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Asymptomatic central line-associated
bloodstream infections in children
implanted with long term indwelling
central venous catheters in a teaching
hospital, Sri Lanka
J. A. A. S. Jayaweera1,2* and D. Sivakumar1
Abstract
Background: Indwelling central venous catheters (CVC) are used to provide long term hemodialysis. The
commonest and the severe complication of CVC is the central line-associated bloodstream infection (CLABSI). This
study was done to assess the etiology and infectious complications of CVC in children on long term hemodialysis.
Methods: Children newly undergoing hemodialysis and having indwelling CVC were included. They were followed up
to a period of 2-years to assess infectious complications. Catheter bundle care approach was employed to prevent
infections and other complications. Automated culture from the central catheter and peripheral vein and 2D
echocardiography were done in each hemodialysis. Serial procalcitonin (PCT) was measured. Differential time of
positivity (DTP) was used to detect CLABSI. During homestay in weekly telephone conversations were done to assess
features of infection, and whenever having, we have asked to admit to the tertiary care unit. Logistic regression was
performed, and the significant outcome variable was considered following multivariable analysis as a risk factor.
Results: Blood cultures were positive in 1090 (74.5%) out of 1462 children. According to DTP, 410 (28%) were having
CLABSI, while 520 (35.6%) were having bacteremia without CLABSI. Out of 410 CLABSI patients, 79 (19.2%) were
asymptomatic. Coagulase-negative Staphylococcus spp. (CoNS) bacteremia was significantly associated with
asymptomatic CLABSI. Right-sided infective endocarditis (RS-IE) was significantly associated with asymptomatic CLABSI
and asymptomatic bacteremia without CLABSI. CoNS was associated significantly in RS-IE following asymptomatic
CLABSI and asymptomatic bacteremia. PCT was in asymptomatic CLABSI was 1.8 ± 0.9 ng/mL while in symptomatic
CLABSI was 11.3 ± 2.5 ng/ml (P = 0.02). CoNS bloodstream infection, tunneled CVC, peripherally inserted central
catheter, femoral site, the number of line days > 90, receipt of vancomycin, meropenem, or linezolid in the 5 days
before CLABSI diagnosis and recurrent bacteremia were risk factors for asymptomatic CLABSI.
(Continued on next page)
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* Correspondence: jaas071@gmail.com; jaas820703@yahoo.com;
jaasjayaweera@rjt.med.ac.lk
1
Department of Microbiology, Faculty of Medicine and Allied Sciences,
Rajarata University of Sri Lanka, Microbiology, Saliyapura, Sri Lanka
2
Teaching Hospital Kandy, Kandy, Sri Lanka
Jayaweera and Sivakumar BMC Infectious Diseases (2020) 20:457
https://doi.org/10.1186/s12879-020-05190-5
(Continued from previous page)
Conclusions: Asymptomatic CLABSI could be a rare occurrence. CoNS was predominantly isolated in patients with
asymptomatic CLABSI. RS- IE is a well-known complication in long term indwelling CVC. CoNS was significantly
associated with RS-IE following asymptomatic CLABSI. Regular procalcitonin, microbiological, and imaging studies
would be essential to detect infectious complications in both symptomatic and asymptomatic patients implanted with
long term indwelling CVCs.
Keywords: Healthcare-associated infections, Central line-associated bloodstream infection, Asymptomatic bacteremia,
Staphylococcus aureus, MRSA, Coagulase-negative Staphylococcus sp., And right sided-infective endocarditis
Background
Long-term central venous catheter (CVC) is an invasive
device that used in children with chronic renal failure.
The device resides in a large central vein, usually the superior vena cava. CVC is used for the administration of
fluids, medications, blood products, collection of blood,
and hemodialysis (HD) [1]. The most common and severe complication associated with CVC is central lineassociated bloodstream infection (CLABSI) [1, 2].
CLABSI rates vary widely, and infection rates depend on
device type and patient population [2]. A study conducted
in a pediatric intensive care unit (PICU) in United State of
America (USA) from 2006 to 2007 reported that incidence
of CLABSI was 3.1 per 1000 central line-days [3]. Another
study revealed that incidence was 4.1 per 1.000 central linedays in third world countries [4]. Children with haemopoietic stem cell transplantation, prevalence of CLABSI was
5.3 per 1000 central-line days and most commonly identified organism was Staphylococcus epidermidis [5].
