Sepsis Overview

Sepsis occurs in infants < 28 days old, and is still a major cause of mortality and morbidity in new-borns today, with an incidence ranging from 1-10/1000 live-births being affected. The systemic infection can be categorised as early-onset or late-onset, with microorganisms such as E.coli and Coagulase-negative staphylococci being associated with the infection. Early-onset sepsis (EOS) is defined as the infection occurring within the first 72 hours of life, with the mortality rate for EOS currently reaching ~3% among term new-borns and ~16% in very-low-birth-weight (VLBW) infants. Late-onset sepsis (LOS) tends to occur during the first 7 days of life, and is generally acquired from the environment. With LOS, mortality rates have been observed to increase with postnatal age, reaching 36% in new-borns aged 8-14 days and 52% in those aged 15-28 days. Several recent studies - including one carried out in Egypt which observed the incidence of sepsis in neonates over a 12-month period – have highlighted the occurrence of multidrug resistant organisms being leading causes of early and late onset sepsis. Both gram-negative bacilli and gram-positive cocci are noted to be highly resistant to various microbials, including ampicillin. This was not only noted in LOS cases, but resistance was also observed in infants diagnosed with early onset sepsis. Thus, the increasing resistance to certain antibiotics for treatment of neonatal sepsis has been bought to global attention with demands for antibiotic regulations being called.

Septicaemia is one of the most prominent infections responsible for the 1.6 million deaths that are caused by neonatal infections in developing countries annually. The bacterial blood stream infection (BSI) can be classified according to the time of onset of the disease – early onset (EOS) which occurs within the first 3 days of life, and late onset (LOS) where infection tends to appear anytime between first week and first month of life, depending on whether the infant was term or born prematurel. With EOS, the acquisition of the microorganisms occurs as a result of transplacental infection, or colonisation of the mother’s genitourinary (GU) tract, thus resulting in the bacterial pathogens being transmitted vertically from mother to infant before or during delivery. Microorganisms most commonly associated with EOS are Group B Streptococcus (GBS), Escherichia coli (E. coli) – which is the second leading cause of EOS, accounting for 24% of all cases, with 81% occurring in preterm infants, – as well as Coagulase-negative Staphylococcus (CoNS) and Haemophilus influenzae. These organisms typically colonise the maternal GU tract leading to contamination of the amniotic fluid, placenta, cervix or vaginal canal. Contamination of the amniotic fluid can occur prior or during labour, meaning the infant may acquire the pathogen in utero or intrapartum. In late-onset sepsis, the pathogens are acquired after birth, normally from nosocomial or community sources. There is some contemplation as to when the period for late-onset sepsis begins, however generally infection is deemed late-onset when it occurs after 6 days of life. With LOS, 70% of infections were associated with Gram-positive organisms; Coagulase-negative Staphylococci contributed 48% of cases and Gram-negative (such as E. coli) bacteria 18%. Invasive microorganisms from the environment may colonise the infant’s skin, respiratory tract, conjunctivae, GI tract and umbilicus, and can acquired vertically or horizontally. Both the E. coli and Staph pathogens are important bacterial agents of sepsis; however, E. coli is a more prominent cause in EOS, whilst CoNS is a major cause for LOS.

Escherichia coli (E. coli), is responsible for a substantial proportion of mortality in infants and is part of one of the most diverse bacterial species. The complex antigenic structure as well as certain virulence factors has been important in neonatal sepsis – the best described virulence factor is the K1 capsular antigen which is present in certain strains and is closely linked to neonatal meningitis. This polysialic acid impairs opsonophagocytic killing meaning those infected with the K1 antigenic strains have an increased morbidity and mortality in comparison to those with other strains. The severity of the disease is associated to the amount and persistence of the K1 antigen in the cerebrospinal fluid.