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 ~  Abstract
 ~ Introduction
 ~ Material and Methods
 ~ Results
 ~ Discussion
 ~ Conclusions
 ~  References
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  Table of Contents  
Year : 2019  |  Volume : 37  |  Issue : 4  |  Page : 521-526

The incidence, aetiology and antimicrobial susceptibility of central line-associated bloodstream infections in intensive care unit patients at a private tertiary care hospital in Mumbai, India

Department of Infection Prevention and Control, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India

Date of Submission01-Jan-2020
Date of Acceptance24-Feb-2020
Date of Web Publication18-May-2020

Correspondence Address:
Dr. Tanu Singhal
Department of Infection Prevention and Control, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Four Bungalows, Andheri West, Mumbai - 400 053, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmm.IJMM_20_3

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 ~ Abstract 

Background: There is a need to generate accurate data on temporal trends in incidence rates, aetiology and antimicrobial susceptibility of central line-associated bloodstream infections (CLABSIs) in the Indian setting. Aim: To study the incidence, aetiology and antimicrobial susceptibility of CLABSI in adult, paediatric and neonatal intensive care units (NICUs) in a tertiary care private hospital in Mumbai, India. Materials and Methods: This is a prospective observational study conducted at the adult, paediatric and NICUs of tertiary care private hospital from 2011 to 2018. CLABSI was defined as per the Centers for Disease Control criteria. Surveillance of CLABSI in the intensive care units (ICUs) was conducted using a form adapted from the International Nosocomial Infection Control Consortium surveillance system. The incidence rates of CLABSI (per 1000 central line days), crude mortality, aetiology and antimicrobial susceptibility were calculated and reported. Results: Six hundred and eighty-six episodes of CLABSI were recorded, and the overall incidence of CLABSI was 5/1000 catheter days, 4.1 in the adult ICU, 5 in the paediatric ICU and 9 in the newborn ICU. Crude mortality in patients with CLABSI in the adult, paediatric and NICUs was 45%, 30% and 7%, respectively. Of the 752 isolates, 80% were Gram negative, 10% Gram positive and 10% yeast. The prevalence of extended-spectrum beta-lactamase producers was 80%, and rates of carbapenem resistance were on an average 50%. Conclusions: The CLABSI rates at a well-equipped tertiary care hospital are still significantly higher than the USA benchmarks. Alarming rates of drug resistance in Gram-negative pathogens were seen.

Keywords: Aetiology, carbapenem resistance, central line-associated bloodstream infection, India, mortality

How to cite this article:
Singhal T, Shah S, Thakkar P, Naik R. The incidence, aetiology and antimicrobial susceptibility of central line-associated bloodstream infections in intensive care unit patients at a private tertiary care hospital in Mumbai, India. Indian J Med Microbiol 2019;37:521-6

How to cite this URL:
Singhal T, Shah S, Thakkar P, Naik R. The incidence, aetiology and antimicrobial susceptibility of central line-associated bloodstream infections in intensive care unit patients at a private tertiary care hospital in Mumbai, India. Indian J Med Microbiol [serial online] 2019 [cited 2020 Sep 30];37:521-6. Available from:

 ~ Introduction Top

Central venous catheters/line (CVCs/CVL) are integral to current-day intensive care practice as a tool for monitoring of haemodynamic variables, delivery of medications, vasopressors, blood products, parenteral nutrition and collection of blood samples. Most of these lines in acute care settings are the short-term percutaneous CVCs placed in the internal jugular, subclavian and femoral veins. Central line catheterisation is sometimes complicated by bloodstream infections resulting in significant morbidity, mortality, antimicrobial resistance, increased duration of hospitalisation and additional medical costs.[1]

The two terms commonly used to describe these bloodstream infections are central line-related bloodstream infections (CRBSIs) and central line-associated bloodstream infections (CLABSIs).[2],[3] The definition of CRBSI is more rigorous. CRBSI is defined as a positive blood culture obtained through a peripheral vein with clinical manifestations of infection (fever, chills and/or hypotension) with no other apparent site of infection (apart from the catheter); one of the following should be present: (i) a positive semi-quantitative central catheter tip culture of more than 15 cfu/ml (ii) or a ratio of 3:1 cfu between the central line and the peripheral vein quantitative blood culture or (iii) a central line culture being positive 120 min earlier than the peripheral vein blood culture collected at the same time with equal volume. Clearly, not all centres and laboratories have resources to diagnose CRBSI. Hence, for surveillance and infection control purposes, CLABSI is preferred. It is defined as a positive peripheral line blood culture with clinical manifestations of infections and no other apparent focus of infection and with a central line which has been in place for more than 48 h or removed the day earlier.

