3.1 Neonatal Sepsis & Infections
Key Takeaways
- Early-onset sepsis (within 72 hours of life) results from vertical transmission and is empirically treated with ampicillin plus gentamicin, switching to ampicillin plus cefotaxime if meningitis is suspected.
- Group B Streptococcus, Escherichia coli, and Listeria monocytogenes are the classic early-onset organisms; coagulase-negative staphylococci predominate in late-onset, catheter-associated sepsis.
- Hypothermia, not fever, is the more common temperature abnormality in neonatal sepsis, and clinical signs overall are frequently nonspecific.
- An immature-to-total neutrophil ratio above 0.2 and a serial CRP trend are more useful than a single elevated white blood cell count for supporting a sepsis diagnosis.
- Blood cultures should always be drawn before starting empiric antibiotics, and neonatal CSF reference ranges differ from those used in older children.
Overview
Neonatal sepsis is a systemic bacterial (occasionally fungal) infection occurring within the first 28 days of life and remains a leading cause of neonatal morbidity and mortality worldwide. The Arab Board written paper repeatedly tests the ability to distinguish early-onset sepsis (EOS) from late-onset sepsis (LOS) by timing, causative organism, and source, and to apply the correct stepwise workup and empiric antibiotic choice.
Early-Onset Sepsis (EOS)
EOS occurs within the first 72 hours of life (some texts use less than 7 days) and results from vertical transmission — organisms ascend from the maternal genital tract before or during labor, or the infant aspirates infected amniotic fluid.
Causative organisms
- Group B Streptococcus (GBS, Streptococcus agalactiae) — historically the leading cause of EOS where universal maternal screening is not practiced
- Escherichia coli (especially the K1 capsular serotype) — the leading cause in very-low-birth-weight infants and a major cause of neonatal meningitis
- Listeria monocytogenes — linked to unpasteurized dairy, meconium-stained amniotic fluid, and a distinctive papular skin/placental rash called granulomatosis infantiseptica
- Other maternal genital-tract organisms: coagulase-negative staphylococci, enterococci, non-typeable Haemophilus influenzae
Maternal and perinatal risk factors
- Maternal GBS colonization on rectovaginal culture at 35–37 weeks, or GBS bacteriuria during this pregnancy
- Prolonged rupture of membranes (PROM) of 18 hours or more before delivery
- Preterm labor, with intact or ruptured membranes
- Intra-amniotic infection (chorioamnionitis) — maternal fever, uterine tenderness, foul-smelling fluid
- A previous infant with invasive GBS disease
- Maternal intrapartum fever of 38 degrees C or higher
Exam trap: an infant born to a mother with unknown GBS status who has any of the above risk factors is managed as though the mother were GBS-positive. Adequate intrapartum antibiotic prophylaxis (IAP) means IV penicillin G (or ampicillin) started at least 4 hours before delivery; cefazolin, or clindamycin/vancomycin guided by susceptibility, is substituted in penicillin-allergic mothers.
The EOS Risk Calculator
Many centers now use a validated early-onset sepsis (EOS) risk calculator (for example, the Kaiser Permanente neonatal sepsis calculator) that combines maternal risk factors — gestational age, highest intrapartum temperature, duration of membrane rupture, GBS status, and the type of intrapartum antibiotics given — with the infant's clinical exam findings to estimate a numeric risk of EOS per 1,000 live births. This risk-stratified approach has measurably reduced unnecessary empiric antibiotic starts and NICU admissions compared with older categorical risk-factor checklists, and reflects current best practice the exam may reference.
Late-Onset Sepsis (LOS)
LOS occurs after 72 hours of life (commonly 7–28 days, extending further in preterm infants) and reflects postnatal, often nosocomial acquisition rather than vertical transmission.
Causative organisms
- Coagulase-negative staphylococci (CoNS) — the most common cause in NICU patients with indwelling central catheters
- Staphylococcus aureus, Klebsiella species, E. coli, Enterobacter species
- Candida species in extremely preterm infants on broad-spectrum antibiotics or with central lines
Risk factors include prematurity, prolonged central-line or ventilator use, and prolonged parenteral nutrition.
Clinical Presentation
The single most important exam concept in this section is that neonatal sepsis signs are nonspecific — any deviation from a newborn's normal behavior should raise suspicion.
- Temperature instability — hypothermia is more common than fever, especially in preterm infants
- Lethargy, poor feeding, irritability, hypotonia
- Respiratory distress, grunting, tachypnea, apnea
- Poor perfusion, mottling, hypotension
- Jaundice (often unconjugated and out of proportion), hepatosplenomegaly
- Seizures or a bulging fontanelle should raise concern for meningitis
Sepsis Workup
| Test | Key teaching point |
|---|---|
| Blood culture | Gold standard; obtain before starting antibiotics |
| CBC with differential | An immature-to-total neutrophil (I:T) ratio above 0.2 is more predictive than an elevated total white cell count; neutropenia in a sick neonate is more concerning than leukocytosis |
| CRP | Rises 6–8 hours after symptom onset; a single normal early value does not exclude sepsis — a serial CRP trend over 24–48 hours is far more useful than one isolated value |
| Lumbar puncture (LP) | Perform if the blood culture is positive, if there are clinical signs of meningitis, or if the infant is critically ill; do not delay giving antibiotics to an unstable infant in order to obtain an LP |
CSF caveat: normal neonatal CSF has higher protein and can contain more white cells than in older children, particularly in preterm infants — do not apply pediatric or adult CSF reference ranges directly to a neonate.
Empiric Antibiotics
- EOS without suspected meningitis: ampicillin plus gentamicin — covers GBS, Listeria, and most strains of E. coli
- EOS with suspected or confirmed meningitis: ampicillin plus cefotaxime for superior CNS penetration
- LOS acquired in the NICU: vancomycin plus an aminoglycoside (or cefepime), guided by unit-specific organism patterns, then narrowed once cultures return at 48–72 hours
- Typical duration: uncomplicated bacteremia about 10 days; GBS meningitis 14–21 days; gram-negative meningitis at least 21 days
A Distinct Red Flag: Neonatal HSV
Congenital TORCH infections are covered in a separate chapter, but neonatal herpes simplex virus (HSV) deserves mention here because it can mimic bacterial late-onset sepsis. A previously well infant who deteriorates in the second week of life with vesicular skin lesions, seizures, and rising liver enzymes despite negative bacterial cultures should prompt CSF HSV PCR testing and empiric high-dose IV acyclovir without waiting for a bacterial culture to turn positive — missing this distinction is a classic exam trap.
A term infant develops respiratory distress and hypothermia at 18 hours of life. The mother's GBS status was unknown, membranes ruptured 22 hours before delivery, and no intrapartum antibiotics were given. There are no signs of meningitis. What is the most appropriate empiric antibiotic regimen while awaiting cultures?
Which of the following statements about the neonatal sepsis workup is correct?
A neonate born through meconium-stained amniotic fluid to a mother who reports eating unpasteurized soft cheese during pregnancy develops a diffuse papular rash and respiratory distress at birth. Which organism is the most likely cause?
A pregnant woman known to be GBS-positive presents in labor and delivers vaginally only 2 hours after intravenous penicillin was started. How should this intrapartum antibiotic prophylaxis be classified, and what does it mean for the newborn?