How are newborns with sepsis treated, and who is most likely to die?
Across 11 mostly low- and middle-income countries, newborns with sepsis received hundreds of different antibiotic combinations that often departed from WHO guidance, many infections resisted recommended drugs, and a simple bedside score picked out babies at high risk of death.
Source
Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS)
Study at a glance
- Design
- Cohort — Prospective observational cohort at 19 hospitals in 11 countries (2018-2020) with daily data on signs, antibiotics and microbiology; Cox models for 28-day mortality derived in a random 85% and validated in the remaining 15%.
- N
- N=3204 · 3,204 infants enrolled; 3,141 started empiric antibiotics; 3,195 had baseline blood cultures; score derivation used 2,726 infants and validation 478.
- Population
- Hospitalised infants under 60 days old with clinical sepsis, mainly in low- and middle-income countries in Asia and Africa.
- Outcome
- Empiric antibiotic regimens and switching, blood-culture pathogens and resistance, and 28-day mortality (plus performance of the NeoSep Severity and Recovery Scores).
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What they did
Hospitals in 11 countries enrolled 3,204 infants under 60 days old with clinically suspected sepsis and followed them daily for 28 days, recording clinical signs, supportive care, every antibiotic given, blood and spinal fluid culture results and survival. The authors grouped the starting antibiotic regimens by the WHO AWaRe categories (Access, Watch, Reserve) and tracked escalation and de-escalation. They then built a baseline NeoSep Severity Score for 28-day death and a daily NeoSep Recovery Score, developing them in a random 85% of infants and testing them in the other 15%.
What they found
Infants were started on 206 different antibiotic combinations; only about a quarter received the WHO first-line Access regimen, 18.0% began on a carbapenem, and 25.3% of regimens were later escalated, while de-escalation was rare (5.9%). About 17.7% had a pathogen in the blood, mostly gram-negative bacteria; 32.6% of Klebsiella pneumoniae and 71.4% of Acinetobacter isolates were carbapenem-resistant, and 61.1% of Staphylococcus aureus were MRSA. Overall 11.3% of infants died within 28 days, rising to 17.7% with a positive culture. The Severity Score separated risk well (C-index 0.76 in validation), with death rates of 1.6%, 11.0% and 27.3% in low, medium and high score groups, and it outperformed a score based on WHO danger signs (0.63).
The limits
What it doesn't show
Because antibiotic choice depended on how sick infants were and on local resources, this observational study cannot say which regimen works best; the authors stress that randomized trials are needed. Sites were mostly urban secondary or tertiary hospitals with good microbiology, so resistance and antibiotic choice may differ in district hospitals, and not all eligible infants were screened, so the sickest babies who died quickly may be under-represented. The scores were validated only internally on a 15% sample containing 42 deaths, so external validation is needed. The provided text also omits most of the Methods section, so enrolment criteria and statistical details are only available in summary form.
Key terms
- Neonatal sepsis
- A life-threatening bloodstream or systemic infection in a newborn or young infant.
- WHO AWaRe classification
- WHO grouping of antibiotics into Access (first-line, narrow), Watch (broader, higher resistance risk) and Reserve (last-resort) to guide stewardship.
- Empiric antibiotic therapy
- Antibiotics started before culture results are known, chosen to cover the most likely pathogens.
- Escalation and de-escalation
- Switching to a broader-spectrum regimen, or narrowing therapy once the pathogen and its susceptibilities are known.
- C-index
- A measure of how well a risk score ranks who has the outcome first; 0.5 is chance and 1.0 is perfect discrimination.
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Quiz yourself
Roughly what share of infants started the WHO first-line Access regimen?
Common questions
Does this study show that carbapenems save more lives than ampicillin plus gentamicin?
No. Sicker babies were more likely to get broad-spectrum drugs, so comparing outcomes by regimen is confounded; only randomized trials such as the planned NeoSep1 trial can answer that.
Why does resistance matter so much here?
The leading killers, Klebsiella and Acinetobacter, were frequently resistant to the WHO-recommended first- and second-line drugs and even to carbapenems, leaving few effective options.
What is the Severity Score for?
It uses signs and infant characteristics available at presentation to identify babies at high risk of death, for example to decide trial eligibility or closer monitoring.
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