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Neonatal Sepsis. Steve Spencer, MD. Objectives. Review of terminologies associated with neonatal infections Review risk factors for neonatal infections Review presentations of neonatal sepsis Review most common organisms and treatments We will concentrate on the child <3 months of age.
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Neonatal Sepsis Steve Spencer, MD
Objectives • Review of terminologies associated with neonatal infections • Review risk factors for neonatal infections • Review presentations of neonatal sepsis • Review most common organisms and treatments • We will concentrate on the child <3 months of age
Cases • You are on-call tonight when the ER calls with two kids
Kid 1 9 week old, term baby 100.6 temp Looks well CBC WNL UA clean Everyone at home with colds Kid 2 12 day old, term baby Fever to 101 Jaundiced Seizures WBC of 3.2 K PLT of 89 Cases Do you treat these kids the same or different and why?
Terminologies • Rule out sepsis • Neonate with fever • Neonatal fever • Neonatal sepsis • Serious Bacterial Infection (SBI) • Occult Bacteremia • Neonate- the first month 28days of life • Infant- up to one year
Back When I was an Intern….. • Any kid 3 months or less with fever got admitted • Kids stayed longer • If it sneezed, writhed, wiggled or wheezed, it got an LP • Kids had to crawl seven miles through the snow, up hill both ways, to daycare…..
Age Groups • Currently ages 0-28 days automatically admitted by most clinicians • 1-3 months is a grey zone guided by clinical opinion • Greater than three months generally not admitted
Why Have Recommendations Changed? • GBS prophylaxis • Immunizations • HIB, Pneumococcus • Better understanding of neonatal physiology • Better laboratory techniques • Better understanding of the disease • Different antibiotics
Definition of Fever • “Gold Standard” is generally thought of as 100.4 (38.0) rectally with a glass mercury thermometer • Lots of ways to take a baby’s temperature • I recommend using a quality thermometer • When in doubt, let the pros sort it out • In Newborn Nursery, need to counsel parents about significance of fever in neonate
Why the Worry? • Neonatal immune system immature • Perinatal exposure to pathogens via birth canal • High rate of infection in kids less than 3 months with fevers • >4% age 0-28 days with bacteremia or meningitis (drops to 1% by 3 months) • Almost 10% with UTI • Rates increase with degree of fever • 39C with >10% rate of bacteremia • Well appearing infant may have an infection
Why not admit everybody? • Not without risk of hospital acquired infection • Cost • Lost time to parents at work • Family stress • etc
What data supports our practice? • Rochester criteria • Philadelphia criteria • Boston criteria • Etc
Risk Factors • Prematurity and low birth weight • Maternal GBS • Prolonged rupture of membranes • Maternal chorioamnionitis • Sibling with sepsis • Meconium at delivery • Need for resuscitation • Male child • Multiple gestation
“Early” Pathogens (first week) • Group B Strep (GBS) • Incidence used to be 4-6/1000 live births (0.4%) • Now <0.1% after prenatal screening guidelines • E. coli • Every few decades flips back and forth with GBS as most common cause • Gram negative rods (esp. in urine) • Occasional Salmonella sepsis • Listeria monocytogenes • Herpes Simplex • Enterovirus
“Late” Pathogens (~1-2 weeks) • GBS or group A strep • Enterics/Enterococcus in urine • HSV • Enterovirus, RSV, Flu
Community Acquired (after 4-6 weeks) • Pneumococcus • Meningococcus • GABHS • Haemophilus influenzae (HIB) not really a problem anymore
Temperature irregularity Fever Hypothermia Tone and Behavior Poor tone Weak suck Shrill cry Weak cry Irritability Skin Poor perfusion Cyanosis Mottling Pallor Petechiae Unexplained jaundice Signs/Symptoms Most by themselves mean little, but three (or two) strikes and you are Out!
