Detection of pathogens associated with early-onset neonatal sepsis in cord blood at birth using quantitative PCR

Background: Early onset neonatal sepsis (EONS) typically begins prior to, during or soon after birth and may be rapidly fatal. There is paucity of data on the aetiology of EONS in sub-Saharan Africa due to limited diagnostic capacity in this region, despite the associated significant mortality and long-term neurological impairment. Methods: We compared pathogens detected in cord blood samples between neonates admitted to hospital with possible serious bacterial infection (pSBI) in the first 48 hours of life (cases) and neonates remaining well (controls). Cord blood was systematically collected at Kilifi County Hospital (KCH) from 2011-2016, and later tested for 21 bacterial, viral and protozoal targets using multiplex PCR via TaqMan Array Cards (TAC). Results: Among 603 cases (101 [17%] of whom died), 179 (30%) tested positive for ≥1 target and 37 (6.1%) tested positive for multiple targets. Klebsiella oxytoca, Escherichia coli/Shigella spp., Pseudomonas aeruginosa, and Streptococcus pyogenes were commonest. Among 300 controls, 79 (26%) tested positive for ≥1 target, 11 (3.7%) were positive for multiple targets, and K. oxytoca and P. aeruginosa were most common. Cumulative odds ratios across controls: cases (survived): cases (died) were E. coli/Shigella spp. 2.6 (95%CI 1.6-4.4); E. faecalis 4.0 (95%CI 1.1-15); S. agalactiae 4.5 (95%CI 1.6-13); Ureaplasma spp. 2.9 (95%CI 1.3-6.4); Enterovirus 9.1 (95%CI 2.3-37); and Plasmodium spp. 2.9 (95%CI 1.4-6.2). Excluding K. oxytoca and P. aeruginosa as likely contaminants, aetiology was attributed in 9.4% (95%CI 5.1-13) cases using TAC. Leading pathogen attributions by TAC were E. coli/Shigella spp. (3.5% (95%CI 1.7-5.3)) and Ureaplasma spp. (1.7% (95%CI 0.5-3.0)). Conclusions: Cord blood sample may be useful in describing EONS pathogens at birth, but more specific tests are needed for individual diagnosis. Careful sampling of cord blood using aseptic techniques is crucial to minimize contamination. In addition to culturable bacteria, Ureaplasma and Enterovirus were causes of EONS.

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Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis

Medical Hypotheses ◽

10.1016/j.mehy.2013.12.017 ◽

2014 ◽

Vol 82 (3) ◽

pp. 310-312 ◽

Cited By ~ 20

Author(s):

Mehmet Nevzat Cizmeci ◽

Semra Kara ◽

Mehmet Kenan Kanburoglu ◽

Serap Simavli ◽

Candan Iltemur Duvan ◽

...

Keyword(s):

Cord Blood ◽

Neonatal Sepsis ◽

Early Onset

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Inflammatory and oxidative parameters in cord blood as diagnostic of early-onset neonatal sepsis: A case-control study

Pediatric Critical Care Medicine ◽

10.1097/pcc.0b013e318198b0e3 ◽

2009 ◽

Vol 10 (4) ◽

pp. 467-471 ◽

Cited By ~ 30

Author(s):

Ana Carolina Cancelier ◽

Fabricia Petronilho ◽

Adalisa Reinke ◽

Larissa Constantino ◽

Roberta Machado ◽

...

