Which preemies are most at risk of late-onset sepsis mortality?

Among very low birthweight (VLBW) preterm infants with Gram-negative bacterial infections, inotropic support requirement, leukopenia, and elevated immature to total neutrophil (I: T) ratio serve as red flags for late-onset sepsis (LOS) mortality, according to a study from Singapore.

“Even as neonatal intensive care continues to improve, sepsis remains a significant cause of mortality and morbidity among preterm infants… Gram-positive bacteria, especially coagulase-negative staphylococci, are the prevalent group of pathogens reported as the cause of LOS in many neonatal intensive care units (NICUs),” the investigators said. [Pediatr Infect Dis J 2006;25:25-29; Early Hum Dev 2012;88:S69-74; PLoS ONE 2019;14:e0225407; J Hosp Infect 2017;97:267-274]

“An understanding of the risk factors associated with mortality among VLBW infants with LOS is important in guiding the formulation of strategies for the treatment and prognostication of outcomes due to LOS,” they added.

In the study, the investigators looked at a cohort of 1,740 infants born <32 weeks gestation and <1,500 gm admitted to a Singaporean tertiary-level NICU. A total of 169 infants (9.7 percent) developed LOS, including 36 with multiple LOS episodes, yielding an overall rate of 118.9 infections per 1,000 infants. The LOS incidence dropped significantly over the study period from 253.2 per 1,000 infants in 2006 to 74.5 per 1,000 infants in 2016 (p=0.009 for analysis of trends). [Front Pediatr 2021;9:801955]

There were 27 (16 percent) infants who died due to complications of LOS. The proportion of LOS deaths over the total number of LOS cases during the first 5 years was comparable to the latter 5 years (14.7 percent vs 17.3 percent; p=0.8). 

Compared with survivors, those who died had lower birth gestational age (median 24 vs 25 weeks; p=0.02) and earlier LOS occurrence (median 10 vs 17 days; p=0.007). There was no difference in the incidence of meningitis (11.1 percent vs 16.9 percent; p=0.3), necrotizing enterocolitis (18.5 percent vs 14.8 percent; p=0.6), or intestinal surgery (18.5 percent vs 23.3 percent; p=0.6).

Gram-negative bacteria accounted for most LOS deaths (21 out of 27, 77.8 percent) and almost all (13 out of 14, 93 percent) fulminant LOS episodes. Mortality was high in the presence of multiorgan failure as evidenced by the need for mechanical ventilation (100 percent vs 79.0 percent; p=0.008), lactate level elevation (12.4 vs 2.1 mmol/L; p<0.001), and inotropic support (92.6 percent vs 37.5 percent; p<0.001).

In multivariable logistic regression analysis, LOS mortality was independently associated with inotrope requirement (adjusted odds ratio [aOR], 22.4, 95 percent confidence interval [CI], 2.9–103.7), low white blood cell counts (<4 × 109/L; aOR, 4.7, 95 percent CI, 1.7–13.2), and high I: T ratio (>0.3; aOR, 3.6, 95 percent CI, 1.3–9.7).

“These imbalances in laboratory parameters are potentially important in the clinical setting as an indicator of increased risk of disease severity and mortality in LOS,” according to the investigators.

“Our data also suggests that empiric antimicrobial coverage for LOS in similar settings needs to treat Gram-negative organisms broadly and effectively,” they added.

The study was limited by the small sample size and the single-centre design. Also, there was a lack of data on breastmilk intake rates, which is known to reduce the risk of sepsis and allow for the development of the appropriate intestinal flora and microbial predominance among preterm infants.