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

doi:10.1136/archdischild-2022-324047

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

Arch Dis Child. 2022 Oct 19;107(11):988-994. doi: 10.1136/archdischild-2022-324047.

Authors

Luisa K Hallmaier-Wacker¹, Amelia Andrews¹, Olisaeloka Nsonwu¹, Alicia Demirjian^{1

2

3}, Russell J Hope¹, Theresa Lamagni⁴, Simon M Collin¹

Affiliations

¹ Healthcare-Associated Infection, Fungal, Antimicrobial Resistance, Antimicrobial Use, and Sepsis Division, UK Health Security Agency (UKHSA), London, UK.
² Evelina London Children's Hospital, London, UK.
³ Faculty of Life Sciences & Medicine, King's College London, London, UK.
⁴ Healthcare-Associated Infection, Fungal, Antimicrobial Resistance, Antimicrobial Use, and Sepsis Division, UK Health Security Agency (UKHSA), London, UK [email protected].

Abstract

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.

Keywords: infectious disease medicine; microbiology; neonatology; sepsis.