|Year : 2021 | Volume
| Issue : 2 | Page : 62-65
Evaluation of some biomarkers in diagnosis of bacterial bloodstream infection in children
Rana Mohammed Abood1, Zainab Fadhel Ashoor1, Yasir Ibrahim Al Saadi2
1 Department of Microbiology, College of Medicine, Mustansiriya University, Baghdad, Iraq
2 Children Welfare Teaching Hospital, Medical City, Ministry of Health, Baghdad, Iraq
|Date of Submission||26-Jul-2021|
|Date of Decision||09-Aug-2021|
|Date of Acceptance||14-Aug-2021|
|Date of Web Publication||15-Dec-2021|
Ms. Rana Mohammed Abood
Department of Microbiology, College of Medicine, Mustansiriya University, Baghdad
Source of Support: None, Conflict of Interest: None
Background: Bloodstream infection (BSI) is a life-threatening condition caused by the presence of microorganisms, generally caused by a range of bacteria in the blood. Objectives: The aim of this study was to evaluate the possible role of procalcitonin (PCT) and C-reactive protein (CRP) as biomarkers of pediatric BSI. Methodology: The study was conducted on 150 blood samples collected from the patient who admitted to Children Welfare Teaching Hospital, Medical City, Baghdad. During the period from November 2020 to March 2021, ninety blood samples from them were positive culture and 60 blood samples were negative culture (control group). The isolates were identified depending on the morphological, microscopic examination, and biochemical tests. Moreover, serum was obtained from all participants for the determination of the screening level of human PCT measured by enzyme-linked immunosorbent assay and CRP by slide agglutination test. Results: The results in this study revealed that the mean levels of serum PCT and CRP in Gram-negative group and Gram-positive group were significantly difference from the control group. Conclusions: The adoption of these biomarkers as routine diagnostic tests for sepsis may help in the early diagnosis of pediatric sepsis.
Keywords: Bacterial bloodstream infection, biomarkers, children
|How to cite this article:|
Abood RM, Ashoor ZF, Al Saadi YI. Evaluation of some biomarkers in diagnosis of bacterial bloodstream infection in children. Mustansiriya Med J 2021;20:62-5
|How to cite this URL:|
Abood RM, Ashoor ZF, Al Saadi YI. Evaluation of some biomarkers in diagnosis of bacterial bloodstream infection in children. Mustansiriya Med J [serial online] 2021 [cited 2022 May 29];20:62-5. Available from: https://www.mmjonweb.org/text.asp?2021/20/2/62/332557
| Introduction|| |
Bloodstream infections (BSIs) are characterized as severe disorders since they are acute events and usually result in serious life-threatening organ dysfunctions such as sepsis and septic shock., Sepsis is considered to be a public health issue and is a leading cause of mortality worldwide, being recently listed as a global health priority by the World Health Organization. BSI may be transient bacteremia, an indication of true systemic infection (endocarditis, osteomyelitis, and pneumonia), or otherwise, contamination from skin flora. Pediatric patients with BSI may present a diagnostic and therapeutic challenge where they often present with fever; however, sometimes, they may present with normal or even low body temperature., Bacteremia refers to any true-positive blood culture, which reflects the presence of viable bacteria in the bloodstream. Gram-negative bacteremia, which often produces sepsis or septic shock associated with their lipopolysaccharide of their cell walls, were at some point the predominant organisms isolated in blood cultures in the hospital setting. Gram-negative organisms such as Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Salmonella spp. played more important roles in children's community-acquired bacteremia., Moreover, Gram-positive organisms including (Staphylococcus aureus, coagulase-negative staphylococci [CONS], and enterococci) have become an important cause of BSIs.
BSI is a potential life-threatening condition that requires early diagnosis and rapid pathogen identification to initiate the correct antibiotic or antifungal therapy., Several biomarkers have been described as either being associated with the presence of BSI or suggested to have prognostic value for the outcome of BSI. The most widely studied marker is C-reactive protein (CRP), which is an acute-phase protein released by the liver after the onset of inflammation. CRP is mostly used to assess the presence of infection and sepsis. Moreover, procalcitonin (PCT) is the prohormone of calcitonin and was first reported as a marker of inflammation in 1993, several studies have been published which investigated its clinical value in the diagnosis of bacterial infections, especially sepsis.,
| Methodology|| |
This study includes (150) blood samples of children, their ages ranging from 1 day to 2 years old. Samples were collected from Children Welfare Teaching Hospital/Medical City/Baghdad. Ninety blood samples from them were positive culture and sixty blood samples were negative culture collected to be comparable to positive culture samples.
