Adjunct Laboratory Tests in the Diagnosis of Early-Onset Neonatal Sepsis

doi:10.1016/j.clp.2009.12.001

Clinics in Perinatology

Volume 37, Issue 2, June 2010, Pages 421-438

https://doi.org/10.1016/j.clp.2009.12.001 Get rights and content

Section snippets

Blood

Samples of blood for culture may be obtained by arterial or venous puncture after preparation of the site with an antibacterial solution (alcoholic solutions of chlorhexidine, iodine, or povidone-iodine are preferable to aqueous povidone-iodine).1, 2, 3 Data regarding sterilization of intravenous catheter sites indicate that cleansing for 30 seconds or two consecutive cleansings are superior to a single, brief (5–10 seconds) disinfection.⁴ Specimens obtained from newly placed intravenous or

Hematological tests

Early observations that neonates with bacterial sepsis often have abnormal white blood cell counts led to the hypothesis that hematologic studies might allow diagnosis of sepsis before results of cultures become available. Because the imperfect sensitivity of any single measurement, including the total white cell count, total neutrophil count, neutrophil count, immature-to-total (I:T) or immature-to-mature neutrophil ratios, soon became apparent, several strategies for combining multiple

Acute-phase reactants

Inflammatory stimuli of any sort, including infection, trauma, or ischemia, cause marginalization, extravasation, and activation of granulocytes and monocytes, with release of multiple proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α).⁶¹ These mediators stimulate production of a variety of proteins referred to as acute-phase reactants. The time courses of these responses in adults have been well characterized (Fig. 1)⁶¹ and follow a similar

ILs and other cytokines

Because acute-phase reactants are produced in response to proinflammatory cytokines, direct measurement of serum cytokine levels promised to provide an earlier indication of infection than could be achieved by measurement of the secondary responses. Initial assessments of several cytokines, including IL-1β,⁸⁹ IL-6,90, 91, 92 IL-8),92, 93, 94 soluble IL-2 receptor (sIL2R),⁹⁵ and TNF-α⁹² demonstrated early responses to bacterial infection in neonates. Initial reports of high sensitivity and

Combination tests

Noting that serum levels of cytokines often return to normal as those of acute-phase reactants rise, several groups have proposed use of combinations of measurements to enhance the likelihood of an abnormal result in the face of uncertainty about the stage of illness at which an infant is evaluated for suspected infection. In concept, elevation of a cytokine level would permit detection of infants early in the course of infection, before CRP elevation is apparent, while the delayed elevation of

Summary

Timely diagnosis of neonatal bacterial infection remains one of the most common and problematic tasks encountered in neonatal medicine. Evaluation of infants at risk for early-onset infection must be based on the pregnancy and intrapartum history and clinical manifestations of illness in the infant, which may be absent or nonspecific. While careful observation for development of clinical signs remains essential to management of these infants, the potential for reduction of morbidity and

First page preview

Click to open first page preview

View PDF

References (99)

R.M. Cowett et al.
Reliability of bacterial culture of blood obtained from an umbilical artery catheter
J Pediatr
(1976)
J.W. Ruderman et al.
Quantitative blood cultures in the diagnosis of sepsis in infants with umbilical and Broviac catheters
J Pediatr
(1988)
D.E. Dietzman et al.
Neonatal Escherichia coli septicemia—bacterial counts in blood
J Pediatr
(1974)
R.L. Schelonka et al.
Volume of blood required to detect common neonatal pathogens
J Pediatr
(1996)
M.E. Pichichero et al.
Detection of neonatal bacteremia
J Pediatr
(1979)
V.E. Visser et al.
Lumbar puncture in the evaluation of suspected neonatal sepsis
J Pediatr
(1980)
S. Fielkow et al.
Cerebrospinal fluid examination in symptom-free infants with risk factors for infection
J Pediatr
(1991)
J.H. Vollman et al.
Early-onset group B streptococcal disease: clinical, roentgenographic, and pathologic features
J Pediatr
(1976)
B.L. Manroe et al.
The neonatal blood count in health and disease. I. Reference values for neutrophilic cells
J Pediatr
(1979)
R.L. Rodwell et al.
Early diagnosis of neonatal sepsis using a hematologic scoring system
J Pediatr
(1988)

S.M. Adler et al.

The erythrocyte sedimentation rate in the newborn period

J Pediatr

(1975)

H.E. Evans et al.

The micro-erythrocyte sedimentation rate in newborn infants

J Pediatr

(1970)

H. Dollner et al.

Early diagnostic markers for neonatal sepsis: comparing C-reactive protein, interleukin-6, soluble tumour necrosis factor receptors and soluble adhesion molecules

J Clin Epidemiol

(2001)

S.M. Garland et al.

