manifestations of infection (ie, fever, chills, and/
or hypotension), and no apparent source for the bloodstream infection except the catheter[21]
(may be referred to as CRBSI in some studies); OR
b) Bloodstream infections are considered to be associated with a central line if the line was in use
during the 48-hour period before the development of the bloodstream infection. (O’Grady,
2011 #13)
Catheter Related Bloodstream Infection (CRBSI) defined as:
c) Clinical manifestations and at least one positive blood culture from a peripheral vein and no
other apparent source, with either positive semiquantitative (.15 CFU/catheter segment) or
quantitative (.103 CFU/catheter segment) culture, whereby the same organism (species and
antibiogram) is isolated from the catheter segment and a peripheral blood sample; simultaneous quantitative cultures of blood samples with a ratio of $3:1 (CVC vs. peripheral); differential period of CVC culture versus peripheral blood culture positivity of 2 h [11, 13]; OR
d) Isolation of the same organism from semiquantitative or quantitative culture segment and from
blood (preferably from a peripheral vein) of a patient with accompanying symptoms of
bloodstream infection and no other apparent source of infection [12, 22]
e) CDC definition cited but not confirmed in text
Note: CDC definition may not have been cited in all cases, but definition was comparable.
Requires positive catheter tip/segment culture and positive peripheral blood culture (ie, requires
catheter removal).
(Ref #72, 73
Alternative of purulence from insertion site)
(Ref #61
Definition also includes positive cultures from CVC)
19
[61–79]
18*
[41, 44, 48, 55,
80–93]
3.
Infectious Disease Society of America [11]
4.
Bacteremia or fungemia in a patient who has an intravascular device and $1 positive result of
culture of blood samples obtained from the peripheral vein, clinical manifestations of infection
(eg fever, chills, and/or hypotension), and no apparent source for bloodstream infection (with
the exception of the catheter). One of the following should be present: a positive result of
semiquantitative ($15 CFU per catheter segment) or quantitative ($1000 CFU per catheter
segment) culture, whereby the same organism (species and antibiogram) is isolated from
a catheter segment and a peripheral blood sample; simultaneous quantitative cultures of blood
samples with a ratio of $3:1 (CVC vs. peripheral); differential time to positivity (ie, a positive
result of culture from a CVC is obtained at least 2 h earlier than is a positive result of culture
from peripheral blood).
Note: IDSA definition may not have been cited in all cases, but definition was comparable
Requires positive culture from CVC blood only.
12
[94–105]
5.
Requires positive blood cultures from both CVC and peripheral blood.
11
[106–116]
6.
Requires positive CVC blood culture, with either a negative peripheral blood culture or a lower
number of CFU in peripheral blood compared with CVC blood culture.
11
[117–127]
7.
Any positive blood culture (with CVC in situ).
9
[128–136]
8.
Clinical manifestations of infection that improve following removal of CVC (may or may not
include positive blood cultures).
8
[137–144]
9.
Includes positive culture swab from CVC site (may include other positive cultures from blood or
catheter tip).
6
[145–150]
10.
a) Greater than 10-fold increase in CFUs of organism/ml of blood obtained through catheter in
comparison with simultaneously obtained peripheral blood cultures;
b) In the absence of peripheral blood cultures, .1000 CFUs of organism/ml of blood obtained
through the catheter; OR
c) Positive catheter-tip culture when removed in clinical setting.
a) $10 CFU/ml through device compared with peripheral;
5
[151–155]
1
[156]
1
[157]
11.
12.
b) .103 CFU/ml through device with negative peripheral cultures;
c) Same organism from CVC sample and from swab of site; OR
d) Relationship between CVC manipulation and onset of fever and rigors.
a) Temperature .38 with chills and rigors within 1 h of flushing or manipulation;
b) Isolation of pathogen from blood culture drawn through catheter but not from another blood
culture drawn from peripheral vein at the same time;
c) Isolation of same pathogen from catheter tip and blood; OR
d) Isolation of same pathogen from blood and purulent material draining from catheter exit site or
subcutaneous tunnel.
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Table 1 continued.
Number
of studies
Definition/reference used or cited in study
13.
Temperature $ 38C with positive blood cultures derived from the catheter and at least one of the
following:
a) Negative peripheral blood cultures;
b) If simultaneously taken peripheral blood cultures were also positive, cultures from the catheter
became positive at least 2 h earlier (differential time to positivity, DTP);
c) Culture of the removed catheter tip grew $15 CFUs of the organism (semi-quantitative
catheter segment culture); OR
d) If peripheral blood cultures were not taken and the tip not removed or not sent for culture,
there was no other obvious clinical, radiological or microbiological focus of infection.
