Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis

https://doi.org/10.1016/j.pcl.2012.12.003Get rights and content

Section snippets

Key points

  • The adoption of Centers for Disease Control and Prevention guidelines for intrapartum antibiotic prophylaxis to reduce vertical transmission of Group B streptococcus (GBS) resulted in an 80% decrease in neonatal GBS sepsis.

  • Nonetheless, GBS and Escherichia coli remain the most common causes of early-onset sepsis in neonates.

  • Coagulase-negative staphylococci are now the most common cause of late-onset neonatal sepsis, particularly in low birth weight infants.

  • Among commonly used biomarkers, limited

Epidemiology of neonatal sepsis

Neonatal sepsis remains a feared and serious complication, especially among very low birth weight (VLBW) preterm infants. Neonatal sepsis is divided into early-onset and late-onset sepsis, based on timing of infection and presumed mode of transmission. Early-onset sepsis (EOS) is defined by onset in the first week of life, with some studies limiting EOS to infections occurring in the first 72 hours that are caused by maternal intrapartum transmission of invasive organisms. Late-onset sepsis

Development of the immune system and increased risk of neonates to infections

The development of the immune system entails a number of changes that occur during the first years of life. Neonates, especially preterm infants, are relatively immunocompromised because of immaturity of the immune system, as well as decreased placental passage of maternal antibodies. Here we highlight some of the components of the neonatal immune system that are immature and contribute to increased susceptibility to serious bacterial, fungal, and viral infections.

Etiologic agents in neonatal sepsis

The etiologic agents associated with neonatal sepsis in the United States have changed over time.5 In this section, we review current data on organisms associated with early-onset and late-onset neonatal sepsis (Table 2).

Group B-streptococcus

Despite widespread use of IAP to prevent vertical transmission of invasive GBS disease, missed opportunities for prevention exist and GBS remains the most common organism associated with EOS in the United States. According to the Centers for Disease Control and Prevention (CDC), rates of early-onset invasive GBS disease have declined by 80% since the CDC prevention guidelines were first published.9 GBS are gram-positive encapsulated bacteria for which 10 different serotypes have been

LOS

The increased survival of preterm low birth weight infants, particularly those who are VLBW, with need for prolonged hospitalization and use of invasive procedures and devices, especially long-term intravascular catheters, results in ongoing risk of infection. LOS is largely caused by organisms acquired from the environment after birth. The following section reviews the most common organisms associated with LOS (see Table 2).

Clinical manifestations

Both EOS and LOS have nonspecific clinical manifestations (Table 3). The importance of a lumbar puncture in neonates with suspected sepsis and without specific CNS clinical manifestations is underscored by studies showing growth of CSF cultures despite negative blood cultures, especially in VLBW infants.72

Diagnostic methods

Early diagnosis of neonatal sepsis is challenging because clinical characteristics are nonspecific and difficult to differentiate from those of noninfectious etiologies, and because the repertoire of ancillary laboratory tests is limited and not always reliable. Blood culture remains the gold standard for diagnosis of neonatal sepsis, but the rate of positivity is low, influenced by factors such as intrapartum antimicrobial administration and limitations in blood volume per culture that can be

Prevention and Infection Control Practices

Prevention of neonatal sepsis is the goal, through implementation of what is known and development of new prevention strategies. Maternal prenatal care continues to be important for prevention of EO GBS sepsis with identification of maternal carriage of GBS through universal screening for all pregnant women. Early recognition of chorioamnionitis, with appropriate antimicrobial therapy for the mother, decreases maternal fetal transmission. The recent CDC GBS prevention guidelines emphasize the

Summary

Neonatal sepsis continues to be a significant cause of morbidity and mortality in term and preterm infants. Although GBS and E coli are the most common pathogens associated with EOS, and CoNS are the most frequently isolated agents in newborns with LOS, other organisms, as well as multidrug-resistant pathogens, need to be considered. Development of accurate novel early diagnostic markers will allow clinicians to better assess the risk of infection and need for antibiotic therapy. Adherence to

First page preview

First page preview
Click to open first page preview

References (141)

  • J.M. Bliss et al.

    Candida virulence properties and adverse clinical outcomes in neonatal candidiasis

    J Pediatr

    (2012)
  • J.C. Forest et al.

    C-reactive protein as biochemical indicator of bacterial infection in neonates

    Clin Biochem

    (1986)
  • C. Chiesa et al.

    C reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period

    Clin Chim Acta

    (2011)
  • J.R. Verani et al.

    Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010

    MMWR Recomm Rep

    (2010)
  • B.J. Stoll et al.

    Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants

    N Engl J Med

    (2002)
  • B.J. Stoll et al.

    Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues

    Pediatrics

    (2011)
  • E.J. Weston et al.

    The burden of invasive early-onset neonatal sepsis in the United States, 2005-2008

    Pediatr Infect Dis J

    (2011)
  • M.J. Bizzarro et al.

