Resident Lecture Resident Lecture Series: SepsisSeries: Sepsis

Nneka I. Nzegwu, DONneka I. Nzegwu, DO

Neonatal-Perinatal Clinical FellowNeonatal-Perinatal Clinical Fellow

Yale-New Haven Children’s Yale-New Haven Children’s HospitalHospital

ObjectivesObjectives

Define early and late onset sepsisDefine early and late onset sepsis

Describe the pathogens that occur in early Describe the pathogens that occur in early and late onset sepsisand late onset sepsis

Describe the risk factors for neonatal sepsisDescribe the risk factors for neonatal sepsis

Create a differential for neonatal sepsisCreate a differential for neonatal sepsis

Describe the workup for neonatal sepsisDescribe the workup for neonatal sepsis

Know empiric treatment for neonatal sepsisKnow empiric treatment for neonatal sepsis

IntroductionIntroduction

Neonatal sepsis is a common Neonatal sepsis is a common cause of morbidity and mortalitycause of morbidity and mortality

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

DefinitionsDefinitions

Early Onset Sepsis (EOS):Early Onset Sepsis (EOS):– Culture proven infection within the first Culture proven infection within the first

72 hours of life72 hours of life

Late Onset Sepsis (LOS):Late Onset Sepsis (LOS):– Culture proven infection after 72 hours Culture proven infection after 72 hours

of lifeof life– Sepsis, UTI, pneumonia, meningitis, Sepsis, UTI, pneumonia, meningitis,

osteomyelitis, NECosteomyelitis, NEC

IncidenceIncidence

1-5 per 1000 live births1-5 per 1000 live births

Higher incidence of neonatal Higher incidence of neonatal sepsis in VLBWssepsis in VLBWs

Mortality rate is high (13-25%)Mortality rate is high (13-25%)

Etiology: EOSEtiology: EOS

Early Onset Sepsis (EOS):Early Onset Sepsis (EOS):– Group B Streptococcus (GBS)Group B Streptococcus (GBS)– E. ColiE. Coli– Listeria monocytogenesListeria monocytogenes– Streptococcus species ie. ViridansStreptococcus species ie. Viridans

Due to maternal or perinatal Due to maternal or perinatal factorsfactors

Etiology: LOSEtiology: LOS

Late Onset Sepsis (LOS):Late Onset Sepsis (LOS):– Coagulase-negative staphylococcusCoagulase-negative staphylococcus– Staphylococcus aureusStaphylococcus aureus– Gram negative bacilli ie. KlebsiellaGram negative bacilli ie. Klebsiella– Candida spp.Candida spp.

Nosocomial or focal infectionNosocomial 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 FactorsRisk Factors

PrematurityPrematurity Low birthweightLow birthweight ROM ROM >> 18 hours 18 hours Maternal peripartum fever or Maternal peripartum fever or

infectioninfection Resuscitation at birthResuscitation at birth Multiple gestationMultiple gestation Male sexMale sex

Clinical Signs and Clinical Signs and SymptomsSymptoms LethargyLethargy Hypo/hyperthermiaHypo/hyperthermia Feeding intoleranceFeeding intolerance JaundiceJaundice Abdominal distentionAbdominal distention VomitingVomiting ApneaApnea

Differential DiagnosisDifferential Diagnosis

RespiratoryRespiratory CardiacCardiac CNSCNS GIGI Inborn errors of metabolismInborn errors of metabolism HematologicHematologic

Sepsis Work-UpSepsis Work-Up

Blood cultures (x 2 due to low Blood cultures (x 2 due to low sensitivity)sensitivity)

Urine culturesUrine cultures

Lumbar punctureLumbar puncture

Tracheal aspiratesTracheal aspirates

CBC with differentialCBC with differential

Management : GBS Management : GBS ProphylaxisProphylaxis

All women screened at 35-37 weeksAll women screened at 35-37 weeks

Intrapartum antibiotics given to:Intrapartum antibiotics given to:– GBS bacteruria during pregnancyGBS bacteruria during pregnancy– GBS positive rectovaginal cultureGBS positive rectovaginal culture– Prior infant w/ EOS GBSPrior infant w/ EOS GBS– GBS unknown with risk factorsGBS unknown with risk factors