Clinical syndrome compatible with sepsis in the absence of any clinically apparent source other
than a central venous access device.
14.
Study
reference
1
[158]
1
[159]
15.
Clinical manifestations and positive venipuncture blood cultures.
1
[160]
16.
2
[162, 163]
17.
Clinical manifestation of infection in absence of any other source of bloodstream infection except
the catheter, in addition to one of following:
a) Catheter colonization with at least 15 CFUs by roll plate or at least 1000 CFUs by sonication
[161] with the same organism isolated from the bloodstream; OR
b) Positive quantitative culture of blood drawn through the catheter, yielding five-fold or greater
colony count than a quantitative culture of concurrently drawn peripheral venous blood
growing the same organism.
a) Clinical signs of infection, but no other identifiable focus of infection; AND
1
[164]
18.
b) Isolation of the same microorganism from blood and exudates from catheter exit site in
presence of signs and inflammation, or isolation of same microorganism from blood and
catheter tip.
High clinical suspicion with fever, requiring catheter removal.
1
[165]
19.
a) Recognized pathogen cultured from one or more blood cultures;
1
[166]
20.
b) Common skin contaminant cultured from two or more blood cultures, both drawn at separate
occasions; OR
c) Skin contaminant identified from at least one blood culture in association with clinical signs
a) Culture of removed catheter tip with same organism isolated from the catheter tip and peripheral blood; OR
b) Indicative differential time to positivity (ie, blood culture from Hickman became positive at least
2 h earlier than positive simultaneously-drawn peripheral blood culture)
1
[167]
21.
No other primary source of infection identified with
1
[168]
22.
a) At least two sets of blood cultures positive for the same organism; OR
b) One positive set accompanied by a positive drainage or catheter tip culture.
a) Clinical manifestations and positive culture; AND
b) Catheter colonized with same organism; OR CVC blood culture $10-fold CFUs than peripheral
blood culture.
1
[169]
23.
Increase in temperature (.38.5 C), associated with chills or rigors which settled spontaneously
or with antipyretic measures, in an otherwise well child, following flushing of the Broviac
catheter; subsequent culture of Broviac intraluminal catheter fluid was undertaken to confirm
infection.
1
[170]
24.
Clinical features with quantitative blood culture ratio of .5:1 (CVC vs peripheral) or isolation of
.100 CFU/ml from CVC-drawn blood culture.
1
[171]
25.
a) Fever or clinical signs/symptoms of infection, blood cultures (at least one from CVC and one
peripheral) are positive; AND
1
[172]
1
[173]
39
[174–212]
b) Insertion site swab, CVC tip culture or positive CVC intraluminal (lock) culture yields growth
identical to blood cultures.
a) Fever .38C with chills and rigors within 1 h after catheter flushing or manipulation;
b) Isolation of a pathogen from CVC-drawn blood culture, but not from a simultaneously-obtained
peripheral blood culture;
c) Isolation of same pathogen from catheter tip and blood; OR
d) Isolation of same organism from blood and from purulent material at exit site or subcutaneous
tunnel.
26.
27.
Not defined
Abbreviations: CFU, colony forming unit; CVC, central venous catheter.
a
Four studies used two definitions.
Where articles cited definite, probable, and possible definitions of CRBSI, only the definite definitions were reviewed.
We also examined whether there was a distinction between
CRBSI and CASBI definitions. Definitions were extracted,
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sorted, and tabulated according to similarity of definition.
Criteria associated with the definitions were examined and
listed for each definition, to determine frequency of cited
criteria.
Table 2.
