Dhum
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A R T I C L E I N F O S U M M A R Y
* Corresponding author. Yasushi Kubota, MD, PhD, Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine,
Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel.: þ81 952 34 2366; fax: þ81 952 34 2017.
E-mail address: kubotay@cc.saga-u.ac.jp (Y. Kubota).
1
Present address: Division of Biomedical Statistics, Department of Integrated Medicine, Graduate School of Medicine in Osaka University, Suita,
Japan.
2
Present address: Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan.
https://doi.org/10.1016/j.infpip.2020.100050
2590-0889/ª 2020 The Authors. Published by Elsevier Ltd on behalf of The Healthcare Infection Society. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
2 H. Kitamura et al. / Infection Prevention in Practice 2 (2020) 100050
factors for the development of CLABSI. However, multivariate analysis adjusted for age,
reason for insertion, insertion site, number of lumens, haemoglobin, percentage of neu-
trophils and platelet counts found no significant differences between the venue where
CVC were inserted and CLABSI development (P ¼ 0.158).
Conclusion: The venue of CVC insertion is unlikely to influence CLABSI development in
patients with haematological diseases.
ª 2020 The Authors. Published by Elsevier Ltd
on behalf of The Healthcare Infection Society. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction between June 2009 and March 2017. Clinical data collected
from medical records included age, sex, underlying disease,
Central venous catheters (CVC) are often inserted into reason for CVC insertion, insertion site, number of CVC lumens,
patients with haematological diseases to deliver intensive venue of insertion, dates of insertion and removal, complete
chemotherapy or haematopoietic stem cell transplants (HSCT). blood counts, percentage of neutrophils and nutritional status
However, the procedures can be associated with serious com- (serum albumin concentrations) at the time of CVC insertion,
plications [1,2], among which, central line-associated blood- CLABSI events, causative pathogens and death during CVC
stream infection (CLABSI) can be life-threatening for patients placement. The ward and treatment room were defined as ISO
with neutropenia [3]. Therefore, CLABSI should be prevented. 14644-1 class 8, whereas the clean room, the intensive care
Several interventions can be applied to reduce risk of CLABSI unit (ICU) and operating room were defined as ISO 14644-1 class
[4e7]. The Centres for Disease Control and Prevention (CDC) 7. Cleanliness is regularly assessed in the hospital to maintain
recommend maximum sterile barrier precautions (MSBP) during consistent standards. The Institutional Review Board at Saga
CVC insertion to prevent intravascular catheter-related infec- University Hospital approved the study (No. 2017-10-Expedited
tions; these include wearing a sterile cap, mask, gown, gloves Review-01).
and full body drape [8,9]. These recommendations were based
on a prospective randomised trial, which found that MSBP CVC insertion and dressing
reduce the risk of catheter-related infections in patients with
solid or haematological tumours. One explanation for this Non-tunnelled CVC were inserted percutaneously using the
finding was that MSBP prevent early contamination of catheters Seldinger technique. Attending physicians selected the loca-
by skin-borne organisms during CVC insertion [10]. By contrast, tions of CVC insertion, where physicians using aseptic tech-
subsequent studies [11,12] did not find that MSBP prevented nique (a cap, mask, sterile gown, sterile gloves and sterile
catheter-related bloodstream infections, but the character- drapes) inserted CV Legaforce catheters (Terumo, Tokyo,
istics of the patients who participated in these studies differed Japan) into patients. Anaesthetists inserted CVC into patients
from those in the study by Raad et al. [10]. Nevertheless, MSBP on the operating room table. Skin was disinfected mainly with
are always implemented during CVC insertion. Risk factors for 10% povidone-iodine in alcohol until September 2012, and
CLABSI include underlying disease, the procedure used for CVC from October 2012 with 1% chlorhexidine gluconate in alco-
insertion, catheter insertion site, duration and reason for hol. After inserting a CVC, the implanted site was cleansed
catheterisation [13]. A recent study showed that catheter- and usually maintained using IV3000 (Smith & Nephew,
isation of the subclavian vein was associated with a lower risk of London, UK) and 10% povidone-iodine from the start of the
bloodstream infection than that of jugular or femoral veins [14]. study until September 2012, followed by Tegaderm chlo-
Catheters are associated with several inherent risks that might rhexidine gluconate I.V. securement dressing (3M Corpo-
contribute to CLABSI, including cutaneous insertion (that can ration, St. Paul, MN, USA) with gel pads containing
introduce skin-borne organisms), contamination of the catheter chlorhexidine and 1% chlorhexidine gluconate from October
hub, lumen, or infusate and haematogenous colonization of CVC 2012 until the end of the study.