Five ml of blood specimen collected from patients, 2.5 to 3.0 ml injected immediately in brain heart infusion, and incubated 24 h before cultured on different media (MacConkey agar and Blood agar). After the growth of bacteria, the isolates were identified by microscopic examination, biochemical tests, analytical profile index 20E, and VITEK-2 system. Another 1 ml of blood specimen was collected in a plain tube and centrifuged to get serum for the screening level of PCT (Human procalcitonin enzyme-linked immunosorbent assay [ELISA] kit/BT LAB-China) by ELISA technique and CRP (CRP– Latex kit/SPINREACT-Spain) by slide agglutination test.
| Results|| |
A total of 150 blood samples obtained from the patients who were submitted to microbiological culture technique unite, samples were 90 (60%) give a positive culture, whereas 60 (40%) were negative culture result. The samples diagnosed with sepsis as confirmed by blood culture results and 30 (20%) of them were Gram negative and 60 (40%) were gram positive as shown in [Figure 1].
|Figure 1: The frequency of culture positive and negative culture cases among study specimens|
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[Table 1] shows the distribution of microorganisms from blood culture. Gram-positive bacteria 60 (66.66%) caused the majority of sepsis as compared with Gram-negative bacteria 30 (33.33%).
|Table 1: Distribution of organisms isolated from blood culture according gender|
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Ten bacterial species were isolated from the total of 90 positive blood culture samples. The most common organisms from blood cultures were CoNS 46 (51.11%), 26 male and 20 female. Followed by Acinetobacters spp., 16 (17.77%), 10 male and six female, S. aureus 10 (11.11%), seven male and three female, K. pneumonia 6 (6.66%), two male and four female, Streptococcus spp. 4 (4.44%), (one male and three female), Pseudomonas spp. 3 (3.33%), (three male), Citrobacter spp. 2 (2.22%), (two male), Proteus spp. 1 (1.11%), (one male only), E. coli, and Salmonella typhi 1 (1.11%) (one female) [Table 1].
According to CRP results in the three studied groups, [Table 2] shows the distribution of bacterial isolates in these groups. A total of 30 Gram-negative group 21 (70.00%) was with CRP positive test, whereas only 9 (30.00%) with CRP-negative test. The Gram-positive group was 17 (56.67%) with CRP-positive test and 13 (43.33%) with CRP-negative test. The control group (negative culture) give 6 (20.00%) CRP-positive test and 24 (80.00%) CRP-negative test, and these results showed a highly significant difference between the three studied groups.
|Table 2: Distribution of sample study according to C-reactive protein in different groups|
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[Table 3] shows the increase in the mean serum level of PCT in Gram-negative group (755.06 ± 56.87) as compared to Gram-positive group, which was (483.05 ± 46.62), whereas in control group was much less (10.52 ± 3.32). A significant difference between three groups was observed.
| Discussion|| |
In the present study, 150 blood samples were obtained for culture from the children who admitted in the hospital. The results revealed out of 150 samples, positive culture 90 (60%) higher than negative culture 60 (40%), and the majority of sepsis was caused by Gram-positive bacteria 60 (66.66%), compared with Gram-negative bacteria 30 (33.33%), the current study is similar to a study conducted by Acquah et al. on pediatric sepsis, who reported a (25.9%) blood culture positivity rate, Gram-positive was the predominant isolates accounting for 60.9%) of the total isolates and Gram-negative comprised (39.1%) all isolates. Another study conducted by Sakyi et al. gives similar results which showed blood culture positivity rate of (23.3%) and the most common bacterial isolates were Gram positive (57.2%), whereas the Gram-negative was 42.8%.
In contrast, much lower positive results were reported from Iran (5.6%) and from Kuwait (8.7%). These variations can be attributed to many different factors, of which antibiotic therapy before the laboratory diagnosis may have had the most important influence on the low culture results, environment factors, and sample collection sites such as general ward, neonatal intensive care unit (NICU,) and pediatric intensive care unit.
In the current study, conduct was showed the most common organisms from blood cultures were coagulase-negative Staphylococci spp., followed by Acinetobacter spp., S. aureus, K. pneumonia, Streptococcus spp., Pseudomonas spp., Citrobacter spp., Proteus spp., E. coli, and Salmonella typhi. This result resembles to a another study who showed that the most common bacterial isolate was coagulase-negative staphylococcus, followed by coagulase-positive staphylococcus, Klebsiella spp., E. coli, Methicillin-resistant S. aureus, and P. aeruginosa. A similar result was reported by Al Mohajer and Darouiche, who found that coagulase-negative Staphylococcus species were reported to be the most common pathogens followed by S. aureus.