Criteria Associated With Definitions of Catheter-Related Bloodstream Infection (CRBSI) in Patients With Cancer
Criteria
Clinical
manifestation
Author
[137–144]
Number
of papers
Present
Resolve
after
CVC
removal
8
U
U
CVC-drawn
blood culture
positive
CVC-tip
culture
positive
Peripheral
blood culture
positive
EITHER CVC
OR peripheral
blood culture
positive
Differential
between
CVC and
peripheral
culturesa
CVC insertion
site culture
positive
U
[77, 172]
2
U
U
U
[158, 162, 163]
3
U
U
U
[150, 172]
2
U
U
U
[23, 51, 53, 58–60,
106, 147, 148]
9
U
U
U
[141, 147]
2
U
U
[28–30, 95, 96,
98–101,
104, 105,
146, 170]
13
U
U
[52, 63, 65–68,
70, 71, 73,
78, 80, 81,
127, 164]
14
U
U
[38, 43, 48–50,
54, 79, 93,
142, 146,
149, 169]
12
U
U
[31, 102, 104]
3
U
[44, 127]
2
U
U
17
U
U
6
U
U
U
U
Defined
as catheterassociated or
catheterrelated
Number of
papers published
from 2006
onwards (n 5 54)
3 CRBSI;
0/8, 0%
1
2
2
2
1/2, 50%
CABSI
CR septicemia
unspecified
CRBSI
3 CRBSI
1/3, 33%
1 CR-infection;
1 CRBSI
1/2, 50%
6 CRBSI;
2/9, 22%
2 unspecified;
1 CABSI
1 CRBSI;
0/2, 0%
1 unspecified
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[24–26, 31, 35–
37, 39–42,
45, 55–57,
103, 160]
[38, 50, 142, 146,
149, 164]
6 CRBSI;
CABSI;
CA-septicemia
CR-septicemia;
intra-catheter
infection
1 unspecified
12 CRBSI
1 CR-septicemia
1 CABSI
4/13, 31%
1
1
3
1
U
10 CRBSI;
U
3/14, 21%
3/12, 25%
1 CR-septicemia
1 unspecified
U
U
3 CRBSI
2/3, 67%
1 CRBSI;
1/2, 50%
1
7
4
6
U
U
CR-septicemia
CABSI;
unspecified;
CRBSI
4 CRBSI;
1 CR-septicemia
1unspecified
11/17, 65%
1/6, 17%
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702
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Table 2 continued.
Criteria
Clinical
manifestation
Number
of papers
Present
[8, 27, 32–34, 43,
128–136, 166]
16
U
[41, 46–48, 80,
81, 85–93,
117, 118, 120,
125, 127, 142,
146, 147,
158, 162, 163,
169, 171]
28
U
Author
Resolve
after
CVC
removal
CVC-drawn
blood culture
positive
CVC-tip
culture
positive
Peripheral
blood culture
positive
EITHER CVC
OR peripheral
blood culture
positive
Differential
between
CVC and
peripheral
culturesa
CVC insertion
site culture
positive
Defined
as catheterassociated or
catheterrelated
Number of
papers published
from 2006
onwards (n 5 54)
d
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[159, 165, 173]
[64, 69, 107–112,
114–116]
U
U
8 CABSI;
3 CRBSI;
3 CR-sepsis;
2 unspecified
8/16, 50%
20 CRBSI;
8/28, 29%
5 CR-septicemia;
1 CA-bacteremia;
2 unspecified
3
U
11
U
U
1 CRBSI;
1 CR sepsis;
1 unspecified
0/3, 0%
5 CRBSI;
1/11, 9%
3 CR septicemia;
3 unspecified
1 CRBSI;
2 unspecified
[94, 97, 103]
3
U
[151–155]
5
.1000 CFUs
[61, 62, 72,
74–76, 126, 167]
8
U
[92, 157, 168, 173]
4
U
[151–155]
5
U
[145, 157]
2
[168,173]
2
U
0/3, 0%
5 CRBSI
0/5, 0%
6 CRBSI;
1/8, 13%
2 CR-septicemia
[82–84, 113, 119,
121–124, 126,
151–157, 167, 173]
Total number of papers
with cited criteria
4 CRBSI
2/4, 50%
5 CRBSI
0/5, 0%
U
2 CRBSI
1/2, 50%
U
CRBSI
0/2; 0%
2 unspecified,
3/19, 16%
U
U
U
19
U
2 CR-septicemia
14 CRBSI;
1 CR infection
135
8
50
50
67
46
45
17
54
Alternative definitions given within one study have been included separately within table.
Abbreviations: CABSI, catheter-associated bloodstream infection; CR, catheter-related; CVC, central venous catheter.
a
Differential is defined as (1) quantitative difference in colony forming unit load (including 1 positive and 1 negative culture result) or (2) differential time to positive detection of growth in blood cultures.