The etiology and the incidence of Chronic Kidney Disease (CKD) could vary with the age [6]. The prevalence of
CKD stage II or lower in children is approximately 18.5–
58.3 per million [7]. Compared to adults, in children CKD
prevalence is much less but underreporting would mask
the true prevalence [8]. In children, structural defects and
obstructive uropathy are common before age 5 while hereditary and acquired kidney diseases are common in 5 to
15 years. CKD requires therapeutic measures [9]. When
the glomerular filtration rate is below 15 ml/min/1.73 m2
,
renal replacement therapy such as peritoneal dialysis,
hemodialysis, or kidney transplantation is indicated [10].
Bacteremia can occur spontaneously following tissue infection, wound care, surgical procedure, and the use of indwelling intravascular catheters [11]. Bacteremia can be
symptomatic or asymptomatic. Bacteremia would lead to
develop deep seated abscesses, pneumonia, meningitis,
and infective endocarditis especially in patients with valvular heart abnormalities [12]. Transient bacteremia is often
asymptomatic, but occasionally can develop fever [13].
The development of symptoms usually suggests more
severe infections and risk for sepsis or septic shock would
be high [11, 14]. CLABSI often leads to continuous
bacteremia. This study was conducted to assess the
etiology and infectious complications of central lineassociated bloodstream infections (CLABSI) in children
on long term HD.
Methods
This was a follow up study. The study was conducted at
a pediatric unit in a tertiary care hospital, Sri Lanka,
from January-2014 to December-2016. Children (2 years
to 12 years) who are newly undergoing hemodialysis and
having an indwelling central venous line were included
and followed up. They were followed up to 2 years to assess any of the infectious complications. Since in all the
patients HD was newly initiated, they were kept > 48 h
in the unit. Once patient becomes stable (creatinine decline and reaches a steady level) and no sign of infection
they were discharged. We have screened occurrence of
CLABSI following after 48 h of insertion of CVC.
Catheter bundle care approach was employed at the
time of insertion and maintenance to prevent infections
and other complications [15]. In each time before initiating HD, blood (includes asymptomatic patients) was
taken from the central line and peripheral site for culture and antimicrobial susceptibility testing (AST). Also,
when the patient presented with fever, blood was taken
from the central line and peripheral site for culture and
antimicrobial susceptibility testing (AST). Every occasion, the same volume of blood was collected under sterile conditions, and BACTEC semi-automated flat form
was used for culture. Differential time positivity (DTP)
was used to detect CLABSI, bacteremia, central line
colonization, and contamination [15, 16]. At day 3 (72 h
following initial blood culture), a peripheral blood culture was done to assess the clearance following
Staphylococcus aureus bacteremia.
Gram staining was performed from all flagged positive
BACTEC bottles and inoculated onto blood (10% CO2),
MacConkey (room air), and chocolate agar (10% CO2)
to detect the microbial etiology. The inoculated plates
were incubated at 35 °C in 10% CO2 to enable bacterial
colonies to develop [17]. Positive culture isolates were
identified using appropriate identification methods, including morphology of colonies, Gram-stain, and an inhouse set of biochemical tests and further confirmed
Jayaweera and Sivakumar BMC Infectious Diseases (2020) 20:457 Page 2 of 10
using Rapid 20 E (Enterobacteriaceae), NE (Non-Enterobacteriaceae) and S (Staphylococcus) semi-automated
identification system.
Serial procalcitonin (PCT) and C-reactive protein
(CRP) were done to assess the clinical status and the response to the antimicrobial treatment. Also, 2D echocardiography was done in every patient, and in patients
with endocarditis serially, it was done to assess the progress/ clinical response. During homestay in weekly telephone conversations were done to assess infectious
complications and, if present, asked to admit as soon as
possible to the tertiary care facility.
Definitions
CLABSI
The Centers for Disease Control and Prevention (CDC)
definitions were used to diagnose CLABSI [18].
Bacteremia without line infection
The quantitative blood cultures were obtained from the
CVC and peripheral vein in same time and isolation of the
same pathogen from both cultures with time to positive
culture (< 2 h) in the CVC and peripheral sample [15, 16].
Central line colonizer
Instances where CVC blood culture is positive but the
percutaneous blood culture remained negative indicate
colonization of the catheter rather than CRBSI. This is
especially applicable to organisms like gram-negative rod
or enterococcus [15, 16].
Asymptomatic bacteremia
Instances where the two peripheral blood culture were
remained positive for same organism but subject remains
without having fever or any other sign/symptom [17].
Exit site infection
Signs of inflammation is limited to catheter exit site
(typically < 2 cm) and having a wound swab/ wound secretion culture positivity [17, 18].
