Beyond Early - and Late - onset Neonatal Sepsis Definitions. What are the Current Causes of Neonatal Sepsis Globally? A Systematic Review and Meta-analysis of the Evidence

Read article: Submitted by: Dr Krist Ewe, Dr Sam Brophy-Williams, Dr Alayne Bennett.Perth Children’s Hospital, Western Australia. 7th October 2024.Supervisor: Dr. Anita Campbell.Background:Neonatal sepsis remains a leading cause of mortality, particularly in low- and lower-middle-income countries (LLMICs). With rising antimicrobial resistance, the aetiology of neonatal sepsis is evolving, creating a need to re-evaluate empirical treatment guidelines. This systematic review and meta-analysis evaluated contemporary bacterial pathogens responsible for early-onset neonatal sepsis (EOS) and late-onset sepsis (LOS) to assess if historical classifications guiding empirical therapy may be out of date.Findings:Analysis of 48 articles covering 757,427 samples from 311,359 neonates across 25 countries revealed:1. Gram-negative bacteria were the predominant cause of both EOS (53%) and LOS (71%) globally. While the review highlighted concerns about plasmid-mediated resistance, it did not provide data on the prevalence of antimicrobial resistance (AMR) in this context, indicating a gap for future research.2. In LLMICs, Klebsiella spp. (31.7%) followed by Staphylococcus aureus (17.5%) were the main causes of EOS, in contrast to Streptococcus agalactiae in high-income settings.3. Current EOS and LOS definitions appear out of date, particularly in LLMICs, as Gram-negative bacteria now dominate both early and late onset neonatal sepsis, challenging previous assumptions about causative pathogens. Take home message:1. An outdated sepsis classification system may guide inappropriate empirical antibiotic prescribing that inadequately covers causative pathogens.2. Harmonizing sepsis definitions across age groups (neonatal, paediatrics and adults) will enable more accurate comparison of sepsis epidemiology.3. New strategies for classifying causative bacteria in neonatal sepsis according to mode of acquisition are needed to evaluate alternative empirical antibiotic regimens and reduce global morbidity and mortality. The authors proposed a contemporary classification of neonatal sepsis involving vertically acquired, horizontally-acquired (nosocomial setting) and horizontally-acquired (community setting).

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Quiz Questions

1.
1. What is the current predominant cause of early-onset sepsis (EOS) in low- and lower-middle-income countries according to the study?
- A.
  A) Streptococcus agalactiae
- B.
  B) Escherichia coli
- C.
  C) Klebsiella spp.
- D.
  D) Staphylococcus aureus
- E.
  E) Acinetobacter spp.
2.
2. What percentage of pathogens causing late-onset sepsis (LOS) were Gram-negative bacteria?
- A.
  29%
- B.
  46.8%
- C.
  52.9%
- D.
  62.6%
- E.
  71%
3.
3. Which of the following statements best reflects a key finding of the study?
- A.
  A) Current definitions of EOS and LOS are still accurate globally
- B.
  B) Streptococcus agalactiae remains the primary cause of EOS in LLMICs
- C.
  C) Empirical antibiotic guidelines are adequately covering causative pathogens
- D.
  D) Current EOS and LOS definitions appear outdated, particularly in LLMICs
- E.
  E) Gram-positive bacteria are the predominant cause of both EOS and LOS globally

Quiz Outcomes

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Results