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

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

3. Introduction Neonatal sepsis is a common cause of morbidity and mortality 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 Neonatal sepsis is a clinical syndrome of systemic illness accompanied by bacteremia in the first month of life

4. Definitions Early Onset Sepsis (EOS): Early Onset Sepsis (EOS): –Culture proven infection within the first 72 hours of life Late Onset Sepsis (LOS): Late Onset Sepsis (LOS): –Culture proven infection after 72 hours of life –Sepsis, UTI, pneumonia, meningitis, osteomyelitis, NEC

5. Incidence 1-5 per 1000 live births 1-5 per 1000 live births Higher incidence of neonatal sepsis in VLBWs Higher incidence of neonatal sepsis in VLBWs Mortality rate is high (13-25%) Mortality rate is high (13-25%)

6. Etiology: EOS Early Onset Sepsis (EOS): Early Onset Sepsis (EOS): –Group B Streptococcus (GBS) –E. Coli –Listeria monocytogenes –Streptococcus species ie. Viridans Due to maternal or perinatal factors Due to maternal or perinatal factors

7. Etiology: LOS Late Onset Sepsis (LOS): Late Onset Sepsis (LOS): –Coagulase-negative staphylococcus –Staphylococcus aureus –Gram negative bacilli ie. Klebsiella –Candida spp. Nosocomial or focal infection Nosocomial or focal infection

8. 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

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

10. Clinical Signs and Symptoms Lethargy Lethargy Hypo/hyperthermia Hypo/hyperthermia Feeding intolerance Feeding intolerance Jaundice Jaundice Abdominal distention Abdominal distention Vomiting Vomiting Apnea Apnea

11. Differential Diagnosis Respiratory Respiratory Cardiac Cardiac CNS CNS GI GI Inborn errors of metabolism Inborn errors of metabolism Hematologic Hematologic

12. Sepsis Work-Up Blood cultures (x 2 due to low sensitivity) Blood cultures (x 2 due to low sensitivity) Urine cultures Urine cultures Lumbar puncture Lumbar puncture Tracheal aspirates Tracheal aspirates CBC with differential CBC with differential

13. Management : GBS Prophylaxis All women screened at 35-37 weeks All women screened at 35-37 weeks Intrapartum antibiotics given to: 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 Temp > 100.4 GA < 37 weeks GA < 37 weeks ROM >18 hours ROM >18 hours

15. Empiric Antibiotic Therapy EOS EOS –Penicillin and Aminoglycoside –Ampicillin and Gentamicin LOS LOS –Vancomycin and Aminoglycoside –Vancomycin and Gentamicin

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

17. Question # 1 What is the major risk factor for neonatal sepsis? 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

18. Question # 1 What is the major risk factor for neonatal sepsis? 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

19. Question # 2 If meningitis is suspected what antibiotic may be added for better CNS penetration? If meningitis is suspected what antibiotic may be added for better CNS penetration? –A. Vancomycin –B. Tobramycin –C. Cefotaxime –D. Ceftriaxone –E. Meropenem

20. Question # 2 If meningitis is suspected what antibiotic may be added for better CNS penetration? If meningitis is suspected what antibiotic may be added for better CNS penetration? –A. Vancomycin –B. Tobramycin –C. Cefotaxime –D. Ceftriaxone –E. Meropenem

21. Question # 3 What is the gold standard for diagnosing neonatal sepsis? What is the gold standard for diagnosing neonatal sepsis? –A. Blood culture –B. Lumbar culture –C. CBC –D. Chest X-ray –E. CRP

22. Question # 3 What is the gold standard for diagnosing neonatal sepsis? What is the gold standard for diagnosing neonatal sepsis? –A. Blood culture –B. Lumbar culture –C. CBC –D. Chest X-ray –E. CRP

23. 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. A. Ampicillin and an aminoglycoside B. B. Clindamycin and a third-generation cephalosporin C. C. Meropenem and an aminoglycoside D. D. Piperacillin and an aminoglycoside E. E. Vancomycin and a third-generation cephalosporin

24. PREP Case # 1 Of the following, the MOST appropriate antibiotic regimen for this infant is A. A. Ampicillin and an aminoglycoside B. B. Clindamycin and a third-generation cephalosporin C. C. Meropenem and an aminoglycoside D. D. Piperacillin and an aminoglycoside E. E. Vancomycin and a third-generation cephalosporin

25. 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

26. 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

27. 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

28. References Fanaroff, A. A. & Martin, R. J. (Eds.). (2010). “Part 2: Postnatal Bacterial Infections”. St. Louis: Mosby, 2010; 793-806. Fanaroff, A. A. & Martin, R. J. (Eds.). (2010). “Part 2: Postnatal Bacterial Infections”. Neonatal- Perinatal Medicine: Diseases of the Fetus and Infant. 9 th 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. 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.

29. 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. 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.