- Email: [email protected]
Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan
J Infect Chemother xxx (2017) 1e5
Contents lists available at ScienceDirect
Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Original Article
Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan Yukiko Kato a, Mao Hagihara a, b, Ai Kurumiya a, Tomoko Takahashi a, Miki Sakata a, Yuichi Shibata a, Hideo Kato a, Arufumi Shiota a, Hiroki Watanabe a, Nobuhiro Asai a, Yusuke Koizumi a, Yuka Yamagishi a, Hiroshige Mikamo a, * a b
Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 19 June 2017 Received in revised form 1 August 2017 Accepted 17 August 2017 Available online xxx
Background: Central line-associated bloodstream infections (CLABSIs) are among the most serious complications especially in blood cancer patients. In January 2013, Centers for Disease and Prevention (CDC) introduced a new surveillance definition of mucosal barrier injury-associated laboratoryconfirmed bloodstream infection (MBI-LCBI). This study was to determine the impact of MBI-LCBI on CLABSIs and compare the clinical characteristics of MBI versus non-MBI-LCBI cases. Patients and methods: We retrospectively reviewed the records of 250 consecutive patients. They were admitted in department of hematology at Aichi Medical University Hospital. We applied the revised 2013 CLABSI surveillance protocol to all CLABSI cases identified during the 47-months period from May 2012 through June 2016. Results: A total of 44 CLABSIs were identified. The median patient age was 65 years (range, 12 to 89). Among 44 patients, 31 patients were diagnosed as leukemia (70.5%) and 12 patients as lymphoma (27.3%). Six patients underwent bone transplantation for leukemia or myelodysplastic syndrome (13.6%). A total of 20 patients (45.5%) were classified as MBI-LCBI and 24 (54.5%) were classified as non-MBI-LCBI. The primary disease type (P ¼ 0.018), neutropenic within 3 days before CLABSI (MBI-LCBI vs. non-MBILCBI: 95.0% vs. 26.3%, P ¼ <0.0001), line(s) removed owing to CLABSI (15.0% vs. 54.2%, P ¼ 0.011) and Gram-negative organisms cultured (70.0% vs. 37.5%, P ¼ 0.004) showed significantly difference between the groups. Conclusion: Our data showed that MBI-LCBI cases account for 45.5% of the CLABSI cases identified in blood cancer patients, and constituted a significant burden to this high-risk patient population. © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Mucosal barrier injury laboratoryconfirmed bloodstream infection (MBI-LCBI) Blood cancer Department of hematology Central lineeassociated bloodstream infections (CLABSIs) Bloodstream infections (BSIs)
1. Introduction Central line-associated bloodstream infections (CLABSIs) lead to increased patient morbidity, mortality, and length of stay and have been estimated to cost [1e4]. Many institutions continue to struggle with high CLABSI rates especially in blood cancer patients
* Corresponding author. 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan. E-mail address: [email protected] (H. Mikamo).
and stem cell transplant patients [5]. Because CLABSIs are among the most serious complications in blood cancer patients. CLABSIs have led to prolonged hospitalization, intensive care admissions, and prolonged antimicrobial treatment. And CLABSIs increased mortality in the population [6]. These facts can result from more frequent use of central lines and from a population at higher risk of infection [7]. Evidence-based guidelines have led to significant reductions in CLABSI rates in recent years [8,9]. Yet, some bloodstream infections (BSIs) are not related to central-line care, while they meet the
http://dx.doi.org/10.1016/j.jiac.2017.08.013 1341-321X/© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kato Y, et al., Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.08.013
2
Y. Kato et al. / J Infect Chemother xxx (2017) 1e5
NHSN CLABSI definition [10e14]. The subset of CLABSIs most likely associated with mucosal barrier injury among oncology patients. The treatment with cytotoxic chemotherapy regimens may compromise the mucosal barriers and lead to translocation of oral and gastrointestinal flora into the bloodstream [15,16]. Hence, unlike CLABSIs, MBI-LCBIs are not expected to be prevented by improved central venous catheter (CVC) maintenance care [17]. In January 2013, Centers for Disease and Prevention (CDC) released a revised NHSN surveillance protocol for CLABSI [18]. It introduced a new surveillance definition of mucosal barrier injury associated laboratory-confirmed bloodstream infection (MBI-LCBI) to prevent misclassification of bloodstream infections caused by oral/intestinal microbiota in cancer patients [19]. However, few data describe the incidence of MBI-LCBIs in blood cancer patients, because this is a recent classification of BSI. Moreover, there are currently no potential strategies to prevent bacteremia secondary to MBI-LCBI in blood cancer patients. Therefore, we retrospectively reviewed patient's data. They were admitted in department of hematology. We applied the MBILCBI definition to determine the influence of separate reporting of MBI-LCBI cases on CLABSI rates and compare the clinical characteristics and outcomes of MBI- versus non-MBI bloodstream infections during the past 4 years. 2. Patients and methods 2.1. Patients We retrospectively reviewed the records of 250 consecutive patients. They were admitted in department of hematology at Aichi Medical University Hospital. The Aichi Medical University Hospital is a large university hospital in Aichi, Japan. It has 900 beds. The department of hematology comprises a separate 40-bed in oncology ward. The most common cancer diagnosis was acute leukemia, followed by lymphoma. 2.2. Study design Certificated infection nurses at our facility applied the revised 2013 NHSN CLABSI surveillance protocol to all CLABSI cases identified during the 47-months period from May 2012 through June 2016. Cases were classified as MBI-LCBI or non-MBI-LCBI. A retrospective review of medical records was conducted to collect demographic and clinical data on each case. Variables collected included age at admission, sex, cancer diagnosis, venous access device removal due to CLABSI, and death. Monthly rates of total CLABSI, MBI-LCBI, and non-MBI-LCBI were calculated per 1000 line-days. Based on the data, we calculated the annual rate of CLABSIs and device use ratio by using the standardized CDC criteria [18]. Length of stay was defined as the number of days from admission to discharge or death. 3. CLABSI and MBI-LCBI definitions A CLABSI was defined as a laboratory confirmed primary bloodstream infection with a central-line was in place for >2 calendar days [18]. If a central line was removed, only a positive blood culture on the day of removal or the next day could be defined as a CLABSI event. Besides, for a CLABSI to be classified as MBI-LCBI, both the organism criterion and clinical condition criterion (described as MBI-LCBI 1: diagnostic criteria I and MBI-LCBI 2: diagnostic criteria II in CDC guideline [18]) had to be satisfied. But, we revised CDC criteria regard to the diarrhea (more than 1 L) as more than 10 times of diarrhea documented in 24-h period.
