neonatal sepsis abbey rupe, md 7.24.2012. 2012 aap clinical report: – management of neonates with...
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Neonatal Sepsis
Abbey Rupe, MD7.24.2012
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• 2012 AAP Clinical Report:– Management of Neonates with Suspected or
Proven Early-Onset Bacterial Sepsis (May 2012)
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Epidemiology
• Overall incidence: 1-5/1000 live births• Term infants: 1-2/1000 live births
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Definitions
• Neonatal sepsis– Infant 28 days of life or younger– Systemic signs of infection– And/or isolation of bacterial pathogen from
bloodstream• Early-onset GBS disease– Birth to 6 days of age
– (some sources: birth to 72 hours)
• Late-onset GBS disease• Symptom onset at >72 hours or ≥ 7 days of age
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Transmission
• Early-onset– Vertical transmission• Ascending contaminated amniotic fluid
– after ROM or via occult tears in placenta
• During vaginal delivery from bacteria colonizing or infecting mother’s lower genital tract
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Transmission
• Late-onset sepsis– Vertical transmissionneonatal
colonizationlater infection OR – Horizontal transmission via direct contact w/ care
providers or environmental sources• Disruption of intact skin or mucosa increases risk of
late-onset sepsis
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Risk factors Early-onset sepsis
• Major risk factors:– Preterm birth– Maternal colonization w/ GBS– ROM > 18 hours– Maternal chorioamnionitis
• Other:– Ethnicity (black women higher rate of GBS colonization– Low SES– Male gender– Low Apgar scores
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Chorioamnionitis
• Risk factors:– Low parity– Spontaneous labor– Longer length of labor and membrane rupture– Multiple digital vaginal exams (esp w/ ruptured
membranes)– Meconium-stained amniotic fluid– Internal fetal or uterine monitoring– Presence of genital tract microorganisms
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Chorioamnionitis
• Definition:– Maternal fever (100.4 or higher), plus 2 of the
following:• Maternal leukocytosis (>15,000)• Maternal tachycardia (>100 bpm)• Fetal tachycardia (>160 bpm)• Uterine tenderness• Foul odor of amniotic fluid
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Infectious agents
• Early-onset:– GBS– E. coli • GBS and E. coli account for 2/3rds • GBS most-common cause in term newborns• E. coli most-common cause in preterm newborns
– Other: Klebsiella, Enterobacter, Listeria
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Infectious agents
• Late-onset:– GBS– E. coli– S. aureus (MSSA and MRSA)• Increasing in incidence• Typically associated with skin, bone, or joint infections
– Other: Klebsiella, Enterobacter, Listeria
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GBS
• 2002: CDC recommendation of universal, culture-based screening with intrapartum antibiotic prophylaxis (IAP) for GBS + women– 80% decrease in early-onset GBS infection– No change in late-onset disease
• Guidelines updated in 2010
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GBS—indications for IAP
• Mother GBS+ within preceding 5 weeks• GBS status unknown and ≥ 1 risk factor
present:– < 37 WGA– ROM ≥ 18 hours– Maternal temp of ≥100.4
• GBS bacteriuria during current pregnancy• Hx of previous infant with GBS disease
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IAP
• Penicillin—drug of choice– Ampicillin is acceptable alternative
• PCN-allergic women at low-risk of anaphylaxis (no hx of anaphylaxis, angioedema, respiratory distress, or urticaria after PCN or cephalosportin administration)
– Cefazolin
• PCN-allergic women at high-risk of anaphylaxis– Clindamycin (if tested and susceptible)– Vancomycin
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IAP
• “Adequate IAP”– PCN, Ampicillin, or cefazolin– First dose administered at least 4 hours prior to
delivery• All three reach high intra-amniotic concentrations
within 3 hours of administration
– “All other antibiotics, doses, or durations are considered inadequate for the purposes of neonatal management”
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Clinical manifestations
• Fetal/delivery room distress– Fetal tachycardia– Meconium-stained amniotic fluid• 2-fold increase for sepsis in infants who did not receive
IAP
– Low Apgar • One case-control study: infants with 5-minute Apgar of
≤6 had a 36-fold higher likelihood of sepsis compared to those with Apgar of 7 or higher
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Clinical manifestations
• Fever (> 50%)• Respiratory distress• Poor feeding• Vomiting• Jaundice• Hepatomegaly• Lethargy• Other: cyanosis, hypothermia, irritability, apnea,
abdominal distention, diarrhea
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Differential Diagnosis
• Other infections– HSV, CMV, syphilis
• Pulm:– TTN, RDS
• CV:– Cyanotic congenital heart disease
• Endo:– Inborn errors of metabolism
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Evaluation
• Blood culture– x1– Need at least 1 ml– Sensitivity to detect bacteremia approx 90%– Common pathogens:• 97% positive by 24 hours• 99% positive by 36 hours
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Evaluation
• CBC with diff– WBC:• Preferable to obtain at 6-12 hours of age
– More likely to be abnormal than if obtained at birth
• I/T ratio:– Poor predictive accuracy, but very high negative predictive
accuracy (99%)
– Platelet count• often low in infected infants• Nonspecific, low sensitivity
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Evaluation
• Acute-Phase Reactants– CRP• Increases within 6-8 hrs of infections episode and peaks
at 24 hours• Sensitivity improves if first determined at 6-12 hours of
age• If obtain 2 normal values (first between 8-24 hours of
age, second 24 hours later), negative predictive accuracy of 99.7%– Could use to stop abx; data insufficient on how elevated
(>1.0) CRP values should affect duration of abx therapy
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Evaluation
• Acute-Phase Reactants:– Procalcitonin• Levels increase within 2 hours of infectious episode,
peak at 12 hours, and normalize within 2-3 days (adult studies)• Slightly more sensitive than CRP, but less specific• Not routinely available in hospital labs
