Deﬁning Bloodstream Infections Related to Central Venous ... · Catheter Related Bloodstream Infection (CRBSI) deﬁned as: c) Clinical manifestations and at least one positive

I N V I T E D A R T I C L E I M M U N O C O M P R O M I S E D H O S T SDavid R. Snydman, Section Editor

Defining Bloodstream Infections Related toCentral Venous Catheters in Patients WithCancer: A Systematic Review

Deborah Tomlinson,1 Leonard A. Mermel,2,3 Marie-Chantal Ethier,1 Anne Matlow,4 Biljana Gillmeister,1 andLillian Sung1,5

1Program in Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada; 2Warren Alpert Medical School of BrownUniversity, Providence, Rhode Island; 3Department of Epidemiology & Infection Control, Rhode Island Hospital, Providence, Rhode Island; 4Division ofInfectious 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 catheter-

associated 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 (n5 39) and the Infectious Diseases Society of America (n5 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 occa-

sionally, 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

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 un-

accompanied 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 cul-

tures [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 po-

tential catheter removal; and this outcome is an im-

portant end point for supportive care clinical trials.

The gold standard for diagnosis of CRBSI is the iso-

lation of the same organism from a peripheral blood

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� The Author 2011. Published by Oxford University Press on behalf of the InfectiousDiseases Society of America. All rights reserved. For Permissions, please e-mail:[email protected]/2011/537-0012$14.00DOI: 10.1093/cid/cir523

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culture as that isolated from the tip of the removed CVC [12].

However, this definition is problematic, because the vast ma-

jority 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 pub-

lished guideline for the prevention of intravascular catheter in-

fection 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 in-

fections 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 rig-

orous, unambiguous definition is required (eg, for CRBSI). The

latter definition requires percutaneously obtained blood sam-

ples 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 percu-

taneously 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 labo-

ratory. Thus, surveillance definitions (ie, for CABSI) are used to

compare the incidence of bloodstream infections associated

with CVCs in different units or institutions. Surveillance defi-

nitions 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 ap-

parent. 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.

METHODS

Search Strategy for Identification of StudiesWe 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

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 re-

view 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 ReviewArticles 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 blood-

stream 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.

Figure 1. Flow diagram of study identification and selection fromliterature search.

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Table 1. Catheter-Related Bloodstream Infection (CRBSI) and Catheter-Associated Bloodstream Infection (CABSI) Definitions Used in190 Studies Involving Patients With Cancer

Definition/reference used or cited in study

Number

of studies

Study

reference

1. Centers for Disease Control and Prevention (CDC)/National Nosocomial Infections Surveillance(NNIS)/Healthcare Infection Control Practices Advisory Committee (HICPAC) [12, 13, 21, 22]:

Catheter Associated Bloodstream Infection (CABSI) defined as:a) Bacteremia/fungemia in a patient with an intravascular catheter with at least one positive bloodculture 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 useduring 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 noother apparent source, with either positive semiquantitative (.15 CFU/catheter segment) orquantitative (.103 CFU/catheter segment) culture, whereby the same organism (species andantibiogram) is isolated from the catheter segment and a peripheral blood sample; simulta-neous quantitative cultures of blood samples with a ratio of $3:1 (CVC vs. peripheral); dif-ferential 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 fromblood (preferably from a peripheral vein) of a patient with accompanying symptoms ofbloodstream infection and no other apparent source of infection [12, 22]

e) CDC definition cited but not confirmed in textNote: CDC definition may not have been cited in all cases, but definition was comparable.

539* a) [8, 23–31]

b) [32–43]c) [44–48]d) [43, 49–54]e) [55–60]

2. Requires positive catheter tip/segment culture and positive peripheral blood culture (ie, requirescatheter removal).

(Ref #72, 73 Alternative of purulence from insertion site)(Ref #61 Definition also includes positive cultures from CVC)

19 [61–79]

3. Infectious Disease Society of America [11]

Bacteremia or fungemia in a patient who has an intravascular device and $1 positive result ofculture 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 (withthe exception of the catheter). One of the following should be present: a positive result ofsemiquantitative ($15 CFU per catheter segment) or quantitative ($1000 CFU per cathetersegment) culture, whereby the same organism (species and antibiogram) is isolated froma catheter segment and a peripheral blood sample; simultaneous quantitative cultures of bloodsamples with a ratio of $3:1 (CVC vs. peripheral); differential time to positivity (ie, a positiveresult of culture from a CVC is obtained at least 2 h earlier than is a positive result of culturefrom peripheral blood).

Note: IDSA definition may not have been cited in all cases, but definition was comparable

18* [41, 44, 48, 55,80–93]

4. 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 lowernumber 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 notinclude positive blood cultures).

8 [137–144]

9. Includes positive culture swab from CVC site (may include other positive cultures from blood orcatheter tip).

6 [145–150]

10. a) Greater than 10-fold increase in CFUs of organism/ml of blood obtained through catheter incomparison with simultaneously obtained peripheral blood cultures;

b) In the absence of peripheral blood cultures, .1000 CFUs of organism/ml of blood obtainedthrough the catheter; OR

c) Positive catheter-tip culture when removed in clinical setting.

5 [151–155]

11. a) $10 CFU/ml through device compared with peripheral;

b) .103 CFU/ml through device with negative peripheral cultures;c) Same organism from CVC sample and from swab of site; ORd) Relationship between CVC manipulation and onset of fever and rigors.

1 [156]

12. 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; ORd) Isolation of same pathogen from blood and purulent material draining from catheter exit site orsubcutaneous tunnel.

1 [157]


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Where articles cited definite, probable, and possible defi-

nitions of CRBSI, only the definite definitions were reviewed.

We also examined whether there was a distinction between

CRBSI and CASBI definitions. Definitions were extracted,

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 1 continued.

Definition/reference used or cited in study

Number

of studies

Study

reference

13. Temperature$ 38Cwith positive blood cultures derived from the catheter and at least one of thefollowing:

a) Negative peripheral blood cultures;b) If simultaneously taken peripheral blood cultures were also positive, cultures from the catheterbecame 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-quantitativecatheter 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.

1 [158]

14. Clinical syndrome compatible with sepsis in the absence of any clinically apparent source otherthan a central venous access device.

1 [159]

15. Clinical manifestations and positive venipuncture blood cultures. 1 [160]

16. Clinical manifestation of infection in absence of any other source of bloodstream infection exceptthe 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 greatercolony count than a quantitative culture of concurrently drawn peripheral venous bloodgrowing the same organism.

2 [162, 163]

17. a) Clinical signs of infection, but no other identifiable focus of infection; AND

b) Isolation of the same microorganism from blood and exudates from catheter exit site inpresence of signs and inflammation, or isolation of same microorganism from blood andcatheter tip.

1 [164]

18. High clinical suspicion with fever, requiring catheter removal. 1 [165]

19. a) Recognized pathogen cultured from one or more blood cultures;

b) Common skin contaminant cultured from two or more blood cultures, both drawn at separateoccasions; OR

c) Skin contaminant identified from at least one blood culture in association with clinical signs

1 [166]

20. a) Culture of removed catheter tip with same organism isolated from the catheter tip and pe-ripheral blood; OR

b) Indicative differential time to positivity (ie, blood culture fromHickman became positive at least2 h earlier than positive simultaneously-drawn peripheral blood culture)

1 [167]

21. No other primary source of infection identified with

a) At least two sets of blood cultures positive for the same organism; ORb) One positive set accompanied by a positive drainage or catheter tip culture.

1 [168]

22. a) Clinical manifestations and positive culture; ANDb) Catheter colonized with same organism; OR CVC blood culture$10-fold CFUs than peripheralblood culture.

1 [169]

23. Increase in temperature (.38.5 C), associated with chills or rigors which settled spontaneouslyor with antipyretic measures, in an otherwise well child, following flushing of the Broviaccatheter; subsequent culture of Broviac intraluminal catheter fluid was undertaken to confirminfection.

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 oneperipheral) are positive; AND

b) Insertion site swab, CVC tip culture or positive CVC intraluminal (lock) culture yields growthidentical to blood cultures.