Reappraisal of C-reactive protein as a screening tool for neonatal sepsis

Pathology

(2003)

M. Assicot et al.

High serum procalcitonin concentrations in patients with sepsis and infection

Lancet

(1993)

D. Gendrel et al.

Procalcitonin as a marker for the early diagnosis of neonatal infection

J Pediatr

(1996)

A. Lapillonne et al.

Lack of specificity of procalcitonin for sepsis diagnosis in premature infants

Lancet

(1998)

J. Messer et al.

Evaluation of interleukin-6 and soluble receptors of tumor necrosis factor for early diagnosis of neonatal infection

J Pediatr

(1996)

M.L. Spear et al.

Soluble interleukin-2 receptor as a predictor of neonatal sepsis

J Pediatr

(1995)

D.P. Calfee et al.

Comparison of four antiseptic preparations for skin in the prevention of contamination of percutaneously drawn blood cultures: a randomized trial

J Clin Microbiol

(2002)

O. Mimoz et al.

Chlorhexidine compared with povidone-iodine as skin preparation before blood culture. A randomized, controlled trial

Ann Intern Med

(1999)

B.W. Trautner et al.

Skin antisepsis kits containing alcohol and chlorhexidine gluconate or tincture of iodine are associated with low rates of blood culture contamination

Infect Control Hosp Epidemiol

(2002)

I. Malathi et al.

Skin disinfection in preterm infants

Arch Dis Child

(1993)

M. Pourcyrous et al.

Indwelling umbilical arterial catheter: a preferred sampling site for blood culture

Pediatrics

(1988)

F. Solorzano-Santos et al.

A blood micro-culture system for the diagnosis of bacteremia in pediatric patients

Scand J Infect Dis

(1998)

J.A. Kellogg et al.

Frequency of low level bacteremia in infants from birth to two months of age

Pediatr Infect Dis J

(1997)

G.J. Noel et al.

Anaerobic bacteremia in a neonatal intensive care unit: an eighteen-year experience

Pediatr Infect Dis J

(1988)

S. Sarkar et al.

A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis

J Perinatol

(2006)

T.E. Wiswell et al.

Multiple site blood cultures in the initial evaluation for neonatal sepsis during the first week of life

Pediatr Infect Dis J

(1991)

S. Sarkar et al.

Multiple site blood cultures are mandatory to document the clearance of bacteremia in neonates with sepsis

Pediatr Res

(2003)

I. Pauli et al.

Early detection of bacteremia in the neonatal intensive care unit using the new BACTEC system

J Perinatol

(1999)

J.A. Garcia-Prats et al.

Rapid detection of microorganisms in blood cultures of newborn infants utilizing an automated blood culture system

Pediatrics

(2000)

Y. Kumar et al.

Time to positivity of neonatal blood cultures

Arch Dis Child Fetal Neonatal Ed

(2001)

W. Janjindamai et al.

Time to positivity of blood culture in newborn infants

Southeast Asian J Trop Med Public Health

(2006)

L. Jardine et al.

Incubation time required for neonatal blood cultures to become positive

J Paediatr Child Health

(2006)

L. Eisenfeld et al.

Systemic bacterial infections in neonatal deaths

Am J Dis Child

(1983)

E. Squire et al.

Diagnosis of neonatal bacterial infection: hematologic and pathologic findings in fatal and nonfatal cases

Pediatrics

(1979)

J.R. Pierce et al.

Immediate postmortem cultures in an intensive care nursery

Pediatr Infect Dis

(1984)

S. Schrag et al.

Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC

MMWR Recomm Rep

(2002)

M.C. Ottolini et al.

Utility of complete blood count and blood culture screening to diagnose neonatal sepsis in the asymptomatic at risk newborn

Pediatr Infect Dis J

(2003)

T.E. Wiswell et al.

No lumbar puncture in the evaluation for early neonatal sepsis: will meningitis be missed?

Pediatrics

(1995)

D.E. Holt et al.

Neonatal meningitis in England and Wales: 10 years on

Arch Dis Child Fetal Neonatal Ed

(2001)

K.E. Shattuck et al.

The changing spectrum of neonatal meningitis over a fifteen-year period

Clin Pediatr (Phila)

(1992)

H.P. Garges et al.

Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters?

Pediatrics

(2006)

S. Hamada et al.

Neonatal group B streptococcal disease: incidence, presentation, and mortality

J Matern Fetal Neonatal Med

(2008)

K. Grimwood et al.

Early-onset neonatal group B streptococcal infections in New Zealand 1998–1999

J Paediatr Child Health

(2002)

M.T. Neto

Group B streptococcal disease in Portuguese infants younger than 90 days

Arch Dis Child Fetal Neonatal Ed

(2008)

J.T. Kanegaye et al.

Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment

Pediatrics

(2001)

P.T. Heath et al.

Neonatal meningitis

Arch Dis Child Fetal Neonatal Ed

(2003)

Cited by (146)

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation
2024, Jornal de Pediatria
To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors.
Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018–June/2019) and after (July/2019–December/2020) the implementation of the sepsis risk calculator.
A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases.
The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.
Early-Onset Sepsis
2023, Principles of Neonatology
Early-onset sepsis is defined by isolation of a pathogenic microbial species from blood or cerebrospinal fluid culture in the first hours to days after birth. Both incidence and associated mortality are highest among preterm, very-low birth weight infants. The pathogenesis of early-onset sepsis derives from ascending colonization of the uterine compartment with normal maternal flora, with subsequent colonization of the fetus and transition to invasive infection in utero or after birth. Specific intrapartum risk factors and circumstances of delivery can be used to determine which newborns are at highest risk of infection and therefore should undergo evaluation and receive empiric antibiotic therapies.
Neonatal sepsis at point of care
2021, Clinica Chimica Acta
Citation Excerpt :
GeneXpert system can detect GBS in new borns in 30 min [18]. Despite these advantages, nucleic acid amplification-based methods suffer that they cannot differentiate between viable and non-viable pathogen within body fluid, as well as the high frequency of detecting contaminates, result in poor clinical correlation [19]. Additionally, detection is achieved at a high threshold cycle value resulting in nonspecific amplification and false-positive detection [20].
Sepsis, which includes infection followed by inflammation, is one of the leading causes of death among neonates worldwide. The major attribute of this disease process is dysregulated host response to infection leading to organ dysfunction and potentially death. A comprehensive understanding of the host response as well as the pathogen itself are important factors contributing to outcome. Early diagnosis is paramount, as it leads to accurate assessment and improved clinical management. Accordingly, a number of diagnostic platforms have been introduced to assess the presence of blood stream pathogens in septic neonates. Unfortunately, current point-of-care (POC) methods rely on a single parameter/biomarker and thus lack a comprehensive evaluation. The emerging field of biosensing has, however, resulted in the development of a wide range of analytical devices that may be useful at POC. This review discusses currently available methods to screen the inflammatory process in neonatal sepsis. We describe POC sensor-based methods for single platform multi-analyte detection and highlight the latest advances in this evolving technology. Finally, we critically evaluate the applicability of these POC devices clinically for early diagnosis of sepsis in neonates.
The Term Newborn: Early-Onset Sepsis
2021, Clinics in Perinatology
Citation Excerpt :
Additional experience with these methods will be necessary before they are adopted into routine practice. Ancillary diagnostic tests, including hematological counts, acute-phase reactants, and a variety of cytokines or chemokines, have been evaluated as potential indicators of neonatal sepsis.54,57 Much of the literature on these biomarkers is compromised by failure to use age-appropriate reference ranges and/or by comparison of infants who are sick (but without EOS) with well controls.
Role of microbiological tests and biomarkers in antibiotic stewardship
2020, Seminars in Perinatology
Citation Excerpt :
In the management of neonatal sepsis, acute phase reactants, such as C-reactive protein (CRP), are used to assist decision-making when culture-based microbiological test results are unavailable or when clinical suspicion for bacterial infection is high despite sterile microbiological test results.6-8 However, since these markers measure the host immune response to a variety of insults, the specificity of these biomarkers for bacterial infection varies widely.4,8-12 While host response biomarkers are direct markers of the patient's physiological state, they remain indirect markers of the pathogen, and antibiotic selection based solely on these tests remains empirical.
Laboratory tests are critical in the detection and timely treatment of infection. Two categories of tests are commonly used in neonatal sepsis management: those that identify the pathogen and those that detect host response to a potential pathogen. Decision-making around antibiotic choice is related to the performance of tests that directly identify pathogens. Advances in these tests hold the key to progress in antibiotic stewardship. Tests measuring host response, on the other hand, are an indirect marker of potential infection. While an important measure of the patient's clinical state, in the absence of pathogen detection these tests cannot confirm the appropriateness of antibiotic selection. The overall impact these tests then have on antibiotic utilization depends the test's specificity for bacterial infection, clinical scenario where it is being used and the decision-rule it is being integrated into for use. In this review we discuss common and emerging laboratory tests available for assisting management of neonatal infection and specifically focus on the role they play in optimizing antibiotic utilization.
Investigating the Association between Serum and Hematological Biomarkers and Neonatal Sepsis in Newborns with Premature Rupture of Membranes: A Retrospective Study
2024, Children

View all citing articles on Scopus

View full text