Tunnel infection
Inflammation extending more than 2 cm from exit site
and associated with pain and tenderness along the subcutaneous track and having a wound swab/ wound secretion culture positivity [18].
Antimicrobial susceptibility testing
The antimicrobial susceptibility testing was performed by
the disc diffusion test based on Clinical and Laboratory
Standards Institute (CLSI) guidelines (M100s27) [19]. The
following antimicrobial agents were tested: ampicillin
(30 μg), amikacin (30 μg), Ciprofloxacin (5 μg), levofloxacin
(5 μg), Trimethoprim/ sulfamethoxazole (1.25/23.25 μg),
gentamicin (10 μg), Vancomycin (30 μg) and Linezolid
(30 μg).
Statistical analysis
Data obtained were double entered into a spreadsheet
database prepared with Microsoft Excel and compared
and cleaned for wrong entries. Statistical analysis was
done using SAS version 9.1 [20]. The association of each
of the categorical variables with the response variable
was assessed by Chi-square test. Further, logistic regression was performed, and variables showing statistically
significant (p < 0.05) association in univariate analysis
with the outcome variable were considered following
multivariate analysis as a risk factor. Further, 2 wayANOVA was performed to assess the significance of
PCT between symptomatic and asymptomatic CLABSI.
Continuous variables were expressed as a measure of
central tendency.
Results
Over the 3 years, 1462 children (2 to 12 years of age)
who are newly undergoing long-term HD were included.
The mean age of the participant was 7.82 ± 2.62 years.
Children with congenital malformations and obstructive
uropathy requiring HD was significant among children
below the age of 5 years (n = 642, mean age 2.82 ± 1.43
years, p = 0.03) while hereditary kidney diseases requiring HD was significant in the age group of 5 to 12 years
(n = 822, mean age 8.82 ± 1.22, p = 0.01).
Blood culture results
Blood cultures were positive in 1090 (74.5%) out of 1462
children on long term HD. According to differential
time positivity, 410 (28%) were having CLABSI while
520 (35.6%) were having bacteremia without CLABSI,
and 160 (11%) were having central venous line colonizers. Remaining 372 (25.4%) was culture negative.
CLABSI
Out of 410 CLABSI patients 331 (80.7%) were symptomatic. They were presented with fever (n = 331), malaise (n =
331), and 58 (17.5%) were septic (fever, tachypnoea, tachycardic, PCT > 0.5 with serum lactate > 4 mmol/L) on admission. Methicillin sensitive Staphylococcus aureus
(MSSA) was the commonest etiology in symptomatic
CLABSI and it was isolated in 212 (64.7%, p = 0.02) patients. Candida albicans (n = 17,4.5%) C. parapsilosis (n =
10, 3.1%) and Gram negatives [multi-drug resistant Klebsiella pneumoniae (n = 10, 3.1%) Escherichia coli (n = 6, 1.5%)
and Citrobacter frundii (n = 3, 0.75%)] were also isolated.
Out of 410 CLABSI patients 79 (19.3%) were asymptomatic. Coagulase negative staphylococcus sp. [S. epidermidis (n = 54, 68.4%), S. hemolyticus (n = 6, 7.7%), S.
schleiferi (n = 5, 6.4%), S. lugdunensis (n = 5, 6.4%) (p =
Jayaweera and Sivakumar BMC Infectious Diseases (2020) 20:457 Page 3 of 10
0.03)] was the commonest etiology for asymptomatic
CLABSI (Fig. 1).
Recurrent bacteremia was detected in both symptomatic (n = 98, 23.9%, P = 0.02) and asymptomatic CLABSI
groups while it was significant in the former. MSSA was
the most frequent etiology in recurrent symptomatic
CLABSI, and it was isolated in 78 (79.5%, p = 0.01)
patients.
Bacteremia without CLABSI
Out of 520 bacteremic patients 398 (76.5%) were symptomatic. They were presented with fever (n = 398), malaise (n = 398), cough (n = 90), difficulty in breathing (n =
88), dysuria (n = 48), backache (n = 22), acute abdomen
(n = 10), alteration of consciousness (n = 8), and 68
(17.1%) were septic (fever, tachypnoea, tachycardic, PCT
> 0.5 with serum lactate > 4 mmol/L) on admission.
