Neonatal sepsis is a type of neonatal infection and specifically refers to the presence in a newborn baby of a bacterial blood stream infection (BSI) (such as meningitis, pneumonia, pyelonephritis, or gastroenteritis) in the setting of fever. Older textbooks may refer to neonatal sepsis as "sepsis neonatorum". Criteria with regards to hemodynamic compromise or respiratory failure are not useful clinically because these symptoms often do not arise in neonates until death is imminent and unpreventable. Neonatal sepsis is divided into two categories: early-onset sepsis (EOS) and late-onset sepsis (LOS). EOS refers to sepsis presenting in the first 7 days of life (although some refer to EOS as within the first 72 hours of life), with LOS referring to presentation of sepsis after 7 days (or 72 hours, depending on the system used). Neonatal sepsis is the single most common cause of neonatal death in hospital as well as community in developing country.
It is difficult to clinically exclude sepsis in newborns less than 90 days old that have fever (defined as a temperature > 38 °C (100.4 °F). Except in the case of obvious acute viral bronchiolitis, the current practice in newborns less than 30 days old is to perform a complete workup including complete blood count with differential, blood culture, urinalysis, urine culture, and cerebrospinal fluid (CSF) studies and CSF culture, admit the newborn to the hospital, and treat empirically for serious bacterial infection for at least 48 hours until cultures are demonstrated to show no growth. Attempts have been made to see whether it is possible to risk stratify newborns in order to decide if a newborn can be safely monitored at home without treatment despite having a fever. One such attempt is the Rochester criteria.
Signs and symptoms
The signs of sepsis are non-specific and include:
- Body temperature changes
- Breathing problems
- Low blood sugar (hypoglycemia)
- Reduced movements
- Reduced sucking
- Swollen belly area
- Yellow skin and whites of the eyes (jaundice).
- hemorrhagic rash
A heart rate above 160 can also be an indicator of sepsis, this tachycardia can present up to 24 hours before the onset of other signs.
- generally well-appearing
- previously healthy
- full term (at ≥37 weeks gestation)
- no antibiotics perinatally
- no unexplained hyperbilirubinemia that required treatment
- no antibiotics since discharge
- no hospitalizations
- no chronic illness
- discharged at the same time or before the mother
- no evidence of skin, soft tissue, bone, joint, or ear infection
- White blood cells (WBCs) count 5,000-15,000/mm3
- absolute band count ≤ 1,500/mm3
- urine WBC count ≤ 10 per high power field (hpf)
- stool WBC count ≤ 5 per high power field (hpf) only in infants with diarrhea
Those meeting these criteria likely do not require a lumbar puncture, and are felt to be safe for discharge home without antibiotic treatment, or with a single dose of intramuscular antibiotics, but will still require close outpatient follow-up.
One risk for Group B streptococcal infection (GBS) is Preterm rupture of membranes. Screening women for GBS (via vaginal and rectal swabbing) and treating culture positive women with intrapartum chemoprophylaxis is reducing the number of neonatal sepsis caused by GBS.
Neonatal sepsis screening:
- DLC (differential leukocyte count) showing increased numbers of polymorphs.
- DLC: band cells > 20%.
- increased haptoglobins.
- micro ESR (Erythrocyte Sedimentation Rate) titer > 15mm.
- gastric aspirate showing > 5 polymorphs per high power field.
- newborn CSF (Cerebrospinal fluid) screen: showing increased cells and proteins.
- suggestive history of chorioamnionitis, PROM (Premature rupture of membranes), etc...
Culturing for microorganisms from a sample of CSF, blood or urine, is the gold standard test for definitive diagnosis of neonatal sepsis. This can give false negatives due to the low sensitivity of culture methods and because of concomitant antibiotic therapy. Lumbar punctures should be done when possible as 10-15% presenting with sepsis also have meningitis, which warrants an antibiotic with a high CSF penetration.
CRP is not very accurate in picking up cases.
Note that, in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is imminent, so, if there is even a remote suspicion of sepsis, they are frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative. In addition to fluid resuscitation and supportive care, a common antibiotic regimen in infants with suspected sepsis is a beta-lactam antibiotic (usually ampicillin) in combination with an aminoglycoside (usually gentamicin) or a third-generation cephalosporin (usually cefotaxime—ceftriaxone is generally avoided in neonates due to the theoretical risk of kernicterus.) The organisms which are targeted are species that predominate in the female genitourinary tract and to which neonates are especially vulnerable to, specifically Group B Streptococcus, Escherichia coli, and Listeria monocytogenes (This is the main rationale for using ampicillin versus other beta-lactams.) Of course, neonates are also vulnerable to other common pathogens that can cause meningitis and bacteremia such as Streptococcus pneumoniae and Neisseria meningitidis. Although uncommon, if anaerobic species are suspected (such as in cases where necrotizing enterocolitis or intestinal perforation is a concern, clindamycin is often added.
Granulocyte-macrophage colony stimulating factor (GM-CSF) is sometimes used in neonatal sepsis. However, a 2009 study found that GM-CSF corrects neutropenia if present but it has no effect on reducing sepsis or improving survival.
Trials of probiotics for prevention of neonatal sepsis have generally been too small and statistically underpowered to detect any benefit, but a randomized controlled trial that enrolled 4,556 neonates in India reported that probiotics significantly reduced the risk of developing sepsis. The probiotic used in the trial was Lactobacillus plantarum.
A very large meta-analysis investigated the effect of probiotics on preventing late-onset sepsis (LOS) in neonates. Probiotics were found to reduce the risk of LOS, but only in babies who were fed human milk exclusively. It is difficult to distinguish if the prevention was a result of the probiotic supplementation or if it was a result of the properties of human milk. It is also still unclear if probiotic administration reduces LOS risk in extremely low birth weight infants due to the limited number of studies that investigated it. Out of the 37 studies included in this systematic review, none indicated any safety problems related to the probiotics. It would be beneficial to clarify the relationship between probiotic supplementation and human milk for future studies in order to prevent late onset sepsis in neonates.
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