1 [172]

26. 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-obtainedperipheral blood culture;

c) Isolation of same pathogen from catheter tip and blood; ORd) Isolation of same organism from blood and from purulent material at exit site or subcutaneoustunnel.

1 [173]

27. Not defined 39 [174–212]

Abbreviations: CFU, colony forming unit; CVC, central venous catheter.a Four studies used two definitions.


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Table 2. Criteria Associated With Definitions of Catheter-Related Bloodstream Infection (CRBSI) in Patients With Cancer

Author

Number

of papers

Criteria

Defined

as catheter-

associated or

catheter-

related

Number of

papers published

from 2006

onwards (n 5 54)

Clinical

manifestation

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

positivePresent

Resolve

after

CVC

removal

[137–144] 8 U U U 3 CRBSI;

1 CABSI2 CR septicemia2 unspecified

0/8, 0%

[77, 172] 2 U U U U 2 CRBSI 1/2, 50%

[158, 162, 163] 3 U U U 3 CRBSI 1/3, 33%

[150, 172] 2 U U U U 1 CR-infection;1 CRBSI

1/2, 50%

[23, 51, 53, 58–60,106, 147, 148]

9 U U U 6 CRBSI;

2 unspecified;1 CABSI

2/9, 22%

[141, 147] 2 U U U 1 CRBSI;

1 unspecified

0/2, 0%

[28–30, 95, 96,98–101,104, 105,146, 170]

13 U U 6 CRBSI;

1 CABSI;1 CA-septicemia3 CR-septicemia;1 intra-catheterinfection

1 unspecified

4/13, 31%

[52, 63, 65–68,70, 71, 73,78, 80, 81,127, 164]

14 U U U 12 CRBSI1 CR-septicemia1 CABSI

3/14, 21%

[38, 43, 48–50,54, 79, 93,142, 146,149, 169]

12 U U U 10 CRBSI;

1 CR-septicemia1 unspecified

3/12, 25%

[31, 102, 104] 3 U U 3 CRBSI 2/3, 67%

[44, 127] 2 U U U 1 CRBSI;

1 CR-septicemia

1/2, 50%

[24–26, 31, 35–37, 39–42,45, 55–57,103, 160]

17 U U 7 CABSI;4 unspecified;6 CRBSI

11/17, 65%

[38, 50, 142, 146,149, 164]

6 U U U 4 CRBSI;

1 CR-septicemia1unspecified

1/6, 17%

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Table 2 continued.

Author

Number

of papers

Criteria

Defined

as catheter-

associated or

catheter-

related

Number of

papers published

from 2006

onwards (n 5 54)

Clinical

manifestation

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

positivePresent

Resolve

after

CVC

removal

[8, 27, 32–34, 43,128–136, 166]

16 U U 8 CABSI;3 CRBSI;3 CR-sepsis;2 unspecified

8/16, 50%

[41, 46–48, 80,81, 85–93,117, 118, 120,125, 127, 142,146, 147,158, 162, 163,169, 171]

28 U U 20 CRBSI;

5 CR-septicemia;1 CA-bacteremia;2 unspecified

8/28, 29%

[159, 165, 173] 3 U 1 CRBSI;1 CR sepsis;1 unspecified

0/3, 0%

[64, 69, 107–112,114–116]

11 U U 5 CRBSI;

3 CR septicemia;3 unspecified

1/11, 9%

[94, 97, 103] 3 U 1 CRBSI;2 unspecified

0/3, 0%

[151–155] 5 .1000 CFUs 5 CRBSI 0/5, 0%

[61, 62, 72,74–76, 126, 167]

8 U U 6 CRBSI;

2 CR-septicemia

1/8, 13%

[92, 157, 168, 173] 4 U U 4 CRBSI 2/4, 50%

[151–155] 5 U 5 CRBSI 0/5, 0%

[145, 157] 2 U U 2 CRBSI 1/2, 50%

[168,173] 2 U U CRBSI 0/2; 0%

[82–84, 113, 119,121–124, 126,151–157, 167, 173]

19 U 2 unspecified,

2 CR-septicemia14 CRBSI;1 CR infection

3/19, 16%

Total number of paperswith cited criteria

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.

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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 ar-

ticles referred to CDC definitions but defined CRBSI with

positive results of culture of percutaneously and CVC-obtained

blood samples without any differential considerations). In ad-

dition, 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; n5 19) [61–79],

and the other by the Infectious Diseases Society of America

(IDSA) included a positive catheter tip culture result or a differ-

ential 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 (n5 12) [94–105], positive result of blood

culture from both CVC and peripheral blood (n5 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 re-

lated 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 (n5 50) or a positive CVC blood culture result (n5 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 mea-

surement 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 defini-

tion 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 con-

clusive for defining a CRBSI or CABSI. A diagnosis of CRBSI

requires removal of the catheter for quantitative or semi-

quantitative catheter tip culture, with concordant growth on

culture of a percutaneously obtained blood sample, at those in-

stitutions 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 mani-

festations of such infections are not sensitive or specific [216].

Definitions of CABSI do not require catheter removal and cath-

eter 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 re-

duced 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 simul-

taneously 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 spec-

ificity, 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 pe-

ripheral 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 di-

agnosis 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.

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 treat-

ment reduces signs of inflammation, and neutropenic patients

have a limited ability to produce purulent exudates. Conse-

quently, 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 assis-

tance 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 In-

stitutes of Health Research (New Investigator Grant to L. S.) and the em-

ployees 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.

References

1. de Jonge RC, Polderman KH, Gemke RJ. Central venous catheter use

in the pediatric patient: mechanical and infectious complications.

Pediatr Crit Care Med 2005; 6:329–39.

2. Division of Nosocomial and Occupational Infectious Diseases, Bureau

of Infectious Diseases, Laboratory Centre for Disease Control, Health

Canada. Preventing infections associated with indwelling intravascular

access devices. Can Commun Dis Rep 1997; 23(Suppl 8):Si–iii, 1–32,

i–iv, 1–16.

3. National Nosocomial Infections Surveillance System. National Nos-

ocomial Infections Surveillance (NNIS) System Report, data sum-

mary from January 1992 through June 2004, issued October 2004. Am

J Infect Control 2004; 32:470–85.

4. Boersma RS, Schouten HC. Clinical practices concerning central venous

catheters in haematological patients. Eur J Oncol Nurs 2010; 14:200–4.

5. Rosenthal VD, Guzman S, Migone O, Crnich CJ. The attributable

cost, length of hospital stay, and mortality of central line-associated

bloodstream infection in intensive care departments in Argentina:

a prospective, matched analysis. Am J Infect Control 2003; 31:

475–80.

6. Worth LJ, Brett J, Bull AL, McBryde ES, Russo PL, Richards MJ.

Impact of revising the National Nosocomial Infection Surveillance

System definition for catheter-related bloodstream infection in ICU:

reproducibility of the National Healthcare Safety Network case defi-

nition in an Australian cohort of infection control professionals. Am J

Infect Control 2009; 37:643–8.

7. Boersma RS, Jie KS, Verbon A, van Pampus EC, Schouten HC.

Thrombotic and infectious complications of central venous catheters

in patients with hematological malignancies. Ann Oncol 2008; 19:

433–42.

8. Dettenkofer M, Ebner W, Bertz H, et al. Surveillance of nosocomial

infections in adult recipients of allogeneic and autologous bone


at FundaÃ§Ã

£o CoordenaÃ

§Ã£o de A

perfeiÃ§oam




ownloaded from


marrow and peripheral blood stem-cell transplantation. Bone Mar-

row Transplant 2003; 31:795–801.

9. Salzman MB, Rubin LG. Intravenous catheter-related infections. Adv

Pediatr Infect Dis 1995; 10:337–68.

10. Hiemenz J, Skelton J, Pizzo PA. Perspective on the management of

catheter-related infections in cancer patients. Pediatr Infect Dis 1986;

5:6–11.

11. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for

the diagnosis and management of intravascular catheter-related in-

fection: 2009 Update by the Infectious Diseases Society of America.

Clin Infect Dis 2009; 49:1–45.

