Acute Leukemia Patients: A CLABSI Risk Special Population

Special Article - Leukemia

Ann Hematol Oncol. 2018; 5(2): 1192.

Acute Leukemia Patients: A CLABSI Risk Special Population

Martinez JM¹*, Santo AE², Godinho A³, Azevedo A4, Felix A5, Chacim S6, Ramada D7, Mariz JM8 and Medeiros R9

¹Registered Nurse, Clinical Nurse Specialist, Hematology- Oncology Department, Instituto Português de Oncologia, Porto

²Hematology-Oncology Department, Molecular Oncology Group-CI, Portuguese Institute of Oncology, Porto

³Registered Nurse, Hematology-Oncology Department, Portuguese Institute of Oncology, Porto

4Registered Nurse, Clinical Nurse Specialist, Hematology- Oncology Department, Portuguese Institute of Oncology, Porto

5Registered Nurse, Hematology-Oncology Department, Portuguese Institute of Oncology, Porto

6Hematology-Oncology Department, Portuguese Institute of Oncology, Porto

7Registered Nurse, Clinical Nurse Specialist, Day Hospital Department of Portuguese Institute of Oncology, Porto

8Hematology-Oncology Department Director, Portuguese Institute of Oncology, Porto

9Molecular Oncology Group-CI, Portuguese Institute of Oncology, Porto

*Corresponding author: Martinez JM, Hematology- Oncology Department, Instituto Português de Oncologia- Porto, R. Dr. Ant Bernardino de Almeida, 4200-072 Porto, Portugal

Received: January 11, 2018; Accepted: February 12, 2018; Published: February 28, 2018


Background: Patients with acute leukemia (AL) have a higher risk of neutropenia. Central venous catheters (CVC) are indispensable devices during chemotherapy treatments and aplasia support.

Methods: This is a single-center, retrospective cohort study, and reporting 154 hospital admission episodes, either for chemotherapy treatment or aplasia support, regarding twenty-eight AL patients using a Hickman CVC for more than 72h, from January 2013 to December 2015.

Results: Overall 3032 CVC manipulations considering a median of 1 CVC manipulations by catheter/day (range, 5 to 0) among 2130 hospital admission days (2007 catheter days) were reported. CLABSI was always identified in neutropenia admissions (1212 neutropenia-days) within cases presenting a median number of CVC manipulations superior to 15. The number of CVC manipulation increases along with cumulative neutropenia days [r=0.752, p=0.000 with an = 0.605]. However no relation was found with the cumulative non-neutropenia days. Taking neutropenia condition into account, CLABSI risk is increased considering cumulative CVC manipulations [CLABSI group, mean±SD, 27.89±3.199; non-CLABSI group, mean±SD, 20.82±1.189; p=0.046]. No CLABSI was identified after the first positivity blood cultures result and no CLABSI was reported by ANC>500 cells.

Conclusion: We conclude that in neutropenic patiens, undergoing induction therapy or in aplasia support, CLABSI risk increases along with cumulative neutropenia days prior CLABSI and CVC manipulations being the AL patients could be considered a CLABSI risk special population.

Keywords: CLABSI; CRBSI; Acute leukemia; Hickman catheter; Neutropenia


Infectious diseases are important causes of both morbidity and mortality in hematology oncology patients. Patients with acute leukemia (AL) have a higher risk of neutropenia due to high-dose chemotherapy treatments and to malignancy itself [1]. Multiple chemotherapy cycles, antibiotic resistant bacteria, and high transfusion rates are known predisposing factors that increase the incidence and prevalence of bloodstream infections (BSI) [1].

There are four major catheter types based on their designs: Nontunnelled CVCs, Tunnelled CVCs (i.e., Hickman or Broviac catheters), Implantable ports and peripherally inserted central catheter (PICC) [2]. The placement and type of CVC depends on the preferences of the patient, the healthcare provider and the IV therapy duration [3]. The Healthcare and Technology Synergy (HAST) framework considers patient, product and practice as the central elements of effective clinical research associated with central venous catheters (CVC) [4]. The real value of CVC management still remains unclear due to the low description and few management details reports [5-6].

Catheter-related occlusion due to mechanical obstructions and catheter-related infection are the most important complications in the management of the central venous devices [7-9]. In AL inpatients the risk of these complications is high due to myelossupresion, especially neutropenia and thrombocytopenia [10]. The most common modifiable risk factors known to increase overall catheter-related bloodstream infection (CRBSI) are CVC-life, parenteral nutrition, multi-lumen CVC, high workload or CVC-associated thrombosis, being the imunocompromised status the highlighted non-modifiable risk factor in hematology oncology patients [1-11]. The principal way for healthcare professionals to reduce and control the pathogenesis of infections in central line devices are the insertion and maintenance procedures [4,6-8]. Several studies report behavioral changes, education of healthcare professionals, insufficiently trained nurses, a low nurse-to-patient ratio and protected environments directly related to infection control strategies [7,12].

This clinical research studies neutropenia and CVCmanipulations associated with central-line associated bloodstream infection (CLABSI) using evidence-based science.

Material and Methods

Selection and description of participants

A single-centre, retrospective cohort study was performed, including all consecutive AL patients using a Hickman CVC for more than 72h, undergoing chemotherapy treatment (CT)or aplasia support from January 2013 to December 2015 at the Haematology Department of the Portuguese Institute of Oncology (Porto).