Because, this study was a retrospective study and it was difficult to determine its volume. 3.1. Analysis A descriptive analysis as well as organism and patient characteristics for the reported MBI-LCBIs and non-MBI-LCBIs in CLABSI patients was performed. All analyses were performed using JMP, version 10.0 (SAS Institute). Two-sided P values 0.05 were considered statistically significant. The study was approved by the Institutional Review Board at Aichi Medical University Hospital (number 28-17). 4. Results A total of 44 CLABSIs were identified during the study period. The median patient age was 65 years (range, 12 to 89), and 26 (59.1%) were male. Among 44 patients, 31 patients were diagnosed as leukemia (70.5%) and 12 patients as lymphoma (27.3%). Six patients underwent bone transplantation for leukemia or myelodysplastic syndrome (13.6%). The median of length of stay (days) was 130 (range, 36e798). Patients did not receive routine prophylactic antimicrobial agents. Empiric antimicrobials, including piperacillin/ tazobactam, meropenem, or cefepime, were used during febrile episodes or when shock was present. All patients received prophylactic antifungal therapy. A total of 20 patients (45.5%) were classified as MBI-LCBI and 24 (54.5%) were classified as non-MBI-LCBI (Fig. 1). Among CLABSI cases, 17 of 33 case (51.5%) were classified with diagnostic criteria I as MBI-LCBI, 3 of 11 (27.3%) were classified with diagnostic criteria II as MBI-LCBI (Fig. 1). Most clinical and demographic characteristic were similar between MBI-LCBI and non-MBI-LCBI cases, except primary disease type (P ¼ 0.018), neutropenic within 3 days before CLABSI (95.0% of MBI-LCBI cases vs. 26.3% of non-MBI-LCBI case, P ¼ <0.0001), line(s) removed owing to CLABSI (15.0% of MBI-LCBI cases vs. 54.2% of non-MBI-LCBI case, P ¼ 0.011) and Gram-negative organisms cultured (70.0% of MBI-LCBI cases vs. 37.5% of non-MBI-LCBI case, P ¼ 0.004) (Table 1). The isolated microorganisms in MBI-LCBI cases differed from non-MBI-LCBI cases. We found more gram-negative (70%) than gram-positive pathogens (30%) in MBI-LCBI cases, while more gram-positive (50%) than gram-negative pathogens (37%) in nonMBI-LCBI cases. The most common organisms cultured from patients with MBI-LBCI were Escherichia coli (25.0%), Klebsiella pneumoniae (15.0%), and Streptococcus mitis (15.0%), whereas the most common organisms cultured from patients with non-MBI-LCBI were Staphylococcus epidermidis (12.5%) followed by Candida parapsilosis (8.3%) (Table 2). Fig. 2 showed that annual rates of CLABSIs before and after removal of cases of MBI-LCBIs from the total. The CLABSI rate including MBI-LCBIs was 3.32 per 1000 central line days. After the number of MBI-LCBI cases was removed from the numerator, the CLABSI rate during the study period decreased from 0.76 to 3.77 infections per 1000 central line days (Fig. 2). 5. Discussion The limitations of the NHSN CLABSI surveillance protocol, especially when applied to immunocompromised patients, have been well described [8,10e12,19]. As previous studies have revealed, BSIs may result from translocation of gut microorganisms related to mucosal barrier injury, due to alteration of normal gastrointestinal microbiota, or loss of mucosal integrity in the setting of impaired host defenses [15,16]. For the reason, given the
Please cite this article in press as: Kato Y, et al., Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.08.013
Y. Kato et al. / J Infect Chemother xxx (2017) 1e5
3
Fig. 1. Classification of CLABSIs as meeting MBI-LCBI or non-MBI-LCBI.
Table 2 Organisms isolated from blood in MBI-LCBI and non-MBI-LCBI.
Table 1 Characteristics of CLABSI cases meeting MBI-LCB or non-MBI-LCBI.
Sex (Male) Age (years)* Primary disease Leukemia Lymphoma Solid tumor Hematopoietic stem cell transplantation Length of stay (days)* ICU transfer within 7 days after infection* Neutropenic within 3 days before CLABSI Line(s) removed owing to CLABSI Localized signs and symptoms of infection** Oral mucositis Diarrhea (10 times) Gram-negative organisms cultured Line days until CLABSI diagnosis*** Death
MBI-LCBI
non-MBI-LCBI
(n ¼ 20)
(n ¼ 24)
P value
13 (65) 52 (12e89)
13 (54.2) 68.5 (16e84)
18 (90.0) 2 (10.0) 0 (0.0) 5 (33.3)
13 (54.2) 10 (41.7) 1 (4.2) 1 (4.3)
0.795
132 (42e798) 2 (10.0)
125 (36e427) 0 (0.0)
0.660 0.200
19 (95.0)
5 (26.3)
<0.0001
3 (15.0)
13 (54.2)
0.011
3 (15.0)
4 (16.7)
>0.999
7 (35.0) 2 (10.0) 14 (70.0)
4 (16.7) 3 (12.5) 9 (37.5)
0.185 >0.999 0.004
47
57
0.530
5 (25.0)
4 (16.7)
0.795
0.467 0.063 0.018
Data are no. (%) of cases unless otherwise indicated. *: median (range). **: Includes documentation of redness, tenderness, and/or purulent drainage at central line insertion site. ***: average. Two-sided P values were calculated using the Fisher exact test for binary variables, Pearson c2 test for primary disease type, and MannWhitney test for continuous variables.