    Seventy-five years of neonatal sepsis at Yale: 1928-2003

    Pediatrics

    (2005)
  • S. Vergnano et al.

    Neonatal infections in England: the NeonIN surveillance network

    Arch Dis Child Fetal Neonatal Ed

    (2011)
  • B.J. Stoll et al.

    Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network

    Pediatrics

    (2002)
  • B.J. Stoll et al.

    Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network

    Pediatrics

    (2010)
  • C.J. Baker et al.

    Policy statement—Recommendations for the prevention of perinatal group B streptococcal (GBS) disease

    Pediatrics

    (2011)
  • S. Kumar et al.

    Recognition of bacterial infection by innate immune sensors

    Crit Rev Microbiol

    (2012)
  • T.R. Kollmann et al.

    Neonatal innate TLR-mediated responses are distinct from those of adults

    J Immunol

    (2009)
  • M.E. Belderbos et al.

    Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors

    PLoS One

    (2012)
  • R. Carr

    Neutrophil production and function in newborn infants

    Br J Haematol

    (2000)
  • O. Levy

    Innate immunity of the newborn: basic mechanisms and clinical correlates

    Nat Rev Immunol

    (2007)
  • A. Guilmot et al.

    Natural killer cell responses to infections in early life

    J Innate Immun

    (2011)
  • J. Tolar et al.

    Immune regulatory cells in umbilical cord blood: T regulatory cells and mesenchymal stromal cells

    Br J Haematol

    (2009)
  • G. Risdon et al.

    Alloantigen priming induces a state of unresponsiveness in human umbilical cord blood T cells

    Proc Natl Acad Sci U S A

    (1995)
  • N. Takahashi et al.

    Change of specific T cells in an emerging neonatal infectious disease induced by a bacterial superantigen

    Microbiol Immunol

    (2009)
  • B. Sautois et al.

    Comparative cytokine production by in vitro stimulated mononucleated cells from cord blood and adult blood

    Exp Hematol

    (1997)
  • P. Palmeira et al.

    IgG placental transfer in healthy and pathological pregnancies

    Clin Dev Immunol

    (2012)
  • A. Malek et al.

    Evolution of maternofetal transport of immunoglobulins during human pregnancy

    Am J Reprod Immunol

    (1996)
  • A. Zandvoort et al.

    The dual function of the splenic marginal zone: essential for initiation of anti-TI-2 responses but also vital in the general first-line defense against blood-borne antigens

    Clin Exp Immunol

    (2002)
  • A.K. Hogasen et al.

    The analysis of the complement activation product SC5 b-9 is applicable in neonates in spite of their profound C9 deficiency

    J Perinat Med

    (2000)
  • T. Suzuki-Nishimura et al.

    Binding of spin-labeled fatty acids and lysophospholipids to hydrophobic region of calmodulin

    J Biochem

    (1991)
  • M.W. Tomlinson et al.

    Rectovaginal Staphylococcus aureus colonization: is it a neonatal threat?

    Am J Perinatol

    (2011)
  • S.J. Schrag et al.

    Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis

    N Engl J Med

    (2000)
  • M.J. Bizzarro et al.

    Changing patterns in neonatal Escherichia coli sepsis and ampicillin resistance in the era of intrapartum antibiotic prophylaxis

    Pediatrics

    (2008)
  • A. Kaczmarek et al.

    Prevalence of genes encoding virulence factors among Escherichia coli with K1 antigen and non-K1 E. coli strains

    J Med Microbiol

    (2012)
  • S.J. Schrag et al.

    Risk factors for invasive, early-onset Escherichia coli infections in the era of widespread intrapartum antibiotic use

    Pediatrics

    (2006)
  • M.N. Al-Hasan et al.

    Antimicrobial resistance trends of Escherichia coli bloodstream isolates: a population-based study, 1998-2007

    J Antimicrob Chemother

    (2009)
  • K.M. Puopolo et al.

    No change in the incidence of ampicillin-resistant, neonatal, early-onset sepsis over 18 years

    Pediatrics

    (2010)
  • J. Versalovic

    Manual of clinical microbiology

    (2012)
  • L.M. Shetron-Rama et al.

    Intracellular induction of Listeria monocytogenes actA expression

    Infect Immun

    (2002)
  • M.A. Moors et al.

    Expression of listeriolysin O and ActA by intracellular and extracellular Listeria monocytogenes

    Infect Immun

    (1999)
  • B. Smith et al.

    Listeria monocytogenes: maternal-foetal infections in Denmark 1994-2005

    Scand J Infect Dis

    (2009)
  • CDC

    From the Centers for Disease Control. Foodborne listeriosis—United States, 1988-1990

    JAMA

    (1992)
  • W.F. Schlech

    Foodborne listeriosis

    Clin Infect Dis

    (2000)
  • Cited by (0)

    View full text