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Evaluation
• Lumbar puncture– When???? Controversial• High-risk, healthy-appearing infant, likelihood of
meningitis is “extremely low”• Infant with clinical signs attributable to a noninfectious
condition (such as RDS), likelihood of meningitis low• Among bacteremic infants: incidence of meningitis as
high as 23%
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Evaluation
• LP:– Perform in:• Infant w/ positive blood culture• Infant whose clinical course or lab data strongly
suggest bacterial sepsis• Infants who initially worsen with antimicrobial therapy
– Threshold to tap gets lower as # of risk factors goes up– Critically ill or likely to have cardiovascular and/or
respiratory compromise during the procedure, can defer until more stable (but don’t delay abx)
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Evaluation
• LP– Send CSF for:• Gram stain• Culture• Cell count with diff• Protein• Glucose• other
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Evaluation
• Urine culture– Not recommended in infant with suspected early-
onset sepsis• UTIs in neonates are due to seeding of kidney during
episode of bacteremia (not ascending infection, as in older infants)
– Include in workup of any infant with suspected late-onset sepsis
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Evaluation
• CXR– Obtain in infant with respiratory distress
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Treatment (early-onset)
• Ampicillin and Gentamicin– Ampicillin: 75-150 mg/kg/day divided q8– Gentamicin: 4 mg/kg/day div q24
• Alternate regimen: Amp + 3rd gen ceph (cefotaxime)– Not more effective– High risk for emergence of ceph-resistant strains
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Treatment
• Duration of abx:– Culture-proven sepsis: 10 days– Meningitis: 14-21 days– Automated blood culture systems ID 97% of pathogens at
24 hours and 99% at 36 hours• Can discontinue empiric abx in well-appearing infant after 48 hours
– Negative culture, but high clinical suspicion for systemic infection • Continue abx until another dx explains the situation OR to complete
10-day course• IAP could cause-negative culture
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Treatment (late-onset)7-28 day old infant
• Re-admitted infant– Amp + gent OR amp + cefotaxime
• Infant hospitalized since birth– Add vanc
• HSV suspected– “ill-appearance,” mucocutaneous vesicles, seizures, or CSF pleocytosis
• S. aureus suspected (soft tissue, skin, joint, or bone involvement)• Vanc + nafcillin + gent
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Outcome
• GBS: overall 5-10% fatality rate– Term infants:
• Early-onset: 2-3%• Late-onset: 1-2 %
• E. coli: overall mortality rate 4-16% (higher in preterm infants)
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Neonatal management
• Infant with signs of sepsis
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Neonatal management
• Infant with signs of sepsis– Full diagnostic evaluation• Blood culture• CBC• CXR if indicated• LP
– Antibiotic therapy
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Neonatal management
• Well-appearing term infant• mother diagnosed with chorioamnionitis
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Neonatal management
• Well-appearing term infant• mother diagnosed with chorioamnionitis– “Limited evaluation”• Blood culture at birth• CBC with diff at birth and/or 6-12 hours of life• NO lumbar puncture
– Antibiotic therapy
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Neonatal management
• Well-appearing term infant• mom GBS negative
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Neonatal management
• Well-appearing term infant• mom GBS negative– Routine clinical care
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Neonatal management
• Well-appearing term infant• mom GBS +• received ampicillin, PCN, or cefazolin ≥4 hours prior
to delivery
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Neonatal management
• Well-appearing term infant• mom GBS +• received ampicillin, PCN, or cefazolin ≥4 hours prior
to delivery (“Adequate IAP”)– Observation for ≥ 48 hours
• **If other discharge criteria are met, could discharge at 24 hours IF– Ready access to medical care– Person able to fully comply with instructions for home observation will be
present
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Neonatal management
• Term, well-appearing infant• Mom GBS +• Mom PCN-allergic and received Vanc• ROM < 18 hours
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Neonatal management
• Term, well-appearing infant• Mom GBS +• Mom PCN-allergic and received Vanc• ROM < 18 hours– Observation for ≥48 hours
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Neonatal management
• Term, well-appearing infant• Mom GBS +• Received 1 dose of ampicillin 2 hours before
delivery• ROM < 18 hours
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Neonatal management
• Term, well-appearing infant• Mom GBS +• Received 1 dose of ampicillin 2 hours before
delivery• ROM < 18 hours– Observation for ≥48 hours
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Neonatal management
• Term, well-appearing infant• Mom GBS +• Received inadequate IAP• ROM ≥18 hours
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Neonatal management
• Term, well-appearing infant• Mom GBS +• Received inadequate IAP• ROM ≥18 hours– “Limited evaluation”• Blood culture at birth• CBC with diff at birth and/or 6-12 hours of life
– Observation for ≥48 hours
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Neonatal management
• Well appearing near-term infant• Mom received inadequate IAP– “Limited evaluation”• Blood culture at birth• CBC with diff at birth and/or 6-12 hours of life
– Observation for ≥48 hours
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Neonatal management
• Term newborn• Tachypneic, no O2 requirement• Mom GBS+, received appropriate IAP
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Neonatal management
• Term newborn• Tachypneic, no O2 requirement• Mom GBS+, received appropriate IAP– DDx: TTN, pneumonia, sepsis– If clinically improving over first 6 hours of life, it is
“reasonable” to withhold antibiotics and monitor closely• If worsens, obtain blood culture, CBC, and start abx