increasing significance of this quality metric, the application of a valid, standardized surveillance definition is imperative, especially for blood cancer patients. Because they are at high risk for BSIs and associated morbidity and mortality [6]. As results, the MBI-LCBI surveillance definition was revised and improved after testing at 94 cancer centers in the United States [20]. In this study, we evaluated all CLABSI events in 250 consecutive patients were admitted in department of hematology at a single center and applied the 2016 NHSN criteria. One of the main goals of this study was to determine the proportion of CLABSIs classified as MBI-LCBI vs non-MBI-LCBI. Another one was to describe the clinical characteristics of patients who developed CLABSI among blood cancer patients. Consequently, MBI-LCBI cases account for 45.5% of the CLABSI cases identified in blood cancer patients. And they constituted a significant burden to this high-risk patient
Organism isolated
Staphylococcus aureus Staphylococcus epidermidis Staphylococcus saprophyticus Staphylococcus haemolyticus Streptococcus mitis Staphylococcus caprae Streputcoccus pneumoniae Conynebacterium jeikeium Escherichia coli Corynebacterium striatum Pseudomonas aeruginosa Enterobacter cloacae Enterococcus faecium Chyrseobactarium indologenes Klebsiella pneumoniae Serratia marcescens Enterobacter asburiae Granulicatella adiacens Fusobacterium sp Bacillus cereus Candida parapsilosis Candida albicans
All CLABSI
MBI-LCBI
non-MBI-LCBI
(n ¼ 44)
(n ¼ 20)
(n ¼ 24)
1 4 1 1 3 1 1 1 6 1 5 2 2 2 5 1 1 1 1 1 2 1
1 (5.0)
1 3 1 1
(4.2) (12.5) (4.2) (4.2)
3 (15.0) 1 (4.2) 1 (4.2) 1 (5.0) 5 (25.0) 2 2 1 1 3
(10.0) (10.0) (5.0) (5.0) (15.0)
1 (4.2) 1 (4.2) 3 1 1 2 1 1 1
(4.2) (4.2) (8.4) (4.2) (4.2) (4.2)
1 (5.0) 1 (4.2) 2 (8.4) 1 (4.2)
Data are shown as n (%). CLABSI, central line-associated bloodstream infection. *MBI-LCBI events met the criteria of the Centers for Disease Control and Prevention National Healthcare Safety Network.
population. Hence, identification of patients at risk for MBI-LCBIs are essential to allow researchers the ability to identify strategies to reduce MBI-LCBI rates in blood cancer patients. As we expected, on the basis of the surveillance definition, neutropenia (within 3 days) was more prevalent in patients with MBI-LCBI. Neutropenia was the MBI underlying condition in 95.0% of our MBI-LCBI cases. In adult hematology, oncology and stem cell transplant settings, MBI-LCBI events were associated mainly with neutropenia [19]. We admitted a statistically significant difference in the frequency of neutropenia between MBI and non-MBI-LCBI events. Of note, 45.5% CLABSI events meeting the criteria for MBI-LCBI appeared to be related to chemotherapy, whose hematopoietic toxicity is not likely to be altered by CLABSI quality improvement interventions, such as re-education of implementation of a standardized schedule for central line dressing, tubing, and injection cap changes; and the introduction of alcohol impregnated port protectors. Thus, such interventions will affect mainly the rate of
Please cite this article in press as: Kato Y, et al., Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.08.013
4
Y. Kato et al. / J Infect Chemother xxx (2017) 1e5
Fig. 2. Annual rates of CLABSI before (White) and after (Black) removal of cases of MBI-LCBIs from the total. Black bars represent the CLABSI rate per 1000 central-line days including MBI-LCBIs. Gray bars represent the CLABSI rates without MBI-LCBIs.
non-MBI-LCBI cases. Some interventions have shown some benefit in the prevention of gastrointestinal or oral mucositis [21,22]. Hence, more research into the prevention of MBI-LCBI is warranted to improve patient outcomes. The organism isolated from blood cultures was often the deciding factor in the classification of MBI-LCBI or non-MBI-LCBI. As previous clinical studies have showed that the types of microorganisms isolated in MBI-LCBI cases differed from non-MBI-LCBI cases [23]. We also found more gram-negative than grampositive pathogens in MBI-LCBI cases (Table 2). This difference may be due to patient characteristics and the use of different chemotherapy regimens. Van der Velden et al. compared myeloablative versus non-myeloablative conditioning regimens [23]. Bacteremia due to oral viridans streptococci and coagulasenegative staphylococci were found in as many as 85% of patients after intensive myeloablative regimens versus none among patients receiving non-myeloablative conditioning regimens. However, our study had several limitations. The first, the sample size of our study group was relatively small, and because it was conducted at a single hospital. The second, the relationship between specific chemotherapy protocols and MBI-LCBI should be studied. Some kinds of chemotherapy could be more affected. But, we could not test the relationship due to the limited number of CLIBSIs (n ¼ 44). The third, NHSN's list of MBI-LCBI eligible organisms is likely not inclusive of all organisms. They may cause bloodstream infection owing to translocation across compromised oral or gastrointestinal mucosa. Hence, careful review of this component of the definition is crucial to ensure data validity and accurate inter facility comparison. Finally, the primary diseases in two groups showed significantly difference. But, we could not test the difference would be affected to our results or not. Further investigation will need to clarify these points for implementation of a standardized CLABSI surveillance protocol that includes the MBILCBI criteria. It could identify more quality improvement opportunities in blood cancer patient populations. In conclusion, the results of this retrospective study showed the impact of the revised CLABSI surveillance protocol in blood cancer patients. MBI-LCBI cases accounted for 45.5% of the CLABSI cases identified in blood cancer patients. And they constituted a significant burden to this high-risk patient population. Our findings identified significant differences between MBI and noneMBI-LCBI cases. And they encourage infection prevention and to implement the MBI-LCBI surveillance protocol. Further analysis of multicenter
