Central venous catheter-related bloodstream infections ( CVC-BSI ) in patients of clinically suspected septicemia

Central venous catheter-related bloodstream infections (CVC-BSI) are associated with morbidity and mortality especially in critically ill patients. This study was performed to find out the rate of CVC-BSI and CVC colonization, causative organism and their antibiogram in patients of Intensive Care Unit (ICU) and Department of Nephrology of tertiary care hospitals. A total of 100 patients from Bangabandhu Sheikh Mujib Medical University (BSMMU) and Dhaka Medical College Hospital (DMCH) who had CVC and clinically suspected of septicemia were included in the study. Paired CVC blood and peripheral venous blood (PVB) samples were collected from each patient and were cultured by automated blood culture method. CVC-BSI was diagnosed in 11% and CVC colonization in 43% patients by Differential time to positivity (DTP) method. Rate of CVC-BSI was 8/1000 CVC days and 11/1000 CVC days in BSMMU and DMCH respectively whereas CVC colonization rate was 32/1000 CVC days and 47.5/1000 CVC days in BSMMU and DMCH. The most common bacteria causing CVC-BSI was Klebsiella spp. (36.4%) followed by Acinetobacter spp. (27.3%), Pseudomonas spp. (18.2%) and E. coli (18.2%). Among bacteria isolated from CVC colonization majority were Pseudomonas spp. (30.23%) and Staphylococcus epidermidis (30.23%) followed by Acinetobacter spp. (27.91%), Enterococcus spp. (6.98%). Most of the isolated bacteria causing CVC-BSI were resistant to commonly used antibiotics, but showed good sensitivity to imipenem and colistin. Information about CVC-BSI, colonization and antibiogram of this study can help to guide the selection of suitable antibiotics for empirical therapy and to improve infection control measures of the hospital.


Introduction
Intravenous catheterization is one of the most common invasive procedures among patients admitted in hospitals.Vascular access poses significant potential risks of catheter related bloodstream infections. 1 Central intravenous catheter are infected with the greatest frequency 2 and central venous catheter-related bloodstream infection (CVC-BSI) is the third most frequent nosocomial infection and is a threat to patient's safety. 3ere is a wide diversity between hospitals in the causative pathogens and their antimicrobial susceptibility pattern.Mansur et al. 4 in Bangladesh in a study reported that rate of CVC-BSI is 14% and the most common causative pathogens were Pseudomonas, Acinetobacter and Staphylococcus aureus.Organisms causing CVC-BSI commonly are Pseudomonas spp, Acinetobacter spp, Klebsiella spp, Proteus spp, Enterobacter spp, E. coli, Staphylococcus aureus, coagulase negative Staphylococcus. 5,6fferential time to positivity (DTP) method is highly sensitive and specific for diagnosing CVC-BSI without removal of CVC. 7,8DTP has been defined as the time difference between the culture of CVC blood and peripheral venous blood (PVB) to become positive and the cutoff value of DTP is ≥120 minutes. 8There are several denominators for detection of CVC-BSI rate, eg.CVC-BSI rate in 100 CVCs or in 1000 CVC days or in 100 patients.The most recommended denominator of detection of CVC-BSI rate is the 1000 CVC days. 9his study was designed to acquire information about the CVC-BSI rate, type of organism causing CVC-BSI and their antibiotic susceptibility pattern in tertiary care hospitals.Eight ml of blood was collected from both the CVC line and peripheral vein.After inoculation of blood into BACTAC culture vials they were transported to the Microbiology laboratory as soon as possible.

This
DTP was done by automated blood culture method as described by Raad et al. 8 Paired vials (each vial containing 8 ml of blood) were introduced into BACTEC 9240 machine (Dickinson and Company, Maryland, USA).All samples were incubated at 37 0 C up to culture positivity and the vials were discarded if no growth was detected within seven days.
The time difference between the CVC blood culture and PVB culture to become positive (DTP) was calculated by following way: DTP of the blood sample (expressed in minutes) = Time taken by peripheral venous blood culture to become positivetime taken by CVC blood culture to become positive Positive sample of CVC blood and PVB were sub-cultured on blood agar and MacConkey agar and incubated aerobically at 37 0 C for 24 hours.If growth was present then identification of the organism was done by colony morphology, Gram staining and biochemical tests.After organism identification antimicrobial sensitivity test was performed by disc diffusion method using Kirby-Bauer technique. 10 Positive CVC-BSI: When difference in time between CVC blood culture positivity and PVB culture positivity is ≥120 minutes and isolated organism is identical in genus, species and antibiotic susceptibility pattern.
2) Non CVC-BSI/ BSI source other than CVC: a) When difference in time between CVC blood culture positivity and PVB culture positivity is <120 minutes or PVB culture become positive earlier than CVC blood culture and isolated organism is identical in genus, species and antibiotic susceptibility pattern.b) If growth is present only in PVB culture but no growth in CVC blood culture.
3) CVC colonization: If growth is present only in CVC blood culture but no growth in PVB culture.
CVC-BSI rate was determined by the following method as mentioned by Salomao et al. 11 CVC-BSI rate = Total no. of CVC-BSI / Total no. of CVC days X 1000 CVC day determination: Total number of days of exposure to CVC by all of the patients in selected population during the selected time period.
Ethical consideration: The protocol of this study was approved by Ethical Clearance Committee (ERC) of Bangabandhu Sheikh Mujib University.Informed written consent was taken from the patient or from their attendant before collection of blood samples.The anonymity of the participants and confidentiality of information was maintained strictly.
Among the isolated Acinetobacter spp.from CVC-BSI patients, 66.67% were sensitive to colistin and imipenem, 33.33% was sensitive to cotrimoxazole.All Pseudomonas spp.were sensitive to imipenem, 50% was sensitive to ceftazidime and colistin; 100% E. coli were sensitive to gentamicin, 50% was sensitive to cotrimoxazole and imipenem.All Klebsiella spp.were sensitive to gentamicin and imipenem, 50% were sensitive to cotrimoxazole and 25% was sensitive to amikacin (Table IV).

