Pathogen Aetiology and Risk Factors for Death Among Neonates with Bloodstream Infections at Lower-tier South African Hospitals: a Cross-sectional Study

Background: Infections are among the top causes of neonatal mortality, particularly in low-income and middle-income countries. We aimed to describe the clinical characteristics of neonates diagnosed with culture-confirmed bloodstream infections at six lower-tier hospitals in South Africa.

Methods: We did a cross-sectional study of culture-confirmed bloodstream infections among neonates (aged 0-27 days) at six lower-tier hospitals in South Africa. Clinical, demographic, and pathogen data from sick, hospitalised neonates were analysed and bloodstream infections were categorised as early-onset sepsis (EOS; 0-2 days of life) or late-onset sepsis (LOS; 3-27 days of life). Incidence of bloodstream infection and crude in-hospital mortality in neonates with bloodstream infection were calculated and factors associated with death were analysed using multivariable logistic regression models.

Findings: From Oct 1, 2019 to Sept 30, 2020, we identified 907 neonatal bloodstream infection episodes. Incidence was 6·4 cases per 1000 patient-days. Most neonates were preterm (median gestation 33 weeks [IQR 29-37]), with 30·5% (n=277) of bloodstream infections classified as EOS and 69·5% (n=630) as LOS. Gram-negative pathogens dominated (63·2% [n=573]), including Klebsiella pneumoniae (25·7% [n=233]) and Acinetobacter baumannii (19·2% [n=174]). Crude in-hospital mortality in neonates with bloodstream infection was 25·5% (n=231), accounting for 21·4% (231 of 1078 cases) of all in-hospital neonatal deaths. Increased all-cause mortality was associated with Gram-negative bloodstream infection (vs Gram-positive pathogens, adjusted odds ratio 3·70 [95% CI 1·46-9·39]; p=0·0059), inborn LOS (vs EOS, 2·42 [1·11-5·29];  p=0·027), preterm birth (5·00 [2·16-11·59]; p=0·0002), and neonatal intensive care unit admission (3·26 [1·51-7·03]; p=0·0026).

Interpretation: Hospitalised, preterm neonates who developed Gram-negative bloodstream infections had high in-hospital mortality. Many small vulnerable newborns require prolonged stays in lower-tier hospitals and acquire life-threatening bloodstream infection; appropriate resources are needed at this level of care to prevent infections and save lives.

Funding: Bill & Melinda Gates Foundation.