Resident Lecture Series: Sepsis

Nneka I. Nzegwu, DO Neonatal-Perinatal Clinical Fellow Yale-New Haven Childrens Hospital

Objectives

Define early and late onset sepsis

Describe the pathogens that occur in early and late onset sepsis Describe the risk factors for neonatal sepsis Create a differential for neonatal sepsis Describe the workup for neonatal sepsis Know empiric treatment for neonatal sepsis

Introduction

Neonatal sepsis is a common cause of morbidity and mortality

Neonatal sepsis is a clinical syndrome of systemic illness accompanied by bacteremia in the first month of life

Definitions

Early Onset Sepsis (EOS):

Culture proven infection within the first 72 hours of life

Late Onset Sepsis (LOS):

Culture proven infection after 72 hours of life Sepsis, UTI, pneumonia, meningitis, osteomyelitis, NEC

Incidence

1-5 per 1000 live births

Higher incidence of neonatal sepsis in VLBWs

Mortality rate is high (13-25%)

Etiology: EOS

Early Onset Sepsis (EOS):

Group B Streptococcus (GBS) E. Coli Listeria monocytogenes Streptococcus species ie. Viridans

Due to maternal or perinatal factors

Etiology: LOS

Late Onset Sepsis (LOS):

Coagulase-negative staphylococcus Staphylococcus aureus Gram negative bacilli ie. Klebsiella Candida spp.

Nosocomial or focal infection

Etiology: Viral Sepsis

Congenital
Enteroviruses (ie. Coxsackievirus A & B) Herpes Simplex Virus TORCH infections ie. CMV, Toxoplasmosis

Acquired
HIV Varicella Respiratory syncytial virus

Can be either early or late onset sepsis

Risk Factors

Prematurity Low birthweight ROM > 18 hours Maternal peripartum fever or infection Resuscitation at birth Multiple gestation Male sex

Clinical Signs and Symptoms

Lethargy Hypo/hyperthermia Feeding intolerance Jaundice Abdominal distention Vomiting Apnea

Differential Diagnosis

Respiratory Cardiac CNS GI Inborn errors of metabolism Hematologic

Sepsis Work-Up

Blood cultures (x 2 due to low sensitivity)

Urine cultures Lumbar puncture

Tracheal aspirates
CBC with differential

Management : GBS Prophylaxis

All women screened at 35-37 weeks

Intrapartum antibiotics given to:
GBS bacteruria during pregnancy GBS positive rectovaginal culture Prior infant w/ EOS GBS GBS unknown with risk factors
Temp > 100.4 GA < 37 weeks ROM >18 hours

Empiric Antibiotic Therapy

EOS
Penicillin and Aminoglycoside Ampicillin and Gentamicin

LOS
Vancomycin and Aminoglycoside Vancomycin and Gentamicin

Prognosis

Low birth weight and gram negative infection are associated with adverse outcomes
Septic meningitis in preterm infants may lead to neurological disabilities
May acquire hydrocephalus or periventricular leukomalacia

Question # 1

What is the major risk factor for neonatal sepsis?

A. Maternal GBS colonization B. Male sex C. Prematurity D. ROM >18 hours E. Low birthweight

Question # 1

What is the major risk factor for neonatal sepsis?

A. Maternal GBS colonization B. Male sex C. Prematurity D. ROM >18 hours E. Low birthweight

Question # 2

If meningitis is suspected what antibiotic may be added for better CNS penetration?
A. Vancomycin B. Tobramycin C. Cefotaxime D. Ceftriaxone E. Meropenem

Question # 2

If meningitis is suspected what antibiotic may be added for better CNS penetration?
A. Vancomycin B. Tobramycin C. Cefotaxime D. Ceftriaxone E. Meropenem

Question # 3

What is the gold standard for diagnosing neonatal sepsis?

A. Blood culture B. Lumbar culture C. CBC D. Chest X-ray E. CRP

Question # 3

What is the gold standard for diagnosing neonatal sepsis?

A. Blood culture B. Lumbar culture C. CBC D. Chest X-ray E. CRP

PREP Case # 1
A 2,700 gram male infant born at 36 weeks gestation is being treated for suspected neonatal sepsis following the development of respiratory distress shortly after birth. His mother had a fever to 102 F (38.9 C) during labor and delivery, but reports she had no illnesses during pregnancy.
Of the following, the MOST appropriate antibiotic regimen for this infant is A. Ampicillin and an aminoglycoside B. Clindamycin and a third-generation cephalosporin C. Meropenem and an aminoglycoside D. Piperacillin and an aminoglycoside E. Vancomycin and a third-generation cephalosporin

PREP Case # 1
Of the following, the MOST appropriate antibiotic regimen for this infant is
A. B. C. D. E.

Ampicillin and an aminoglycoside Clindamycin and a third-generation cephalosporin Meropenem and an aminoglycoside Piperacillin and an aminoglycoside Vancomycin and a third-generation cephalosporin

PREP Case # 2
You are called to labor and delivery to attend the vaginal delivery of a 37 weeks' gestation male to a 24-year-old primiparous mother. She reports that her membranes ruptured 36 hours ago. She is afebrile. Of the following, the maternal condition that is MOST likely to require antibiotic therapy for this neonate is
A. Chorioamnionitis B. Diabetes mellitus C. Group B streptococcal colonization D. Preeclampsia E. Urinary tract infection in the first trimester

PREP Case # 2
You are called to labor and delivery to attend the vaginal delivery of a 37 weeks' gestation male to a 24-year-old primiparous mother. She reports that her membranes ruptured 36 hours ago. She is afebrile.
Of the following, the maternal condition that is MOST likely to require antibiotic therapy for this neonate is A. Chorioamnionitis B. Diabetes mellitus C. Group B streptococcal colonization D. Preeclampsia E. Urinary tract infection in the first trimester

Summary

Neonatal sepsis is a common cause of morbidity and mortality Blood culture is the gold standard for diagnosis Universal GBS prophylaxis of pregnant women has significantly decreased the rate of GBS EOS

References

Fanaroff, A. A. & Martin, R. J. (Eds.). (2010). Part 2: Postnatal Bacterial Infections. NeonatalPerinatal Medicine: Diseases of the Fetus and Infant. 9th ed.: October 2010; St. Louis: Mosby, 2010; 793-806.
Gomella, TL, Cunningham, MD, Eyal FG, and Zenk KE. Zenk. "Sepsis." Neonatology: management, procedures, on-call problems, diseases, and drugs. 6th ed. New York: Lange Medical Books/McGrawHill Medical Pub. Division, 2009; 665-672.

References

Bentlin MR, Rugolo LMSS. Late-onset Sepsis: Epidemiology, Evaluation, and Outcome. Neoreviews 2010; 11(8): e426-e435. Pupulo KM. Epidemiology of Neonatal Early-onset Sepsis. Neoreviews 2008; Volume 9(12): e571e578. Centers for Disease Control and Prevention. Prevention of Perinatal Group B Streptococcal Disease. MMWR 2010; 59(RR-10): 1-32.