RESULTS
As noted above, 190 articles were included in our review. Table 1
lists the definitions used, demonstrating a large amount of
variability. Only 14 of these articles predated the development of
the Centers for Disease Control and Prevention (CDC) CRBSI
definition (ie, articles were published before or during 1990).
There were 16 unique CRBSI and/or CABSI definitions. A total
of 39 articles that reported CRBSI and/or CABSI in patients with
cancer did not cite or reference any definition of CRBSI and/or
CABSI [174–212]. Despite several recent articles referring to
central line–associated bloodstream infection [213–215], we did
not find this term in the studies included in our review.
Of the remaining 151 studies, the most common definition
cited was that stated by the CDC (n 5 39) [8, 23–60]. This
definition [13] is applied often, but its use is not limited to
surveillance studies. The CDC definition is the only apparent
definition that specifies a difference between CABSI and CRBSI.
However, despite referencing the CDC definitions, the actual
definition used varied from the CDC definitions (eg, some articles referred to CDC definitions but defined CRBSI with
positive results of culture of percutaneously and CVC-obtained
blood samples without any differential considerations). In addition, the term CABSI was used often interchangeably with
CRBSI. A few studies cited CABSI as the outcome measure,
which does not include catheter tip cultures [32–36].
The next most frequently used definitions included aspects of
the CDC definition; one definition included a positive catheter
tip culture result (ie, requiring catheter removal; n 5 19) [61–79],
and the other by the Infectious Diseases Society of America
(IDSA) included a positive catheter tip culture result or a differential growth rate or quantitative results between percutaneously
and CVC-obtained blood cultures (n 5 18) [41, 44, 48, 55,
80–93].
Other definitions that do not require the presence of clinical
manifestations were requirement of a positive result of culture of
CVC blood sample only (n 5 12) [94–105], positive result of blood
culture from both CVC and peripheral blood (n 5 11) [106–116],
differential between CVC and peripheral blood cultures (n 5 11)
[117–127], any positive blood culture result (n 5 9) [128–136],
and positive result of culture of a CVC exit site sample (n 5 6)
[145–150]. Some studies defined CRBSI as improvement of clinical
manifestations after removal of the CVC (n 5 8) [137–144].
Table 2 shows the various components included for each
definition. Fifty-four definitions of CRBSI and/or CABSI
were included in 42 articles published since 2006. Among all
included articles, clinical manifestations were most frequently
cited (n 5 135). Three studies citing clinical manifestations of
infection were concerned only with symptoms if they were related to flushing or manipulation of the CVC, as shown in Table
2 [156, 157, 173]. Positive peripheral blood culture result was the
next most frequently cited criterion (n 5 67), with a similar
number of definitions requiring a positive catheter tip culture
result (n 5 50) or a positive CVC blood culture result (n 5 50).
Table 2 also shows the proportion of studies with a combination
of criteria that were published more recently (ie, during or after
2006). Although obvious trends were not apparent, 65% of 17
studies requiring clinical manifestations and peripheral blood
cultures were published during or after 2006.
For the diagnosis of CRBSI without CVC removal, experts
have recommended use of quantitative blood cultures or measurement of the differential time to positivity of blood cultures
[19]. Differential microbial load or time to positivity between
peripheral and CVC blood cultures were included as criteria for
CRBSI in 45 studies in our review, with only 11 of these studies
published within the past 5 years. One study included a definition of CRBSI that compared the results of quantitative blood
cultures of the lumens of double-lumen CVCs [82].
DISCUSSION
Despite past efforts to attain a standard definition for CRBSI or
CABSI [15, 19], a consistent definition for such infections in
patients with cancer has not yet been used in the literature.
A considerable number of articles (39 [21%] of 190) did not
report the definition or cite a reference for a definition, but these
were included in our review to emphasize the lack of uniformity
in the study of CRBSI or CABSI. Although the CDC definition
was most frequently cited, this accounted for only 39 (26%) of
the 151 studies that provided a definition for CRBSI or CABSI as
an outcome. After 1990, CDC definitions accounted for 34 (25%)
of the 137 definitions used. Surprisingly, we found 26 definitions
used in studies of CRBSI and/or CABSI in patients with cancer.
Criteria including clinical manifestations alone are not conclusive for defining a CRBSI or CABSI. A diagnosis of CRBSI
requires removal of the catheter for quantitative or semiquantitative catheter tip culture, with concordant growth on
culture of a percutaneously obtained blood sample, at those institutions not using differential time to positivity or quantitative
blood cultures to diagnose CRBSI [11]. However, only 15%–25%
of CVCs removed because of suspected infection actually have
significant microbial growth, which implies that clinical manifestations of such infections are not sensitive or specific [216].