This contrasts with a study in Bangladesh where showed that Acinetobacter spp. was the most prevalent organism in NICU patients, followed by Pseudomonas spp., CoNS., Klebsiella, and Moraxella spp. respectively, S. aureus, Enterobacter spp., E. coli, and Enterococci spp. Another study in China revealed the S. aureus is the most common microorganism isolated from the blood culture-positive cases followed by A. baumannii, K. pneumonia, Staphylococcus epidermis, Enterococcus spp., P. aeruginosa, and E. coli, respectively.
This may be due to the fact that most CoNS are the normal flora of the skin. Hence, during the blood collection, they may contaminate the blood. And also, it may be the expanding use of intravascular catheters and indwelling prosthetic devices causing the increase of nosocomial bacteremia caused by CoNS because they infect a wide variety of prosthetic medical devices.
Regarding to the CRP, among 30 samples, Gram-negative group was 21 (70.00%), CRP-positive test (+Ve), and 9 (30.00%) CRP-negative test (-Ve), whereas Gram-positive group was 17 (56.67%), CRP-positive test (+Ve) and 13 (43.33%) CRP negative test (-Ve), but control (negative culture) was 6 (20.00%) CRP-positive test (+Ve) and 24 (80.00%) CRP negative test (-Ve). These percentages similar to study conduct in Turkey showed that the median CRP level was (47.8 mg/dl) (10.2–119.5) in the sepsis group and (18.6 mg/dl) (4.9–66.1) in the nonsepsis group. Similar study in Jordan showed that the concentration of CRP was significantly higher in sepsis group (median 44.0 mg/l) than that in probable sepsis group and no sepsis group (medians of 21.5 and 1.0 mg/l, respectively).
The results of this study were in contrasts with another study who found that the mean of CRP levels between both groups (positive and negative blood culture) was similar (105 ± 105 vs. 119 ± 110 mg/L). In addition, CRP cannot be recommended as a sole indicator of neonatal sepsis, but it may be used as part of a sepsis workup and in combination with other laboratory tests.
In this study revealed that the serum level of PCT that determining by ELISA method. The mean of PCT level in Gram-negative group was 755.06 ± 56.87 and 483.05 ± 46.62 in Gram-positive group but in control group was (10.52 ± 3.32). This results in agreement with other study that showed the median values of PCT: 0.56 ng/mL (0.33–1.32) were in control group, 2.69 ng/mL (1.10–5.29) were in group with Gram-positive, and 9.36 ng/mL (3.11–39.35) in patients with Gram-negative group. A similar study in Ghana revealed that the PCT (ng/L) level in sepsis group was 632.8 (465.70–1468.0) whereas in control group was 434.20 (345.0–523.3). In contrasts with others who showed that the median PCT values for Gram-positive versus Gram-negative bacteremia were nearly identical; 15.58 ng/mL (interquartile range 0.67, 35.01) versus 13.72 ng/mL (interquartile range 0.63, 34.13).
| Conclusions|| |
The most common cause of BSI was Gram-positive bacteria such as CoNS and S. aureus followed by Gram-negative bacteria such as Acinetobacter spp. PCT and CRP markers could help the clinicians to diagnose most cases of pediatric sepsis; the rapid diagnosis of sepsis will reduce the morbidity and mortality by starting the antibiotic treatment as soon as possible. Therefore, using of these biomarkers as routine diagnostic tests for sepsis will aid in the early diagnosis of pediatric sepsis.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Loonen AJ, de Jager CP, Tosserams J, Kusters R, Hilbink M, Wever PC, et al.
Biomarkers and molecular analysis to improve bloodstream infection diagnostics in an emergency care unit. PLoS One 2014;9:e87315.
Cohen J, Vincent JL, Adhikari NK, Machado FR, Angus DC, Calandra T, et al.
Sepsis: A roadmap for future research. Lancet Infect Dis 2015;15:581-614.
Leal HF, Azevedo J, Silva GE, Amorim AM, de Roma LR, Arraes AC, et al.
Bloodstream infections caused by multidrug-resistant gram-negative bacteria: Epidemiological, clinical and microbiological features. BMC Infect Dis 2019;19:609.