from distant infection [15]. However, few studies have exam-
ined whether the venue of CVC insertion affects the develop-
ment of CLABSI [16,17]. Patients with haematological diseases, Definition of CLABSI
especially leukaemia, who undergo chemotherapy or HSCT are
at high risk of infection due to neutropenia and immunosup- We defined CLABSI as a laboratory-confirmed bloodstream
pression. Thus, the relationship between the venue of CVC infection (LCBI) according to the CDC guidelines [18] as LCBI
insertion and CLABSI development should be clarified. We ret- 1, in which a recognised pathogen cultured from one or more
rospectively investigated whether differences in the cleanliness blood specimens was not related to infection at any other
of venues during CVC insertion influence the development of site, or as LCBI 2, in which fever (>38 C), chills or hypo-
CLABSI in patients with haematological diseases. tension, signs, symptoms and positive laboratory results
were not related to infection at any other site and a common
Methods skin contaminant was cultured from two or more blood
specimens drawn on separate occasions. Patients who met at
Study design, patients and data collection least one of these criteria were diagnosed with CLABSI. We
also applied the criteria for mucosal barrier injury-
This retrospective study included 279 patients with hae- laboratory confirmed bloodstream infection (MBI-LCBI) to
matological diseases managed at Saga University Hospital the patients with CLABSI [19].
H. Kitamura et al. / Infection Prevention in Practice 2 (2020) 100050 3
Table I
Surveillance of central line-associated bloodstream infection
Characteristics No. of CVC Total of No. of CLABSI CLABSI rate per
insertions catheter days events 1,000 catheter days
Total 545 23,434 55 2.35
Reasons of CVC insertions
Chemotherapy 328 14,963 32 2.14
Autologous HSCT 50 1,350 2 1.48
Allogeneic HSCT 59 3,413 16 4.69
Other 108 3,708 5 1.35
CVC insertion sites
Internal jugular vein 490 21,504 50 2.33
Subclavian vein 32 1,537 4 2.60
Femoral vein 23 393 1 2.54
Number of lumens of CVC
Single lumen 102 3,813 5 1.31
Double lumen 360 15,401 33 2.14
Triple lumen 83 4,220 17 4.03
Venue of CVC insertions
Operating room 305 13,139 39 2.97
Ward 226 9,720 15 1.54
ICU 7 293 1 3.41
Clean room 4 139 0 0.00
Treatment room 3 143 0 0.00
Change of disinfectant and dressing
June 2009eSeptember 2012 193 7,497 20 2.67
October 2012eMarch 2017 352 15,937 35 2.20
CLABSI, central line-associated bloodstream infection; CVC, central venous catheter; HSCT, haematopoietic stem cell transplantation; ICU,
intensive care unit.
Pathogens causing CLABSI sensitivity analyses, which also did not find any significant
differences (HR, 1.54; 95% CI, 0.80e2.97; P ¼ 0.197 and HR,
Pathogens isolated in patients with CLABSI are shown in 1.56; 95% CI, 0.81e2.99; P ¼ 0.181, respectively).
Supplemental Table I. Staphylococcus epidermidis was the
most common pathogen, followed by S. aureus, Bacillus cereus
and Corynebacterium striatum. Discussion
Here, we investigated whether the development of CLABSI
Comparison of venues where patients underwent CVC
in patients with haematological diseases was associated with
insertion CVC insertion at venues with different standards of cleanliness.
The results showed that the median duration of catheterisation
Among 545 CVC insertions, 226 (42.6%) in 153 and 305
was 35.0 days and that the rate of CLABSI was 2.35 per 1,000
(57.4%) in 190 patients proceeded in wards and in the oper-
catheter days. Although more CVC were inserted for HSCT in
ating room, respectively. Table II shows inter-group compar-
the operating room than in the ward, multivariate analysis
isons. Among 54 CLABSI, significantly more occurred in the
showed that the venue of CVC insertion did not significantly
operating room than in the ward (P ¼ 0.030). Age, reason for
affect CLABSI development.
CVC insertion, CVC insertion site, CVC lumens and number of
Previous reports have described that patients with haema-
CVC insertions per year significantly differed between the
tological malignancies are catheterised for a mean of
groups. Haemoglobin values, WBC counts, percentage of
17.3e22.6 days [1,21,22], whereas the mean duration of
neutrophils, absolute neutrophil counts and platelet counts
catheterisation in the present study was 42.3 days, and inclu-
were significantly lower, whereas albumin values were sig-
ded patients who received allogeneic HSCT. A non-tunnelled
nificantly higher when a CVC was inserted in the operating
CVC was inserted during each period of chemotherapy or
room.