Definitions of CABSI do not require catheter removal and catheter tip culture, but this term needs to be applied with greater
homogeneity with the realization that its original intent is for
surveillance purposes and comparisons of rates of infection in
different patient care units or different institutions; lastly, it
should be used with a clear understanding that CABSI has reduced specificity and an increased number of false-positive results
[13]. To avoid the removal of a catheter and the risk associated
with placement of a new catheter, other diagnostic tests, such as
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differential quantitative blood cultures of samples taken simultaneously from the catheter and a peripheral vein, have been
proposed [216]. The IDSA has adopted this as one of their
measures in the diagnosis of CRBSI, and we found 15 studies that
used this microbiologic method. However, despite its high specificity, this culture method is labor intensive and costly [216].
The measurement of differential time to positivity between
cultures of CVC-obtained and percutaneously obtained blood
samples has also been used to diagnose CRBSI. The CDC and
IDSA have incorporated this criterion into their definitions. This
is defined as the time to positive detection of growth in peripheral blood cultures minus that of the CVC-obtained blood
cultures. Blot et al [216] used a cutoff value of 1120 minutes,
the differential time to positivity of the paired blood samples,
and reported 91% specificity and 94% sensitivity for the diagnosis of CRBSI. However, because the accuracy of this method
depends on inoculum size, it is important that the same volume
of blood per bottle be submitted for culture. This may be
a problem when it is difficult to obtain percutaneous blood
samples (eg, in infants and children) [19]. Nevertheless, this is
a preferred method for the diagnosis of CRBSI in institutions
that do not perform quantitative blood cultures [19, 93]. Of
note, only 45 (30%) of 190 studies in our review used differential
time to positivity of blood cultures.
Of note, 67 (44%) of 151 CRBSI definitions provided in
studies required performance of peripheral blood cultures. Some
investigators have suggested that peripheral cultures are not
necessary in the assessment of febrile patients with cancer [95].
However, omission of percutaneously obtained blood cultures
would reduce specificity and may lead to excessive antimicrobial
use, and it would lessen the rigor of epidemiological studies and
the interpretation of trials designed to measure the impact of
interventions aimed at reducing CRBSIs.
Because of the reluctance to obtain peripheral blood samples
from children with a CVC in place, there has been interest in
obtaining samples from different CVC lumens and using
quantitative blood cultures or assessing differential time to
positivity to diagnose CRBSI. A 5-fold difference in colony
forming units or a differential growth time of $180 minutes
between samples obtained from different catheter lumens has
been suggested as a way to define CRBSI [19, 82, 84]. However,
only 2 studies in our review that cited use of the IDSA definition
used this technique [82, 84]. Of interest, a recent study that
investigated CRBSI in double- and triple-lumen catheters in
a population that included patients with cancer concluded that
blood samples should be obtained from all lumens [217].
Capdevilla et al [16] applied a definition of isolation of $100
colony-forming units/mL in a quantitative blood culture from
a CVC as highly suggestive of a CRBSI. Gaur et al [84] found
that this definition had a positive predictive value of 79%–92%,
depending on the approach used to analyze the data.
704
d
CID 2011:53 (1 October)
d
IMMUNOCOMPROMISED HOSTS
An important factor to consider in patients with cancer is the
requirement that signs and symptoms of infection be present to
meet criteria for CRBSI [218]. However, corticosteroid treatment reduces signs of inflammation, and neutropenic patients
have a limited ability to produce purulent exudates. Consequently, signs and symptoms of CVC-related infections may
differ in this population, although it is not yet known whether
a definition specific to patients with cancer is necessary.
Our review has shown that, because of the many definitions
used, it is difficult to make comparisons across studies. The
incidences of CRBSI or CABSI vary considerably depending on
the definition adopted. Future research should determine
whether a different definition of CRBSI and CABSI in adult and
pediatric patients with cancer is needed.
Notes
Acknowledgments. We thank Elizabeth Uleryk, for her valuable assistance with the search strategies necessary for this review, and Rhonda
Adams for retrieving many of the articles that we reviewed.
Financial support. This work was supported by the Canadian Institutes of Health Research (New Investigator Grant to L. S.) and the employees of Kraft Canada Inc.
Potential conflicts of interest. All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
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