Feeding Problems Vomiting Diarrhea Abdominal distension Hypo or Hyperglycemia Cardiopulmonary Tachypnea Retractions Tachycardia for age Bradycardia in first few days of life Hypotension for age Low PO2 Signs/Symptoms
Signs/Symptoms • Sunken fontanelle • Bulging or pulsating fontanelle • Neck stiffness CAN NOT be used • Babies can be bacteremic but look well • Presence of a “cold” does not change anything
Study in India found that any two of these signs had an almost 100% sensitivity for sepsis and over 90% mortality Reduced sucking Weak cry Cool extremities Vomiting Poor tone Retractions PIDJ April 2005
Labs • Normal WBC (5-15K) is better than high WBC is better than very high WBC (over 35K) which is better than very low WBC (<5K) • Less than 28 days- blood, urine, CSF cultures +/- stool • Get urine culture, even if UA WNL • >28 days see handout • CXR if respiratory symptoms
Lab Dilemmas- Urine collection • Don’t use bag urines! • A negative culture on a bag urine is negative • A positive means nothing • Cath or Suprapubic aspirate? • SPA- any growth is considered a positive • Cath • Can have false positives, especially if uncirc’d male • New debates on what constitutes a positive culture • Most references use >10K CFU’s as positive, some use as little as 1K (equals one plaque) • Microbiologists feel we should use 100K on all samples regardless of source
The Bloody Tap • Don’t ask me, you should have gotten it right the first time
The Bloody Tap • No right answer • Results can vary based on the amount of blood in amount of CSF, what is the HCT, what is the peripheral WBC count etc. Some use CBC to CSF ratios. • Sometimes seems like too many WBC’s or seems OK • Sometimes just need to re-tap
Treatment • Age 0 to ~4-6 weeks • Ampicillin/Aminoglycoside • Ampicillin/Cefotaxime • Amp kills GBS and Listeria • Gent and Cefotaxime for GNR’s • Ceftriaxone not used- causes neonatal hepatitis and biliary sludging
Disadvantages Ototoxicity Nephrotoxicity Need for levels Advantages Little resistance Cheap (30 cents or so a dose) Highly concentrated in urine No need for levels if QD dosing in a 48 hour admission Aminoglycosides
Treatment • After 4-6 weeks, ampicillin and a 3rd generation cephalosporin • Offers better coverage for community acquired organisms • At 4-8 weeks, switch to cephalosporin alone.
What About Herpes? • Some clinicians begin acyclovir on all neonatal admissions for fever • We use the guideline of “Fever Plus” • HSV is rare & tends to present in certain ways • Fever in addition to • Hepatitis/jaundice • Meningitis • Seizures • Thrombocytopenia • Vesicles • Rash/purpera
HSV Risk Factors • Maternal history- only present in • Maternal primary infection- as many as 50% of babies infected • Active lesions • ROM > 4-6 hours • Fetal scalp electrode • Prematurity • Caregiver with cold sore/fever blister
HSV in Neonate • Three types • SEM (Skin, Eye, Mucous membranes)- 15% • Isolated CNS- 35% • Disseminated (+/- CNS)- 50% • 75% HSV-2 25% HSV-1 • Incidence 1:1K-5K births
HSV timing • SEM (Skin, Eye, Mucous membranes)- can be early • Isolated CNS- 2-3 weeks • Disseminated (+/- CNS, +/-SEM)- ~1 week
HSV Labs- three points • CSF PCR alone DOES NOT rule out HSV • CSF PCR alone DOES NOT rule out HSV • CSF PCR alone DOES NOT rule out HSV
HSV Labs- if do it, do it right • CSF for PCR (>98% sensitive, >95% specific) and/or culture (30-50%) • CSF tends to be “bloody”– 100-200 RBC with elevated WBC • Mucous membrane cultures • Eyes, ears, anus, mouth, nose, vesicles if present, some add urine • In nursery, wait 24 hours after birth to culture (indicates active infection)
HSV Labs cont. • LFT’s • I now get for any R/O SBI kid that I am worried enough about to get a BMP • Serial CBC’s • Thrombocytopenia • Leukopenia • Tzank smear of lesions(~40% sensitive, not specific) • DFA or EIA of lesions (80% sensitive) • Serology NOT useful
Imaging • Classic CT/MRI - temporal lobe lesion but may have many presentations to include hydrocephalus
HSV treatment • Acyclovir 20mg/kg/dose Q8 hrs • SEM only- 14 days • Disseminated (no CNS)- 21 days • CNS- at least 21 days (PCR must clear)
Kid 1 9 week old, term baby 100.6 temp Looks well CBC WNL UA clean Everyone at home with colds Kid 2 12 day old, term baby Fever to 101 Jaundiced Seizures WBC of 3.2 K PLT of 89 Cases