HSCT, then immediately removed depending on the recovery
status of the patients. The removal of a CVC can occasionally
Impact of the venue of CVC insertion be problematic when patients with haematological diseases
have neutropenia or thrombocytopenia or have completed an
We estimated the unadjusted OR (95% CI) in univariate intensive course of chemotherapy or HSCT and have difficulties
analyses and found that the venue of CVC insertion was sig- with oral ingestion. Tunnelled CVC have not been inserted for
nificantly associated with CLABSI events (Table III). Risk of long-term treatment in our department. They are inserted into
CLABSI was higher when CVC were inserted in the operating patients with solid tumours in the operating room at our hos-
room than in the ward (OR, 2.12; 95% CI, 1.14e3.94; P ¼ 0.017). pital. Therefore, our findings cannot be applied to tunnelled
In addition, allogeneic HSCT, a triple lumen catheter, haemo- CVC insertion in haematological patients because this has not
globin, WBC count and percentage of neutrophils were sig- been validated in such patients.
nificantly associated with CLABSI. Age, sex, CVC insertion sites, The suggested rates of catheter-related bloodstream
absolute neutrophil count, platelet count, albumin and infections in patients with haematological diseases range from
changes of disinfectants and dressings were not associated 5.6 e 16.3 per 1,000 catheter days [7,21e23]. Here, we found a
with CLABSI. CLABSI rate (including patients treated with HSCT) of 2.35 per
We adjusted for confounding factors using multivariate 1,000 catheter days, which was lower than that in previous
analyses with three models. Significantly associated variables studies, despite prolonged catheterisation. One reason for this
in the univariate analysis were adjusted for either the venue of might have been meticulous daily management of the CVC
CVC insertion or CLABSI events in Model 1, which was the pri- implant port. The CLABSI rate was highest among patients who
mary analysis [20]. The number of CLABSI events did not sig- had undergone allogeneic HSCT, perhaps because of prolonged
nificantly differ between the ward and the operating room. neutropenia and extreme immunosuppression. Placement of a
Model 2 (complete model) was adjusted for all other variables. CVC with multiple lumens significantly increases the CLABSI
Model 3 (reduced model) was adjusted for variables deter- rate, according to Templeton et al. and Bicudo et al. [24,25].
mined using backward stepwise selection. Models 2 and 3 Although multiple-lumen CVC are often inserted for chemo-
showed that the venue of CVC insertion was not significantly therapy or HSCT, it is best avoided wherever possible. Previous
associated with the development of CLABSI (P ¼ 0.178 and P ¼ findings indicate that the major causative pathogens are
0.229, respectively; Table IV). The number of CLABSI events did coagulase-negative staphylococci, S. aureus, corynebacteria,
not significantly differ in a subgroup of patients with CVC enterococci, Gram-negative bacteria and Candida species [26].
inserted into the internal jugular vein (data not shown). Here, we identified Gram-positive cocci, Gram-positive bacilli
We also compared the amount of elapsed time between CVC and Gram-negative bacilli in 74%, 21% and 5% of patients,
insertion and diagnosis of CLABSI between the ward and the respectively.
operating room. The incidence of CLABSI was higher among We predicted that the rate of CLABSI development after CVC
those inserted with a CVC in the operating room than the ward insertion would be lower in the operating room than in the ward
(Log-rank P ¼ 0.017; Figure 1). The unadjusted model showed because of a difference in air cleanliness. Inter-group compar-
that CLABSI events occurred significantly earlier after CVC isons showed that CVC for HSCT were inserted mostly in the
insertion in the operating room than the ward (HR, 2.13; 95% CI, operating room, and that WBC and absolute neutrophil counts
1.16e3.94; P ¼ 0.015). However, CVC insertion in the operating were significantly lower in the operating room than in the ward.