MBI-LCBI data is still necessary. But, our results lend support to CDC's intention to separate MBI-LBCI data from CLABSI data used for reporting purposes. Authorship statement All authors meet the ICMJE authorship criteria. Conflict of interest None declared. Acknowledgements This study was supported by the Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare, Japan (H28-Shinkou-Ippan-003). All authors thank all clinicians and pharmacists that have assisted with the provision of data for this project. References [1] Digiovine B, Chenoweth C, Watts C, Higgins M. The attributable mortality and costs of primary nosocomial bloodstream infections in the intensive care unit. Am J Respir Crit Care Med 1999;160:976e81. [2] Warren DK, Quadir WW, Hollenbeak CS, Elward AM, Cox MJ, Fraser VJ. Attributable cost of catheter-associated bloodstream infections among intensive care patients in a nonteaching hospital. Crit Care Med 2006;34: 2084e9. [3] Mermel LA. Prevention of intravascular catheter-related infections. Ann Intern Med 2000;132:391e402. [4] Elward AM, Hollenbeak CS, Warren DK, Fraser VJ. Attributable cost of nosocomial primary bloodstream infection in pediatric intensive care unit patients. Pediatrics 2005;115:868e72. [5] Dudeck MA, Weiner LM, Allen-Bridson K, Malpiedi PJ, Peterson KD, Pollock DA, et al. National Healthcare Safety Network (NHSN) report, data summary for 2012, device-associated module. Am J Infect Control 2013;41: 1148e66. [6] Poutsiaka DD, Price LL, Ucuzian A, Chan GW, Miller KB, Snydman DR. Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality. Bone Marrow Transpl 2007;40:63e70. [7] Gaur AH, Bundy DG, Gao C, Werner EJ, Billett AL, Hord JD, et al. Surveillance of hospital-acquired central line-associated bloodstream infections in pediatric hematology-oncology patients: lessons learned, challenges ahead. Infect Control Hosp Epidemiol 2013;34:316e20. [8] O'Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, et al. Guidelines for the prevention of intravascular cathetererelated infections. Am J Infect Control 2011;39:S1e34.
Please cite this article in press as: Kato Y, et al., Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.08.013
Y. Kato et al. / J Infect Chemother xxx (2017) 1e5 [9] Marschall J, Mermel LA, Fakih M, Hadaway L, Kallen A, O'Grady NP, et al. Strategies to prevent central lineeassociated bloodstream infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014;35:753e71. [10] Steinberg JP, Robichaux C, Tejedor SC, Reyes MD, Jacob JT. Distribution of pathogens in central line-associated bloodstream infection among patients with and without neutropenia following chemotherapy: evidence for a proposed modification to the current surveillance definition. Infect Control Hosp Epidemiol 2013;34:171e5. [11] Sexton DJ, Chen LF, Anderson DJ. Current definitions of centralline associated bloodstream infections: is the emperor wearing clothes? Infect Control Hosp Epidemiol 2010;31:1286e9. [12] Fraser TG, Gordon SM. CLABSI rates in immunocompromised patients: a valuable patient centered outcome? Clin Infect Dis 2011;52:1446e50. [13] Digiorgio MJ, Fatica C, Oden M, Bolwell B, Sekeres M, Kalaycio M, et al. Development of a modified surveillance definition of central line-associated bloodstream infections for patients with hematologic malignancies. Infect Control Hosp Epidemiol 2012;33:865e8. [14] Worth LJ, Slavin MA, Brown GV, Black J. Catheter-related bloodstream infections in hematology: time for standardized surveillance? Cancer 2007;109: 1215e26. [15] Tancrede CH, Andremont AO. Bacterial translocation and gram negative bacteremia in patients with hematological malignancies. J Infect Dis 1985;152:99e103. [16] Blijlevens NM, Donnelly JP, De Pauw BE. Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transpl 2000;25:1269e78.
5
[17] Metzger KE, Rucker Y, Callaghan M, Churchill M, Jovanovic BD, Zembower TR, et al. The burden of mucosal barrier injury laboratory-confirmed bloodstream infection among hematology, oncology, and stem cell transplant patients. Infect Control Hosp Epidemiol 2015;36:119e24. [18] CDC/NHSN Surveillance Definition of Healthcare-Associated Infection and Criteria for Specific Types of Infections in the Acute Care Setting https://www. cdph.ca.gov/programs/hai/Documents/Slide-Set-20-Infection-DefinitionsNHSN-2013.pdf. [Accessed 27 April 2017]. [19] Steinberg JP, Coffin SE. Improving the central line-associated bloodstream infection surveillance definition: a work in progress. Infect Control Hosp Epidemiol 2013;34:777e9. [20] See I, Iwamoto M, Allen-Bridson K, Horan T, Magill SS, Thompson ND, et al. Mucosal barrier injury laboratory-confirmed bloodstream infection: results from a field test of a new National Healthcare Safety Network definition. Infect Control Hosp Epidemiol 2013;34:769e76. [21] Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014;120:1453e61. [22] Gibson RJ, Keefe DM, Lalla RV, Bateman E, Blijlevens N, Fijlstra M, et al. Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer 2013;21:313e26. [23] van der Velden WJ, Herbers AH, Feuth T, Schaap NP, Donnelly JP, Blijlevens NM, et al. Intestinal damage determines the inflammatory response and early complications in patients receiving conditioning for a stem cell transplantation. PLoS One 2010;5, e15156.
