Neonatal Sepsis

Abbey Rupe, MD7.24.2012

• 2012 AAP Clinical Report:– Management of Neonates with Suspected or

Proven Early-Onset Bacterial Sepsis (May 2012)

Epidemiology

• Overall incidence: 1-5/1000 live births• Term infants: 1-2/1000 live births

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

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

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

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

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

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

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

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

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

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

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

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”

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

Clinical manifestations

• Fever (> 50%)• Respiratory distress• Poor feeding• Vomiting• Jaundice• Hepatomegaly• Lethargy• Other: cyanosis, hypothermia, irritability, apnea,

abdominal distention, diarrhea

Differential Diagnosis

• Other infections– HSV, CMV, syphilis

• Pulm:– TTN, RDS

• CV:– Cyanotic congenital heart disease

• Endo:– Inborn errors of metabolism

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

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

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

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

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%

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)

Evaluation

• LP– Send CSF for:• Gram stain• Culture• Cell count with diff• Protein• Glucose• other

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

Evaluation

• CXR– Obtain in infant with respiratory distress

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

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

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

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)

Neonatal management

• Infant with signs of sepsis

Neonatal management

• Infant with signs of sepsis– Full diagnostic evaluation• Blood culture• CBC• CXR if indicated• LP

– Antibiotic therapy

Neonatal management

• Well-appearing term infant• mother diagnosed with chorioamnionitis

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

Neonatal management

• Well-appearing term infant• mom GBS negative

Neonatal management

• Well-appearing term infant• mom GBS negative– Routine clinical care

Neonatal management

• Well-appearing term infant• mom GBS +• received ampicillin, PCN, or cefazolin ≥4 hours prior

to delivery

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

Neonatal management

• Term, well-appearing infant• Mom GBS +• Mom PCN-allergic and received Vanc• ROM < 18 hours

Neonatal management

• Term, well-appearing infant• Mom GBS +• Mom PCN-allergic and received Vanc• ROM < 18 hours– Observation for ≥48 hours

Neonatal management

• Term, well-appearing infant• Mom GBS +• Received 1 dose of ampicillin 2 hours before

delivery• ROM < 18 hours

Neonatal management

• Term, well-appearing infant• Mom GBS +• Received 1 dose of ampicillin 2 hours before

delivery• ROM < 18 hours– Observation for ≥48 hours

Neonatal management

• Term, well-appearing infant• Mom GBS +• Received inadequate IAP• ROM ≥18 hours

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

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

Neonatal management

• Term newborn• Tachypneic, no O2 requirement• Mom GBS+, received appropriate IAP

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