12. Pearson ML, Hierholzer WJ Jr, Garner JS, et al. Guideline for pre-

vention of intravascular device-related infections. Am J Infect Control

1996; 24:262–93.

13. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the pre-

vention of intravascular catheter-related infections. Am J Infect

Control 2011; 39(Suppl 1):S1–34.

14. Raad II, Bodey GP. Infectious complications of indwelling vascular

catheters. Clin Infect Dis 1992; 15:197–208.

15. Mermel LA. Defining intravascular catheter-related infections: a plea

for uniformity. Nutrition 1997; 13(Suppl 4):2S–4S.

16. Capdevila JA, Planes AM, Palomar M, et al. Value of differential

quantitative blood cultures in the diagnosis of catheter-related sepsis.

Eur J Clin Microbiol Infect Dis 1992; 11:403–7.

17. Fatkenheuer G, Buchheidt D, Cornely OA, et al. Central venous

catheter (CVC)-related infections in neutropenic patients—guidelines

of the Infectious Diseases Working Party (AGIHO) of the German

Society of Hematology and Oncology (DGHO). Ann Hematol 2003;

82(Suppl 2):S149–57.

18. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline

for the use of antimicrobial agents in neutropenic patients with

cancer: 2010 update by the Infectious Diseases Society of America.

Clin Infect Dis 2011; 52:e56–93.

19. Flynn PM. Diagnosis and management of central venous catheter-

related bloodstream infections in pediatric patients. Pediatr Infect Dis

J 2009; 28:1016–7.

20. Worth LJ, Slavin MA, Brown GV, Black J. Catheter-related blood-

stream infections in hematology: time for standardized surveillance?

Cancer 2007; 109:1215–26.

21. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC defi-

nitions for nosocomial infections. Am J Infect Control 1988; 16:128–40.

22. Pearson ML. Guideline for prevention of intravascular device-related

infections. Hospital Infection Control Practices Advisory Committee.

Infect Control Hosp Epidemiol 1996; 17:438–73.

23. Chang L, Tsai JS, Huang SJ, Shih CC. Evaluation of infectious com-

plications of the implantable venous access system in a general

oncologic population. Am J Infect Control 2003; 31:34–9.

24. Chelliah A, Heydon KH, Zaoutis TE, et al. Observational trial of

antibiotic-coated central venous catheters in critically ill pediatric

patients. Pediatr Infect Dis J 2007; 26:816–20.

25. Ishizuka M, Nagata H, Takagi K, Kubota K. Total parenteral nutrition

is a major risk factor for central venous catheter-related bloodstream

infection in colorectal cancer patients receiving postoperative che-

motherapy. Eur Surg Res 2008; 41:341–5.

26. Simon A, Fleischhack G, Hasan C, Bode U, Engelhart S, Kramer MH.

Surveillance for nosocomial and central line-related infections among

pediatric hematology-oncology patients. Infect Control Hosp Epi-

demiol 2000; 21:592–6.

27. Simon A, Fleischhack G, Wiszniewsky G, Hasan C, Bode U, Kramer

MH. Influence of prolonged use of intravenous administration sets in

paediatric cancer patients on CVAD-related bloodstream infection

rates and hospital resources. Infection 2006; 34:258–63.

28. Simon A, Ammann RA, Wiszniewsky G, Bode U, Fleischhack G,

Besuden MM. Taurolidine-citrate lock solution (TauroLock) signifi-

cantly reduces CVAD-associated grampositive infections in pediatric

cancer patients. BMC Infect Dis 2008; 8:102.

29. Keung YK, Watkins K, Chen SC, Groshen S, Levine AM, Douer D.

Increased incidence of central venous catheter-related infections in bone

marrow transplant patients. Am J Clin Oncol 1995; 18:469–74.

30. Keung YK, Watkins K, Chen SC, Groshen S, Silberman H, Douer D.

Comparative study of infectious complications of different types

of chronic central venous access devices. Cancer 1994; 73:2832–7.

31. Abedin S, Kapoor G. Peripherally inserted central venous catheters are

a good option for prolonged venous access in children with cancer.

Pediatr Blood Cancer 2008; 51:251–5.

32. Adler A, Yaniv I, Solter E, et al. Catheter-associated bloodstream in-

fections in pediatric hematology-oncology patients: factors associated

with catheter removal and recurrence. J Pediatr Hematol Oncol 2006;

28:23–8.

33. Adler A, Yaniv I, Steinberg R, et al. Infectious complications of im-

plantable ports and Hickman catheters in paediatric haematology-

oncology patients. J Hosp Infect 2006; 62:358–65.

34. Allen RC, Holdsworth MT, Johnson CA, et al. Risk determinants for

catheter-associated blood stream infections in children and young

adults with cancer. Pediatr Blood Cancer 2008; 51:53–8.

35. Boswald M, Lugauer S, Regenfus A, et al. Reduced rates of catheter-

associated infection by use of a new silver-impregnated central venous

catheter. Infection 1999; 27(Suppl 1):S56–60.

36. Chaberny IF, Ruseva E, Sohr D, et al. Surveillance with successful

reduction of central line-associated bloodstream infections among

neutropenic patients with hematologic or oncologic malignancies.

Ann Hematol 2009; 88:907–12.

37. Horvath B, Norville R, Lee D, Hyde A, Gregurich M, Hockenberry M.

Reducing central venous catheter-related bloodstream infections in

children with cancer. Oncol Nurs Forum 2009; 36:232–8.

38. Moller T, Borregaard N, Tvede M, Adamsen L. Patient education—a

strategy for prevention of infections caused by permanent central

venous catheters in patients with haematological malignancies:

a randomized clinical trial. J Hosp Infect 2005; 61:330–41.

39. Shah SS, Manning ML, Leahy E, Magnusson M, Rheingold SR, Bell

LM. Central venous catheter-associated bloodstream infections in

pediatric oncology home care. Infect Control Hosp Epidemiol 2002;

23:99–101.

40. Worth LJ, Seymour JF, Slavin MA. Infective and thrombotic com-

plications of central venous catheters in patients with hematological

malignancy: prospective evaluation of nontunneled devices. Support

Care Cancer 2009; 17:811–8.

41. Worth LJ, Black J, Seymour JF, Thursky KA, Slavin MA. Surveillance

for catheter-associated bloodstream infection in hematology units:

quantifying the characteristics of a practical case definition. Infect

Control Hosp Epidemiol 2008; 29:358–60.

42. Yoshida J, Ishimaru T, Kikuchi T, et al. Central line-associated blood-

stream infection: is the hospital epidemiology of methicillin-resistant

Staphylococcus aureus relevant? J Infect Chemother 2010; 16:33–7.

43. Luft D, Schmoor C, Wilson C, et al. Central venous catheter-

associated bloodstream infection and colonisation of insertion site

and catheter tip: what are the rates and risk factors in haematology

patients? Ann Hematol 2010; 89:1265–75.

44. Hung MC, Chen CJ, Wu KG, Hung GY, Lin YJ, Tang RB. Sub-

cutaneously implanted central venous access device infection in pediatric

patients with cancer. J Microbiol Immunol Infect 2009; 42:166–71.

45. Kaufman LJ, Clark TW, Roberts DA, et al. Do simultaneous bilateral

tunneled infusion catheters in patients undergoing bone marrow

transplantation increase catheter-related complications? J Vasc Interv

Radiol 2004; 15:57–61.

46. Ruschulte H, Franke M, Gastmeier P, et al. Prevention of central

venous catheter related infections with chlorhexidine gluconate im-

pregnated wound dressings: a randomized controlled trial. Ann

Hematol 2009; 88:267–72.

47. Stamou SC, Maltezou HC, Pourtsidis A, Psaltopoulou T, Skondras C,

Aivazoglou T. Hickman-Broviac catheter-related infections in chil-

dren with malignancies. Mt Sinai J Med 1999; 66:320–6.


at FundaÃ§Ã

£o CoordenaÃ

§Ã£o de A

perfeiÃ§oam




ownloaded from


48. Raad I, Hanna H, Boktour M, et al. Management of central venous

catheters in patients with cancer and candidemia. Clin Infect Dis

2004; 38:1119–27.