Please cite this article in press as: Kato Y, et al., Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.08.013
Contents lists available at ScienceDirect
Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Original Article
Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan Yukiko Kato a, Mao Hagihara a, b, Ai Kurumiya a, Tomoko Takahashi a, Miki Sakata a, Yuichi Shibata a, Hideo Kato a, Arufumi Shiota a, Hiroki Watanabe a, Nobuhiro Asai a, Yusuke Koizumi a, Yuka Yamagishi a, Hiroshige Mikamo a, * a b
Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 19 June 2017 Received in revised form 1 August 2017 Accepted 17 August 2017 Available online xxx
Background: Central line-associated bloodstream infections (CLABSIs) are among the most serious complications especially in blood cancer patients. In January 2013, Centers for Disease and Prevention (CDC) introduced a new surveillance definition of mucosal barrier injury-associated laboratoryconfirmed bloodstream infection (MBI-LCBI). This study was to determine the impact of MBI-LCBI on CLABSIs and compare the clinical characteristics of MBI versus non-MBI-LCBI cases. Patients and methods: We retrospectively reviewed the records of 250 consecutive patients. They were admitted in department of hematology at Aichi Medical University Hospital. We applied the revised 2013 CLABSI surveillance protocol to all CLABSI cases identified during the 47-months period from May 2012 through June 2016. Results: A total of 44 CLABSIs were identified. The median patient age was 65 years (range, 12 to 89). Among 44 patients, 31 patients were diagnosed as leukemia (70.5%) and 12 patients as lymphoma (27.3%). Six patients underwent bone transplantation for leukemia or myelodysplastic syndrome (13.6%). A total of 20 patients (45.5%) were classified as MBI-LCBI and 24 (54.5%) were classified as non-MBI-LCBI. The primary disease type (P ¼ 0.018), neutropenic within 3 days before CLABSI (MBI-LCBI vs. non-MBILCBI: 95.0% vs. 26.3%, P ¼ <0.0001), line(s) removed owing to CLABSI (15.0% vs. 54.2%, P ¼ 0.011) and Gram-negative organisms cultured (70.0% vs. 37.5%, P ¼ 0.004) showed significantly difference between the groups. Conclusion: Our data showed that MBI-LCBI cases account for 45.5% of the CLABSI cases identified in blood cancer patients, and constituted a significant burden to this high-risk patient population. © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Mucosal barrier injury laboratoryconfirmed bloodstream infection (MBI-LCBI) Blood cancer Department of hematology Central lineeassociated bloodstream infections (CLABSIs) Bloodstream infections (BSIs)
1. Introduction Central line-associated bloodstream infections (CLABSIs) lead to increased patient morbidity, mortality, and length of stay and have been estimated to cost [1e4]. Many institutions continue to struggle with high CLABSI rates especially in blood cancer patients
* Corresponding author. 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan. E-mail address: [email protected] (H. Mikamo).
and stem cell transplant patients [5]. Because CLABSIs are among the most serious complications in blood cancer patients. CLABSIs have led to prolonged hospitalization, intensive care admissions, and prolonged antimicrobial treatment. And CLABSIs increased mortality in the population [6]. These facts can result from more frequent use of central lines and from a population at higher risk of infection [7]. Evidence-based guidelines have led to significant reductions in CLABSI rates in recent years [8,9]. Yet, some bloodstream infections (BSIs) are not related to central-line care, while they meet the
http://dx.doi.org/10.1016/j.jiac.2017.08.013 1341-321X/© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kato Y, et al., Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.08.013
2
Y. Kato et al. / J Infect Chemother xxx (2017) 1e5
NHSN CLABSI definition [10e14]. The subset of CLABSIs most likely associated with mucosal barrier injury among oncology patients. The treatment with cytotoxic chemotherapy regimens may compromise the mucosal barriers and lead to translocation of oral and gastrointestinal flora into the bloodstream [15,16]. Hence, unlike CLABSIs, MBI-LCBIs are not expected to be prevented by improved central venous catheter (CVC) maintenance care [17]. In January 2013, Centers for Disease and Prevention (CDC) released a revised NHSN surveillance protocol for CLABSI [18]. It introduced a new surveillance definition of mucosal barrier injury associated laboratory-confirmed bloodstream infection (MBI-LCBI) to prevent misclassification of bloodstream infections caused by oral/intestinal microbiota in cancer patients [19]. However, few data describe the incidence of MBI-LCBIs in blood cancer patients, because this is a recent classification of BSI. Moreover, there are currently no potential strategies to prevent bacteremia secondary to MBI-LCBI in blood cancer patients. Therefore, we retrospectively reviewed patient's data. They were admitted in department of hematology. We applied the MBILCBI definition to determine the influence of separate reporting of MBI-LCBI cases on CLABSI rates and compare the clinical characteristics and outcomes of MBI- versus non-MBI bloodstream infections during the past 4 years. 2. Patients and methods 2.1. Patients We retrospectively reviewed the records of 250 consecutive patients. They were admitted in department of hematology at Aichi Medical University Hospital. The Aichi Medical University Hospital is a large university hospital in Aichi, Japan. It has 900 beds. The department of hematology comprises a separate 40-bed in oncology ward. The most common cancer diagnosis was acute leukemia, followed by lymphoma. 2.2. Study design Certificated infection nurses at our facility applied the revised 2013 NHSN CLABSI surveillance protocol to all CLABSI cases identified during the 47-months period from May 2012 through June 2016. Cases were classified as MBI-LCBI or non-MBI-LCBI. A retrospective review of medical records was conducted to collect demographic and clinical data on each case. Variables collected included age at admission, sex, cancer diagnosis, venous access device removal due to CLABSI, and death. Monthly rates of total CLABSI, MBI-LCBI, and non-MBI-LCBI were calculated per 1000 line-days. Based on the data, we calculated the annual rate of CLABSIs and device use ratio by using the standardized CDC criteria [18]. Length of stay was defined as the number of days from admission to discharge or death. 3. CLABSI and MBI-LCBI definitions A CLABSI was defined as a laboratory confirmed primary bloodstream infection with a central-line was in place for >2 calendar days [18]. If a central line was removed, only a positive blood culture on the day of removal or the next day could be defined as a CLABSI event. Besides, for a CLABSI to be classified as MBI-LCBI, both the organism criterion and clinical condition criterion (described as MBI-LCBI 1: diagnostic criteria I and MBI-LCBI 2: diagnostic criteria II in CDC guideline [18]) had to be satisfied. But, we revised CDC criteria regard to the diarrhea (more than 1 L) as more than 10 times of diarrhea documented in 24-h period.