Keyword(s):

Cord Blood ◽

Neonatal Sepsis ◽

Early Onset ◽

Case Control Study ◽

Case Control ◽

Control Study

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Statistical validity of interleukin-6 as a biomarker for the diagnosis of early-onset neonatal sepsis

Microbiology Research ◽

10.4081/mr.2012.e5 ◽

2012 ◽

Vol 3 (1) ◽

pp. 5 ◽

Cited By ~ 2

Author(s):

Sriparna Basu ◽

Shashikant Dewangan ◽

Shampa Anupurva ◽

Ashok Kumar

Keyword(s):

Risk Factors ◽

Blood Culture ◽

Cord Blood ◽

Interleukin 6 ◽

Neonatal Sepsis ◽

Early Onset ◽

Diagnostic Marker ◽

Statistical Validity ◽

Sepsis Screening ◽

Early Diagnostic

Use of empirical antibiotics in neonates with risk factors of early-onset neonatal sepsis (EOS) is a common practice. A laboratory parameter is needed to help in the accurate diagnosis of EOS to avoid unnecessary use of antibiotics. The aim of this prospective observational cohort study was to compare the statistical validity of cord blood interleukin-6 (IL-6) with conventional sepsis screening as an early diagnostic marker for EOS. Eighty-seven neonates with antenatal risk factors for sepsis were followed up for 72 h for the development of EOS. Cord blood was collected for measurement of IL-6 concentrations. Blood culture and conventional sepsis screening (total leukocyte count, absolute neutrophil count, C-reactive protein and micro-erythrocyte sedimentation rate) were sent for analysis soon after delivery. The study group comprised of symptomatic neonates with positive blood culture (n=36). An equal number of gestational-age matched asymptomatic neonates without risk factor of sepsis served as controls. Statistical validity of IL-6 was compared with sepsis screening parameters as the diagnostic marker for EOS. Gram negative organisms were the predominant cause of EOS. The most commonly isolated organism was <em>Acinetobacter baumanii</em>. The sensitivity and specificity of IL-6 with a cut-off value of 40.5 pg/mL and area under curve of 0.959 were 92.3 and 90.48%, respectively. In contrast, the sensitivity and specificity of different parameters of sepsis screening ranged from 37.5-68.75% and 47.95-57.35%, respectively. In conclusion, cord blood IL-6 can be used as a highly sensitive and specific early diagnostic marker of EOS at a cut-off concentration of 40.5 pg/mL.

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EVALUATION OF CORD BLOOD CULTURE AS AN EARLY PREDICTOR FOR THE DETECTION OF EARLY ONSET NEONATAL SEPSIS IN TERTIARY CENTRE OF CENTRAL INDIA.

10.36106/gjra/2510225 ◽

2021 ◽

pp. 84-86

Author(s):

Gagandeep Shukla ◽

Urvashi Channa

Keyword(s):

Blood Culture ◽

Cord Blood ◽

Neonatal Sepsis ◽

Early Onset ◽

Sequential Sampling ◽

Venous Blood ◽

Central India ◽

Neonatal Morbidity ◽

Peripheral Venous Blood ◽

Tertiary Centre

BACKGROUND : Neonatal sepsis is one of the major causes of neonatal morbidity and mortality. Peripheral venous blood culture and sensitivity is gold standard for the diagnosis of neonatal sepsis. Low sensitivity of blood culture in newborn is due to small volume of blood sample collected from neonates & antibiotics given before sampling. AIM : To evaluate the utility & compare the Umblical cord blood culture(UCBC) with Peripheral venous blood culture(PVBC) for detection of Early Onset Neonatal Sepsis(EONS) METHOD : 100 inborn neonates with two or more risk factors for EONS, chosen by sequential sampling method were included in this prospective analytical study. Blood samples were collected from umbilical cord and peripheral vein for culture. Sepsis screen was done to corroborate the diagnosis of neonatal sepsis. RESULT : Out of 100 neonates, 21 belongs to sepsis; 14 to probable sepsis; 65 to no sepsis. UCBC had Sensitivity-65.71% , Specicity-93.84%, PPV-85.18% , NPV-83.56% & PVBC had Sensitivity-60% , Specicity-95.38% , PPV-87.5% , NPV-81.57%. CONCLUSION : UCBC is simple and convenient method for the diagnosis of EONS compared to PVBC. Organisms grown are comparable to PVBC sample.

