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 ~  Materials and Me...
 ~ Results
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  Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 37  |  Issue : 3  |  Page : 376-380
 

Central line-associated bloodstream infections in cancer patients: An experience from a tertiary care cancer centre


1 Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Hospital Administration, All India Institute of Medical Sciences, New Delhi, India
3 Department of Medical Oncology, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India

Date of Submission23-Sep-2019
Date of Decision02-Nov-2019
Date of Acceptance15-Nov-2019
Date of Web Publication29-Jan-2020

Correspondence Address:
Dr. Hitender Gautam
Department of Microbiology, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_19_352

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 ~ Abstract 


Introduction: Central venous catheters (CVCs) implanted in patients with malignancies may often be associated with local or central line-associated bloodstream infections (CLABSI), which are a major source of morbidity and rarely mortality, making such patients' care difficult and complicated. Materials and Methods: This retrospective study is a single-centre's experience including both paediatric and adult patients with malignancy, who had a CVC inserted and were receiving care at cancer centre of our hospital over a period between January 2017 and June 2018. Results: In the period from January 2017 to June 2018, 73 confirmed cases of CLABSIs among cancer patients were included in this study. The rate of CLABSIs was estimated as 2.1 episodes/1000 CVC days. Out of 73 CLABSI cases, Gram-negative bacilli were the predominant causative agents of CLABSI constituting 72.6% (n = 53/73) of isolated organisms, 21.9% (n = 16/73) of infections were caused by Gram-positive cocci while polymicrobial infections accounted for 5.4% (n = 4/73) of these cases. Conclusion: Over the last 20 years, an epidemiologic shift has occurred among CLABSI in cancer patients. These findings should be considered with the development of interventions that will prevent Gram-negative CLABSI after CVC insertion. To our knowledge, this is the first study reporting data on the incidence of CLABSIs in cancer patients at tertiary care hospital from North Indian hospital.


Keywords: Central line-associated bloodstream infection, central venous catheters, malignancies


How to cite this article:
Agrawal SK, Gautam H, Choudhary AH, Das BK, Kumar L, Kapil A. Central line-associated bloodstream infections in cancer patients: An experience from a tertiary care cancer centre. Indian J Med Microbiol 2019;37:376-80

How to cite this URL:
Agrawal SK, Gautam H, Choudhary AH, Das BK, Kumar L, Kapil A. Central line-associated bloodstream infections in cancer patients: An experience from a tertiary care cancer centre. Indian J Med Microbiol [serial online] 2019 [cited 2020 Apr 2];37:376-80. Available from: http://www.ijmm.org/text.asp?2019/37/3/376/277069





 ~ Introduction Top


Central venous catheters (CVCs) have significantly improved the quality of life for patients with malignancies during the past few decades and today are considered an important and indispensable part of treatment for patients receiving antineoplastic therapy.[1] They provide a safe means of chemotherapy administration or supportive treatments such as antibiotics, blood products, parenteral nutrition or intravenous fluids under emergency conditions. However, CVCs implanted in patients with malignancies may often be associated with local or bloodstream infections (central line-associated bloodstream infections [CLABSIs]), which are a major source of morbidity and rarely mortality, making such patients' care difficult and complicated. When present, the CVC is considered the source of the blood stream infection (BSI) when no other source is identified. Bacteraemias related to CVCs also lead to additional days and costs of hospitalisation.[2] The rate of CVC-BSI across Indian hospitals range from 4.01/1000 catheter days to 9.26/1000 catheter days citing the need for effective infection control programmes including surveillance and antibiotic policies.[3],[4],[5]

Mostly Gram-positive cocci (GPC) have been implicated to be the aetiological agents of CLABSI. However, few studies report Gram-negative bacilli (GNB) as the culprits.[6],[7],[8] Furthermore, the empiric coverage should be based on local antimicrobial susceptibility data and the severity of disease. It is crucial for institutions to identify local patterns of microorganisms and their susceptibilities in order to appropriately inform choice of empiric antibiotics for these infections and to promote antibiotic stewardship.

To the best of our knowledge, bacteriological profile of CLABSI in cancer patients and the antibiograms of the isolates are not well studied in our region of the country. Most of the reported data are from intensive care unit studies that do not emphasize on cancer patients.[9] Accordingly, we planned to conduct this study to determine the microbiological profile of the cancer patient developing CLABSI and the antibiotic susceptibility pattern of the organism isolated. Having these data available will help in understanding the actual burden and deriving the preventive measures for such infections, as well as provide insight for correct use of antibiotics according to their antibiogram in our health-care settings.


 ~ Materials and Methods Top


Study design and data collection

This retrospective study is a single-centre's experience including both paediatric and adult patients with malignancy, who had a CVC inserted and were receiving care at medical/surgical oncology department of our hospital over a period between January 2017 and June 2018. All data included were obtained from patients records. We report a retrospective review of 73 cases of confirmed CLABSI in cancer patients. Cancer diagnosis was classified as either haematologic malignancy or solid tumour.