Patients older than 18 years old with newly diagnosed or relapsed acute leukemia admitted for CT or aplasia support and with a CVC inserted during the study period were included. Patients in supportive care, who had previous hematopoietic stem cells transplantation, with clinical septicemia at the moment of the CVC introduction, with insertion procedure complications or with acute promyelocytic leukemia diagnosis were excluded. One hundred and twenty three hematology-oncology patients placed a long-term catheter in the study period, AL (n=32). After inclusion and exclusion criteria (septicemia n=3, insertion procedure complication n=1), twenty eight AL patients with a Hickman catheter were included.

Data collection

Data concerning each patient’s background was collected from the medical records. The daily data assessment ended when the CVC was removed for sepsis or end of treatment. When the final eligible patient was admitted to the study a minimum of one-month follow up was considered. The baseline demographic data was collected on the day of CVC placement and assessment was encompassed in every hospital admission.

Neutropenia and central-line infections definitions

Neutropenia [13] was considered when ANC (Absolute Neutrophil Count) =500 cells, or when no differential count was available and WBC (White Blood Count) =1600 cells was reported (previous statistical correlation analysis). A total of continue neutropenia-days was considered duration of neutropenia. Overall neutropenia-days related to catheter-days were considered Neutropenia Ratio (NR). Neutropenia days-prior CLABSI were considered the number of neutropenia-days since the first neutropenia-day to CLABSI reported.

CLABSI and CRBSI rates were calculated considering BCs yielding an organism (positive culture in peripheral vein and at least one CVC-line) per 1000 CVC-days. CLABSI was considered in patients with a central line in place within 48-hour period and bloodstream infection that is not related to an infection at another site [12]. Differential Time Positivity was reported (samples from CVC lines become positive 120 minutes or more before peripheral vein samples), CRBSI was considered [12]. The ratio between the mucosal injury barrier microorganism (MBIm) [14] and total of microorganism recovered was considered MBIm ratio.

CVC manipulations and catheter-related occlusions definitions

Manipulation was considered in every approach to CVC with at least one open line. One manipulation of the CVC was considered every time the CVC line was opened to change the administration sets, collect blood samples or blood cultures (BC). When transfusion support was performed two manipulations were considered.

Occlusion was considered when the capacity to blood withdrawal was compromised and the ability to flush fluids is lost. Partial occlusion (inability to aspirate blood but ability to infuse through the catheter) and complete occlusion (inability to aspirate blood and infuse through the catheter) were reported. Catheter-related occlusion was calculated considering the occlusion events per 1000 CVC-days [2,9]

Technical department information

The department consisted of 20 beds distributed among eight double and four single rooms, all equipped with positive pressure ventilation and HEPPA filters. The insertion of CVCs is performed by medical staff in an operating room [7] located in the department, and daily management of CVCs is performed by nursing staff. During the study period, no other relevant departmental changes were implemented, including CVC insertion, CVC management procedures, indication for BC, and BC assessment.

Blood cultures collection and empirical antibiotic use policy

BC collected by control indication and non-department and hospital acquired infections were not included in the study [12]. For every episode with an indication for BCs, samples were collected first from a peripheral vein followed by the CVC line with no more than five minutes between samples to reduce DTP results bias [12-15]. BC collection was performed by one nurse. BC samples were collected with a minimum of 5mlof blood, when possible, in BACTED PLUS Aerobic/F® vials and analyzed by the microbiology department. In an attempt to reduce false positive BC results due to positive needleless connector and negative hub contamination, needleless connectors were removed before collecting BC samples. Large spectrum antibiotherapy was started as per the 2009 Infectious Diseases Society of America Guidelines for Intravascular Catheter-related Infection, recommended to treat gram-negative bacterial infections in patients undergoing neutropenia or septicemia special conditions [16].

Device management

The management of CVCs followed the CDC (2011) guideline recommendations [13]. Hickman catheters (Vygon®) without any antimicrobials were inserted in the subclavian vein. All catheters were double lumen (CH/F 7, lumen no.1=0.6, lumen no.2=1.0). No antibiotic prophylaxis was performed. Specific technical information of CVC management included the use of: chlorhexidine 2% in alcohol 70% solution for needleless connector disinfection, split septum needleless connector (Bionecteur, Vygon®) and sodium heparin 20 IU/ml (Fibrilin®) to CVC-lock.

Data analysis

Data analysis was conducted using IBM SPSS Statistics for Windows (SPSS Inc., Version 24.0) licensed by ICBAS-UP (Instituto de Ciências Biomédicas Abel Salazar-Universidade do Porto; Master Degree Oncology Program. A continuous variable was reported by median or mean (when appropriate) and range. Categorical variables were reported as frequency and percentages. Any association between two continuous quantitative variables was analyzed by Pearson´s test. Normality tests reported a sample without normal distribution, considering that hypothesis tests were analyzed by non-parametric test. A p value of =0.05 was determined to be significant.

Protection of personal data

The study was approved by the Ethics Committee (CES IPO: 137/2016) of the Portuguese Institute of Oncology (Porto) on 16 June, 2016. All data was treated in compliance with the Portuguese Law n° 67/98 of 26 October concerning the protection of personal data.


A total of 28 patients diagnosed with AL among 154 hospital admission episodes related by CLABSI/non-CLABSI [13(8.4%)/141(91.6%)] were reported (Table 1). Among this sample, median age of 49 years [range, 68 to 23] summarized in 21(75%) female and 7(25%) male patients were identified. No CLABSI risk were found considering diagnose [RR 0.976, 95% CI, 0.887-1.074], relapse [RR 2.267, 95% CI, 0.688-7.472], age [=50/>50 years, reference group] [RR 0.922, CI 95%, 0.325-2.618] and gender [RR 2.000, 95% CI, 0.663-6.034]. Reasons for hospital admission were induction [32(20.8%)], aplasia support [48(31.2%)], CT [70(45.4%)], and CT + aplasia [4(2.6%)].