Neonatal Sepsis: Early and Late Onset

Neonatal Sepsis

• The neonatal period poses the highest risk for acquiring severe invasive bacterial infections in childhood.
• Neonatal infections are categorized as early-onset and late-onset sepsis during the first few weeks of life.
• Early-onset sepsis (within 72 hours after birth) occurs due to vertical exposure from ascending infection or exposure to high bacterial load during birth, especially after membrane rupture.
• Common organisms causing early-onset sepsis include group B streptococcus and Gram-negative organisms like E. coli, Klebsiella, and Pseudomonas; Listeria monocytogenes is a rare cause.
• Late-onset infection (after 72 hours of birth) usually originates from the infant's environment, particularly the hospital, suggesting it could be preventable.
• Coagulase-negative staphylococcus (CONS) is the most common pathogen in late-onset infections, but a broad range of organisms is possible.
• Gram-positive bacteria in late-onset infections include Staphylococcus aureus and Enterococcus fecalis.
• Gram-negative bacteria in late-onset infections include Escherichia coli, Pseudomonas, Klebsiella, and Serratia species.

Neonatal Sepsis - Risk factors

• Prematurity, especially when coupled with prolonged rupture of membranes and preterm
• Prolonged rupture of membranes (over 18 hours) or prelabor rupture of membranes.
• Intrapartum fever exceeding 38°C or chorioamnionitis
• Previous child with GBS infection
• Group B Streptococcus bacteriuria during pregnancy.
• Indwelling central venous catheters for parenteral nutrition.
• Invasive procedures that compromise the skin's protective barrier.
• Tracheal tubes
• Ineffective hand hygiene practices.

Neonatal Sepsis - Symptoms

• Respiratory distress
• Fever or temperature instability like hypothermia
• Poor feeding
• Vomiting
• Apnoea and bradycardia
• Abdominal distension
• Jaundice
• Neutropenia
• Hypoglycaemia/hyperglycaemia
• Shock
• Irritability
• Seizures
• Lethargy
• In meningitis, symptoms include a tense or bulging fontanelle and head retraction (opisthotonos)

Neonatal Sepsis - Lab Tests

• Septic screen including blood cultures
• Chest X-ray
• Full blood count to detect neutropenia
• Acute-phase reactant (C-reactive protein) is helpful but takes 12-24 hours to rise; two consecutive normal values provide strong evidence against infection.

Neonatal Sepsis - Treatment

• Antibiotics are started immediately without culture results.
• Intravenous antibiotics are given to cover group B streptococci, L. monocytogenes, and other Gram-positive organisms (benzylpenicillin or ampicillin), combined with Gram-negative coverage (aminoglycoside like gentamicin).
• If cultures and C-reactive protein are negative and the infant shows no clinical signs of infection, antibiotics are stopped after 36–48 hours.
• If the blood culture is positive or neurological/generalized signs are present, CSF must be examined and cultured.
• Initial therapy for late-onset sepsis (e.g., with flucloxacillin and gentamicin) intends to cover most staphylococci and Gram-negative bacilli.
• If the organism resists initial antibiotics or the infant's condition doesn't improve, specific antibiotics (vancomycin for coagulase-negative staphylococci or enterococci) or broad-spectrum antibiotics (meropenem) are indicated.
• Prolonged or broad-spectrum antibiotic use predisposes premature babies to invasive fungal infections like Candida albicans.
• Serial measurements of an acute-phase reactant (C-reactive protein) are helpful to monitor response to therapy

Neonatal Meningitis

• Neonatal meningitis is rare, but carries a high mortality rate.
• Survivors are at risk for serious sequelae.
• Presentation involves a bulging fontanelle and hyperextension of neck and back (opisthotonos), are late signs and are rarely seen in newborn infants.
• For meningitis ampicillin or penicillin and a third-generation cephalosporin (e.g. cefotaxime, which has CSF penetration) are administered.
• Complications include cerebral abscess, ventriculitis, hydrocephalus, hearing loss and neurodevelopmental impairment.

Congenital Infections

• Congenital infections are acquired transplacentally during gestation and include fungal, bacterial, and viral pathogens.
• Types of congenital infections: toxoplasmosis, rubella, cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus, congenital syphilis, parvovirus, human immunodeficiency virus (HIV), hepatitis B, Zika virus, Neisseria gonorrhoeae, Chlamydia, and Mycobacterium tuberculosis.
• Evaluation of patients with suspected congenital infection necessitates isolating the organism through culture (for rubella, CMV, HSV, gonorrhea, and M. tuberculosis).
• Evaluation of patients with suspected congenital infection necessitates identifying the antigen of the pathogen (for hepatitis B and Chlamydia RUBELLA trachomatis).
• Evaluation of patients with suspected congenital infection necessitates identifying the pathogen's genome with polymerase chain reaction (PCR).
• Evaluation of patients with suspected congenital infection necessitates identifying specific fetal production of antibodies which are immunoglobulin M [IgM] or increasing titer of IgG for Toxoplasma, syphilis, parvovirus, HIV, or Borrelia

Toxoplasmosis

• Causative agent: Toxoplasma gondii
• Maternal is from cats and raw meat or immunosuppression
• High-risk exposure is at 10-24-wk gestation
• Clinical presentation involves Hydrocephalus, abnormal spinal fluid, intracranial calcifications, chorioretinitis, jaundice, hepatosplenomegaly, and fever.
• Many infants are asymptomatic at birth
• Treatment: pyrimethamine plus sulfadiazine

Congenital Rubella

• Causative agent: Rubella virus
• Maternal sources include unimmunized seronegative mother; fever ± rash
• Detectable defects with infection: by 8 wk, 85% // 9-12 wk, 50% //13-20 wk, 16%
• Virus may be present in infant's throat for 1 yr
• Prevention through vaccine
• Clinical presentation includes Intrauterine growth restriction, microcephaly, microphthalmia, cataracts, glaucoma, “salt and pepper” chorioretinitis, hepatosplenomegaly, jaundice
• Also includes PDA, deafness, blueberry muffin rash, anemia, thrombocytopenia, leukopenia, metaphyseal lucencies, B-cell and T-cell deficiency.
• Infant may be asymptomatic at birth

Congenital CMV

• Causative agent: CMV
• Sexually transmitted disease: primary genital
• Infection may be asymptomatic
• Infant may have viruria for 1-6 yr
• Clinical presentation includes Sepsis, intrauterine growth restriction, chorioretinitis, microcephaly, periventricular calcifications and blueberry muffin rash
• Also includes anemia,thrombocytopenia, neutropenia, hepatosplenomegaly, jaundice, deafness, and pneumonia
• Many asymptomatic at birth
• Prevention through CMV-negative blood products and possible treatment through ganciclovir

Congenital Herpes

• Causative agent: Herpes simplex type 2 or 1 virus
• Maternal sources includes sexually transmitted disease and primary genital
• infection may be asymptomatic, intrauterine infection rare and acquisition at time of birth more common
• Clinical presentation includes Intrauterine infection: chorioretinitis, skin lesions,microcephaly and Postnatal: encephalitis, localized or disseminated disease, skin vesicles, keratoconjunctivitis
• Treatment is acyclovir