49. Abi-Said D, Raad I, Umphrey J, et al. Infusion therapy team and

dressing changes of central venous catheters. Infect Control Hosp

Epidemiol 1999; 20:101–5.

50. Chambers ST, Sanders J, Patton WN, et al. Reduction of exit-site in-

fections of tunnelled intravascular catheters among neutropenic pa-

tients by sustained-release chlorhexidine dressings: results from a

prospective randomized controlled trial. J Hosp Infect 2005; 61:53–61.

51. Karthaus M, Doellmann T, Klimasch T, Krauter J, Heil G, Ganser A.

Central venous catheter infections in patients with acute leukemia.

Chemotherapy 2002; 48:154–7.

52. Nosari A, Nichelatti M, De Gasperi A, et al. Incidence of sepsis in

central venous catheter-bearing patients with hematologic malig-

nancies: preliminary results. J Vasc Access 2004; 5:168–73.

53. Yucel N, Lefering R, Maegele M, et al. Reduced colonization and

infection with miconazole-rifampicin modified central venous cath-

eters: a randomized controlled clinical trial. J Antimicrob Chemother

2004; 54:1109–15.

54. Velasco M, Rovira M, Mensa J, Almela M, Carreras E. Utility of daily

catheter-drawn blood cultures to predict catheter-related bacteremia

in hematopoietic stem cell transplanted patients. Turkish J Hematol

2009; 26:67–71.

55. Pasqualotto AC, de Moraes AB, Zanini RR, Severo LC. Analysis of

independent risk factors for death among pediatric patients with

candidemia and a central venous catheter in place. Infect Control

Hosp Epidemiol 2007; 28:799–804.

56. Gebauer B, Teichgraber UM, Werk M, Beck A, Wagner HJ. Sono-

graphically guided venous puncture and fluoroscopically guided

placement of tunneled, large-bore central venous catheters for bone

marrow transplantation—High success rates and low complication

rates. Support Care Cancer 2008; 16:897–904.

57. Liu CY, Huang LJ, Wang WS, et al. Candidemia in cancer patients:

impact of early removal of non-tunneled central venous catheters on

outcome. J Infect 2009; 58:154–60.

58. Rotstein C, Brock L, Roberts RS. The incidence of first Hickman

catheter-related infection and predictors of catheter removal in cancer

patients. Infect Control Hosp Epidemiol 1995; 16:451–8.

59. Ruggiero A, Barone G, Margani G, Nanni L, Pittiruti M, Riccardi R.

Groshong catheter-related complications in children with cancer.

Pediatr Blood Cancer 2010; 54:947–51.

60. Nosari AM, Nador G, de Gasperi A, et al. Prospective monocentric

study of non-tunnelled central venous catheter-related complications

in hematological patients. Leuk Lymphoma 2008; 49:2148–55.

61. Anaissie E, Samonis G, Kontoyiannis D, et al. Role of catheter colo-

nization and infrequent hematogenous seeding in catheter-related

infections. Eur J Clin Microbiol Infect Dis 1995; 14:134–7.

62. Andrivet P, Bacquer A, Ngoc CV, et al. Lack of clinical benefit from

subcutaneous tunnel insertion of central venous catheters in immu-

nocompromised patients. Clin Infect Dis 1994; 18:199–206.

63. Bakker J, van Overhagen H, Wielenga J, et al. Infectious com-

plications of radiologically inserted Hickman catheters in patients with

hematologic disorders. Cardiovasc Intervent Radiol 1998; 21:116–21.

64. Bock SN, Lee RE, Fisher B, et al. A prospective randomized trial

evaluating prophylactic antibiotics to prevent triple-lumen catheter-

related sepsis in patients treated with immunotherapy. J Clin Oncol

1990; 8:161–9.

65. Bouza E, Alvarado N, Alcala L, Perez MJ, Rincon C, Munoz P.

A randomized and prospective study of 3 procedures for the diagnosis

of catheter-related bloodstream infection without catheter with-

drawal. Clin Infect Dis 2007; 44:820–6.

66. Bouza E, Munoz P, Lopez-Rodriguez J, et al. A needleless closed

system device (CLAVE) protects from intravascular catheter tip and

hub colonization: a prospective randomized study. J Hosp Infect

2003; 54:279–87.

67. Butt T, Afzal RK, Ahmad RN, Hussain I, Anwar M. Central venous

catheter-related bloodstream infections in cancer patients. J Coll

Physicians Surg Pak 2004; 14:549–52.

68. Carbon RT, Lugauer S, Geitner U, et al. Reducing catheter-associated

infections with silver-impregnated catheters in long-term therapy of

children. Infection 1999; 27(Suppl 1):S69–73.

69. Goey SH, Verweij J, Bolhuis RL, et al. Tunnelled central venous

catheters yield a low incidence of septicaemia in interleukin-2-treated

patients. Cancer Immunol Immunother 1997; 44:301–4.

70. Koldehoff M, Zakrzewski JL. Taurolidine is effective in the treatment

of central venous catheter-related bloodstream infections in cancer

patients. Int J Antimicrob Agents 2004; 24:491–5.

71. Liaw CC, Chen JS, Chang HK, Huang JS, Yang TS, Liau CT. Symp-

toms and signs of port-related infections in oncology patients related

to the offending pathogens. Int J Clin Pract 2008; 62:1193–8.

72. Uderzo C, D’Angelo P, Rizzari C, et al. Central venous catheter-related

complications after bone marrow transplantation in children with he-

matological malignancies. Bone Marrow Transplant 1992; 9:113–7.

73. Abdelkefi A, Achour W, Ben Othman T, et al. Difference in time to

positivity is useful for the diagnosis of catheter-related bloodstream

infection in hematopoietic stem cell transplant recipients. BoneMarrow

Transplant 2005; 35:397–401.

74. Jaeger K, Osthaus A, Heine J, et al. Efficacy of a benzalkonium

chloride-impregnated central venous catheter to prevent catheter-

associated infection in cancer patients. Chemotherapy 2001; 47:50–5.

75. Jaeger K, Zenz S, Juttner B, et al. Reduction of catheter-related in-

fections in neutropenic patients: a prospective controlled randomized

trial using a chlorhexidine and silver sulfadiazine-impregnated central

venous catheter. Ann Hematol 2005; 84:258–62.

76. Ostendorf T, Meinhold A, Harter C, et al. Chlorhexidine and silver-

sulfadiazine coated central venous catheters in haematological

patients—A double-blind, randomised, prospective, controlled trial.

Support Care Cancer 2005; 13:993–1000.

77. Forchielli ML, Lo CW, Richardson D, Gura K, Walker WA, Tonelli E.

Central venous line related bacteremia during total parenteral nutrition

and/or chemotherapy infusions in children. Ann Ig 1997; 9:35–40.

78. Raad I, Narro J, Khan A, Tarrand J, Vartivarian S, Bodey GP. Serious

complications of vascular catheter-related Staphylococcus aureus bac-

teremia in cancer patients. Eur J Clin Microbiol Infect Dis 1992; 11:

675–82.

79. Malgrange VB, Escande MC, Theobald S. Validity of earlier positivity

of central venous blood cultures in comparison with peripheral blood

cultures for diagnosing catheter-related bacteremia in cancer patients.

J Clin Microbiol 2001; 39:274–8.

80. Cesaro S, Corro R, Pelosin A, et al. A prospective survey on incidence

and outcome of Broviac/Hickman catheter-related complications in

pediatric patients affected by hematological and oncological diseases.

Ann Hematol 2004; 83:183–8.

81. Chaftari AM, Hachem R, Mulanovich V, et al. Efficacy and safety of

daptomycin in the treatment of Gram-positive catheter-related blood-

stream infections in cancer patients. Int J Antimicrob Agents 2010;

36:182–6.

82. Franklin JA, Gaur AH, Shenep JL, Hu XJ, Flynn PM. In situ diagnosis

of central venous catheter-related bloodstream infection without

peripheral blood culture. Pediatr Infect Dis J 2004; 23:614–8.

