Newborn Management Chorioamnionitis

Labor & Delivery Spontaneous labor Epidural ROM of clear fluid for 3 hours prior to delivery 2 maternal temps of 100.4, no antibiotics Category 2 FHTs with variable decelerations SVD of female infant Apgars 6/8; required brief CPAP/30% oxygen for transition After delivery, maternal temp of 102.2 with shaking chills

Newborn management Infant admitted to Intermediate NICU for antibiotics (Ampicillin and Gentamicin) and monitoring VS: T 99.4, HR 188, RR 84, 61/39, 98% in RA HR and RR normal by 2 hours of age, no oxygen required PE: caput, mild tachypnea – no distress, well perfused. Cord blood culture drawn CBC at birth with WBC of 21,000 and I:T ratio of 0.27

Newborn management Infant became hypoglycemic to 22mg/dL despite nursing so was transferred to the NICU for IV fluids at ~8 hours. Cord blood culture grew E. coli at 10.5 hours. E coli resistant to Ampicillin, but sensitive to 3rd generation cephalosporins and aminoglycosides LP obtained on day 3 (after several unsuccessful attempts). RBC 1130, WBC 35, glucose 37 and protein 167 Culture & meningitis panel negative (after >72 hours antibiotics) Second blood culture remained negative. Infant treated with Cefotaxime for 21 days for presumed E coli meningitis due to pleocytosis.

Impact on the Neonate FIRS: Fetal inflammatory response syndrome Perinatal death Asphyxia Early-onset sepsis Pneumonia IVH Cerebral white matter damage Long term disability including CP 4 fold increase in near term/term Clinics in Perinatology. Tita, Alan T.N., MD, PhD; Andrews, William W., PhD, MD. Published May 31, 2010. Volume 37, Issue 2. Pages 339-354.

Current recommendations CDC AAP 2010 Guidelines for Prevention of Perinatal GBS disease If maternal chorioamnionitis (clinically diagnosed): Limited evaluation: blood culture at birth and CBC with diff at birth or 6-12 hours Antibiotic therapy – no guidance on duration 2012 Management of Neonates with Suspected or Proven EOS Clarified in 2014 If maternal chorioamnionitis: Blood culture at birth with CBC/diff +/- CRP at 6-12 hours Antibiotic therapy Blood culture negative: D/C antibiotics by 48-72 hours Blood culture positive: LP, continue antibiotics

Alternatives… Eunice Kennedy Shriver NICHD Chorioamnionitis Workshop Executive Summary Higgins. Chorioamnionitis Workshop Executive Summary. Obstet Gynecol 2016.

Neonatal sepsis calculator kp.org\eoscalc

What is “not well-appearing”? Clinical illness: Persistent need for NCPAP / HFNC / mechanical ventilation (outside of the delivery room) Hemodynamic instability requiring vasoactive drugs Neonatal encephalopathy /Perinatal depression Seizure Apgar Score @ 5 minutes < 5 Need for supplemental O2 > 2 hours to maintain oxygen saturations > 90% (outside of the delivery room) Equivocal: abnormality can be intermittent Persistent physiologic abnormality > 4 hrs Tachycardia (HR > 160) Tachypnea (RR > 60) Temperature instability (> 100.4˚F or < 97.5˚F) Respiratory distress (grunting, flaring, or retracting) not requiring supplemental O2 Two or more physiologic abnormalities lasting for > 2 hrs Well appearing: no persistent physiologic abnormalities .

Diagnostic tests Single blood culture of at least 1 ml Lumbar puncture Blood culture can be negative in up to 38% of infants with meningitis Indicated if positive blood culture, strongly suspect bacterial sepsis, clinical course worsens Tracheal aspirate immediately after intubation Not recommended: Urine culture Gastric aspirate Body surface cultures

Biomarkers Acute phase proteins Cell surface antigens CRP, procalcitonin Cell surface antigens CD64 expression increases with bacterial infection Cytokines & chemokines IL-6, TNFα, IL-1 Soluble adhesion molecules E-selectin, ICAM C- Reactive Protein

Treatment Most common pathogens are GBS and Escherichia coli Ampicillin 100mg/kg/dose Q 12h Gentamicin 4mg/kg/dose Q 24h This combination has synergistic activity against GBS and Listeria Together they cover most strains of E coli 3rd generation cephalosporins (Cefotaxime) can replace Gentamicin Increased risk resistance and invasive candidiasis Use for gram negative meningitis given excellent CSF penetration

Duration of antimicrobial therapy Evidence is limited! NICHD Executive Summary: “in most well-appearing neonates, there is no compelling evidence that antimicrobial agents need to be continued beyond 48 hours, especially when blood cultures are negative and irrespective of how “abnormal” lab data are…” AAP guidelines recommend against treatment of infants with sterile cultures for longer than 48-72 hours on basis of lab alone. What is the validity of blood cultures in neonates born to women who received broad spectrum antibiotics before delivery?

Consequences of current practice Increased number of neonates exposed to antimicrobial agents with potential toxicities Exposure to a NICU environment with increased risk of acquiring infections with multidrug resistant bacteria. Mother-baby separation interferes with bonding and successful breastfeeding Altered gut microbiome Fosters development of antibiotic resistant flora Painful procedures (IV(s), LP)