Pediatrics Dr.

Sawsan Ali

"Neonatal infections" lecture 1

Pathogenesis and Epidemiology

Infections are a frequent and important cause of neonatal and infant morbidity
and mortality. As many as 2% of fetuses are infected in utero, and up to 10% of infants
have infections in the 1st month of life.

Why infection in neonate is different?

1.Different mode of transmission.
2.Immunological deficiency.
3.Coexisting condition often complicate the diagnosis of neonatal infection.
4.The clinical manifestations of newborn infections vary, include subclinical infection,
mild to severe manifestations of focal or systemic infection, and rarely, congenital
syndromes.
5. Maternal infection that is the source for trans-placental infections, often undiagnosed
because the mother was either asymptomatic or had nonspecific signs and symptoms at
the time of acute infection.
6. A wide variety of etiologic agents including bacteria, viruses, fungi, protozoa, and
mycoplasmas.
7.Immature, very low birthweight (VLBW) newborns have improved survival but
remain in the hospital for a long time in an environment that puts them at continuous
risk for acquired infections.

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Etiology of Fetal and Neonatal Infection
A number of agents may infect newborns in utero, intrapartum, or postpartum.
1. Intrauterine trans-placental infections of significance to the fetus and/or
newborn include syphilis, rubella, CMV, toxoplasmosis, parvovirus B19, and
varicella. Although HSV, HIV, HBV, HCV, and (TB) can each result in trans-
placental infection, the most common mode of transmission for these agents is
intrapartum.
2. Intrapartum (during labor and delivery with passage through an infected birth
canal): HIV, HSV, HBV.
3. Postpartum; either from contact with an infected mother or caretaker (e.g. TB)
or with infected breast milk (HIV).

Sepsis and Meningitis

The incidence of sepsis is approximately 1:1500 in full-term infants and 1:250 in

preterm infants. The six-fold higher rate of sepsis among preterm infants compared with
term infants relates to the more immature immunologic systems of preterm infants and
to their prolonged periods of hospitalization, which increased risk of nosocomially
acquired infections.
The causative organisms isolated most frequently are the same as for neonatal
sepsis: group B streptococci, E. coli, and L. monocytogenes. Gram-negative organisms,
such as Klebsiella and Serratia marcescens, are more common in less developed
countries and coagulase-negative staphylococci need to be considered in VLBW infants.

Clinical Criteria for the Diagnosis of Sepsis:

Neurologic: convulsions, drowsy or unconscious, decreased activity, bulging fontanel
Respiratory: respiratory rate >60 breaths/min, grunting, severe chest indrawing, central
cyanosis
Cardiac: poor perfusion, rapid and weak pulse
Gastrointestinal: jaundice, poor feeding, abdominal distention
Dermatologic: skin pustules, periumbilical erythema or purulence
Musculoskeletal: edema or erythema overlying bones or joints

Other: temperature >37.7°C or < 35.5°C.

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Neonatal sepsis presents during 2 periods; Early-onset sepsis (from birth to 7 days) and
Late onset sepsis (from 8 to 28 days).

Early Onset Sepsis

Often begins in utero and usually is a result of infection caused by the bacteria in the
mother's genitourinary tract (vertical mother-to-child transmission) so acquired before
or during delivery.

Organisms related to this sepsis include group B streptococci, E. coli, Klebsiella, L.

monocytogenes, and nontypable H. influenza.
Risk factors for early-onset sepsis include:

1. Vaginal colonization with group B streptococci.

2. Prolonged rupture of the membranes (>18 hours).
3. Amnionitis.
4. Maternal fever or leukocytosis.
5. Fetal tachycardia.
6. Preterm birth.
7. Male gender is unexplained additional risk factors for neonatal sepsis.

Clinical manifestations:
Poor feeding, pallor, apnea, lethargy, hypothermia, or an abnormal cry-may be
nonspecific. Profound neutropenia, hypoxia, and hypotension may be refractory to
treatment with broad-spectrum antibiotics, mechanical ventilation, and vasopressors
such as dopamine and dobutamine.