83. Gaur AH, Flynn PM, Giannini MA, Shenep JL, Hayden RT. Difference

in time to detection: a simple method to differentiate catheter-related

from non-catheter-related bloodstream infection in immunocom-

promised pediatric patients. Clin Infect Dis 2003; 37:469–75.

84. Gaur AH, Flynn PM, Heine DJ, Giannini MA, Shenep JL, Hayden RT.

Diagnosis of catheter-related bloodstream infections among pediatric

oncology patients lacking a peripheral culture, using differential time

to detection. Pediatr Infect Dis J 2005; 24:445–9.

85. Abdelkefi A, Achour W, Othman TB, et al. Use of heparin-coated

central venous lines to prevent catheter-related bloodstream infection.

J Support Oncol 2007; 5:273–8.


at FundaÃ§Ã

£o CoordenaÃ

§Ã£o de A

perfeiÃ§oam




ownloaded from


86. Abdelkefi A, Achour W, Torjman L, et al. Detection of catheter-

related bloodstream infections by the Gram stain-acridine orange

leukocyte cytospin test in hematopoietic stem cell transplant recipi-

ents. Bone Marrow Transplant 2006; 37:595–9.

87. Abdelkefi A, Othman TB, Kammoun L, et al. Prevention of central

venous line-related thrombosis by continuous infusion of low-dose

unfractionated heparin, in patients with haemato-oncological disease.

A randomized controlled trial. Thromb Haemost 2004; 92:654–61.

88. Fratino G, Molinari AC, Parodi S, et al. Central venous catheter-related

complications in children with oncological/hematological diseases: an

observational study of 418 devices. Ann Oncol 2005; 16:648–54.

89. Penel N, Neu JC, Clisant S, Hoppe H, Devos P, Yazdanpanah Y. Risk

factors for early catheter-related infections in cancer patients. Cancer

2007; 110:1586–92.

90. Viale P, Pagani L, Petrosillo N, et al. Antibiotic lock-technique for the

treatment of catheter-related bloodstream infections. J Chemother

2003; 15:152–6.

91. Abdelkefi A, Torjman L, Ladeb S, et al. Randomized trial of

prevention of catheter-related bloodstream infection by continuous

infusion of low-dose unfractionated heparin in patients with hema-

tologic and oncologic disease. J Clin Oncol 2005; 23:7864–70.

92. Slobbe L, Doorduijn JK, Lugtenburg PJ, et al. Prevention of catheter-

related bacteremia with a daily ethanol lock in patients with tunnelled

catheters: a randomized, placebo-controlled trial. PLoS One 2010;

5:e10840.

93. Raad I, Hanna HA, Alakech B, Chatzinikolaou I, Johnson MM,

Tarrand J. Differential time to positivity: a useful method for di-

agnosing catheter-related bloodstream infections. Ann Intern Med

2004; 140:18–25.

94. Barbaric D, Curtin J, Pearson L, Shaw PJ. Role of hydrochloric acid in

the treatment of central venous catheter infections in children with

cancer. Cancer 2004; 101:1866–72.

95. Cesaro S, Tridello G, Cavaliere M, et al. Prospective, randomized trial

of two different modalities of flushing central venous catheters in

pediatric patients with cancer. J Clin Oncol 2009; 27:2059–65.

96. Dannenberg C, Bierbach U, Rothe A, Beer J, Korholz D. Ethanol-lock

technique in the treatment of bloodstream infections in pediatric

oncology patients with Broviac catheter. J Pediatr Hematol Oncol

2003; 25:616–21.

97. Early TF, Gregory RT, Wheeler JR, Snyder SO Jr, Gayle RG. Increased

infection rate in double-lumen versus single-lumen Hickman cathe-

ters in cancer patients. South Med J 1990; 83:34–6.

98. Lim SH, Smith MP, Machin SJ, Goldstone AH. Prophylactic teico-

planin during insertion of Hickman catheters. Br J Haematol 1990;

76(Suppl 2):27–9.

99. Lim SH, Smith MP, Machin SJ, Goldstone AH. Teicoplanin and pro-

phylaxis of Hickman catheter insertions. Eur J Surg Suppl 1992: 39–42.

100. Lim SH, Smith MP, Machin SJ, Goldstone AH. A prospective ran-

domized study of prophylactic teicoplanin to prevent early Hickman

catheter-related sepsis in patients receiving intensive chemotherapy for

haematological malignancies. Eur J Haematol Suppl 1993; 54:10–3.

101. Lim SH, Smith MP, Salooja N, Machin SJ, Goldstone AH. A pro-

spective randomized study of prophylactic teicoplanin to prevent

early Hickman catheter-related sepsis in patients receiving intensive

chemotherapy for haematological malignancies. J Antimicrob Che-

mother 1991; 28:109–16.

102. Vassilomanolakis M, Plataniotis G, Koumakis G, et al. Central

venous catheter-related infections after bone marrow transplantation in

patients with malignancies: a prospective study with short-course-

vancomycin prophylaxis. Bone Marrow Transplant 1995; 15:77–80.

103. Vlasveld LT, Rodenhuis S, Rutgers EJ, et al. Catheter-related com-

plications in 52 patients treated with continuous infusion of low dose

recombinant interleukin-2 via an implanted central venous catheter.

Eur J Surg Oncol 1994; 20:122–9.

104. Nieboer P, de Vries EG, Mulder NH, et al. Factors influencing catheter-

related infections in the Dutch multicenter study on high-dose

chemotherapy followed by peripheral SCT in high-risk breast cancer

patients. Bone Marrow Transplant 2008; 42:475–81.

105. Ozyuvaci E, Kutlu F. Totally implantable venous access devices via

subclavian vein: a retrospective study of 368 oncology patients. Adv

Ther 2006; 23:574–81.

106. Abbas AA, Fryer CJ, Paltiel C, et al. Factors influencing central line

infections in children with acute lymphoblastic leukemia: results of

a single institutional study. Pediatr Blood Cancer 2004; 42:325–31.

107. DesJardin JA, Falagas ME, Ruthazer R, et al. Clinical utility of blood

cultures drawn from indwelling central venous catheters in hospital-

ized patients with cancer. Ann Intern Med 1999; 131:641–7.

108. Goldschmidt H, Hahn U, Salwender HJ, et al. Prevention of catheter-

related infections by silver coated central venous catheters in onco-

logical patients. Zentralbl Bakteriol 1995; 283:215–23.

109. Gorelick MH, Owen WC, Seibel NL, Reaman GH. Lack of association

between neutropenia and the incidence of bacteremia associated with

indwelling central venous catheters in febrile pediatric cancer patients.

Pediatr Infect Dis J 1991; 10:506–10.

110. Harter C, Salwender HJ, Bach A, Egerer G, Goldschmidt H, Ho AD.

Catheter-related infection and thrombosis of the internal jugular vein

in hematologic-oncologic patients undergoing chemotherapy: a pro-

spective comparison of silver-coated and uncoated catheters. Cancer

2002; 94:245–51.

111. Hartmann LC, Urba WJ, Steis RG, et al. Use of prophylactic anti-

biotics for prevention of intravascular catheter-related infections in

interleukin-2-treated patients. J Natl Cancer Inst 1989; 81:1190–3.

112. Lee SH, Hahn ST. Comparison of complications between transjugular

and axillosubclavian approach for placement of tunneled, central

venous catheters in patients with hematological malignancy: a pro-

spective study. Eur Radiol 2005; 15:1100–4.

113. Rackoff WR, Weiman M, Jakobowski D, et al. A randomized, con-

trolled trial of the efficacy of a heparin and vancomycin solution in

preventing central venous catheter infections in children. J Pediatr

1995; 127:147–51.

114. Raucher HS, Hyatt AC, Barzilai A, et al. Quantitative blood cultures in

the evaluation of septicemia in children with Broviac catheters.

J Pediatr 1984; 104:29–33.

115. Sanchez-Munoz A, Aguado JM, Lopez-Martin A, et al. Usefulness of

antibiotic-lock technique in management of oncology patients with

uncomplicated bacteremia related to tunneled catheters. Eur J Clin

Microbiol Infect Dis 2005; 24:291–3.