Methicillin sensitive S. aureus (MSSA) was the commonest etiology and was isolated in 245 (61.5%, p = 0.03) patients. Methicillin resistant S. aureus (MRSA) in 42
(10.5%) patients while coagulase negative staphylococcus
sp.(45, 11.3%) [S. epidermidis (n = 27,6.8%), S. hemolyticus (n = 18, 4.5%))], E. fecalis (n = 8, 2%), E. faceum (n =
4, 1%), Candida albicans (n = 8,2%) C. parapsilosis (n =
8, 2%), C. tropicalis (n = 7,2%) and K. pneumoniae (n =
10, 2.5%) E. coli (n = 16, 4%), Pseudomonas aeruginosa
(n = 8, 4%), and C. frundii (n = 6, 3%) was also isolated.
Out of 520 bacteremic patients 122 (23.4%) were asymptomatic. Coagulase negative staphylococcus sp. [S. epidermidis (n = 86, 70.5%), S. hemolyticus (n = 14, 11.4%), S.
schleiferi (n = 6, 5%), S. lugdunensis (n = 3, 2.5%) (p =
0.01)] was the commonest etiology for asymptomatic
bacteremic and C. parapsilosis (n = 3, 2.5%), C. albicans
(n = 3, 2.5%) MSSA (n = 3, 2.5%) MRSA (1,0.8%), Escherichia coli (n = 3, 2.5%) was also isolated (Fig. 2).
Recurrent bacteremia was detected in both symptomatic (n = 78, 19.6%, P = 0.04) and asymptomatic groups
while it was significant in the former. MSSA was the
most frequent etiology in recurrent symptomatic
bacteremia, and it was isolated in 58 (74.3%, p = 0.03)
patients.
Venous catheter colonizer (VCC)
Out of 160 VCC, coagulase negative Staphylococcus sp.
[S. epidermidis (n = 86, 53.7%), S. hemolyticus (n = 16,
10%), S. schleiferi (n = 8, 5%), S. lugdunensis (n = 4, 2.5%)
(p = 0.01)] was the commonest while C. parapsilosis (n =
12, 7.5%), C. albicans (n = 8, 5%), MSSA (n = 8, 5%)
MRSA (4,2.5%), Escherichia coli (n = 4, 2.5%), Acinetobacter bahumanii (n = 4, 2.5%), C. frundii (n = 4, 2.5%)
and P. aeruginosa (n = 4, 2.5%) was also isolated.
In all patients with bacteremia, procalcitonin was elevated (> 0.5 ng/ml). PCT was in asymptomatic CLABSI
was 1.8 ± 0.9 while in symptomatic CLABSI was 11.3 ±
2.5 (p = 0.01).
Antimicrobial susceptibility pattern of isolated microbes
from asymptomatic and symptomatic CLABSI
Compared to S. epidermidis isolates following symptomatic CLABSI, S. epidermidis isolates following asymptomatic CLABSI were having significant resistance to
oxacillin, cefoxitin, ciprofloxacin, levofloxacin, Trimethoprim/ sulfamethoxazole, Amikacin, gentamicin,
erythromycin, and clindamycin while all were susceptible
to vancomycin, linezolid, and tigecycline (Table 1).
Other infective complications
Central venous catheter exit site (n = 98, 6.7%) and tunnel
infections (n = 70, 4.8%) were detected in long term indwelling venous catheters. Exit site infection was observed
7.5 ± 6.25 months, and tunnel infection was observed 11 ±
Fig. 1 Microbial etiology in symptomatic and symptomatic patients with central line-associated bloodstream infections. MSSA- Methicillinsensitive S. aureus, MRSA- Methicillin-resistant S. aureus, CoNS- Coagulase-negative Staphylococcus sp.
Jayaweera and Sivakumar BMC Infectious Diseases (2020) 20:457 Page 4 of 10
2.75 months following the insertion of a venous catheter.
Further, venous catheter blockage was detected in 88
(6%), and in all, including exit and tunnel infections catheter, revisal was done to minimize systemic infections.
The blockage was observed 0.82 ± 0.43 years following the
insertion of a central venous catheter.
Right sided infective endocarditis (IE) was detected in
122 (8.3%) patients and was observed 8.6 ± 3 months following insertion of venous catheter. It was detected in
CLABSI symptomatic (n = 29, 24.5%), CLABSI asymptomatic (n = 42, 34.5%), symptomatic (n = 14, 11.5%) and
asymptomatic bacteremic (n = 36, 29.5%) patients and is
significant in asymptomatic CLABSI and asymptomatic
bacteremic patients (Table 2).