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Stoll, et al. Early Onset Neonatal Sepsis: The Burden of Group B Streptococcal and E. coli Disease Continues. Pediatrics. 2011;127(5); 817-826

PEDIATRICS ◽

10.1542/peds.2011-1344 ◽

2011 ◽

Vol 128 (2) ◽

pp. 390-390 ◽

Cited By ~ 1

Keyword(s):

Neonatal Sepsis ◽

Early Onset ◽

E Coli ◽

Group B

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Early Onset Neonatal Sepsis: The Burden of Group B Streptococcal and E. coli Disease Continues

PEDIATRICS ◽

10.1542/peds.2010-2217 ◽

2011 ◽

Vol 127 (5) ◽

pp. 817-826 ◽

Cited By ~ 538

Author(s):

B. J. Stoll ◽

N. I. Hansen ◽

P. J. Sanchez ◽

R. G. Faix ◽

B. B. Poindexter ◽

...

Keyword(s):

Neonatal Sepsis ◽

Early Onset ◽

E Coli ◽

Group B

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Bacterial Isolates of Early Onset Neonatal Sepsis and Their Antibiotic Susceptibility Pattern

Chattagram Maa-O-Shishu Hospital Medical College Journal ◽

10.3329/cmoshmcj.v17i1.39434 ◽

2018 ◽

Vol 17 (1) ◽

pp. 3-8 ◽

Cited By ~ 1

Author(s):

Md Abdul Mannan ◽

Shahed Iqbal ◽

SM Rezaul Karim ◽

Talim Uddin Ahmed ◽

Md Hakimul Haque Khan ◽

...

Keyword(s):

Neonatal Sepsis ◽

Early Onset ◽

Late Onset ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Late Onset Sepsis ◽

Early Onset Sepsis ◽

Sensitivity Pattern ◽

Rule Out

Background: Neonatal infections are the commonest cause of neonatal mortality along with perinatal asphyxia and consequence of Prematurity and Low Birth Weight (LBW) in Bangladesh. Early Onset Neonatal Sepsis (EONS) is neonatal sepsis occurring within the first 72 hours of birth and it is much more fulminant and has a higher mortality than Late Onset Sepsis (LOS). Sepsis in neonate remains a significant cause of mortality and morbidity in developing countries. Changing bacterial flora and emergence of resistant strains adds to the problem. Thus, neonatal sepsis requires accurate and timely clinical and laboratory diagnosis and proper management for better outcome. The organisms responsible for Early Onset Sepsis (EOS) are different than Late Onset Sepsis (LOS). In this study an attempt has been made to know the positivity rate of EOS and profile of bacteria responsible for EOS and determine the antimicrobial sensitivity pattern that were investigated for rule out sepsis. Methods: This was a prospective observation single centre study over a period of nine months (January to September, 2017) conducted on neonates born at Ad-din Medical College Hospital (AMCH), Dhaka and subsequently admitted in Neonatal Intensive Care Unit (NICU) within 72 hours of birth that were investigated for rule out sepsis. Dual blood sample for cultures from separate area along with essential investigations were sent by collecting samples under aseptic precautions. Empirical antimicrobial therapy was started according to antimicrobial guidelines in the NICU. The blood cultures test were carried out by BD BACTEC automated blood culture system and susceptibility testing was done for all blood culture isolates according to the criteria of the National Committee for Clinical Laboratory Standards by disk diffusion method. Results: A total of 700 neonates were investigated to rule out sepsis and 5.43% neonates were found with culture proven sepsis in the study. The gram positive bacteria accounted for 71% and gram negative 29% of the total isolates. Out of total 38 isolates, Coagulase-Negative Staphylococci (CONS) (68.4%) was the commonest followed by Acinetobacter (18.4%) and E. coli (7.9%) was common culture isolates. Among the gram positive, CONS (96.3%) was commonest isolate and in gram negative Acinetobacter (63.6%) was the most prevalent bacteria followed by E.coli (27.3%). Gram positive isolate, especially CONS (68.4%) was the major culprit for the early onset sepsis. Among the commonly used antibiotics, the susceptibilities were remarkably low to Amikacin (16%) in comparison to Ampicillin (42%) Cefotaxime (45%) and moderately high to Gentamicin (58%) for both gram positive & gram negative isolates. All (100%) gram positive isolates were resistant to Amikacin. Majority of the gram positive showed low susceptibilities to Meropenem (22%) Ciprofloxacin (41%) Ampicillin (48%) & Oxacillin (48%) in comparison to Cefotaxime (52%) Levofloxacin (55%) Gentamicin (70%), Linezolid (70%) and Vancomycin (74%). 50% of Coagulase Negative Staphylococcus (CONS) were resistant to Methicillin/Oxacillin. The sensitivity pattern of majority of gram negative isolates showed high level of resistance to Piperacillin+Tazobacterm (9%) and Ampicillin (27%) Gentamicin (27%) Cefotaxime (27%) less sensitive to Ciprofloxacin (45%); moderately high to Levofloxacin (54%) & Amikacin (54%) and highly sensitive to Imipenem/Meropenem (73%) & Colistin (91%). Gentamicin (58%) and Levofloxacin (55%) were showed marginal superiority compared to Ampicillin (42%) and Cefotaxime (45%) for effective coverage of both. Conclusion: Present study indicated that gram positive species especially CONS continue to be the predominant causative organism followed by Acinetobacter and E. coli in gram negative species. The antibiotic susceptibility profile suggested that for a given cohort empiric (initial) choice of Ampicillin and Gentamicin in EOS. Routine bacterial surveillance and their sensitivity patterns must be an essential component of neonatal care Chatt Maa Shi Hosp Med Coll J; Vol.17 (1); Jan 2018; Page 3-8