In the initial stages of early-onset septicemia in a preterm infant, it is often

difficult to differentiate sepsis from RDS. Because of this difficulty, premature infants
with RDS receive broad-spectrum antibiotics.

The clinical manifestations of sepsis are difficult to separate from the

manifestations of meningitis in the neonate.

Investigations:
Infants with early-onset sepsis should be evaluated by blood and CSF cultures,
CSF Gram stain, cell count, and protein and glucose levels. Normal newborns generally
have an elevated CSF protein content (100 to 150 mg/dL) and may have 25 to 30/mm3

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white blood cells (mean 9/mm3), which are 75% lymphocytes in the absence of
infection.

In addition to culture, other methods of identifying the pathogenic bacteria are

the determination of bacterial antigen in samples of blood, urine, or CSF.

In cases of neonatal meningitis, the ratio of CSF glucose to blood glucose usually
is less than 50%.

The PCR test primarily is used to identify viral infections. Serial complete blood
counts should be performed to identify neutropenia, an increased number of immature
neutrophils (bands), and thrombocytopenia.

C-reactive protein levels are often elevated in neonatal patients with bacterial
sepsis. A chest radiograph also should be obtained to determine the presence of
pneumonia. Arterial blood gases should be monitored to detect hypoxemia and
metabolic acidosis. Blood pressure, urine output, and peripheral perfusion should be
monitored to determine the need to treat septic shock with fluids and vasopressor agents.

Treatment:
The mainstay of treatment for sepsis and meningitis is antibiotic therapy.
Antibiotics are used to suppress bacterial growth, allowing the infant's defense
mechanisms time to respond. In addition, support measures, such as assisted ventilation
and cardiovascular support, are equally important to the management of the infant.
A combination of ampicillin and an aminoglycoside (usually gentamicin) for 10
to 14 days is effective treatment against most organisms responsible for early-onset
sepsis. The combination of ampicillin and cefotaxime also is proposed as an alternative
method of treatment. If meningitis is present, the treatment should be extended to 21
days or 14 days after a negative result from a CSF culture.
Intrapartum antibiotics are used to reduce vertical transmission of GBS as well
as to lessen neonatal morbidity after preterm rupture of membranes. Intrapartum
chemoprophylaxis does not reduce the rates of late-onset GBS disease and has no effect
on the rates of infection with non-GBS pathogens.

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 Late Onset Sepsis

Late-onset sepsis (8 to 28 days) usually occurs in a healthy full-term infant who

was discharged in good health from the normal newborn nursery.
Clinical manifestations may include lethargy, poor feeding, hypotonia, apathy,
seizures, bulging fontanel, fever, and direct-reacting hyperbilirubinemia. In addition to
bacteremia, hematogenous seeding may result in focal infections, such as meningitis (in
75% of cases), osteomyelitis (group B streptococci, S. aureus), arthritis (gonococcus, S.
aureus, Candida albicans, gram-negative bacteria), and urinary tract infection (gram-
negative bacteria).

The evaluation of infants with late-onset sepsis is similar to that for infants with early-
onset sepsis, with special attention given to a careful physical examination of the bones
(infants with osteomyelitis may exhibit pseudo-paralysis) and to the laboratory
examination and culture of urine obtained by sterile supra-pubic aspiration or urethral
catheterization.

Late-onset sepsis may be caused by the same pathogens as early-onset sepsis, but
infants exhibiting sepsis late in the neonatal period also may have infections caused by
the pathogens usually found in older infants (H. influenzae, S. pneumoniae, and
Neisseria meningitidis). In addition, viral agents (HSV, CMV, or enteroviruses) may
manifest with a late-onset, sepsis-like picture.

Because of the increased rate of resistance of H. influenzae and pneumococcus to

ampicillin, some centers begin treatment with ampicillin and a third-generation
cephalosporin (and vancomycin if meningitis is present) when sepsis occurs in the last
week of the first month of life. The treatment of late-onset neonatal sepsis and meningitis
is the same as that for early-onset sepsis.

*** Good Luck ***