room and the ward did not significantly differ between after The main reason for CVC insertion in the operating room for
adjustment by Model 1 (HR: 1.57, 95% CI: 0.82e3.00, P ¼ 0.174; myelosuppressed patients who were to undergo HSCT is physi-
Table IV). Models 2 and 3 as shown in Table IV, were used in cian preference based on the perception of a higher standard of
H. Kitamura et al. / Infection Prevention in Practice 2 (2020) 100050 5
Table II
Baseline characteristics of patients with CVC inserted in a ward or operating room
Variables Ward group, n¼226 Operating room group, n¼305 P value
Median age, years (IQR) 63 (53e70) 59 (49e66) 0.003
Male, n (%) 136 (60.2) 176 (57.7) 0.629
Underlying diseases, n (%) 0.101
Acute myeloid leukaemia 78 (34.5) 124 (40.7)
Acute lymphoblastic leukaemia 18 (8.0) 34 (11.1)
Mixed-phenotype acute leukaemia 2 (0.9) 2 (0.7)
Acute undifferentiated leukaemia 1 (0.4) 1 (0.3)
Chronic myelogenous leukaemia 2 (0.9) 2 (0.7)
Chronic lymphocytic leukaemia 0 (0.0) 1 (0.3)
Myelodysplastic syndrome 5 (2.2) 4 (1.3)
Hodgkin’s lymphoma 2 (0.9) 3 (1.0)
Non-Hodgkin’s lymphoma 109 (48.2) 105 (34.4)
Multiple myeloma/Plasmacytoma/Amyloidosis 8 (3.5) 25 (8.2)
Benign haematological disease 1 (0.4) 4 (1.3)
Reasons for CVC insertions, n (%) <0.001
Chemotherapy 163 (72.1) 163 (53.4)
Autologous HSCT 6 (2.7) 44 (14.4)
Allogeneic HSCT 4 (1.8) 52 (17.0)
Other 53 (23.5) 46 (15.1)
CVC insertion sites, n (%) <0.001
Internal jugular vein 194 (85.8) 284 (93.1)
Subclavian vein 12 (5.3) 19 (6.2)
Femoral vein 20 (8.8) 2 (0.7)
Number of lumens of CVC, n (%) <0.001
Single lumen 45 (19.9) 57 (18.7)
Double lumen 166 (73.5) 189 (62.0)
Triple lumen 15 (6.6) 59 (19.3)
Median Hb, g/dL (IQR) 9.8 (8.2e11.7) 9.3 (7.5e10.8) 0.001
Median WBC count,/mL (IQR) 4,800 (3,125e7,075) 4,000 (2,500e6,400) 0.035
Median percentage of neutrophils, % (IQR) 62.3 (44.9e75.8) 58.4 (36.8e71.4) 0.022
Median absolute neutrophil count,/mL (IQR) 2,827 (1,463e4,605) 2,158 (1,222e3,770) 0.014
Absolute neutrophil count <1,000/mL, n (%) 45 (19.9) 65 (21.3) 0.775
Median platelet count,/mL (IQR) 145,000 (62,250e24,075) 123,000 (35,000e203,000) 0.001
Median albumin, g/dL (IQR) 3.4 (2.8e3.9) 3.5 (2.8e4.0) 0.033
Year, n (%) <0.001
2009 8 (3.5) 29 (9.5)
2010 16 (7.1) 27 (8.9)
2011 32 (14.2) 34 (11.1)
2012 32 (14.2) 25 (8.2)
2013 15 (6.6) 43 (14.1)
2014 9 (4.0) 67 (22.0)
2015 52 (23.0) 45 (14.8)
2016 46 (20.4) 33 (10.8)
2017 16 (7.1) 2 (0.7)
Change of disinfectant and dressing, n (%) 1.000
June 2009eSeptember 2012 80 (35.4) 109 (35.7)
October 2012eMarch 2017 146 (64.6) 196 (64.3)
Median duration of catheterisation, days (IQR) 34 (21e62) 35 (21e57) 0.953
CLABSI event, n (%) 15 (6.6) 39 (12.8) 0.030
Death during CVC placement, n (%) 30 (13.3) 46 (15.1) 0.644
Data are shown as n (%) or as medians with IQR. CLABSI, central line-associated bloodstream infection; CVC, central venous catheter; Hb, hae-
moglobin; HSCT, haematopoietic stem cell transplantation; IQR, interquartile range; WBC, white blood cells.
cleanliness. Univariate analysis revealed that more CLABSI increase risk for CLABSI is controversial. One retrospective
events occurred after insertion in the operating room than in study found that an operating room was more significantly
the ward. However, the difference did not reach significance in associated with the development of central line infections than
multivariate analyses. Whether venues of CVC insertion a surgical ICU [16], whereas a prospective observational study
6 H. Kitamura et al. / Infection Prevention in Practice 2 (2020) 100050