Discussion
Central venous catheter-related bloodstream infections (CVC-BSI) are common type of nosocomial bloodstream infections. 6,12Although there are valid guidelines for good practice in central venous catheterization, CVC-BSI still is a serious problem especially in patients with long term catheterization. 13C-BSI and CVC colonization were detected by DTP method which is a newer and valid method for CVC-BSI diagnosis without removing the CVC.CVC-BSI rate was detected in 11% patients, CVC colonization 43% and non CVC-BSI was 10% in this study by DTP method.
A cutoff value of DTP≥120 minutes was taken as standard value for diagnosing CVC-BSI which is supported by the findings of Blot et al. 14 who found that DTP of ≥120 minutes was sensitive and specific for diagnosing CVC-BSI.
The rate of CVC-BSI and CVC colonization were lower in patients of ICU of BSMMU than the patients of ICU of DMCH.The reason of low CVC-BSI in patients of ICU of BSMMU may be due to better infection control practice, such as CVC care, nurse patient ratio, visitor restriction, waste disposal etc. which is supervised by an infection control team.Holton et al. 9 mentioned that effective infection control system, standardized CVC care and patient's immune status may contribute to the lower rate of CVC-BSI.
CVC colonization was found in 43% cases.Ideally intravenous catheters should remain sterile because bacteria from the colonization may cause silent infection and eventually clinical sepsis if the colonized catheters remain in situ for longer period. 5Such kind of colonized catheter should not be disregarded and as these organisms are potential pathogens that may sometimes cause diseases in the host these colonizing bacteria should be considered as a threat and patients with colonized catheters should be followed up for features of bloodstream infection.
The rate of CVC-BSI was found  11 and India. 15ssible explanation of infection by these resistant strains in ICU is the selection pressure exerted by extensive use of antibiotics and may be due to transmission of resistant clones between the patients. 23Infections with resistant strains are transmitted among the patients due to inadequate implementation of infection control measures in institutes. 24nclusion: The rate of CVC-BSI and CVC colonization were significant and the isolated organisms from CVC-BSI were resistant to most of the common antibiotics used.Knowledge of this antimicrobial susceptibility pattern may aid to make an empirical antibiotic protocol.
cross sectional descriptive type of study was conducted during the period of July 2011 to June 2012.Study population: Patients having clinical signs symptoms of septicemia who had CVC for more than 48 hours that was given after admission in Intensive Care Unit (ICU) and in Department of Nephrology.Sample Size: A total of 100 patients (23 from ICU of BSMMU and 41 from ICU of DMCH and 36 patients from Department of Nephrology of DMCH) were enrolled.All laboratory works were performed in the Department of Microbiology and Immunology, BSMMU, Shahbagh, Dhaka.

Fig. 1 :
Fig. 1: Show the graphical presentation of detection of CVC-BSI by DTP method.

Table I :
Rate of CVC-BSI and CVC colonization detected among the patients of different institutes

Table II :
Rate of CVC-BSI and CVC colonization in 1000 CVC days among the episodes.

Table III :
Bacteria isolated from CVC-BSI and CVCcolonization.

Table IV :
Antibiotic susceptibility pattern of bacteria isolated from CVC-BSI.
Most of the organisms causing CVC-BSI were resistant to common antibiotics used in ICU of BSMMU and DMCH.All isolated Gram negative bacilli were resistant to ciprofloxacin, ceftriaxone and netilmicin.Klebsiella spp.and E. coli were also 100% resistant to ceftazidime.Pseudomonas spp.showed 100% resistance to tazobactam-piperacillin, gentamicin and amikacin; Acinetobacter spp.were 100% resistant to gentamicin, amikacin, ceftazidime and tazobactam-piperacillin.This sensitivity pattern was consistent with the antibiogram of organism isolated from ICU patients of CVC-BSI in several studies done in Brazil