USA Surgery Today

Despite improvement in morbidity and mortality from neonatal bacterial sepsis since the mid-1970s, the incidence of sepsis during the first week of life has been unchanged and about fivefold greater among premature infants (5 in 1,000 preterm infants:Zebeta) than full-term infants (about 1 in 1,000 term newborns). In addition, 25% to 33% of premature infants who require longer than 2 weeks of hospitalization during the neonatal period develop at least one episode of systemic bacterial infection. The systemic pathogen most commonly recovered after the first week of life is coagulase-negative staphylococcus.

The high rate of invasive disease among premature infants is caused by humoral, cellular, and environmental factors (34:Zebeta). Transplacental transport of maternal immunoglobulin G (IgG:Zebeta) provides the full-term infant with concentrations of IgG equal to or greater than maternal concentrations. This transport process increases significantly after 20 weeks of gestation; about two-thirds of the IgG acquired by the fetus during pregnancy is transported during the last third of gestation. Lack of transplacentally acquired IgG in the extremely premature infant results in quantitative and qualitative humoral susceptibility to bacterial infection. In addition, concentrations of the principal nonspecific humoral effector response proteins of the classic and alternative pathways of complement activation are significantly lower than in adults and do not reach adult levels until 3 to 6 months of age.

Immunologic cellular defense is impaired by the premature infant’s reduced ability to respond to antigenic stimulation, owing to altered T lymphocyte–B lymphocyte cooperation in antigen recognition and antibody synthesis.

Environmental factors also increase the risk for systemic bacterial infection. Use of arterial or central venous catheters provides potential sites for nosocomial bacterial invasion. Poor skin integrity, alteration of gastric pH, and catabolic nutritional status may also contribute to enhanced susceptibility to systemic infection.

Although the morbidity and mortality of systemic bacterial infection in premature infants are significant, the initial clinical symptoms of sepsis may be subtle and nonspecific until infection is significantly advanced. Early detection and treatment, prompted by consideration of sepsis as a possible cause whenever clinically significant deterioration occurs, are critical in optimizing outcome. Clinical presentation of sepsis may range from mild feeding intolerance or an increase in frequency of apnea, both frequently seen in premature infants in response to noninfectious stimuli, to rapidly evolving hypotension and shock. Laboratory investigations may assist in the diagnosis; metabolic acidosis and hypoxemia, leukopenia, neutropenia, or thrombocytopenia may be important indicators of evolving infection. Antibiotic coverage is frequently indicated before results of relevant systemic cultures, usually of blood, urine, and possibly cerebrospinal fluid, are available. Choice of antibiotics varies with the specific clinical situation, but use of a penicillin and an aminoglycoside has been effective in many different clinical settings.

The organisms most commonly seen in septic infants in the first week of life include group B ОІ-hemolytic streptococcus (about 33%:Zebeta), Escherichia coli and other gram-negative enteric organisms (about 33%), and a group of less common organisms, including Listeria monocytogenes and nontypeable Haemophilus influenzae. The incidence of early onset group B streptococcal infection has been decreasing due intrapartum chemoprophylaxis. However, there are some indications that it may be replaced by increased frequency of infections with gram-negative organisms. Initial antibiotic choices are usually ampicillin and an aminoglycoside. After the first week of life, coagulase-negative staphylococci are the most commonly encountered organisms. Fungal pathogens may also contribute significantly to serious infections after the first week of life. The most commonly encountered fungi are species of Candida and Malassezia, opportunistic organisms that require additional antifungal coverage (usually amphotericin B:Zebeta) for successful eradication. Because of the pronounced changes in glomerular filtration rate, hepatic blood flow, volume of drug distribution, and hemodynamic stability that occur during the first weeks of life in premature infants and during episodes of systemic infection, careful monitoring of antibiotic pharmacokinetics is critical to avoid toxicity or subtherapeutic concentrations of antibiotics. The dosing of these agents must also be carefully monitored.