The incidence of CLABSI depends on compliance to infection control practices. The developed countries have managed to reduce the incidence of CLABSI to very low rates due to strict infection control practices and good nurse–patient ratios. In the resource-limited settings, these rates are often high due to lack of resources, trained staff, frequent attrition and unfavourable nurse: patient ratio.[2] The International Nosocomial Infection Control Consortium (INICC) has evaluated extensively CLABSI rates in developing countries through multicentric studies. However, it is important to have reliable data from single centres on the incidence of CLABSI which adhere to a comprehensive infection control policy. Single-centre data from India are very limited. Like the incidence, the aetiology of CLABSI in developed world is significantly different from the resource-limited setting; Gram-positive isolates predominate in the former unlike Gram-negative in the latter. Knowledge of aetiology and antimicrobial susceptibility is crucial to design empiric treatment regimens for healthcare-associated infections in a particular unit, track antimicrobial resistance patterns and measure the success of antimicrobial stewardship programs. While country-specific data about aetiology and antimicrobial susceptibility are useful, most units need to collate their own data to formulate their own regimens.

This study was conducted with the objective of establishing benchmarks for CLABSI rates in Indian intensive care units (ICUs) as well as track aetiology and antimicrobial susceptibilities of these nosocomial infections.

 ~ Material and Methods Top

This is a 8-year prospective study conducted at a 750-bedded private tertiary care multi-specialty hospital in Mumbai, India, which was commissioned in January 2009. All patients admitted to the adult, paediatric and neonatal ICUs (NICUs) with an indwelling percutaneous CVL including umbilical venous line and peripherally inserted central catheters during the study period between January 2011 and December 2018 were included in the study. Patients with implanted CVC and ports were excluded. The study was approved by the Institutional Ethics and Research Committee.

The hospital has a well-developed system for surveillance of CLABSI as per the INICC methodology.[2] Patients with suspected CLABSI were subjected to two sets of blood cultures drawn from the central line as well as peripheral venipuncture. Blood culture bottles were placed in automated blood culture system (BacT/ALERT BioMérieux, BACTEC BD). Flag-positive blood culture bottles were subcultured on 5% sheep blood agar and MacConkey's agar plates and incubated overnight at 37°C. The next morning, culture plates were examined and colony morphology was noted. Culture isolates were identified and susceptibility was done using automated system (Vitek Compact 2). If the blood cultures did not flag for 7 days, they were reported negative. The Clinical and Laboratory Standards Institute breakpoints were used for defining susceptibility; for tigecycline breakpoints were those recommended by the US Food and Drug Administration. Colistin susceptibility was determined using VITEK from 2011-2017 and broth microdilution (BMD) 2018 onwards. 2 was considered as the susceptibility breakpoint. CLABSI was defined as episodes of sepsis developing in the study patients after 48 h of admission to the ICU with positive cultures from both central line and peripheral venipuncture. Patients with sepsis and a positive central line culture but negative cultures from the peripheral venipuncture/or when peripheral cultures could not be sent due to venous access problems were considered as CLABSI if no other focus of infection was found on clinical examination and investigations (e.g. chest X-ray, urine cultures and abdominal imaging). The incidence rate of CLABSI was expressed as number of episodes per 1000 central line days. Aetiology and antimicrobial susceptibility was tabulated and expressed as simple percentages. Crude mortality of patients having CLABSI at the time of transfer from the ICU was calculated as a percentage.

CDC guidelines for prevention of CLABSI were followed at the study centre.[3] This bundle included trained personnel for insertion of CVC, maximum barrier precautions while insertion, skin cleaning with 2% alcoholic chlorhexidine three times, change of gauze dressing every 2 days and transparent dressing every 7 days, use of needleless connectors, wiping surface of the needleless device with alcohol for 15–20 s before access, removal of CVC when not needed, closed systems for IV fluids, no stock solutions, use of prefilled flushing syringes, daily bathing of patients with central lines with 4% chlorhexidine-based soap, terminating total parenteral nutrition solutions within 12 h of opening the bag, routine change of administration sets and connectors every 72 h and finally care to transfuse blood products within 30 min of receipt at the bedside. The use of chlorhexidine-impregnated dressing at the catheter exit site was started since July 2015. Process surveillance to measure compliance to the prevention bundle was done periodically. Occurrence of a CLABSI triggered an investigation to determine any breach of infection control practices and the same reinforced. The hospital also initiated a comprehensive antimicrobial stewardship program in January 2018 with an audit of the use of certain antibiotics including polymyxins, tigecycline, minocycline, fosfomycin, daptomycin and echinocandins with feedback to consultants about stopping/de-escalation of these antibiotics at 48–72 h.