Further, catheter tip endocarditis (n = 88, 6%) and left
sided IE (n = 31, 2.1%) was detected in all above mentioned groups. Catheter tip endocarditis was observed
6.25 ± 2.9 months following insertion of venous catheter
and it was significantly detected in asymptomatic
bacteremic (without CLABSI) (n = 48, 54.5%, p = 0.03)
and non bacteremic children (n = 39, 44.3%, p = 0.04).
Coagulase negative Staphylococcus sp.[s. epidermidis
Fig. 2 Microbial etiology in symptomatic and symptomatic bacteremic patients. MSSA- Methicillin-sensitive S. aureus, MRSA- Methicillin-resistant S.
aureus, CoNS- Coagulase-negative Staphylococcus sp.
Table 1 Antimicrobial susceptibility profile of coagulase-negative Staphylococcus sp. (CoNS) isolates in asymptomatic and
symptomatic central line-associated bloodstream infections
Antibiotic CLABSI P
value Symptomatic- CoNS Asymptomatic- CoNS
S. epidermidis
(n = 10)
S. hemolyticus
(n = 6)
S. epidermidis
(n = 54)
S. hemolyticus
(n = 6)
S. schleiferi
(n = 5)
S. lugdunensis
(n = 5)
Ampicillin (30 μg) 2 (20%) 1 (17%) 47 (87.3%) * 6 (100%) 5 (100%) 5 (100%) 0.03*
Cefoxitin (30 μg) 2 (20%) 1 (17%) 45 (85.7%) ** 6 (100%) 5 (100%) 5 (100%) 0.02**
Oxacillin 2 (20%) 1 (17%) 45 (85.7%) *** 6 (100%) 5 (100%) 5 (100%) 0.03***
Ciprofloxacin (5 μg) 1 (10%) 1 (17%) 45 (85.7%) α 4 (67%) 5 (100%) 5 (100%) 0.03α
Levofloxacin (5 μg) 2 (20%) 1 (17%) 45 (85.7%) μ 4 (67%) 4 (80%) 5 (100%) 0.03μ
Trimethoprim/ sulfamethoxazole
(1.25/23.25 μg)
1 (10%) 1 (17%) 42 (79.3%) 4 (67%) 5 (100%) 5 (100%) 0.03
Amikacin (30 μg) 3 (30) 1 (17%) 42 (79.3%) 4 (67%) 5 (100%) 5 (100%) 0.03
Gentamicin (10 μg) 2 (20) 1 (17%) 42 (79.3%) 4 (67%) 5 (100%) 5 (100%) 0.03
Erythromycin (30 μg) 2 (20) 1 (17%) 42 (79.3%) 4 (67%) 5 (100%) 5 (100%) 0.03
Clindamycin (30 μg) 2 (20) 1 (17%) 42 (79.3%) 4 (67%) 5 (100%) 5 (100%) 0.03
vancomycin 0 0 0 0 0 0 –
Linezolid 0 0 0 0 0 0 –
Tigecycline 0 0 0 0 0 0 –
P < 0.05 taken as significant
* Ampicillin resistance is significantly low in S. epidermidis; ** Cefoxitin resistance is significantly low in S. epidermidis; *** Oxacillin resistance is significantly low
in S. epidermidis; α Ciprofloxacin resistance is significantly low in S. epidermidis; μ Levofloxacin resistance is significantly low in S. epidermidis
Jayaweera and Sivakumar BMC Infectious Diseases (2020) 20:457 Page 5 of 10
(n = 18, 37.5%), S. hemolyticus (n = 12, 25%), S. schleiferi
(n = 6, 12.5%), S. lugdunensis (n = 3, 6.25%) (p = 0.01)]
was the commonest while C. parapsilosis (n = 4, 8.3%),
C. albicans (n = 3, 6.25%), MSSA (n = 1, 1.1%) and
MRSA (n = 1, 1.1%) also isolated from the blood
cultures.
Patients with left sided IE was observed 0.42 ± 0.34
years following insertion of venous catheter and it was
detected in symptomatic bacteremic (n = 19, 61.2%, p =
0.03) and symptomatic CLABSI children (n = 12, 38.7%,
p = 0.04). MRSA in 12 (38.7%), MSSA (n = 10, 34%), E.
fecalis (n = 3, 10%), E. faceum (n = 3, 10%), C. albicans
(n = 2, 6.7%) and C. parapsilosis (n = 1, 3.3%) was detected in patients with left sided IE.
Following univariate analysis, coagulase-negative
Staphylococcus sp., tunneled central venous catheter, PICC,
femoral site, a number of line-days > 90, receipt of vancomycin, meropenem or linezolid in the 5 days before obtaining blood cultures and recurrent bacteremia was
significantly associated with increased risk of asymptomatic
CLABSI. Further, receipt of vancomycin, meropenem, or linezolid in the 5 days before obtaining blood cultures was
significantly associated with non-bacteremia (Table 3).
