Changes in Pathogens Causing Early-Onset Sepsis in Very-Low-Birth-Weight Infants

Stoll, Barbara J.; Hansen, Nellie I.; Fanaroff, Avroy A.; Wright, Linda L.; Carlo, Waldemar A.; Ehrenkranz, Richard A.; Lemons, James A.; Donovan, Edward F.; Stark, Ann R.; Tyson, Jon E.; Oh, William; Bauer, Charles R.; Korones, Sheldon B.; Shankaran, Seetha; Laptook, Abbot R.; Stevenson, David K.; Papile, L.A.; Poole, W. Kenneth

doi:10.1056/nejmoa012657

Cited by 719 publications

(451 citation statements)

References 31 publications

Supporting

Mentioning

385

Contrasting

Unclassified

Order By: Relevance

“…Late-onset sepsis (LOS) is sepsis occurring after 72 h in NICU infants and 7 days of life in term infants, has been variably defined as occurring up to the age of Ͻ90 or 120 days, and may be caused by vertically or horizontally acquired pathogens (2,3,(5)(6)(7). Early-onset neonatal infections of viral or fungal etiology may also occur at Ͻ7 days of life and must be distinguished from bacterial sepsis (8,9).…”

mentioning

confidence: 99%

Early-Onset Neonatal Sepsis

et al. 2014

View full text Add to dashboard Cite

SUMMARY 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.

show abstract

mentioning

confidence: 99%

Early-Onset Neonatal Sepsis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Escherichia coli K1 is the predominant pathogen causing neonatal meningitis and septicemia (6). The mortality and morbidity due to E. coli K1 has remained significant in the last few decades, despite the use of effective antimicrobial therapy.…”

mentioning

confidence: 99%

Experimental Validation of the Predicted Binding Site of Escherichia coli K1 Outer Membrane Protein A to Human Brain Microvascular Endothelial Cells

Pascal

Abrol

Mittal

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Escherichia coli K1, the most common cause of meningitis in neonates, has been shown to interact with GlcNAc1-4GlcNAc epitopes of Ecgp96 on human brain microvascular endothelial cells (HBMECs) via OmpA (outer membrane protein A). However, the precise domains of extracellular loops of OmpA interacting with the chitobiose epitopes have not been elucidated. We report the loop-barrel model of these OmpA interactions with the carbohydrate moieties of Ecgp96 predicted from molecular modeling. To test this model experimentally, we generated E. coli K1 strains expressing OmpA with mutations of residues predicted to be critical for interaction with the HBMEC and tested E. coli invasion efficiency. For these same mutations, we predicted the interaction free energies (including explicit calculation of the entropy) from molecular dynamics (MD), finding excellent correlation (R 2 ‫؍‬ 90%) with experimental invasion efficiency. Particularly important is that mutating specific residues in loops 1, 2, and 4 to alanines resulted in significant inhibition of E. coli K1 invasion in HBMECs, which is consistent with the complete lack of binding found in the MD simulations for these two cases. These studies suggest that inhibition of the interactions of these residues of Loop 1, 2, and 4 with Ecgp96 could provide a therapeutic strategy to prevent neonatal meningitis due to E. coli K1.Neonatal bacterial meningitis is one of the most serious infections of the central nervous system, resulting in significant neurological sequelae (such as hearing loss, convulsive disorders, abnormal speech patterns, cortical blindness, and mental retardation) in half of the survivors (1-4). The incidence of bacterial meningitis in infants is about five cases per 100,000 live births per year in developed countries but can be 10 times higher in underdeveloped countries (5).Escherichia coli K1 is the predominant pathogen causing neonatal meningitis and septicemia (6). The mortality and morbidity due to E. coli K1 has remained significant in the last few decades, despite the use of effective antimicrobial therapy. This poor outcome is due to increased antibiotic resistance of E. coli, possibly due to their use in food stock (7) and the high adaptive mutation ability of E. coli (shown to be on the order of 10 Ϫ5 per genome per generation) (8).Our previous experimental studies in the newborn rat model of hematogenous meningitis demonstrated that a high degree of bacteremia is required for the onset of meningitis (9). We showed that the entry of E. coli K1 into human brain microvascular endothelial cells (HBMEC), 3 which comprise the lining of the blood-brain barrier, requires the expression of a 35-kDa OmpA (outer membrane protein A) in E. coli K1 (10).In addition, we and others (9 -12) showed that OmpA expression is important for entry of monocytes, macrophages, and dendritic cells, indicating the important role of this protein in the pathogenesis of neonatal meningitis by E. coli K1. We also showed that the interaction of OmpA with Ecgp96 (a homologue of Hs...

show abstract

“…In recent reports (14,15), S. aureus was found to be responsible for 7.8% of cases of late-onset sepsis (LOS) and 3% of cases of early-onset sepsis (EOS) in very-low-birth-weight (Ͻ1,500 g) neonatal infants. Furthermore, methicillin-resistant Staphylococcus aureus (MRSA), either nosocomially or community acquired, has emerged as a challenging pathogen in NICUs (7,13).…”

mentioning

confidence: 99%

Long Persistence of Methicillin-Susceptible Strains of Staphylococcus aureus Causing Sepsis in a Neonatal Intensive Care Unit

Gómez-González¹,

Alba

Otero³

et al. 2007

J Clin Microbiol

View full text Add to dashboard Cite

show abstract

Changes in Pathogens Causing Early-Onset Sepsis in Very-Low-Birth-Weight Infants

Abstract: Early-onset sepsis remains an uncommon but potentially lethal problem among very-low-birth-weight infants. The change in pathogens over time from predominantly gram-positive to predominantly gram-negative requires confirmation by ongoing surveillance.

Cited by 719 publications

References 31 publications

Early-Onset Neonatal Sepsis

Early-Onset Neonatal Sepsis

Experimental Validation of the Predicted Binding Site of Escherichia coli K1 Outer Membrane Protein A to Human Brain Microvascular Endothelial Cells

Long Persistence of Methicillin-Susceptible Strains of Staphylococcus aureus Causing Sepsis in a Neonatal Intensive Care Unit

Contact Info

Product

Resources

About