116. Vokurka S, Kabatova-Maxova K, Skardova J, Bystricka E. Antimi-

crobial chlorhexidine/silver sulfadiazine-coated central venous cath-

eters versus those uncoated in patients undergoing allogeneic stem cell

transplantation. Support Care Cancer 2009; 17:145–51.

117. Benezra D, Kiehn TE, Gold JW, Brown AE, Turnbull AD, Armstrong

D. Prospective study of infections in indwelling central venous

catheters using quantitative blood cultures. Am J Med 1988; 85:

495–8.

118. Douard MC, Arlet G, Leverger G, et al. Quantitative blood cultures

for diagnosis and management of catheter-related sepsis in pediatric

hematology and oncology patients. Intensive Care Med 1991; 17:

30–5.

119. Germanakis I, Christidou A, Galanakis E, Kyriakakis I, Tselentis Y,

Kalmanti M. Qualitative versus quantitative blood cultures in the

diagnosis of catheter-related bloodstream infections in children with

malignancy. Pediatr Blood Cancer 2005; 45:939–44.

120. Germanakis J, Stiakaki E, Galanakis E, et al. Prognostic value of

quantitative blood cultures for the outcome of central venous cath-

eters in children. Scand J Infect Dis 2002; 34:680–2.

121. Ghanem GA, Boktour M, Warneke C, et al. Catheter-related

Staphylococcus aureus bacteremia in cancer patients: high rate of com-

plications with therapeutic implications. Medicine (Baltimore) 2007;

86:54–60.

122. Henrickson KJ, Axtell RA, Hoover SM, et al. Prevention of central

venous catheter-related infections and thrombotic events in immu-


at FundaÃ§Ã

£o CoordenaÃ

§Ã£o de A

perfeiÃ§oam




ownloaded from


nocompromised children by the use of vancomycin/ciprofloxacin/

heparin flush solution: a randomized, multicenter, double-blind trial.

J Clin Oncol 2000; 18:1269–78.

123. Logghe C, Van Ossel C, D’HooreW, Ezzedine H,Wauters G, Haxhe JJ.

Evaluation of chlorhexidine and silver-sulfadiazine impregnated

central venous catheters for the prevention of bloodstream infection in

leukaemic patients: a randomized controlled trial. J Hosp Infect 1997;

37:145–56.

124. Schwartz C, Henrickson KJ, Roghmann K, Powell K. Prevention of

bacteremia attributed to luminal colonization of tunneled central

venous catheters with vancomycin-susceptible organisms. J Clin

Oncol 1990; 8:1591–7.

125. Wurzel CL, Halom K, Feldman JG, Rubin LG. Infection rates of

Broviac-Hickman catheters and implantable venous devices. Am J Dis

Child 1988; 142:536–40.

126. Elishoov H, Or R, Strauss N, Engelhard D. Nosocomial colonization,

septicemia, and Hickman/Broviac catheter-related infections in bone

marrow transplant recipients. A 5-year prospective study. Medicine

(Baltimore) 1998; 77:83–101.

127. Engelhard D, Elishoov H, Strauss N, et al. Nosocomial coagulase-

negative staphylococcal infections in bone marrow transplantation

recipients with central vein catheter. A 5-year prospective study.

Transplantation 1996; 61:430–4.

128. Daghistani D, Horn M, Rodriguez Z, Schoenike S, Toledano S. Pre-

vention of indwelling central venous catheter sepsis. Med Pediatr

Oncol 1996; 26:405–8.

129. Eastman ME, Khorsand M, Maki DG, et al. Central venous device-

related infection and thrombosis in patients treated with moderate

dose continuous-infusion interleukin-2. Cancer 2001; 91:806–14.

130. Escudier B, Lethiec JL, Angevin E, et al. Totally implanted catheters to

reduce catheter-related infections in patients receiving interleukin-2:

a 2-year experience. Support Care Cancer 1995; 3:297–300.

131. Jones GR, Konsler GK, Dunaway RP, Lacey SR, Azizkhan RG. Pro-

spective analysis of urokinase in the treatment of catheter sepsis in

pediatric hematology-oncology patients. J Pediatr Surg 1993; 28:350–5.

132. Jones PM. Indwelling central venous catheter–related infections and

two different procedures of catheter care. Cancer Nurs 1987; 10:123–30.

133. King DR, KomerM,Hoffman J, et al. Broviac catheter sepsis: the natural

history of an iatrogenic infection. J Pediatr Surg 1985; 20:728–33.

134. Sanders J, Pithie A, Ganly P, et al. A prospective double-blind ran-

domized trial comparing intraluminal ethanol with heparinized saline

for the prevention of catheter-associated bloodstream infection in

immunosuppressed haematology patients. J Antimicrob Chemother

2008; 62:809–15.

135. Shah SS, Downes KJ, Elliott MR, Bell LM, McGowan KL, Metlay JP.

How long does it take to "rule out" bacteremia in children with central

venous catheters? Pediatrics 2008; 121:135–41.

136. Soo RA, Gosbell IB, Gallo JH, et al. Hickman catheter complications

in a haematology unit, 1996–98. Intern Med J 2002; 32:100–3.

137. Dugdale DC, Ramsey PG. Staphylococcus aureus bacteremia in pa-

tients with Hickman catheters. Am J Med 1990; 89:137–41.

138. Kelly C, Dumenko L, McGregor SE, McHutchion ME. A change in

flushing protocols of central venous catheters. Oncol Nurs Forum

1992; 19:599–605.

139. Press OW, Ramsey PG, Larson EB, Fefer A, Hickman RO. Hickman

catheter infections in patients with malignancies. Medicine (Balti-

more) 1984; 63:189–200.

140. Solomon B, Moore J, Arthur C, Prince HM. Lack of efficacy of twice-

weekly urokinase in the prevention of complications associated with

Hickman catheters: a multicentre randomised comparison of uroki-

nase versus heparin. Eur J Cancer 2001; 37:2379–84.

141. Volkow P, Vazquez C, Tellez O, et al. Polyurethane II catheter as long-

indwelling intravenous catheter in patients with cancer. Am J Infect

Control 2003; 31:392–6.

142. Astagneau P, Maugat S, Tran-Minh T, et al. Long-term central ve-

nous catheter infection in HIV-infected and cancer patients: a mul-

ticenter cohort study. Infect Control Hosp Epidemiol 1999; 20:

494–8.

143. Kim SH, Kang CI, Kim HB, et al. Outcomes of Hickman catheter

salvage in febrile neutropenic cancer patients with Staphylococcus

aureus bacteremia. Infect Control Hosp Epidemiol 2003; 24:897–904.

144. Babu R, Turner A, Nicholls G, Spicer RD. Surgical risk factors for

Hickman catheter sepsis: a prospective study. Pediatr Surg Int 2004;

20:369–71.

145. Carratala J, Niubo J, Fernandez-Sevilla A, et al. Randomized, double-

blind trial of an antibiotic-lock technique for prevention of Gram-

positive central venous catheter-related infection in neutropenic patients

with cancer. Antimicrob Agents Chemother 1999; 43:2200–4.

146. Das I, Philpott C, George RH. Central venous catheter-related septi-

caemia in paediatric cancer patients. J Hosp Infect 1997; 36:67–76.

147. Kappers-Klunne MC, Degener JE, Stijnen T, Abels J. Complications

from long-term indwelling central venous catheters in hematologic

patients with special reference to infection. Cancer 1989; 64:1747–52.

148. Kim DH, Bae NY, Sung WJ, et al. Hickman catheter site infections

after allogeneic stem cell transplantation: a single-center experience.

Transplant Proc 2004; 36:1569–73.

149. Lai CH, Wong WW, Chin C, et al. Central venous catheter-related

Stenotrophomonas maltophilia bacteraemia and associated relapsing

bacteraemia in haematology and oncology patients. Clin Microbiol

Infect 2006; 12:986–91.

150. Simon C, Suttorp M. Results of antibiotic treatment of Hickman-

catheter-related infections in oncological patients. Support Care Cancer

1994; 2:66–70.