 ~ Results Top

A total of 25,359 patients with central lines (CVC) were enrolled in the study and 686 were diagnosed to have CLABSI. The total number of central line days was 159,990. The mean overall incidence of CLABSI was 5.0/1000 central line days. The mean rate for the adult ICU was 4.1/1000 catheter days, 5/1000 catheter days for the paediatric (medical, general surgical and cardiac surgical) ICU and 9/1000 catheter days for the newborn ICU. The mean incidence of CLABSI declined from 5.4/1000 central line days to 2.4/1000 central line days in the adult ICU, 9.35 to 2.25 in the paediatric ICU and 19.3 to 0 in the newborn ICU between 2011 and 2018, respectively [Figure 1]. The figure also shows a significant skew of data for the newborn ICU which necessitated us to calculate the median rates for NICU which was 5/1000 catheter days.
Figure 1: Mean yearly rates of central line-associated bloodstream infection in the adult, paediatric and newborn intensive care units

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The crude mortality rate at the time of transfer out from the ICU in adult, paediatric and NICUs was 45%, 30% and 7%, respectively. Besides this, 7% of cases of CLABSI in the adult ICU (but none from the paediatric and NICU) left the hospital against medical advice whose outcomes are not known.

In this study amongst 686 CLABSI episodes, a total of 752 isolates were recovered. The most common causative organisms were Gram-negative bacilli (79.5%) followed by Gram-positive cocci (10%) and the remaining were yeast. The organism profile and trend over the years is depicted in [Figure 2]. Klebsiella pneumoniae was the most common pathogen, accounting for 29% of all isolates. Of the Gram-negative isolates (n = 602), K. pneumoniae was the most common organism (38%), Acinetobacter baumannii 21%, Pseudomonas aeruginosa 13%, Escherichia coli 10% and other Gram-negative bacteria (GNB) constituting 18% (Enterobacter, Serratia and Stenotrophomonas maltophilia amongst others). Of the Gram-positive isolates (n = 80), Enterococcus was most common (51%), followed by Staphylococcus aureus(24%), coagulase-negative Staphylococcus (19%) and Streptococcus species 6%. Candida auris was the most common Candida species accounting for almost one-third of all isolates (31%), followed by Candida tropicalis (22%), Candida albicans (19%) and Candida parapsilosis (10%). Other yeast isolates (18%) included Candida glabrata (3), Candida krusei (2), Candida rugosa (2), Candida pelliculosa (1), Trichosporon asahii (2), Kodamaea ohmeri (2) and Saccharomyces cerevisiae (1). C. auris was identified as Candida haemulonii by the automated system up till 2017.
Figure 2: Aetiology of central line-associated bloodstream infection 2011–2018 (n = 752)

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The change in antimicrobial susceptibility pattern of Enterobacteriaceae family and non-fermenters (Pseudomonas and Acinetobacter) is depicted in [Table 1] and [Table 2]. The extended-spectrum beta-lactamase (ESBL) rates in Enterobacteriaceae remained stable varying between 78% in 2012 and 81% in 2018, with a mean rate of 83%. However, a significant decline in susceptibility was noted in Enterobacteriaceae between 2011 and 2018 to all the commonly used antibiotics. Declines were also noted in Pseudomonas and Acinetobacter susceptibility between 2011 and 2018. Colistin resistance emerged over the course of time. Of the 16 colistin-resistant strains causing CLABSI in the past 8 years, 75% (12/16) were K. pneumoniae, followed by A. baumannii (3) and P. aeruginosa (1). In 2017, 12% of K. pneumoniae were colistin resistant. Most of the colistin-resistant isolates had MIC of more than 16.
Table 1: Antimicrobial susceptibility of Enterobacteriaceae

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Table 2: Antimicrobial susceptibility of the non-fermenters (Acinetobacter and Pseudomonas)

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The prevalence of methicillin resistance in S. aureus was 37% and in CONS was 79%. Around 12% of the enterococci were vancomycin resistant and 70% were ampicillin resistant. The overall prevalence of fluconazole resistance was 13% (excluding intrinsically resistant yeast isolates).

 ~ Discussion Top

This is the largest and longest single-centre study of CLABSI in India till date. The mean overall incidence of CLABSI in our study was 5.0/1000 catheter days. [Table 3] compares the rates reported by us with INICC, other Indian studies and finally the National Healthcare Safety Network (NHSN) network of the USA.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22] INICC Global rates for the periods of 2012–2017 and that for Indian ICUs (2004–2013) approximate around 5/1000 catheter days which is also our estimate.[4],[5],[6] Single-centre and some multicentre Indian studies have reported rates usually around centring around 7–14[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] widely ranging from 0.48 (at a rural hospital[18]) and 2.79[19] to 47.1.[20] In a pooled study across four hospitals, Singh et al. reported a rate of 2.4/1000 catheter days in 2012.[21] Limitations of currently available Indian studies include small sample size, variable definitions and relatively old data. However, to sum it all up, our rates and those of INICC are significantly higher than those reported by the NHSN for 2018 in acute care hospitals (0.83/1000 catheter days for adult and paediatric ICUs and 0.97 for NICU).[7] In fact, the actual difference may be higher since studies show that CLABSI rates may be underestimated in resource-limited settings.[2]
Table 3: Mean central line-associated bloodstream infection rates/1000 catheter days in current and other studies

