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Management of Neonatal Sepsis. Niki Kosmetatos, MD Anthony Piazza, MD J. Devn Cornish, MD Emory University Department of Pediatrics. Incidence. Mortality 13-69% world wide 13-15% of all neonatal deaths (US) Meningitis 0.4-2.8/1000 live births (US 0.2-0.4/1000)
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Management of Neonatal Sepsis Niki Kosmetatos, MD Anthony Piazza, MD J. Devn Cornish, MD Emory University Department of Pediatrics
Incidence • Mortality • 13-69% world wide • 13-15% of all neonatal deaths (US) • Meningitis • 0.4-2.8/1000 live births (US 0.2-0.4/1000) • Mortality 13-59%; US 4% of all neonatal deaths • Sepsis • 1-21/1000 world wide; US1-8/1000 live births • Culture proven 2/1000 (3-8% of infants evaluated for sepsis) • Prematures <1000 g 26/1000 1000 - 2000 g 8-9/1000
Predisposing Factors General Host Factors Prematurity Race – GBS sepsis blacks>whites Sex – sepsis & meningitis more common in males, esp. gram negative infections Birth asphyxia, meconium staining, stress Breaks in skin & mucous membrane integrity (e.g. omphalocoele, meningomyelocoele) Environmental exposure Procedures (e.g. lines, ET-tubes)
Predisposing Factors • Maternal/Obstetrical Factors • General– socioeconomic status, poor prenatal care, vaginal flora, maternal substance abuse, known exposures, prematurity, twins • Maternal infections –chorioamnionitis (1-10% of pregnancies), fever (>38° C/100.4° F), sustained fetal tachycardia, venereal diseases, UTI/bacteriuria, foul smelling lochia, GBS+, other infections • Obstetrical manipulation – amniocentesis, amnioinfusion, prolonged labor, fetal monitoring, digital exams, previa/abruption? • Premature & Prolonged ROM, preterm labor
Predisposing Factors Overall sepsis rate 8/1000 Maternal Fever 4/1000 PROM 10-13/1000 Fever & PROM 87/1000
Preterm Labor/PROM • Prematurity (~10%) 15-25% due to maternal infection • >18-24h term; >12-18h preterm • Bacterial infection • synthesis of PG • Macrophage TNF/IL stimulate PG synthesis, cytokine release** • Release of collagenase & elastase ROM • + Amniotic fluid cultures 15% (with intact membranes)
SEPSIS ORGANISMS • Group B strep (most common G+) • Coliforms(E. coli most common G-) • Listeria • Nosocomial infections • Staph epidermidis • Candida • Note: 50% G+ and 50% G-
Routes of Infection • Transplacental/Hematogenous • Ascending/Birth Canal • Nosocomial
Transplacental/Hematogenous • Organisms (Not just “TORCHS”) Syphilis Herpes* Toxoplasmosis Gonorrhea Rubella Mumps Cytomegalovirus TB Acute Viruses HIV Coxsackie Polio Adenovirus GBS Echo Malaria Enterovirus Lyme Varicella Parvovirus*
Ascending/Birth Canal • Organisms - GI/GU flora, Cervical/Blood E. Coli Herpes GBS Candida Chlamydia HIV UreaplasmaMycoplasma Listeria Hepatitis Enterococcus Anaerobes Gonorrhea Syphilis HPV
Nosocomial • Organisms – Skin Flora, Equipment/Environment Staphylococcus – Coagulaseneg & pos MRSA Klebsiella Pseudomonas/Proteus Enterobacter Serratia Rotavirus Clostridia – C dificile Fungi
Infection Timing • Onset • Early Onset 1st 24 hrs 85 % 24-48 hrs 5% • Late Onset 7-90 days
Symptoms • Non-specific/Common • Respiratory distress (90%) - RR, apnea (55%), hypoxia/vent need (36%), flaring/grunting • Temperature instability, feeding problems • Lethargy-irritability (23%) • Gastrointestinal – poor feeding, vomiting, abdominal distention, ileus, diarrhea • Color—Jaundice, pallor, mottling • Hypo- or hyperglycemia • Cardiovascular – Hypotension(5%), hypoperfusion, tachycardia • Metabolic acidosis NICHD data
Symptoms • Less common • Seizures • DIC • Petechiae • Hepatosplenomegaly • Sclerema • Meningitis symptoms • Irritability, lethargy, poorly responsive • Changes in muscle tone, etc.
Evaluation • Non-specific • CBC/diff, platelets – ANC, I/T ratio • Radiographs • CRP • Fluid analysis – LP, U/A • Glucose, lytes, gases • Specific – Cultures, stains • Other – immunoassays, PCR, DNA microarray
Results “Trigger Points” • CBC • WBC <5.0, abs neutro <1,750, bands >2.0 • I/T ratio > 0.2* • Platelets < 100,000 • CRP > 1.0 mg/dl • CSF > 20 WBC’s with few or no RBC’s • Radiographs: infiltrates on CXR, ileus on KUB, periosteal elevation, etc.