According to multivariate analysis coagulase negative
staphylococcus sp. blood stream infection (OR: 7.6, 95%
CI: 6.5–8.3, P = 0.03), having tunneled CVC (OR: 4.4,
95% CI: 3.8–4.9, P = 0.03), peripherally inserted central
catheter (OR: 4.9, 95% CI: 3.9–6.2, P = 0.02), femoral site
(OR: 3.7, 95% CI: 2.8–4.3, P = 0.01), number of line days
> 90 (OR: 2.1, 95% CI: 1.3–4.0, P = 0.02), receipt of
vancomycin, meropenem or linezolid in the 5 days prior
to CLABSI diagnosis (OR: 2.1, 95% CI: 1.3–4.0, P = 0.02)
and recurrent bacteremia (OR: 8.7, 95% CI: 7.8–9.3, P =
0.01) were associated with asymptomatic CLABSI in patients with long term hemodialysis (Table 4).
Discussion
CVCs are not without risk and following placement it can
develop multiple complications. Significant morbidity,
mortality can result following complications and can cause
a significant burden leading to high expenditure, prolonged hospitalization, and poor quality of life [21–23].
To our knowledge, this is the first report of asymptomatic CLABSI in patients who are undergoing long
term HD. Transient asymptomatic bacteremia is a
known phenomenon, while CLABSI is often symptomatic and followed with continuous bacteremia [5, 6].
Contrary, asymptomatic CLABSI could be a rare occurrence, and we were able to explore it following screening
blood cultures in every patient before each HD. CoNS
was predominantly isolated in patients with asymptomatic CLABSI, while MSSA was predominantly isolated in
patients with symptomatic CLABSI. Zierdt in 1983 has
described that the intermittent or transient or asymptomatic S. epidermidis bacteremia can frequently occur
inpatients and as well as in healthy humans [24].
Right-sided IE is a well-known complication following
long term indwelling CVCs [15]. Often is diagnosed with
screening echocardiography following MSSA, MRSA
bacteremia or candidemia, and instances where having
an inadequate response following appropriate antimicrobials in other bacteremia (CoNS, Enterococcus sp., any of
Table 2 The microbial etiology for right-sided infective endocarditis in symptomatic and asymptomatic central line-associated
bloodstream infections and bacteremia without central line infection patients
Isolated
microbes
Right sided infective endocarditis (n = 122, 8.3%) P
value CLABSI (72, 59%) Bacteremia without CLABSI (50, 41%)
Symptomatic (n = 30, 24.5%) Asymptomatic (n = 42, 34.5%) Symptomatic (n = 14, 11.5%) Asymptomatic (n = 36, 29.5%) 0.03
MSSA 12** 13** 4 6 0.03**
MRSA 12£ 13£ 7£ 7 0.02£
CoNS 2 14α 1 16α 0.02α
S. epidermidis 1 6 – 9 0.07
S. hemolyticus 1 1 1 2 0.08
S. schleiferi – 1 – 4 0.07
S. lugdunensis – 1 – 1 0.07
Enterococcus sp. 2 1 – 1 0.08
C. albicans 3 1 1 2 0.07
C. parapsilosis 1 1 1 4 0.08
CLABSI central line-associated bloodstream infections, MSSA Methicillin-sensitive S. aureus, MRSA Methicillin-resistant S. aureus, CoNS Coagulase-negative
Staphylococcus sp.
