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

摘要

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 Gramnegative 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.