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

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

Luisa K Hallmaier-Wacker  1 , Amelia Andrews  1 , Olisaeloka Nsonwu  1 , Alicia Demirjian  1   2   3 , Russell J Hope  1 , Theresa Lamagni  4 , Simon M Collin  1
Affiliations

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

Luisa K Hallmaier-Wacker et al. Arch Dis Child. .

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.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Study selection, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.
Figure 2
Figure 2
Countries represented in the included studies that used blood culture as primary diagnostic method (n=152). Ten of the 152 studies provided data on Gram-negative bacteraemia and meningitis (China ×2, India, Kenya, USA ×3, Canada, Israel, Italy); 7 studies (Malawi, Namibia, Canada, France, Korea, Taiwan, UK) provided data on meningitis only.
Figure 3
Figure 3
Incidence of infant Gram-negative (GN) bacteraemia per 1000 live births by country income. HIC, high-income countries; LMIC, low-income/middle-income countries. *Ramchandar et al 21 include military base study sites outside the USA.
Figure 4
Figure 4
Incidence per 1000 live births of early-onset Gram-negative (GN) bacteraemia by income group. HIC, high-income countries; LMIC, low-income/middle-income countries.
Figure 5
Figure 5
Incidence per 1000 live births of late-onset Gram-negative (GN) bacteraemia by country income. HIC, high-income countries; LMIC, low-income/middle-income countries.
See this image and copyright information in PMC

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