P < 0.05 taken as significant
** MSSA was associated significantly in symptomatic and asymptomatic CLABSI, £
MRSA was associated significantly in right sided IE following symptomatic,
asymptomatic CLABSI and symptomatic bacteremic without CLABSI and α CoNS was associated significantly in right sided IE following asymptomatic CLABSI and
asymptomatic bacteremic without CLABSI
Jayaweera and Sivakumar BMC Infectious Diseases (2020) 20:457 Page 6 of 10
significant bacteremia) [22–25]. In here, CoNS was significantly associated with right-sided IE following
asymptomatic CLABSI and asymptomatic bacteremia
without CLABSI patients. Kendirli et al. in 2017 found
that S. epidermidis was commonly identified in children
with CLABSI [26]. Another study revealed that S. aureus
was the most common organism responsible for right
sided IE and IE in tricuspid valve develop more
frequently in heroin users [27]. Further, MSSA or
MRSA, Streptococci spp. or Enterococci spp. is responsible for acute IE [28]. In here, MSSA was associated significantly following right sided-IE in symptomatic and
asymptomatic CLABSI patients while MRSA was associated significantly in right-sided IE following symptomatic, asymptomatic CLABSI and symptomatic bacteremia
without CLABSI patients. The above scenarios were
Table 3 Univariate analysis of risk factors for asymptomatic central line-associated bloodstream infections in children on
hemodialysis
Variables CLABSI (n = 410) Nonbacteremics
Odds ratio
(95% CI)
Symptomatic
Odds ratio (95%
CI)
Asymptomatic
Odds ratio (95%
CI)
Microbial etiology
MSSA 2.2 (1.1–3.9)
MRSA 2.4 (1.9–3.1)
CoNS 3.4 (2.9–3.8)
Female sex – –
Type of CVC
Tunneled 2.7 (1.8–4.3)
Non-tunneled –––
Site of insertion
Internal jugular –––
PICC 2.9 (1.9–4.2)
Subclavian –––
Femoral 2.7 (1.8–4.3)
Number of line-days > 90 2.3 (1.3–4.0)
Duration of hospital stay –––
Receipt of vancomycin, meropenem or linezolid in the 5 days prior to obtaining blood
cultures
3.7 (2.8–4.6) 4.7 (3.8–
5.3)
No. of times intravenous medications given in the prior day (mean ± SD) –––
Recurrent bacteremia 2.7 (1.8–4.3)
All significant (P < 0.05) values are displayed with the odds ratio
CLABSI central line-associated bloodstream infections, MSSA Methicillin-sensitive S. aureus, MRSA Methicillin-resistant S. aureus, CoNS Coagulase-negative
Staphylococcus sp., CVC central venous catheter, PICC peripherally inserted central catheter, SD standard deviation and CI confidence interval
Table 4 Multivariate analysis of risk factors for asymptomatic central line-associated bloodstream infections in children on
hemodialysis
Variables Asymptomatic CLABSI
Odds ratio (95% CI) P value
CoNS bloodstream infection 7.6 (6.5–8.3) 0.01
Tunneled-CVC 4.4 (3.8–4.9) 0.03
Site of insertion -PICC 4.9 (3.9–6.2) 0.02
Site of insertion -Femoral 3.7 (2.8–4.3) 0.01
Number of line-days > 90 2.1 (1.3–4.0) 0.02
Receipt of vancomycin, meropenem or linezolid in the 5 days prior to CLABSI diagnosis 3.7 (2.8–4.6) 0.01
Recurrent bacteremia 8.7 (7.8–9.3) 0.01
CLABSI central line-associated bloodstream infections, MSSA Methicillin-sensitive S. aureus, MRSA Methicillin-resistant S. aureus, CoNS Coagulase-negative
Staphylococcus sp., CVC central venous catheter, PICC peripherally inserted central catheter and CI- confidence interval
P < 0.05 taken as significant
Jayaweera and Sivakumar BMC Infectious Diseases (2020) 20:457 Page 7 of 10
detected as an outcome of screening blood cultures and
echocardiography. Application of such practice in busy
and resource-limited clinical setup needs to be validated.
Contrast to S. epidermidis following symptomatic
CLABSI, S. epidermidis following asymptomatic CLABSI
had significant antimicrobial resistance. It could be an outcome following the segregation of multiple genetic segments in microbial DNA. Since bacterial genetic capacity is
often constant, this would reduce the virulence capacity.
Various studies have shown that the genetic perturbations
responsible for antibiotic resistance modulate bacterial biology and fitness [29]. In many cases, measurements of bacterial growth in animal hosts have revealed fitness and
virulence attenuations that agree with in vitro tests, leading
to the view that pathogens incur fitness trade-offs that compromise their pathogenic potential. Perhaps, the drug resistance increases pathogen fitness during infection [30, 31].
Based on multivariate analysis having a CoNS bloodstream infection and tunneled CVC were risk factors for
the development of asymptomatic CLABSI in patients
with long term HD. Having tunneled CVC is a known
risk factor in CLABSI [32]. Further, the peripherally
inserted central catheter (PICC) and femoral site were
risk factors for the development of asymptomatic
CLABSI in patients with long term HD. Both PICC [33]
and femoral site [34] is known risk factor in CLABSI.