Treatment • Prevention – vaccines, GBS prophylaxis, HAND-WASHING • Supportive – respiratory, metabolic, thermal, nutrition, monitoring drug levels/toxicity • Specific – antimicrobials, immune globulins • Non-specific – IVIG, NO inhibitors & inflammatory mediators
GBS SEPSIS RISK FACTORS • Gestational age • Maternal well-being • Ruptured membranes > 18 hours • Location of delivery • Infant/Fetal symptomatology • Clinical suspicion
Mothers in labor or with ROM should be treated if: • Chorioamnionitis • History of previous GBS+ baby • Mother GBS+ or GBS-UTI this preg. • Mother’s GBS status unknown and: • < 37 wks gestation • ROM ≥ 18 hrs • Maternal temp ≥ 38o (100.4oF)
GBS SEPSIS INFANTS TO BE SCREENED • Maternal “chorioamnionitis” • Maternal illness (i.e. UTI, pneumonia) • Maternal peripartum fever > 38o(100.4oF) • Prolonged ROM ≥ 18 hrs (≥ 12 hrs preterm) • Mother GBS+ with inadequate treatment (< 4 hrs) • No screening necessary if C-section delivery with intact membranes
GBS SEPSIS INFANTS TO BE SCREENED • Prolonged labor (> 20 hrs) • Home or contaminated delivery • “Chocolate-colored”/foul smelling amniotic fluid • Persistent fetal tachycardia • SYMPTOMATIC INFANT • treat immediately (in DR if possible)
GBS SEPSIS SEPSIS SCREEN • CBC with differential • Platelet count • Blood culture x 1 (ideally 1 ml) • Chest X-ray &/or LP if symptomatic • Close observation and frequent clinical evaluation • Role of CRP
Algorithm for Neonate whose MotherReceivedIntrapartum Antibiotics Maternal Rx for GBS? Maternal antibiotics for suspected chorioamnionitis? Signs of neonatal sepsis? Full diagnostic evaluation * Empiric therapy++ Gestational age <35 weeks? Limited evaluation$ & Observe ≥ 48 hours If sepsis is suspected, full diagnostic evaluation and empiric therapy ++ Duration of IAP before delivery < 4 hours # No evaluation No therapy Observe ≥ 48 hours** YES YES YES NO NO * CBC, blood cx, & CXR if resp sx. If ill consider LP. ++ Duration of therapy may be 48 hrs if no sx. $ CBC with differential and blood culture # Applies only to penicillin, Ampicillin, or cefazolin. ** If healthy & ≥ 38 wks & mother got ≥ 4 hours IAP, may D/C at 24 hrs. NO
Careful Observation & Immediate Antibiotics Careful Observation pending review of screen • Symptomatic INFANT • Maternal intrapartum fever > 38.6o • “Chocolate” or foul smelling fluid • Ill mother • Fetal tachycardia • Home delivery • Maternal fever < 38.6o • PROM • Mat GBS with < 2 dose abx (-) Screen(+) Screen(-) Screen(+) Screen Cont abx until bld cx neg for 48o if asympt. Use clini-cal judgement for cessation of abx if pt is/was sympt d/c abx; careful obs and monit bld cx until d/c Careful obs and monit bld cx until d/c Initiate abx & cont until bl cx (-) for 48o. Clinical judgement for cessation of abx if pt sympt Blood Culture Positive Initiate, resume or continue abx therapy and treat for 7-10 days for gram pos organism or longer if gram neg organism cultured. LP may be performed at the discretion of attending, especially in seriously symptomatic pt
SEPSIS SIGNS and SYMPTOMS • temp instability • lethargy • poor feeding/residuals • resp distress • glucose instability • poor perfusion • hypotension • bloody stools • abdominal distention • bilious emesis • apnea • tachycardia • skin/joint findings
SEPSIS LABORATORY EVALUATION • Provide added value when results are normal • high negative predictive value • low positive predictive value • abnl results could be due to other reasons and not infection • IT < 0.3, ANC > 1,500 (normal) do not start abx, or d/c abx if started, if pt remains clinically stable • IT > 0.3, ANC < 1,500 consider initiation of abx pending bldcx in “at-risk” pt who was not already begun on antibiotics for other factors
SEPSIS LABORATORY EVALUATION • Positive screen • total WBC < 5,000 – I/T > 0.3 • ANC < 1,500 – platelets < 100,000 • Additional work-up • CXR, urine cx, and LP as clinically indicated • CRP • no added value for diagnosis of early onset sepsis • best for negativepredicativevalue or when used serially • not to be used to decide about rx, duration of rx or need for LP • positive results for a single value obtained at 24 hrs ranges > 4.0 - 10.0 mg/dL
SEPSIS TREATMENT • Review protocol • Antibiotics • Ampicillin 100 mg/kg/dose IV q 12 hours • Gentamicin 3.5 mg/kg/dose IV q 24 hours • IM route may be used in asymptomatic pt on whom abx are initiated for maternal risk factors or to avoid delays when there is difficulty obtaining IV • For meningitis: Ampicillin 200-300 mg/kg/d • Symptomatic management • respiratory, cardiovascular, fluid support
Prognosis • Fatality rate 2-4 times higher in LBW than in term neonates • Overall mortality rate 15-40% • Survival less likely if also granulocytopenic (I:T > 0.80 correlates with death and may justify granulocyte transfusion).