151. Biffi R, De Braud F, Orsi F, et al. Totally implantable central venous

access ports for long-term chemotherapy. A prospective study ana-

lyzing complications and costs of 333 devices with a minimum follow-

up of 180 days. Ann Oncol 1998; 9:767–73.

152. Biffi R, Martinelli G, Pozzi S, et al. Totally implantable central venous

access ports for high-dose chemotherapy administration and autol-

ogous stem cell transplantation: analysis of overall and septic com-

plications in 68 cases using a single type of device. Bone Marrow

Transplant 1999; 24:89–93.

153. Groeger JS, Lucas AB, Coit D, et al. A prospective, randomized

evaluation of the effect of silver impregnated subcutaneous cuffs for

preventing tunneled chronic venous access catheter infections in

cancer patients. Ann Surg 1993; 218:206–10.

154. Groeger JS, Lucas AB, Thaler HT, et al. Infectious morbidity associ-

ated with long-term use of venous access devices in patients with

cancer. Ann Intern Med 1993; 119:1168–74.

155. La Quaglia MP, Lucas A, Thaler HT, Friedlander-Klar H, Exelby PR,

Groeger JS. A prospective analysis of vascular access device-related

infections in children. J Pediatr Surg 1992; 27:840–2.

156. Biagi E, Arrigo C, Dell’Orto MG, et al. Mechanical and infective central

venous catheter-related complications: a prospective non-randomized

study using Hickman and Groshong catheters in children with hema-

tological malignancies. Support Care Cancer 1997; 5:228–33.

157. Castagnola E, Molinari AC, Giacchino M, et al. Incidence of catheter-

related infections within 30 days from insertion of Hickman-Broviac

catheters. Pediatr Blood Cancer 2007; 48:35–8.

158. Chee L, Brown M, Sasadeusz J, MacGregor L, Grigg AP. Gram-

negative organisms predominate in Hickman line-related infections in

non-neutropenic patients with hematological malignancies. J Infect

2008; 56:227–33.

159. Coyle VM, McMullan R, Morris TC, Rooney PJ, Hedderwick S.

Catheter-related bloodstream infection in adult haematology patients:

catheter removal practice and outcome. J Hosp Infect 2004; 57:325–31.

160. Guiot HF, Helmig-Schurter AV, van ’t Noordende JM. The relevance of

cultures of catheter-drawn blood and heparin-lock fluid to diagnose

infection in hematologic patients. Ann Hematol 1992; 64:28–34.

161. Maki DG, Weise CE, Sarafin HW. A semiquantitative culture method

for identifying intravenous-catheter-related infection. N Engl J Med

1977; 296:1305–9.


at FundaÃ§Ã

£o CoordenaÃ

§Ã£o de A

perfeiÃ§oam




ownloaded from


162. Hanna H, Benjamin R, Chatzinikolaou I, et al. Long-term silicone central

venous catheters impregnated with minocycline and rifampin decrease

rates of catheter-related bloodstream infection in cancer patients: a pro-

spective randomized clinical trial. J Clin Oncol 2004; 22:3163–71.

163. Hanna HA, Raad I. Blood products: a significant risk factor for long-

term catheter-related bloodstream infections in cancer patients. Infect

Control Hosp Epidemiol 2001; 22:165–6.

164. Huang WT, Chen TY, Su WC, Yen CJ, Tsao CJ. Implantable venous

port-related infections in cancer patients. Support Care Cancer 2004;

12:197–201.

165. Koolen DA, van Laarhoven HW, Wobbes T, Punt CJ. Single-centre

experience with tunnelled central venous catheters in 150 cancer pa-

tients. Neth J Med 2002; 60:397–401.

166. Handrup MM, Moller JK, Frydenberg M, Schroder H. Placing of

tunneled central venous catheters prior to induction chemotherapy in

children with acute lymphoblastic leukemia. Pediatr Blood Cancer

2010; 55:309–13.

167. Park KH, Cho OH, Lee SO, et al. Outcome of attempted Hickman

catheter salvage in febrile neutropenic cancer patients with Staphy-

lococcus aureus bacteremia. Ann Hematol 2010; 89:1163–9.

168. Pegues D, Axelrod P, McClarren C, et al. Comparison of infections in

Hickman and implanted port catheters in adult solid tumor patients.

J Surg Oncol 1992; 49:156–62.

169. Raad II, Hohn DC, Gilbreath BJ, et al. Prevention of central venous

catheter-related infections by using maximal sterile barrier precautions

during insertion. Infect Control Hosp Epidemiol 1994; 15:231–8.

170. Rao JS, O’Meara A, Harvey T, Breatnach F. A new approach to the

management of Broviac catheter infection. J Hosp Infect 1992; 22:109–16.

171. Seifert H, Cornely O, Seggewiss K, et al. Bloodstream infection in

neutropenic cancer patients related to short-term nontunnelled

catheters determined by quantitative blood cultures, differential time

to positivity, and molecular epidemiological typing with pulsed-field

gel electrophoresis. J Clin Microbiol 2003; 41:118–23.

172. van Rooden CJ, Schippers EF, Guiot HF, et al. Prevention of coagulase-

negative staphylococcal central venous catheter-related infection using

urokinase rinses: a randomized double-blind controlled trial in patients

with hematologic malignancies. J Clin Oncol 2008; 26:428–33.

173. Viscoli C, Castagnola E, Giacchino M, et al. Bloodstream infections in

children with cancer: a multicentre surveillance study of the Italian

association of paediatric haematology and oncology. Supportive

therapy Group—infectious diseases Section. Eur J Cancer 1999; 35:

770–4.

174. Addeo A, Tonda L, Sirgiovanni MP, Giacoletti G, Citro R, Ramus GV.

Complication rates in the clinical practice of long-term use central

venous catheters in cancer patients. Eur J Oncol 2009; 14:27–31.

175. Andremont A, Paulet R, Nitenberg G, Hill C. Value of semi-

quantitative cultures of blood drawn through catheter hubs for esti-

mating the risk of catheter tip colonization in cancer patients. J Clin

Microbiol 1988; 26:2297–9.

176. Aquino VM, Sandler ES, Mustafa MM, Steele JW, Buchanan GR.

A prospective double-blind randomized trial of urokinase flushes

to prevent bacteremia resulting from luminal colonization of

subcutaneous central venous catheters. J Pediatr Hematol Oncol 2002;

24:710–3.

177. Arul GS, Lewis N, Bromley P, Bennett J. Ultrasound-guided percu-

taneous insertion of Hickman lines in children. Prospective study of

500 consecutive procedures. J Pediatr Surg 2009; 44:1371–6.

178. Averbuch D, Makhoul R, Rotshild V, Weintraub M, Engelhard D.

Empiric treatment with once-daily cefonicid and gentamicin

for febrile non-neutropenic pediatric cancer patients with

indwelling central venous catheters. J Pediatr Hematol Oncol 2008;

30:527–32.

179. Barriga FJ, Varas M, Potin M, et al. Efficacy of a vancomycin solution

to prevent bacteremia associated with an indwelling central venous

catheter in neutropenic and non-neutropenic cancer patients. Med

Pediatr Oncol 1997; 28:196–200.

180. Benhamou E, Fessard E, Com-Nougue C, et al. Less frequent catheter

dressing changes decrease local cutaneous toxicity of high-dose che-

motherapy in children, without increasing the rate of catheter-related

infections: results of a randomised trial. Bone Marrow Transplant

2002; 29:653–8.

181. Biffi R, Orsi F, Pozzi S, et al. Best choice of central venous insertion site

for the prevention of catheter-related complications in adult patients

who need cancer therapy: a randomized trial. Ann Oncol 2009;

20:935–40.

182. Castagnola E, Fratino G, Valera M, Giacchino M, Haupt R, Molinari

AC. Correlation between "malfunctioning events" and catheter-

related infections in pediatric cancer patients bearing tunneled in-

dwelling central venous catheter: results of a prospective observational

study. Support Care Cancer 2005; 13:757–9.

183. Chatzinikolaou I, Hanna H, Graviss L, et al. Clinical experience with

minocycline and rifampin-impregnated central venous catheters in

bone marrow transplantation recipients: efficacy and low risk of de-

veloping staphylococcal resistance. Infect Control Hosp Epidemiol

2003; 24:961–3.

