Incidence and aetiology of infant Gram-negative bacteraemia and meningitis: systematic review and meta-analysis

Luisa K. Hallmaier-Wacker, Amelia Andrews, Olisaeloka Nsonwu, Alicia Demirjian, Russell J. Hope, Theresa Lamagni*, Simon M. Collin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Background One in six infant deaths worldwide are caused by invasive bacterial infections, of which a substantial but unquantified proportion are caused by Gram-negative bacteria. Methods We conducted a systematic review of studies published from 31 May 2010 to 1 June 2020 indexed in MEDLINE, Embase and Global Health databases. We performed meta-analyses of the incidence of Gram-negative bacteraemia and of individual Gram-negative species as proportions of all infant bacteraemia, stratified by onset (early vs late) and country income (low/middle vs high). Results 152 studies from 54 countries were included, 60 in high-income countries (HIC) and 92 in low-income/middle-income countries (LMIC). Gram-negatives represented a higher proportion (53%, 95% CI 49% to 57%) of all infant bacteraemia in LMIC compared with HIC (28%, 95% CI 25% to 32%). Incidence of infant Gram-negative bacteraemia was 2.01 (95% CI 1.15 to 3.51) per 1000 live births; it was five times higher in LMIC (4.35, 95% CI 2.94 to 6.43) compared with HIC (0.73, 95% CI 0.39 to 7.5). In HIC, Escherichia coli was the leading Gram-negative pathogen, representing 19.2% (95% CI 15.6% to 23.4%) of early and 7.3% (95% CI 5.3% to 10.1%) of all late-onset bacteraemia; Klebsiella spp were the next most common cause (5.3%) of late-onset bacteraemia. In LMIC, Klebsiella spp caused 16.4% (95% CI 11.5% to 22.7%) of early and 15.0% (95% CI 10.1% to 21.8%) of late-onset bacteraemia, followed by E. coli (early-onset 7.50%, 95% CI 4.98% to 11.1%; late-onset 6.53%, 95% CI 4.50% to 9.39%) and Pseudomonas spp (early-onset 3.93%, 95% CI 2.04% to 7.44%; late-onset 2.81%, 95% CI 1.99% to 3.95%). Conclusion E. coli, Klebsiella and Pseudomonas spp cause 20%-28% of early-onset infant bacteraemia and 14% cases of infant meningitis worldwide. Implementation of preventive measures could reduce the high incidence of Gram-negative bacteraemia in LMIC. PROSPERO registration number CRD42020191618.

Original languageEnglish
Pages (from-to)988-994
Number of pages7
JournalArchives of Disease in Childhood
Issue number11
Publication statusPublished - 16 Jun 2022

Bibliographical note

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© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.


  • infectious disease medicine
  • microbiology
  • neonatology
  • sepsis


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