Early-onset neonatal sepsis

Abstract

Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS.

FIG 1

Centers for Disease Control and Prevention (CDC) algorithm for secondary prevention of early-onset group B streptococcus (GBS) disease among newborns. (Adapted from reference .)

FIG 2

Schematic representation of events associated with the formation of deep cortical white matter lesions in periventricular leukomalacia. GW, gestational weeks. (Adapted from reference with permission of the publisher.)

FIG 3

CDC-recommended regimens for intrapartum antibiotic prophylaxis for prevention of early-onset GBS disease. IV, intravenously. *, broader-spectrum agents, including an agent active against GBS, might be necessary for treatment of chorioamnionitis. †, doses ranging from 2.5 to 3.0 million units are acceptable for the doses administered every 4 hours following the initial dose. The choice of dose within that range should be guided by which formulations of penicillin G are readily available to reduce the need for pharmacies to specially prepare doses. §, penicillin-allergic patients with a history of anaphylaxis, angioedema, respiratory distress, or urticaria following administration of penicillin or a cephalosporin are considered to be at high risk for anaphylaxis and should not receive penicillin, ampicillin, or cefazolin for GBS intrapartum prophylaxis. For penicillin-allergic patients who do not have a history of those reactions, cefazolin is the preferred agent because pharmacologic data suggest it achieves effective intra-amniotic concentrations. Vancomycin and clindamycin should be reserved for penicillin-allergic women at high risk for anaphylaxis. , if laboratory facilities are adequate, clindamycin and erythromycin susceptibility testing should be performed on prenatal GBS isolates from penicillin-allergic women at high risk for anaphylaxis. If no susceptibility testing is performed or the results are not available at the time of labor, vancomycin is the preferred agent for GBS intrapartum prophylaxis for penicillin-allergic women at high risk for anaphylaxis. **, resistance to erythromycin is often but not always associated with clindamycin resistance. If an isolate is resistant to erythromycin, it might have inducible resistance to clindamycin, even if it appears susceptible to clindamycin. If a GBS isolate is susceptible to clindamycin and resistant to erythromycin and testing for inducible clindamycin resistance has been performed and is negative (no inducible resistance), then clindamycin can be used for GBS intrapartum prophylaxis instead of vancomycin. (Adapted from reference .)