184. Cheong K, Perry D, Karapetis C, Koczwara B. High rate of compli-

cations associated with peripherally inserted central venous catheters

in patients with solid tumours. Intern Med J 2004; 34:234–8.

185. Edwards DP, Brookstein R. Hickman lines inserted and managed by

a general surgical team: Longevity and complications. Br J Clin Pract

1997; 51:47–8.

186. Elihu A, Gollin G. Complications of implanted central venous cath-

eters in neutropenic children. Am Surg 2007; 73:1079–82.

187. Haimi-Cohen Y, Husain N, Meenan J, Karayalcin G, Lehrer M, Rubin

LG. Vancomycin and ceftazidime bioactivities persist for at least 2

weeks in the lumen in ports: Simplifying treatment of port-associated

bloodstream infections by using the antibiotic lock technique. Anti-

microb Agents Chemother 2001; 45:1565–7.

188. Harms D, Gortitz I, Lambrecht W, Kabisch H, Erttmann R,

Janka-Schaub G. Infectious risks of Broviac catheters in children with

neoplastic diseases: a matched pairs analysis. Pediatr Infect Dis J 1992;

11:1014–8.

189. Hemsworth S, Selwood K, van Saene R, Pizer B. Does the number of

exogenous infections increase in paediatric oncology patients when

sterile surgical gloves are not worn for accessing central venous access

devices? Eur J Oncol Nurs 2007; 11:442–7.

190. Hengartner H, Berger C, Nadal D, Niggli FK, Grotzer MA. Port-

A-Cath infections in children with cancer. Eur J Cancer 2004; 40:

2452–8.

191. Henneberg SW, Jungersen D, Hole P. Durability of central venous

catheters. A randomized trial in children with malignant diseases.

Paediatr Anaesth 1996; 6:449–51.

192. Jones PG, Hopfer RL, Elting L. Semiquantitative cultures of in-

travascular catheters from cancer patients. Diagn Microbiol Infect Dis

1986; 4:299–306.

193. Krog MP, Ekbom A, Nystrom-Rosander C. Central venous catheters

in acute blood malignancies. Cancer 1987; 59:1358–61.

194. La Quaglia MP, Caldwell C, Lucas A, et al. A prospective random-

ized double-blind trial of bolus urokinase in the treatment of es-

tablished Hickman catheter sepsis in children. J Pediatr Surg 1994;

29:742–5.

195. Laurenzi L, Natoli S, Benedetti C, et al. Cutaneous bacterial coloni-

zation, modalities of chemotherapeutic infusion, and catheter-related

bloodstream infection in totally implanted venous access devices.

Support Care Cancer 2004; 12:805–9.

196. Ley BE, Jalil N, McIntosh J, et al. Bolus or infusion teicoplanin for

intravascular catheter associated infections in immunocompromised

patients? J Antimicrob Chemother 1996; 38:1091–5.

197. Ljungman P, Hagglund H, Bjorkstrand B, Lonnqvist B, Ringden O.

Perroperative teicoplanin for prevention of Gram-positive infections in

neutropenic patients with indwelling central venous catheters: a ran-

domized, controlled study. Support Care Cancer 1997; 5:485–8.


at FundaÃ§Ã

£o CoordenaÃ

§Ã£o de A

perfeiÃ§oam




ownloaded from


198. Matsuzaki A, Suminoe A, Koga Y, Hatano M, Hattori S, Hara T. Long-

term use of peripherally inserted central venous catheters for cancer

chemotherapy in children. Support Care Cancer 2006; 14:153–60.

199. Nam SH, Kim DY, Kim SC, Kim IK. Complications and risk factors of

infection in pediatric hemato-oncology patients with totally implant-

able access ports (TIAPs). Pediatr Blood Cancer 2010; 54:546–51.

200. Nouwen JL, van Belkum A, de Marie S, et al. Clonal expansion of

Staphylococcus epidermidis strains causing Hickman catheter-related

infections in a hemato-oncologic department. J Clin Microbiol 1998;

36:2696–702.

201. Olson TA, Fischer GW, Lupo MC, et al. Antimicrobial therapy of

Broviac catheter infections in pediatric hematology oncology patients.

J Pediatr Surg 1987; 22:839–42.

202. Pedersen G, Norgaard M, Kiiveri M, et al. Risk of bacteremia in patients

with hematological and other malignancies after initial placement of a

central venous catheter. J Long Term Eff Med Implants 2007; 17:303–11.

203. Rackoff WR, Ge J, Sather HN, Cooper HA, Hutchinson RJ, Lange BJ.

Central venous catheter use and the risk of infection in children with

acute lymphoblastic leukemia: a report from the Children’s Cancer

Group. J Pediatr Hematol Oncol 1999; 21:260–7.

204. Ranson MR, Oppenheim BA, Jackson A, Kamthan AG, Scarffe JH.

Double-blind placebo controlled study of vancomycin prophylaxis for

central venous catheter insertion in cancer patients. J Hosp Infect

1990; 15:95–102.

205. Rasero L, Degl’Innocenti M, Mocali M, et al. Comparison of two

different time interval protocols for central venous catheter dressing

in bone marrow transplant patients: results of a randomized, multi-

center study. Haematologica 2000; 85:275–9.

206. Rizzari C, Palamone G, Corbetta A, Uderzo C, Vigano EF, Codecasa

G. Central venous catheter-related infections in pediatric hematology-

oncology patients: role of home and hospital management. Pediatr

Hematol Oncol 1992; 9:115–23.

207. Samaras P, Dold S, Braun J, et al. Infectious port complications are

more frequent in younger patients with hematologic malignancies

than in solid tumor patients. Oncology 2008; 74:237–44.

208. Scheinemann K, Ethier MC, Dupuis LL, et al. Utility of peripheral

blood cultures in bacteremic pediatric cancer patients with a central

line. Support Care Cancer 2010; 18:913–9.

209. Schwarz RE, Groeger JS, Coit DG. Subcutaneously implanted central

venous access devices in cancer patients: a prospective analysis.

Cancer 1997; 79:1635–40.

210. Stoiser B, Kofler J, Staudinger T, et al. Contamination of central

venous catheters in immunocompromised patients: a comparison

between two different types of central venous catheters. J Hosp Infect

2002; 50:202–6.

211. Strahilevitz J, Lossos IS, Verstandig A, Sasson T, Kori Y, Gillis S.

Vascular access via peripherally inserted central venous catheters

(PICCs): experience in 40 patients with acute myeloid leukemia at

a single institute. Leuk Lymphoma 2001; 40:365–71.

212. Walshe LJ, Malak SF, Eagan J, Sepkowitz KA. Complication rates

among cancer patients with peripherally inserted central catheters.

J Clin Oncol 2002; 20:3276–81.

213. Wylie MC, Graham DA, Potter-Bynoe G, et al. Risk factors for central

line-associated bloodstream infection in pediatric intensive care units.

Infect Control Hosp Epidemiol 2010; 31:1049–56.

214. Powers RJ, Wirtschafter DW. Decreasing central line associated

bloodstream infection in neonatal intensive care. Clin Perinatol 2010;

37:247–72.

215. Li S, Bizzarro MJ. Prevention of central line associated blood-

stream infections in critical care units. Curr Opin Pediatr 2011; 23:

85–90.

216. Blot F, Nitenberg G, Brun-Buisson C. New tools in diagnosing catheter-

related infections. Support Care Cancer 2000; 8:287–92.

217. Guembe M, Rodriguez-Creixems M, Sanchez-Carrillo C, Perez-Parra

A, Martin-Rabadan P, Bouza E. Howmany lumens should be cultured

in the conservative diagnosis of catheter-related bloodstream in-

fections? Clin Infect Dis 2010; 50:1575–9.

218. Randolph AG, Brun-Buisson C, Goldmann D. Identification of cen-

tral venous catheter-related infections in infants and children. Pediatr

Crit Care Med 2005; 6(Suppl 3):S19–24.


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£o CoordenaÃ

§Ã£o de A

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