Because, this study was a retrospective study and it was difficult to determine its volume. 3.1. Analysis A descriptive analysis as well as organism and patient characteristics for the reported MBI-LCBIs and non-MBI-LCBIs in CLABSI patients was performed. All analyses were performed using JMP, version 10.0 (SAS Institute). Two-sided P values 0.05 were considered statistically significant. The study was approved by the Institutional Review Board at Aichi Medical University Hospital (number 28-17). 4. Results A total of 44 CLABSIs were identified during the study period. The median patient age was 65 years (range, 12 to 89), and 26 (59.1%) were male. Among 44 patients, 31 patients were diagnosed as leukemia (70.5%) and 12 patients as lymphoma (27.3%). Six patients underwent bone transplantation for leukemia or myelodysplastic syndrome (13.6%). The median of length of stay (days) was 130 (range, 36e798). Patients did not receive routine prophylactic antimicrobial agents. Empiric antimicrobials, including piperacillin/ tazobactam, meropenem, or cefepime, were used during febrile episodes or when shock was present. All patients received prophylactic antifungal therapy. A total of 20 patients (45.5%) were classified as MBI-LCBI and 24 (54.5%) were classified as non-MBI-LCBI (Fig. 1). Among CLABSI cases, 17 of 33 case (51.5%) were classified with diagnostic criteria I as MBI-LCBI, 3 of 11 (27.3%) were classified with diagnostic criteria II as MBI-LCBI (Fig. 1). Most clinical and demographic characteristic were similar between MBI-LCBI and non-MBI-LCBI cases, except primary disease type (P ¼ 0.018), neutropenic within 3 days before CLABSI (95.0% of MBI-LCBI cases vs. 26.3% of non-MBI-LCBI case, P ¼ <0.0001), line(s) removed owing to CLABSI (15.0% of MBI-LCBI cases vs. 54.2% of non-MBI-LCBI case, P ¼ 0.011) and Gram-negative organisms cultured (70.0% of MBI-LCBI cases vs. 37.5% of non-MBI-LCBI case, P ¼ 0.004) (Table 1). The isolated microorganisms in MBI-LCBI cases differed from non-MBI-LCBI cases. We found more gram-negative (70%) than gram-positive pathogens (30%) in MBI-LCBI cases, while more gram-positive (50%) than gram-negative pathogens (37%) in nonMBI-LCBI cases. The most common organisms cultured from patients with MBI-LBCI were Escherichia coli (25.0%), Klebsiella pneumoniae (15.0%), and Streptococcus mitis (15.0%), whereas the most common organisms cultured from patients with non-MBI-LCBI were Staphylococcus epidermidis (12.5%) followed by Candida parapsilosis (8.3%) (Table 2). Fig. 2 showed that annual rates of CLABSIs before and after removal of cases of MBI-LCBIs from the total. The CLABSI rate including MBI-LCBIs was 3.32 per 1000 central line days. After the number of MBI-LCBI cases was removed from the numerator, the CLABSI rate during the study period decreased from 0.76 to 3.77 infections per 1000 central line days (Fig. 2). 5. Discussion The limitations of the NHSN CLABSI surveillance protocol, especially when applied to immunocompromised patients, have been well described [8,10e12,19]. As previous studies have revealed, BSIs may result from translocation of gut microorganisms related to mucosal barrier injury, due to alteration of normal gastrointestinal microbiota, or loss of mucosal integrity in the setting of impaired host defenses [15,16]. For the reason, given the
Please cite this article in press as: Kato Y, et al., Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.08.013
Y. Kato et al. / J Infect Chemother xxx (2017) 1e5
3
Fig. 1. Classification of CLABSIs as meeting MBI-LCBI or non-MBI-LCBI.
Table 2 Organisms isolated from blood in MBI-LCBI and non-MBI-LCBI.
Table 1 Characteristics of CLABSI cases meeting MBI-LCB or non-MBI-LCBI.
Sex (Male) Age (years)* Primary disease Leukemia Lymphoma Solid tumor Hematopoietic stem cell transplantation Length of stay (days)* ICU transfer within 7 days after infection* Neutropenic within 3 days before CLABSI Line(s) removed owing to CLABSI Localized signs and symptoms of infection** Oral mucositis Diarrhea (10 times) Gram-negative organisms cultured Line days until CLABSI diagnosis*** Death
MBI-LCBI
non-MBI-LCBI
(n ¼ 20)
(n ¼ 24)
P value
13 (65) 52 (12e89)
13 (54.2) 68.5 (16e84)
18 (90.0) 2 (10.0) 0 (0.0) 5 (33.3)
13 (54.2) 10 (41.7) 1 (4.2) 1 (4.3)
0.795
132 (42e798) 2 (10.0)
125 (36e427) 0 (0.0)
0.660 0.200
19 (95.0)
5 (26.3)
<0.0001
3 (15.0)
13 (54.2)
0.011
3 (15.0)
4 (16.7)
>0.999
7 (35.0) 2 (10.0) 14 (70.0)
4 (16.7) 3 (12.5) 9 (37.5)
0.185 >0.999 0.004
47
57
0.530
5 (25.0)
4 (16.7)
0.795
0.467 0.063 0.018
Data are no. (%) of cases unless otherwise indicated. *: median (range). **: Includes documentation of redness, tenderness, and/or purulent drainage at central line insertion site. ***: average. Two-sided P values were calculated using the Fisher exact test for binary variables, Pearson c2 test for primary disease type, and MannWhitney test for continuous variables.