Contrary, no evidence of higher infection risk when the
catheter is inserted into the subclavian, jugular, or femoral vein, as demonstrated for adult patients [33]. A
number of line days > 90 was a risk factor for the development of asymptomatic CLABSI in patients with long
term HD. The risk of bacteremia is highest in
hemodialysis patients using a CVC for vascular access,
and increases in a linear fashion with the duration of
catheter use [2, 4–8]. Prolonged use of CVC (7 or more
days) considered the risk for CLABSI [31]. A study by
Costello et al. analyzed 3319 admissions to the pediatric
cardiac intensive care unit found that a central venous
line in place for ≥7 days [34]. Also, receipt of vancomycin, meropenem, or linezolid in the 5 days before
CLABSI diagnosis was a risk factor for the development
of asymptomatic CLABSI in patients with long term
hemodialysis. Receipt of high-end antibiotics (vancomycin, meropenem, or linezolid) would suppress the
symptoms of bacteremia in great. Because the use of
such broad-spectrum antibiotics around 5 days would
suppress the bacteremia leading state of partially treated
[35]. Depending on etiology for bacteremia without detected focus, at least 7–14 days of therapy is recommended [28]. Furthermore, recurrent bacteremia was a
risk factor for the development of asymptomatic CLABSI
in patients with long term hemodialysis. Recurrent
bacteremia is a risk factor for the development of
CLABSI [36, 37].
Here, PCT was in asymptomatic CLABSI was 1.8 ± 0.9
ng/mL while in symptomatic CLABSI was 11.3 ± 2.5 ng/
mL. The procalcitonin cut-off value to detect sepsis was
≥0.5 ng/mL, with a corresponding sensitivity of 76% and
specificity of 69%. Different studies done in different settings the procalcitonin had a fair diagnostic accuracy for
bacteremia in adult patients suspected of infection or
sepsis. Perhaps, low procalcitonin levels can be used to
rule out the presence of bacteremia [38, 39].
Limitations
We have not performed anaerobic blood cultures to detect any of anaerobic etiology. Specific fungal cultures
using a semi-automated platform was also not performed. We have used only the DTP method to detect
CLABSI. The overall sensitivity and specificity of a DTP
of ≥120 min for diagnosing CLABSI were 85% (95% confidence interval [CI], 74 to 93%) and 82% (95% CI, 66 to
92%), respectively. Further, we have not performed S.
epidermidis molecular genetics related to antimicrobial
resistance. Due to the low number of MSSA and MRSA
cases, risk factor analysis was unable to perform related
to symptomatic and asymptomatic CLABSI.
Conclusions
Asymptomatic CLABSI could be a rare occurrence.
CoNS was predominantly isolated in patients with
asymptomatic CLABSI. Right-sided IE is a well-known
complication following long term indwelling central venous catheters. CoNS was significantly associated with
right-sided IE following asymptomatic CLABSI and
asymptomatic bacteremia without CLABSI patients.
Regular procalcitonin, microbiological, and imaging
studies will be essential to detect infectious complications in both symptomatic and asymptomatic children
implanted with long term indwelling CVCs.
Abbreviations
CVC: Central venous catheter; CLABSI: Central line-associated bloodstream infection; USA: United State of America; PICC: Peripherally inserted central
catheter; HD: Hemodialysis; CoNS: Coagulase-negative Staphylococcus sp.; RSIE: Right-sided infective endocarditis; CKD: Chronic Kidney disease;
DTP: Differential time positivity; PCT: Procalcitonin; MRSA: Methicillin-resistant
Staphylococcus aureus; MSSA: Methicillin sensitive Staphylococcus aureus;
CI: Confidence interval
Acknowledgments
I would like to acknowledge Dr. A. Joseph for providing support during
bacterial culture, microbial identification, and antimicrobial susceptibility
testing.
Authors’ contributions
JAASJ designed the study, and all authors participated in data analysis. JAASJ
and DS carried out the lab work. JAASJ drafted the manuscript, and the final
manuscript was read and approved by both authors.
Funding
No funding.
Jayaweera and Sivakumar BMC Infectious Diseases (2020) 20:457 Page 8 of 10
Availability of data and materials
The datasets used and analyzed in the current study are available from the
corresponding author on reasonable request.
Ethics approval and consent to participate
Ethical approval for all experimental protocol/s was approved by the ethical
review and publication committee, Teaching Hospital Kandy, Sri Lanka, and
to participate in the study informed written consent obtained from the legal
guardians/ parents. Further all experiments were performed in accordance
with relevant guidelines and regulations.
Consent for publication
Not applicable.
Competing interests
The authors declare that there is no conflict of interest regarding the
publication of this article.
Received: 17 February 2020 Accepted: 22 June 2020
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