Study highlights poor outcomes in very preterm infants with early-onset sepsis

1. Very preterm infants with early-onset sepsis had longer hospital stays, lower rates of survival, and a significantly increased risk of morbidity compared to uninfected infants.

2. Approximately one-third of causative bacteria were not Escherichia coli or Group B Streptococcus.

Evidence Rating Level: 2 (Good)

Study Rundown: Preterm infants are at high risk for developing early-onset sepsis (EOS), which is associated with significant morbidity and mortality. Current guidelines recommend that the majority of very preterm infants be empirically treated with antibiotics targeting Group B Streptococcus (GBS) and Escherichia coli (E.coli). However, recent studies indicate a significant increase in E. coli resistance to the standard regimen of ampicillin plus gentamicin. This study aimed to identify the microbiology of bacteria involved in EOS, as well as related outcomes, among more than 80,000 very-low birthweight (weight < 1500 grams, VLBW) or very preterm (22 to 29 weeks’ gestation) infants from a large network of NICUs across the country. Overall, the incidence of EOS was 13.5 per 1000. The risk of death amongst these infants was significant; approximately one-third of them died. They also experienced higher rates of significant morbidity, including intraventricular hemorrhage, retinopathy of prematurity, and chronic lung disease. The risk of EOS was inversely related to gestational age. Importantly, about one-third of EOS cases were not due to E. coli or GBS. This study did not determine the etiology of preterm birth and therefore could not classify infants as low or high risk of EOS as per the American Academy of Pediatrics guidelines. However, this data indicates the substantial negative impact of EOS and the need to consider revising antimicrobial guidelines to include the use of more broad-spectrum agents.

Click to read the study in PEDIATRICS

Relevant Reading: Early-onset neonatal sepsis

In-Depth [prospective cohort]: In this prospective cohort study, data was collected between January 2018 to December 2019, across 753 centers in 49 states in the United States through the Vermont Oxford Network (VON). Infants born weighing between 401 to 1500 g or at 22 to 29 weeks’ gestation were followed from birth until discharge, death, or first birthday. Early-onset sepsis was diagnosed by culture-confirmed bacteria in the blood or cerebrospinal fluid within the first 3 days of life. Survival to discharge, in addition to two secondary outcomes (survival without morbidity and survival with major neonatal morbidity) were monitored. Major morbidities were defined as late-onset sepsis, chronic lung disease, severe intraventricular hemorrhage, pneumothorax, necrotizing enterocolitis, and cystic periventricular leukomalacia. In total, 84,333 very preterm or VLBW infants were included in the analysis, with 1139 diagnosed with early-onset sepsis (13.5 per 1000, 99% CI 12.5-14.6). E. coli (47%) and GBS (19%) were the most common bacteria identified. Infants with early-onset sepsis were more likely to have longer lengths of stay (92 vs. 66 days), lower rates of survival to discharge (67.5% vs. 90.4%, aRR 0.82 [95% CI 0.79-0.85]), and lower rates of survival without morbidity (26.2% vs. 59.4%, aRR 0.66 [95% CI 0.60-0.72]).

Image: PD

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