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

Abstract

BackgroundOne in six infant deaths worldwide are caused by invasive bacterial infections, of which a substantial but unquantified proportion are caused by Gram-negative bacteria.MethodsWe 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).Results152 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%).ConclusionE. 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 numberCRD42020191618.

Bacterial meningitis in Africa

“…Ampicillin-resistant: Ceftriaxone 100.0 mg divided into two doses OR cefotaxime 200.0 to 300.0 mg divided into four doses PLUS gentamicin 7.5 mg divided into three doses. Length therapy, 21 days ( 131 ).…”

Global, regional, and national burden of meningitis and its aetiologies, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

“… 1 , 35 , 36 , 37 A systematic review found that K pneumoniae is the leading cause of Gram-negative meningitis and bacteraemia in low-income and middle-income countries. 38 Despite its high fatal burden, K pneumoniae is not included as a priority pathogen in WHO's meningitis global roadmap, 13 possibly because of a scarcity of global data on meningitis due to K pneumonaie before this study. K pneumoniae is also not included in most commercially available PCR or rapid diagnostic tests.…”

Antibiotic susceptibility of Escherichia coli isolated from neonates admitted to neonatal intensive care units across China from 2015 to 2020

“…Escherichia coli is one of the most well-adapted and pathogenically versatile bacterial organisms ( Riley, 2020 ). It is the main pathogen causing neonatal meningitis and sepsis especially in developing countries ( Tan, 2020 ; van der Flier, 2021 ; Wen et al., 2021 ; Hallmaier-Wacker et al., 2022 ), also a common pathogen of ventilator associated pneumonia (VAP) in hospitals( Scamardo et al., 2020 ). According to the data from the Neonatal Monitoring Network released by NICHD (the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network) in 2020 ( Stoll et al., 2020 ), the most frequent pathogens of early onset neonatal sepsis were E. coli (36.6%) and Group B streptococcus (30.2%), and E. coli mainly occurred in premature infants (51.9%).…”