Demographic data and clinical variables including age, sex, type of malignancy and clinical characteristics of infections (CVC days until the infectious episode), laboratory (absolute neutrophil count <0.5 × 109/L) and microbiology data, for each patient, were collected. The infection density was estimated as a number of episodes/1000 CVC days and was calculated using the following formula: number of CLABSIs × 1000/number of central line days.[4]

It is important to highlight that during the study period CVC manipulations of all hospitalised patients were being undertaken by experienced and well-trained nursing staff, with implementation of sterile procedures for tubing care and the application of 0.5% chlorhexidine gluconate in 60% isopropyl alcohol for skin disinfection at catheter insertion sites, along with heparin flushing, according to evidence-based recommendations of previous studies.[5],[10]

CLABSI and pathogen definitions were based on the Centers for Disease Control/National Healthcare Safety Network criteria.[11] Isolates were identified with Matrix-assisted Laser Desorption Ionization-Time of Flight Mass Spectroscopy. Antibiotic susceptibility was done using disc diffusion method as per the Clinical and Laboratory Standards Institute guidelines.


 ~ Results Top


Patient characteristics

In the period from January 2017 to June 2018, 73 confirmed cases of CLABSI among cancer patients were included in this study. The patients' age ranged from 3 to 62 years, with a mean age of 36.6 years. There were 40 (54.7%) male and 33 (45.2%) were female with male-to-female ratio was 1.2. The majority of patients (87.67%) had haematologic malignancies as opposed to solid tumour (12.32%). The rate of CLABSIs was estimated as 2.1 episodes/1000 CVC days. Although 79.4% (n = 59) of all CVCs were <20 days old at the time of CLABSI, 13 patients had CVCs that had been present for ≥60 days and 1 CVC was present for >100 days.

Microbiology and laboratory data

Out of 73 CLABSI cases, Gram-negative rods were the predominant causative agents of CLABSI, constituting 72.6% (n = 53/73) of isolated organisms. 21.9% (n = 16/73) of infections were caused by GPC, while polymicrobial infections accounted for 5.4% (n = 4/73) of these cases. Of the GPC isolated, Staphylococcus aureus were isolated from two cases, Staphylococcus epidermidis (n = 3), Staphylococcus haemolyticus (n = 2) and Staphylococcus hominis (n = 1). Furthermore, there were 8 cases involving Enterococcus faecium. On the other hand, GNB were involved in 72.6% (n = 53/73) of cases (Klebsiella pneumoniae, Acinetobacter baumannii, Klebsiella oxytoca,  Escherichia More Details coli and Pseudomonas aeruginosa) as shown in [Table 1]. Moreover, polymicrobial infections accounted for 5.4% (n = 4/73) of these episodes (two cases involving co-infection with E. coli and K. pneumoniae, as well as two cases involving A. baumannii in combination with P. aeruginosa and S. epidermidis, respectively). Three patients experienced two or more episodes of CLABSIs, with S. epidermidis being responsible for the majority of cases.
Table 1: Isolates of central line-associated bloodstream infections (n=73)

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Among the Gram-positive cases, 2 (12.5%) episodes of S. aureus (one case with methicillin-resistant and 1 case with methicillin-sensitive strains) were isolated, while out of all (n = 6) coagulase-negative staphylococci isolates, 3 (50%) were methicillin-resistant and 3 CLABSI cases involved vancomycin-resistant E. faecium strain. Most of the GPC showed complete susceptibility to vancomycin and linezolid. Higher rate of resistance was seen among coagulase-negative staphylococci isolates as compared to S. aureus among various groups of antibiotics tested [Table 2].
Table 2: Antibiotic resistance pattern of Gram-positive cocci

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Resistance pattern of GNB to various antibiotics is shown in [Table 3]. Of 53 Gram-negative isolates, 31 (58.4%) were extended-spectrum beta-lactamase (ESBL) producing. ESBL production was observed to be maximum in K. pneumonia (86.5%) followed by P. aeruginosa (60%), E. coli (55.5%) and A. baumannii (25%). High rates of ciprofloxacin resistance were detected for K. pneumoniae (91.3%) and E. coli (88.88%). Furthermore, higher resistance for the aminoglycosides was observed against P. aeruginosa (66.66%) and K. pneumoniae (30.76%). While 6 (63.3%) of Acinetobacter species showed resistance to meropenem but none for colistin. 66.66% of Pseudomonas spp. were sensitive to piperacillin-tazobactam and 33.33% were meropenem sensitive. All ESBL-producing GNB were sensitive to colistin.
Table 3: Antibiotic resistance pattern of Gram-negative bacilli

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Risk factors

Younger age (<15 years old) seemed to increase the odds for a CVC-related infection, but this did not reach statistical significance (odds ratio 1.91, P = 0.44). In particular, when comparing the different age groups there was no difference concerning the relative risk for a CLABSI between children <5 years old, children 5–15 years old and adults >15 years old (P = 0.6). Patients with longer periods of catheterisation seemed to be more prone to CVC infections, as the majority of patients (70%) had their first episode of bacteraemia after the first 20 days of CVC carriage. As far as myelotoxicity is concerned, the relative risk for a CVC infection was found to be a greater in patients with neutropenia (P = 0.001). Intensive chemotherapy (P < 0.005) as well as prolonged hospitalisation with frequent inpatient manipulations (P < 0.005) also proved to be significant risk factors for CLABSIs. Moreover, 55% of patients responded quickly to empirical therapy, while 45% of patients eventually had to receive therapy based on susceptibility pattern. Gram-negative or Gram-positive infections were not associated with CVC removal and had a favourable outcome. No infection related fatality was recorded.