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Evaluation of Cefotaxime and Desacetylcefotaxime Concentrations in Cord Blood after Intrapartum Prophylaxis with Cefotaxime

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01429-08 ◽

2009 ◽

Vol 53 (6) ◽

pp. 2342-2345 ◽

Cited By ~ 3

Author(s):

Jacques Lepercq ◽

Jean Marc Treluyer ◽

Christelle Auger ◽

Josette Raymond ◽

Elisabeth Rey ◽

...

Keyword(s):

Cord Blood ◽

Neonatal Sepsis ◽

Premature Rupture ◽

Group B Streptococci ◽

E Coli ◽

Preterm Premature Rupture ◽

The Family ◽

Early Neonatal Sepsis ◽

Blood Specimens ◽

Group B

ABSTRACT Preterm premature rupture of the membranes is associated with a high risk of neonatal sepsis. An increase in the incidence of early-onset neonatal sepsis due to ampicillin-resistant Escherichia coli in premature infants has been observed in the past few years. Intrapartum prophylaxis with ampicillin has proven to be efficient for the prevention of early neonatal sepsis due to group B streptococci. To date, there is no strategy for the prevention of early neonatal sepsis due to ampicillin-resistant E. coli. Our aim was to investigate whether a standardized dosage regimen of intrapartum cefotaxime could provide concentrations in the cord blood greater than the cefotaxime MIC90 for E. coli. Seven pregnant women hospitalized with preterm premature rupture of the membranes and colonized with ampicillin-resistant isolates of the family Enterobacteriaceae were included. Cefotaxime was given intravenously during delivery, as follows: 2 g at the onset of labor and then 1 g every 4 h until delivery. Blood specimens were collected from the mother 30 min after the first injection and just before the second injection, and at birth, blood specimens were simultaneously collected from the mother and the umbilical cord. The concentrations of cefotaxime in the cord blood ranged from 0.5 to 8.5 mg/liter. The MIC90 of cefotaxime for E. coli strains (0.125 mg/liter) was achieved in all cases. This preliminary study supports the use of cefotaxime for intrapartum prophylaxis in women colonized with ampicillin-resistant isolates of Enterobacteriaceae. The effectiveness of this regimen for the prevention of neonatal sepsis needs to be evaluated with a larger population.

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