Maternal and Neonatal Sepsis Allana Oak, D.O. & John Morrison, M.D. Kentucky Perinatal Association June 5, 2017

Objectives Describe maternal and newborn sepsis risk factors and pathogens Review signs and symptoms, antibiotic coverage and optimal treatment of sepsis.

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Maternal Sepsis 3rd most common direct cause of maternal mortality Global Maternal and Neonatal Sepsis Initiative

WHO definition of Maternal Sepsis Maternal sepsis is a life threatening condition defined as organ dysfunction resulting from infection during pregnancy, childbirth, post-abortion or postpartum period

Maternal Sepsis More prevalent in developing nations (HIV, malaria, lack of access to care) In US usually due to puerperal sepsis and UTI Pyelonephritis Chorioamnionitis Septic Abortion Pneumonia

Chorioamnionitis Intra-Amniotic Infection (IAI) Intraamniotic Infection or Inflammation (Triple I) Amniotic Fluid Fetus Umbilical Cord Placenta Fetal membranes

Pathogenesis - IAI Migration of cervical flora Hematogenous spread Invasive procedure Infection from peritoneum via Fallopian tube

Incidence of IAI Varies widely across US Multifactorial (study type, diagnostic criteria used) Increased in preterm infants (5-10%) Decreases as patient approaches term (1-4%) 7% with PROM 12% primary Cesarean delivery 20% > 8 digital vaginal exams

Risk Factors – Maternal Sepsis Longer labor Length of ROM Multiple digital vaginal exams Cervical insufficiency Nulliparity MSAF Internal fetal or uterine monitoring Presence of genital tract infections/pathogens ETOH and tobacco abuse Previous IAI

Microbiology - IAI POLYMICROBIAL Genital mycoplasms Anaerobes Ureaplasma Mycoplasma Anaerobes Garnderella vaginalis preterm Enteric Gram negative bacilli Group B Streptococcus

Clinical Findings - IAI Fever (100%) Maternal leukocytosis ( WBC > 15,000; 70-90%) Maternal tachycardia ( > 100/min; 50-80%) Fetal tachycardia (> 160/min; 40-70%) Uterine tenderness (4-25%) Bacteremia (5-10%) Group B strep E. Coli Purulent or malodorous amniotic fluid IAI may be subclinical – preterm labor, PPROM

Maternal Sequelae - IAI Dysfunctional labor Dysfunctional myometrial contractility due to inflammation Increase risk of Cesarean Uterine atony – postpartum hemorrhage – transfusion Localized infection Wound infection Endomyometritis Septic pelvic thrombophlebitis Pelvic abscess

Sepsis - IAI 18% of maternal sepsis due to IAI Coagulopathy Adult Respiratory Distress Syndrome Multisystem organ failure Elevated lactic acid associated with adverse outcomes Good news! Morbidity/mortality low if broad spectrum antibiotics initiated

Differential Diagnosis Most s/s nonspecific Maternal tachycardia – infection or pain? Maternal fever – infection or epidural? Maternal leukocytosis – infection? Labor? Steroids? Fetal tachycardia – infection? Hypoxemia? Maternal fever?

Differential Diagnosis Labor Fever, maternal tachycardia, leukocytosis, uterine tenderness Placental abruption Uterine tenderness, maternal tachycardia Usually have vaginal bleeding, absence of fever Other infections Pyelonephritis, influenza, appendicitis, pneumonia Maternal tachycardia, fever, fetal tachycardia

Diagnostic Criteria - Presumptive Fever >102.2 >100.4 two occasions, 30 min apart PLUS Fetal tachycardia >160/min for > 10 min Maternal WBC >15,000, bandemia Purulent fluid Cervical os, spec exam

Diagnostic Criteria - Confirmed Positive Gram stain of amniotic fluid Low glucose level in amniotic fluid Positive amniotic fluid culture High WBC in amniotic fluid In the absence of a bloody tap Histopathologic evidence Infection inflammation

Amniotic Fluid Analysis Gold standard is culture Most specific Disadvantage – days to get results Gram stain 6 WBCs/hpf Glucose concentration < 14 mg/dl WBC concentration >30 cells/mm3 Leukocyte esterase activity Chemstrip 9

Amniocentesis - IAI Preterm labor eval Initial tests with 67% false positive rate Proceed with caution if acting prior to culture results Traumatic tap

Future tests...... Interleukin – 6 (IL-6) Proteomic biomarkers Cervicovaginal fluid Predictive of microbial invasion of amniotic cavity Preterm labor and intact membranes Proteomic biomarkers Amniotic fluid Maternal serum C – reactive protein Not useful for prediction of IAI

Maternal Management Antibiotics Delivery

Delivery! Delivery is the cure! Induction of Labor Cesarean if indiciated Wound infection Endomyometritis Venous thrombosis

Broad Spectrum Antibiotics Vaginal delivery Ampicillin 2g IV every 6 hours PLUS Gentamicin 5mg/kg once daily Amp/Sulbactam 3g every 6 hours Ticarcillin-clavulanate 3.1 g every 4 hours Cefoxitin 2g every 6 hours

Broad Spectrum Antibiotics Cesarean delivery Add anaerobic coverage Ampicillin 2g every 6 hours PLUS Gentamicin 5 mg/kg once daily PLUS Clindamycin 900mg or metronidazole 500mg Amp/Sulbactam 3g every 6 hours Ticarcillin-clavulanate 3.1 g every 4 hours Cefoxitin 2g every 6 hours PLUS

Antibiotics - IAI Penicillin – allergic patients Vancomycin 1g IV every 12 hours Group B Streptococcus carriers Already receiving intrapartum Pen G Need to broaden coverage in presence of IAI Duration of therapy unclear Intrapartum plus one additional postpartum dose? Afebrile and symptomatic x 24 hours? No oral antibiotics after parenteral therapy

Intrapartum Management - IAI Fetal monitoring Antipyretics Maternal fever and fetal acidosis = 12.5% risk of neonatal encephalopathy Reduces fetal tachycardia Reduces need for Cesarean Postpartum care

Fetal and Neonatal Outcome Adverse effects of IAI Perinatal death, asphyxia, early-onset neonatal sepsis, septic shock, pneumonia, meninigitis, IVH, cerebral white matter damage, long term disability i.e. Cerebral palsy, pretem birth morbidity/mortality 40% cases of early- onset neonatal sepsis Get ready Dr. Morrision......

Prevention - IAI Educate L&D staff on signs and symptoms of IAI Prompt administration of broad spectrum antibiotics Modifiable risk factors Conduct of labor Minimize # of vaginal exams Screen and treat for GBS Prenatal counseling Discussion of PROM Substance abuse counseling

Conclusion Intra-amniotic infection refers to infection of the amniotic fluid, membranes, placenta, umbilical cord and/or decidua IAI is polymicrobial Presumptive diagnosis Maternal fever plus, FHR, maternal WBC, purulent fluid Confirmed diagnosis Amniotic fluid analysis and culture; histopath May result in labor abnormalities Dysfunctional labor Postpartum hemorrhage Broad spectrum antibiotics Delivery is the cure!

Questions?

Neonatal Sepsis Take it away Dr. Morrison!!!