Temp Temp >> 100.4 100.4 GA GA << 37 weeks 37 weeks ROM ROM >>18 hours18 hours

Empiric Antibiotic Empiric Antibiotic TherapyTherapy EOSEOS

– Penicillin and AminoglycosidePenicillin and Aminoglycoside– Ampicillin and GentamicinAmpicillin and Gentamicin

LOSLOS– Vancomycin and AminoglycosideVancomycin and Aminoglycoside– Vancomycin and GentamicinVancomycin and Gentamicin

PrognosisPrognosis

Low birth weight and gram Low birth weight and gram negative infection are associated negative infection are associated with adverse outcomeswith adverse outcomes

Septic meningitis in preterm Septic meningitis in preterm infants may lead to neurological infants may lead to neurological disabilitiesdisabilities– May acquire hydrocephalus or May acquire hydrocephalus or

periventricular leukomalaciaperiventricular leukomalacia

Question # 1Question # 1

What is the major risk factor for What is the major risk factor for neonatal sepsis?neonatal sepsis?– A. Maternal GBS colonizationA. Maternal GBS colonization– B. Male sexB. Male sex– C. PrematurityC. Prematurity– D. ROM D. ROM >>18 hours18 hours– E. Low birthweightE. Low birthweight

Question # 1

What is the major risk factor for What is the major risk factor for neonatal sepsis?neonatal sepsis?– A. Maternal GBS colonizationA. Maternal GBS colonization– B. Male sexB. Male sex– C. PrematurityC. Prematurity– D. ROM D. ROM >>18 hours18 hours– E. Low birthweightE. Low birthweight

Question # 2Question # 2

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

Question # 2

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

Question # 3Question # 3

What is the gold standard for What is the gold standard for diagnosing neonatal sepsis?diagnosing neonatal sepsis?– A. Blood cultureA. Blood culture– B. Lumbar cultureB. Lumbar culture– C. CBCC. CBC– D. Chest X-rayD. Chest X-ray– E. CRPE. CRP

Question # 3

What is the gold standard for What is the gold standard for diagnosing neonatal sepsis?diagnosing neonatal sepsis?– A. Blood cultureA. Blood culture– B. Lumbar cultureB. Lumbar culture– C. CBCC. CBC– D. Chest X-rayD. Chest X-ray– E. CRPE. 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 aminoglycosideB. Clindamycin and a third-generation cephalosporinC. Meropenem and an aminoglycosideD. Piperacillin and an aminoglycosideE. Vancomycin and a third-generation cephalosporin

PREP Case # 1

Of the following, the MOST appropriate antibiotic regimen for this infant is

A. Ampicillin and an aminoglycosideB. Clindamycin and a third-generation cephalosporinC. Meropenem and an aminoglycosideD. Piperacillin and an aminoglycosideE. 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. ChorioamnionitisB. Diabetes mellitusC. Group B streptococcal colonizationD. PreeclampsiaE. 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. ChorioamnionitisB. Diabetes mellitusC. Group B streptococcal colonizationD. PreeclampsiaE. 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

ReferencesReferences

Fanaroff, A. A. & Martin, R. J. (Eds.). (2010). “Part Fanaroff, A. A. & Martin, R. J. (Eds.). (2010). “Part 2: Postnatal Bacterial Infections”. 2: Postnatal Bacterial Infections”. Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 9th ed.: October 2010; St. Louis: Mosby, St. Louis: Mosby, 2010; 793-806.2010; 793-806.

Gomella, TL, Cunningham, MD, Eyal FG, and Zenk Gomella, TL, Cunningham, MD, Eyal FG, and Zenk KE. Zenk. "Sepsis." Neonatology: management, KE. Zenk. "Sepsis." Neonatology: management, procedures, on-call problems, diseases, and procedures, on-call problems, diseases, and drugs. 6th ed. New York: Lange Medical drugs. 6th ed. New York: Lange Medical Books/McGraw-Hill Medical Pub. Division, 2009; Books/McGraw-Hill Medical Pub. Division, 2009; 665-672. 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-Pupulo KM. Epidemiology of Neonatal Early-onset Sepsis. onset Sepsis. NeoreviewsNeoreviews 2008; Volume 2008; Volume 9(12): e571-e578.9(12): e571-e578.

Centers for Disease Control and Prevention. Prevention of Perinatal Group B Streptococcal Disease. MMWR 2010; 59(RR-10): 1-32.