Infection and Sepsis.

. Infants are at increased risk for infec­tion due to the immaturity and relative inexperience of their immune system. Preterm infants are at even higher risk because the majority of maternal antibodies are trans­ferred during the latter weeks of gestation. In addition, preterm infants often require invasive treatments that fur­ther increase their susceptibility to microbial invasion. Ma­ternal risk factors that increase the likelihood of infection in the preterm infant include inadequate prenatal care, poor nutrition, low socioeconomic status, prolonged rup­ture of membranes, maternal fever, foul-smelling amniotic fluid, or presence of a urinary tract infection. Neonatal fac­tors associated with the development of infection include antenatal or intrapartal asphyxia, congenital abnormalities, male sex, multiple gestations, concurrent neonatal diseases, invasive diagnostic or therapeutic procedures, iatrogenic complications, and administration of medications that alter normal microbial flora.

Newborns are at risk for infection by bacterial, viral, fungal, or protozoal microorganisms; the most common form is bacterial sepsis or bloodstream infection. Bacterial sepsis is characterized by signs of systemic infection in the presence of bacteria in the bloodstream. The incidence of bacterial sepsis in the newborn is about 1 to 8 newborns per every 1000 live births and 160 to 300 per 1000 new­borns less than 1500 g (very low birth weight [VLBW]).²⁵,²⁶ Almost 30% of babies admitted to neonatal intensive care units may have positive blood cultures. Because of the se­vere consequences of untreated bacterial sepsis and the association of infection as the cause of preterm labor, pre­term babies often are treated for sepsis despite the absence of a confirmatory positive blood culture. Incidence of in­fection can vary by geographic region, nursery, and time of year. Mortality of neonatal bacterial sepsis is about 25% despite the use of potent antibacterial agents and support­ive care.²⁶,²⁷ Sepsis from group B beta-hemolytic strepto­coccus carries a higher mortality rate.²⁸

Microorganisms. The microorganisms responsible for new­born infection have changed over the past decades. Because there are significant regional variations, it is necessary to know the specific microorganisms and antibacterial agent susceptibilities in specific institutions, as well as the general predominant bacterial patterns. In this way, early therapy can be selected for the most likely bacteria when sepsis is suspected. Early diagnosis and treatment of the bacterial sepsis provides better outcomes. Group B strep­tococcus and E. coli account for 70% to 80% of positive blood cultures in the neonatal population.²⁶ Other bacte­ria, such as Listeria monocytogenes, enterococci, and gram-negative enteric bacilli (other than E. coli), occur less commonly but must be considered.

Group B beta-hemolytic streptococcus (GBS) is the most common bacteria causing early-onset bacterial sepsis in newborns, especially preterm newborns. Streptococci are gram-positive diplococcal bacteria that exist in pairs or chains during replication. GBS can be found in cultures of body fluids, blood, urine, cerebrospinal fluid (CSF), or other bodily secretions of infected newborns. Early-onset GBS disease typically presents with respiratory distress, hypo­tension, and other signs characteristic of sepsis. Signs of neurologic involvement are more common in late-onset infection.

Administration of antimicrobial agents to mothers during the intrapartal period or to newborns immediately postpartum has been shown to reduce the risk for early-onset group B streptococcal infection. The Centers for Disease Control (CDC), in collaboration with the Ameri­can College of Obstetricians and Gynecologists and the American Academy of Pediatrics, developed guidelines for prevention of neonatal GBS disease in 1996.²⁵,²⁹,³⁰ These guidelines recommended the use of either a risk-based approach or a screening-based approach. The risk-based approach resulted in a 40% reduction, and the screening-based approach resulted in an 80% reduction in the oc­currence of neonatal GBS disease.²⁹,³⁰ Subsequent studies show there has been a 65% reduction of GBS disease in areas where surveillance data were collected.²⁵ GBS disease continues to be a threat to the newborn owing to the high mortality and morbidity of the disease and the increased survival of smaller and more preterm newborns with a higher risk for GBS disease.

Patterns of Bacterial Sepsis. Bacterial sepsis occurs in two dis­tinct patterns, early onset and late onset, that differ in clin­ical presentation, epidemiology, pathogenesis, and prognosis. Early-onset infection is a severe, rapidly progres­sive, multiorgan system illness that occurs within the first few days of life. Pneumonia is common in early-onset in­fection. There may be a history of obstetrical complica­tions, such as prolonged rupture of membranes, prolonged second stage of labor, or leaking membranes. The micro­organisms causing early-onset infection are those that are usually found in the mother's genital tract and include streptococci, L. monocytogenes, and E. coli. Mortality of early-onset infection, reported as 5% to 50%, is high.

Late-onset infection occurs after post-birth day 5. It has a slower progression than early-onset infection and usu­ally has a focal site. Meningitis is seen more often with late-onset infection than with early-onset infection. In ad­dition to those microorganisms responsible for early-onset infection, Staphylococcus aureus, Staphylococcus epidermidis, and other enterobacteria as well as pseudomonads are common in late-onset infections. The mortality rate for late-onset infection is about 2% to 6%.²⁶

Manifestations of Bacterial Sepsis. The manifestations of bacte­rial infection in the newborn result from two sources: the effects of the bacterial invasion of the microorganism and the response of the newborn's immune system to the in­vasion. Bacteria release endotoxins and other vasoactive substances, causing central vasodilation, peripheral vaso-constriction, and systemic hypovolemia. The immune

response to the endotoxins leads to hemodynamic, meta­bolic, respiratory, central nervous system, gastrointestinal, and dermatologic changes.

The signs of bacterial sepsis in a newborn, which can occur in all body systems, are generally nonspecific and are not easily distinguished from other causes. Therefore, it is important to have a high index of suspicion for sepsis in the newborn, especially the preterm newborn. The ob­servation that there has been a subtle change in a baby's general condition, often marked by the nursing assess­ment that the baby "is not doing right," may be the first indication of infection. However, as the septicemia pro­gresses, the signs become more severe and more specific.

Optimal prognosis depends on early diagnosis and implementation of appropriate therapy; thus, frequent and careful assessment and evaluation of the baby's phys­ical condition can have a significant impact on outcome. Table 2-3 outlines the assessment for indicators of infec­tion in the newborn and infant.