increasing significance of this quality metric, the application of a valid, standardized surveillance definition is imperative, especially for blood cancer patients. Because they are at high risk for BSIs and associated morbidity and mortality [6]. As results, the MBI-LCBI surveillance definition was revised and improved after testing at 94 cancer centers in the United States [20]. In this study, we evaluated all CLABSI events in 250 consecutive patients were admitted in department of hematology at a single center and applied the 2016 NHSN criteria. One of the main goals of this study was to determine the proportion of CLABSIs classified as MBI-LCBI vs non-MBI-LCBI. Another one was to describe the clinical characteristics of patients who developed CLABSI among blood cancer patients. Consequently, MBI-LCBI cases account for 45.5% of the CLABSI cases identified in blood cancer patients. And they constituted a significant burden to this high-risk patient
Organism isolated
Staphylococcus aureus Staphylococcus epidermidis Staphylococcus saprophyticus Staphylococcus haemolyticus Streptococcus mitis Staphylococcus caprae Streputcoccus pneumoniae Conynebacterium jeikeium Escherichia coli Corynebacterium striatum Pseudomonas aeruginosa Enterobacter cloacae Enterococcus faecium Chyrseobactarium indologenes Klebsiella pneumoniae Serratia marcescens Enterobacter asburiae Granulicatella adiacens Fusobacterium sp Bacillus cereus Candida parapsilosis Candida albicans
All CLABSI
MBI-LCBI
non-MBI-LCBI
(n ¼ 44)
(n ¼ 20)
(n ¼ 24)
1 4 1 1 3 1 1 1 6 1 5 2 2 2 5 1 1 1 1 1 2 1
1 (5.0)
1 3 1 1
(4.2) (12.5) (4.2) (4.2)
3 (15.0) 1 (4.2) 1 (4.2) 1 (5.0) 5 (25.0) 2 2 1 1 3
(10.0) (10.0) (5.0) (5.0) (15.0)
1 (4.2) 1 (4.2) 3 1 1 2 1 1 1
(4.2) (4.2) (8.4) (4.2) (4.2) (4.2)
1 (5.0) 1 (4.2) 2 (8.4) 1 (4.2)
Data are shown as n (%). CLABSI, central line-associated bloodstream infection. *MBI-LCBI events met the criteria of the Centers for Disease Control and Prevention National Healthcare Safety Network.
population. Hence, identification of patients at risk for MBI-LCBIs are essential to allow researchers the ability to identify strategies to reduce MBI-LCBI rates in blood cancer patients. As we expected, on the basis of the surveillance definition, neutropenia (within 3 days) was more prevalent in patients with MBI-LCBI. Neutropenia was the MBI underlying condition in 95.0% of our MBI-LCBI cases. In adult hematology, oncology and stem cell transplant settings, MBI-LCBI events were associated mainly with neutropenia [19]. We admitted a statistically significant difference in the frequency of neutropenia between MBI and non-MBI-LCBI events. Of note, 45.5% CLABSI events meeting the criteria for MBI-LCBI appeared to be related to chemotherapy, whose hematopoietic toxicity is not likely to be altered by CLABSI quality improvement interventions, such as re-education of implementation of a standardized schedule for central line dressing, tubing, and injection cap changes; and the introduction of alcohol impregnated port protectors. Thus, such interventions will affect mainly the rate of
Please cite this article in press as: Kato Y, et al., Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.08.013
4
Y. Kato et al. / J Infect Chemother xxx (2017) 1e5
Fig. 2. Annual rates of CLABSI before (White) and after (Black) removal of cases of MBI-LCBIs from the total. Black bars represent the CLABSI rate per 1000 central-line days including MBI-LCBIs. Gray bars represent the CLABSI rates without MBI-LCBIs.
non-MBI-LCBI cases. Some interventions have shown some benefit in the prevention of gastrointestinal or oral mucositis [21,22]. Hence, more research into the prevention of MBI-LCBI is warranted to improve patient outcomes. The organism isolated from blood cultures was often the deciding factor in the classification of MBI-LCBI or non-MBI-LCBI. As previous clinical studies have showed that the types of microorganisms isolated in MBI-LCBI cases differed from non-MBI-LCBI cases [23]. We also found more gram-negative than grampositive pathogens in MBI-LCBI cases (Table 2). This difference may be due to patient characteristics and the use of different chemotherapy regimens. Van der Velden et al. compared myeloablative versus non-myeloablative conditioning regimens [23]. Bacteremia due to oral viridans streptococci and coagulasenegative staphylococci were found in as many as 85% of patients after intensive myeloablative regimens versus none among patients receiving non-myeloablative conditioning regimens. However, our study had several limitations. The first, the sample size of our study group was relatively small, and because it was conducted at a single hospital. The second, the relationship between specific chemotherapy protocols and MBI-LCBI should be studied. Some kinds of chemotherapy could be more affected. But, we could not test the relationship due to the limited number of CLIBSIs (n ¼ 44). The third, NHSN's list of MBI-LCBI eligible organisms is likely not inclusive of all organisms. They may cause bloodstream infection owing to translocation across compromised oral or gastrointestinal mucosa. Hence, careful review of this component of the definition is crucial to ensure data validity and accurate inter facility comparison. Finally, the primary diseases in two groups showed significantly difference. But, we could not test the difference would be affected to our results or not. Further investigation will need to clarify these points for implementation of a standardized CLABSI surveillance protocol that includes the MBILCBI criteria. It could identify more quality improvement opportunities in blood cancer patient populations. In conclusion, the results of this retrospective study showed the impact of the revised CLABSI surveillance protocol in blood cancer patients. MBI-LCBI cases accounted for 45.5% of the CLABSI cases identified in blood cancer patients. And they constituted a significant burden to this high-risk patient population. Our findings identified significant differences between MBI and noneMBI-LCBI cases. And they encourage infection prevention and to implement the MBI-LCBI surveillance protocol. Further analysis of multicenter