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We were able to demonstrate a significant reduction in CLABSI rates after implementation and strengthening of a comprehensive CLABSI bundle across all ICUs and particularly in the NICU. Several recent studies have shown a significant impact in reducing CLABSI with implementation of educational programs and prevention bundles in Indian ICUs.[22],[23],[24],[25] In our experience, regular process surveillance (compliance to the prevention bundle), outcome surveillance (rates of CLABSI per 1000 CL days), corrective and preventive action for CLABSI and monthly reporting to healthcare workers at infection control meetings of compliance and CLABSI rates and their consequences have helped reduce the incidence of CLABSI. The greatest decline was noted between 2011 and 2014. However later on, a significant decline in rates was not observed. A major factor responsible for the inability to bring down rates further is significant attrition of nursing staff. A spike in CLABSI and other healthcare-acquired infection rates is also seen every monsoon when the ICU occupancy goes up significantly due to illnesses such as dengue, influenza, malaria and leptospirosis and resultant unfavourable nurse: patient ratio.

The crude mortality rate noted in our study, particularly in the adult ICU, approached 50%. This rate is higher than reported by other studies and could be attributed to the high prevalence of carbapenem resistance. Although the incidence rates in the newborn ICU were the highest, the mortality here was the lowest.

Our observation of Gram-negative organisms, chiefly Klebsiella being the most common cause of CLABSI, is a finding similar to that reported from previous Indian studies.[8],[9],[12],[13],[16],[17] However, there are several Indian studies that reported Gram-positive organisms, chiefly S. aureus and CONS as the most common isolates.[l0],[11],[14],[15],[18], [19,[20] Data from the West implicates CONS, S. aureus, Enterococci and Candida species as common pathogens causing CLABSI with Gram-negative bacilli accounting for only 20% of the infections.[1],[3]

Antimicrobial resistance is a problem for pathogens causing CLABSIs globally as well as in India, particularly in ICUs.[4],[5],[6],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] Our study reported an overall ESBL prevalence rate of 80%, carbapenem susceptibility of approximately 60% and beta-lactam/beta-lactamase inhibitors (BL-BLIs) susceptibility of approximately 50% in Enterobacteriaceae. The susceptibility in the non-fermenters was even more dismal with susceptibility for both carbapenems and BL-BLIs only 40%. In our study, carbapenem resistance in Gram-negative bacilli increased from 20% in 2012 to approximately 68.5% in 2018. This has led to excessive use of polymyxins with consequent emergence of colistin resistance.

Resistance in Gram-positive isolates was a less dismal; one-third of S. aureus isolates were methicillin resistant while methicillin-resistant rates in CONS was 80%. No vancomycin resistance was observed. Ampicillin resistance in Enterococcus was common (70%). The finding of predominant non-albicans Candida as a cause of candidemia in our study is in agreement with the study by Chakrabarti et al. in Indian ICUs.[26] The rise in C. auris is a cause of concern since the organism is multidrug resistant, commonly misidentified and can cause outbreaks.

The main strength of the study lies in its large sample size, use of standardised definitions and methodology, prospective nature and involvement of the same infection control team throughout the study. The study also nicely demonstrates a fall in CLABSI rates over the initial period and the rise in antimicrobial resistance. Although it is a single-centre study, its results are in close agreement with the INICC studies in resource-limited setting as well as other Indian ICUs. Some of the limitations of the study include inability to estimate the 28-day mortality, the attributable mortality associated with CLABSI, risk factors for CLABSI and outcomes dependent on the etiologic agents, especially between carbapenem-resistant and carbapenem-susceptible isolates.

 ~ Conclusions Top

The biggest benefit of this study for us was benchmarking ourselves against global and regional standards, early detection of outbreaks and institution of corrective measures, tracking antimicrobial resistance and designing empiric regimens for treatment of healthcare-associated infections. Although we demonstrated a decrease in CLABSI rates with regular surveillance and multidisciplinary implementation of a prevention bundle, there is still a lot of scope to reduce these rates further since they are still significantly above the NHSN benchmarks. Though the aetiology of CLABSI has remained the same throughout the years at our centre with almost 80% of infections caused by GNB, rise in resistance rates is alarming. A robust antimicrobial stewardship program apart from a good infection control program is needed to help stem this rise in antimicrobial resistance.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 ~ References Top

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O'Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, et al. Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control 2011;39:S1-34.  Back to cited text no. 3
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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]


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