 ~ Discussion Top


A CLABSI could be a potential major complication in cancer patients, possibly leading to catheter removals and replacements, delay in administration of chemotherapy and additional days of hospitalisation.[1],[12] In this study, we investigated the rate of CLABSI and clinical and microbiological profile in cancer patients.

Blood culture is a useful tool for the diagnosis of a CLABSI episode, but it remains controversial which cultures (peripheral or CVC) should be used for the infection diagnosis.[13] However, due to lack of evidence, experts still suggest to obtain blood cultures from all sources during the infectious episode. In the present study, quantitative cultures and time-to-positivity analysis could not be performed. Our study is one of the first describing clinical and microbiological profiles of CLABSI in cancer patients at a North Indian tertiary care cancer hospital.

Adler et al. observed a rate of 2.264 CLABSIs/1000 catheter days, whereas Allen et al. found 1.6 catheter-related infections/1000 CVC days.[14],[15] We found CLABSI rate of 2.1 episodes/1000 CVC days in our study.

With regard to risk factors for CLABSIs, younger age increased the odds for a CVC-related infection, which is inconsistent with the previous study done by Tardáguila et al.[16] Multiple studies highlighted the fact that neutropenia in cancer patients is a significant risk factor correlated with infections and similar results were observed in our study too.[17]

Most of the CLABSI episodes took place during the phase of induction, mainly during the first 6 months of treatment, which is comparable to previous studies.[3],[18],[19],[20] This is probably related to prolonged and severe myelotoxicity, especially during the first 6 months of chemotherapy, along with the fact that this period requires frequent hospitalisations and CVC manipulations. Patients with haematologic malignancies were also found to be more prone to CLABSIs, compared to those with solid tumours, a fact that could be probably related to chemotherapy protocols leading to longer periods of myelotoxicity in cancer patients.[3],[18],[21] On the contrary, a previous study found no significant difference in the incidence of CLABSIs between patients with solid tumours and hematologic malignancies.[15]

Interestingly, in the present study GNB outnumbered GPC in causation of CLABSI which is in consistent with the previous study from our centre.[22] This is in contrast with previous studies where, GPC were the predominant pathogens responsible for CLABSIs.[1],[17] In present study, the K. pneumoniae and A. baumanni were common GNB, whereas Katsibardi et al. found that the most common isolated Gram-negative pathogens were E. coli and P. aeruginosa.[17] Some other recent studies also noted a significant proportion of Gram-negative bacterial cultures, but Enterobacter spp., E. coli and Klebsiella spp. were more frequently isolated.[23],[24]

The duration of catheterisation is an important factor that determines the risk of catheter-related infections.[25] Our study confirmed the fact that catheterisation for more than 20 days was significantly associated with the risk of infection (P < 0.05).

In the present study, CVC-related infections were generally treated effectively through empirical therapy. Our results are consistent with prior research among paediatric oncology patients receiving care in hospital settings.[3],[17],[26] Some studies have shown benefit from use of antimicrobial lock therapy whereas, Wolf et al. in haematology-oncology patients with CLABSIs, found no evidence of benefit from antibiotic lock therapy.[27]

Based on the current literature, long-term catheters should be removed from patients with CLABSI associated with any of the following conditions: severe sepsis, suppurative thrombophlebitis, endocarditis, BSI that continues despite 72 h of antimicrobial therapy to which the infecting microbes are susceptible or infections due to S. aureus, P. aeruginosa, fungi or mycobacteria.[28] CVC was not removed in the majority of CLABSIs (85%) and no fatal infection was recorded in the present study.

The current study has some limitations. There are inherent limitations of retrospective design of study like, increased risk of bias, cannot control exposure or outcome assessment, and instead relied on accurate recordkeeping. Nonetheless, our study provides important descriptions of this relatively less understood population and provides a platform for future prospective studies.


 ~ Conclusion Top


Over the last 20 years, an epidemiologic shift has occurred among CLABSI in cancer patients. These findings should be considered with the development of interventions that will prevent Gram-negative CLABSI after CVC insertion. To our knowledge, this is the first study reporting data on the incidence of CLABSIs in cancer patients at tertiary care hospital from North Indian hospital. The outcome of our study emphasises on the importance of proper CVC manipulations made only by experienced medical staff and the education of patients' relatives regarding patients care at home. Further research is needed in order to conclude on appropriate protocols for CVC care and use.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 ~ References Top

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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