MBI-LCBI data is still necessary. But, our results lend support to CDC's intention to separate MBI-LBCI data from CLABSI data used for reporting purposes. Authorship statement All authors meet the ICMJE authorship criteria. Conflict of interest None declared. Acknowledgements This study was supported by the Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare, Japan (H28-Shinkou-Ippan-003). All authors thank all clinicians and pharmacists that have assisted with the provision of data for this project. References [1] Digiovine B, Chenoweth C, Watts C, Higgins M. The attributable mortality and costs of primary nosocomial bloodstream infections in the intensive care unit. Am J Respir Crit Care Med 1999;160:976e81. [2] Warren DK, Quadir WW, Hollenbeak CS, Elward AM, Cox MJ, Fraser VJ. Attributable cost of catheter-associated bloodstream infections among intensive care patients in a nonteaching hospital. Crit Care Med 2006;34: 2084e9. [3] Mermel LA. Prevention of intravascular catheter-related infections. Ann Intern Med 2000;132:391e402. [4] Elward AM, Hollenbeak CS, Warren DK, Fraser VJ. Attributable cost of nosocomial primary bloodstream infection in pediatric intensive care unit patients. Pediatrics 2005;115:868e72. [5] Dudeck MA, Weiner LM, Allen-Bridson K, Malpiedi PJ, Peterson KD, Pollock DA, et al. National Healthcare Safety Network (NHSN) report, data summary for 2012, device-associated module. Am J Infect Control 2013;41: 1148e66. [6] Poutsiaka DD, Price LL, Ucuzian A, Chan GW, Miller KB, Snydman DR. Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality. Bone Marrow Transpl 2007;40:63e70. [7] Gaur AH, Bundy DG, Gao C, Werner EJ, Billett AL, Hord JD, et al. Surveillance of hospital-acquired central line-associated bloodstream infections in pediatric hematology-oncology patients: lessons learned, challenges ahead. Infect Control Hosp Epidemiol 2013;34:316e20. [8] O'Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, et al. Guidelines for the prevention of intravascular cathetererelated infections. Am J Infect Control 2011;39:S1e34.
Please cite this article in press as: Kato Y, et al., Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.08.013
Y. Kato et al. / J Infect Chemother xxx (2017) 1e5 [9] Marschall J, Mermel LA, Fakih M, Hadaway L, Kallen A, O'Grady NP, et al. Strategies to prevent central lineeassociated bloodstream infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014;35:753e71. [10] Steinberg JP, Robichaux C, Tejedor SC, Reyes MD, Jacob JT. Distribution of pathogens in central line-associated bloodstream infection among patients with and without neutropenia following chemotherapy: evidence for a proposed modification to the current surveillance definition. Infect Control Hosp Epidemiol 2013;34:171e5. [11] Sexton DJ, Chen LF, Anderson DJ. Current definitions of centralline associated bloodstream infections: is the emperor wearing clothes? Infect Control Hosp Epidemiol 2010;31:1286e9. [12] Fraser TG, Gordon SM. CLABSI rates in immunocompromised patients: a valuable patient centered outcome? Clin Infect Dis 2011;52:1446e50. [13] Digiorgio MJ, Fatica C, Oden M, Bolwell B, Sekeres M, Kalaycio M, et al. Development of a modified surveillance definition of central line-associated bloodstream infections for patients with hematologic malignancies. Infect Control Hosp Epidemiol 2012;33:865e8. [14] Worth LJ, Slavin MA, Brown GV, Black J. Catheter-related bloodstream infections in hematology: time for standardized surveillance? Cancer 2007;109: 1215e26. [15] Tancrede CH, Andremont AO. Bacterial translocation and gram negative bacteremia in patients with hematological malignancies. J Infect Dis 1985;152:99e103. [16] Blijlevens NM, Donnelly JP, De Pauw BE. Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transpl 2000;25:1269e78.
5
[17] Metzger KE, Rucker Y, Callaghan M, Churchill M, Jovanovic BD, Zembower TR, et al. The burden of mucosal barrier injury laboratory-confirmed bloodstream infection among hematology, oncology, and stem cell transplant patients. Infect Control Hosp Epidemiol 2015;36:119e24. [18] CDC/NHSN Surveillance Definition of Healthcare-Associated Infection and Criteria for Specific Types of Infections in the Acute Care Setting https://www. cdph.ca.gov/programs/hai/Documents/Slide-Set-20-Infection-DefinitionsNHSN-2013.pdf. [Accessed 27 April 2017]. [19] Steinberg JP, Coffin SE. Improving the central line-associated bloodstream infection surveillance definition: a work in progress. Infect Control Hosp Epidemiol 2013;34:777e9. [20] See I, Iwamoto M, Allen-Bridson K, Horan T, Magill SS, Thompson ND, et al. Mucosal barrier injury laboratory-confirmed bloodstream infection: results from a field test of a new National Healthcare Safety Network definition. Infect Control Hosp Epidemiol 2013;34:769e76. [21] Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014;120:1453e61. [22] Gibson RJ, Keefe DM, Lalla RV, Bateman E, Blijlevens N, Fijlstra M, et al. Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer 2013;21:313e26. [23] van der Velden WJ, Herbers AH, Feuth T, Schaap NP, Donnelly JP, Blijlevens NM, et al. Intestinal damage determines the inflammatory response and early complications in patients receiving conditioning for a stem cell transplantation. PLoS One 2010;5, e15156.
Please cite this article in press as: Kato Y, et al., Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.08.013