Resident Lecture Series: Sepsis

Resident Lecture Series: Sepsis Nneka I. Nzegwu, DO Neonatal-Perinatal Clinical Fellow Yale-New Haven Children’s 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 # 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

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 • 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 # 1 Of the following, the MOST appropriate antibiotic regimen for this infant is • 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”. Neonatal-Perinatal 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/McGraw-Hill 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): e571-e578. • Centers for Disease Control and Prevention. Prevention of Perinatal Group B Streptococcal Disease. MMWR 2010; 59(RR-10): 1-32.

Resident Lecture Series: Sepsis