Ayoola OO, Adeyemo AA, Osinusi K. Predictors of bacteraemia among febrile infants in Ibadan, Nigeria. J Health Popul Nutr 2002;20:223-9.
Ladhani S, Konana OS, Mwarumba S, English MC. Bacteraemia due to Staphylococcus aureus
. Arch Dis Child 2004;89:568-71.
Al Mohajer M, Darouiche RO. Sepsis syndrome, bloodstream infections, and device-related infections. Med Clin North Am 2012;96:1203-23.
Calitri C, Virano S, Scolfaro C, Raffaldi I, De Intinis G, Gregori G, et al.
Community-acquired bloodstream infections among paediatric patients admitted to an Italian tertiary referral centre: A prospective survey. Infez Med 2012;20:176-81.
Luthander J, Bennet R, Giske CG, Nilsson A, Eriksson M. The aetiology of paediatric bloodstream infections changes after pneumococcal vaccination and group B streptococcus prophylaxis. Acta Paediatr 2015;104:933-9.
Kullberg BJ, Arendrup MC. Invasive candidiasis. N Engl J Med 2015;373:1445-56.
Vincent JL. Clinical sepsis and septic shock--definition, diagnosis and management principles. Langenbecks Arch Surg 2008;393:817-24.
Emonet S, Schrenzel J. How could rapid bacterial identification improve the management of septic patients? Expert Rev Anti Infect Ther 2011;9:707-9.
Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: A systematic review and meta-analysis. Crit Care Med 2006;34:1996-2003.
Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341:515-8.
Giamarellos-Bourboulis EJ, Grecka P, Poulakou G, Anargyrou K, Katsilambros N, Giamarellou H. Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia. Clin Infect Dis 2001;32:1718-25.
Petrikkos GL, Christofilopoulou SA, Tentolouris NK, Charvalos EA, Kosmidis CJ, Daikos GL. Value of measuring serum procalcitonin, C-reactive protein, and mannan antigens to distinguish fungal from bacterial infections. Eur J Clin Microbiol Infect Dis 2005;24:272-5.
Acquah SE, Quaye L, Sagoe K, Ziem JB, Bromberger PI, Amponsem AA. Susceptibility of bacterial etiological agents to commonly-used antimicrobial agents in children with sepsis at the tamale teaching hospital. BMC Infect Dis 2013;13:89.
Sakyi SA, Enimil A, Adu DK, Ephraim RD, Danquah KO, Fondjo L, et al.
Individual and combined bioscore model of presepsin, procalcitonin, and high sensitive C – Reactive protein as biomarkers for early diagnosis of paediatric sepsis. Heliyon 2020;6:e04841.
Mehdinejad M, Khosravi AD, Morvaridi A. Study of prevalence and antimicrobial susceptibility pattern of bacteria isolated from blood cultures. J Biol Sci 2009;9:249-53.
Gomaa HH, Udo EE, Rajaram U. Neonatal septicemia in Al-Jahra hospital, Kuwait: Etiologic agents and antibiotic sensitivity patterns. Med Princ Pract 2001;10:145-50.
Akter M, Jahan N, Islam MN, Chowdhury F, Hoque SM, Khanom S, et al
. Multidrugs resistant Acinetobacte
r SPP. Blood stream infection in neonatal intensive care unit of an urban specialized hospital in Dhaka. J Dhaka Med Coll 2015;24:47-52.
Zhou B, Liu X, Wu JB, Jin B, Zhang YY. Clinical and microbiological profile of babies born with risk of neonatal sepsis. Exp Ther Med 2016;12:3621-5.
Dursun A, Ozsoylu S, Akyildiz BN. Neutrophil-to-lymphocyte ratio and mean platelet volume can be useful markers to predict sepsis in children. Pak J Med Sci 2018;34:918-22.
Khassawneh M, Hayajneh WA, Kofahi H, Khader Y, Amarin Z, Daoud A. Diagnostic markers for neonatal sepsis: Comparing C-reactive protein, interleukin-6 and immunoglobulin M. Scand J Immunol 2007;65:171-5.
Fendler WM, Piotrowski AJ. Procalcitonin in the early diagnosis of nosocomial sepsis in preterm neonates. J Paediatr Child Health 2008;44:114-8.
Nellis ME, Pon S, Giambrone AE, Coleman NE, Reiss J, Mauer E, et al.
The diagnostic accuracy of serum procalcitonin for bacteremia in critically ill children. Infect Dis Clin Pract (Baltim Md) 2016;24:343-7.
[Table 1], [Table 2], [Table 3]