Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study

Milton, Rebecca; Gillespie, David; Dyer, Calie; Taiyari, Khadijeh; Carvalho, Maria J.; Thomson, Kathryn; Sands, Kirsty; Portal, Edward; Hood, Kerenza; Ferreira, Ana Carolina Almeida de Oliveira; Hender, Thomas; Kirby, Nigel; Mathias, Jordan; Nieto, Maria; Watkins, William J.; Bekele, Delayehu; Abayneh, Mahlet; Solomon, Semaria; Basu, Sulagna; Nandy, Ranjan K.; Saha, Bijan; Iregbu, Kenneth; Modibbo, Fatima; Uwaezuoke, Stella; Zahra, Rabaab; Shirazi, Haider; Najeeb, Syed U; Mazarati, Jean-Baptiste; Rucogoza, Aniceth; Gaju, Lucie; Mehtar, Shaheen; Bulabula, Andre N H; Whitelaw, Andrew; Walsh, Timothy R.; Chan, Grace J; Odumade, Oludare A.; Ambachew, Rozina; Yohannes, Zenebe Gebre; Metaferia, Gesit; Workneh, Redeat; Biteye, Tefera; Mohammed, Yahya Zekaria; Teklu, Alula M.; Balkachew, Nigatu; Gezahegn, Wendimagegn; Chakravorty, Partha Sarathi; Naha, Sharmi; Mukherjee, Anuradha; Umar, Khairiyya Muhammad; Akunna, Asunugwo Vivian; Nsude, Queen; Uke, Ifeoma; Okenu, Mary-Joe; Akpulu, Chinenye; Mmadueke, Chukwuemeka; Yakubu, Samuel; Audu, Lamidi Isah; Idris, Nura; Gambo, Safiya; Ibrahim, Jamila; Chinago, Edwin; Yusuf, Ashiru; Gwadabe, Shamsudden; Adeleye, Adeola; Aliyu, Muhammad; Muhammad, Amina; Kassim, Aishatu; Mukaddas, Aisha Sani; Khalid, Rashida Yakubu; Alkali, Fatima Ibrahim; Muhammad, Maryam Yahaya; Tukur, Fatima Muhammad; Muhammad, Surayya Mustapha; Shittu, Adeola; Bello, Murjanatu; ad, Fatima Habib Sa; Zulfiqar, Shaheed; Muhammad, Adil; Jan, Muhammad Hilal; Paterson, Lauren

doi:10.1016/s2214-109x(22)00043-2

Cited by 77 publications

(69 citation statements)

References 33 publications

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“…Further details of the study design and sociodemographic and clinical characteristics of mothers and neonates are described elsewhere 41 …”

Section: Methodsmentioning

confidence: 99%

“…Further details of the study design and sociodemographic and clinical characteristics of mothers and neonates are described elsewhere 41 According to the established protocol, rectal samples were to be taken from all mothers on recruitment and from neonates aged ≥7 d up to 60 d with clinically suspected sepsis. However, during the course of the present study, rectal samples were taken from neonates with clinically suspected sepsis from 0 d of life onward and these samples were also characterized and included in the present study.…”

Section: Methodsmentioning

confidence: 99%

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Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries

et al. 2022

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Early development of the microbiome has been shown to affect general health and physical development of the infant and, although some studies have been undertaken in high-income countries, there are few studies from low- and middle-income countries. As part of the BARNARDS study, we examined the rectal microbiota of 2,931 neonates (term used up to 60 d) with clinical signs of sepsis and of 15,217 mothers screening for blaCTX-M-15, blaNDM, blaKPC and blaOXA-48-like genes, which were detected in 56.1%, 18.5%, 0% and 4.1% of neonates’ rectal swabs and 47.1%, 4.6%, 0% and 1.6% of mothers’ rectal swabs, respectively. Carbapenemase-positive bacteria were identified by MALDI-TOF MS and showed a high diversity of bacterial species (57 distinct species/genera) which exhibited resistance to most of the antibiotics tested. Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae/E. cloacae complex, the most commonly found isolates, were subjected to whole-genome sequencing analysis and revealed close relationships between isolates from different samples, suggesting transmission of bacteria between neonates, and between neonates and mothers. Associations between the carriage of antimicrobial resistance genes (ARGs) and healthcare/environmental factors were identified, and the presence of ARGs was a predictor of neonatal sepsis and adverse birth outcomes.

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“…Further details of the study design and sociodemographic and clinical characteristics of mothers and neonates are described elsewhere 41 …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries

et al. 2022

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“…The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) Study conducted an international prospective observational cohort study across 12 clinical sites that highlighted the burden and high mortality of neonatal sepsis among facility-born neonates in low-income and middle-income countries ( 44 ). Based on data from the Global Burden of Disease Study 2019, similar results were obtained ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Quality assessment of clinical practice guidelines for neonatal sepsis using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument: A systematic review of neonatal guidelines

et al. 2022

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Background and objectiveNeonatal sepsis (NS) continues to be a critical healthcare priority for the coming decades worldwide. The aim of this study was to critically appraise the quality of recent clinical practice guidelines (CPGs) for neonatal sepsis and to summarize and compare their recommendations.MethodsThis study involves a systematic review of CPGs. We identified clinical questions and eligibility criteria and searched and screened for CPGs using bibliographic and CPG databases and professional societies. Each included CPG was assessed by four independent appraisers using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) instrument. We summarized the recommendations in a comparison practical table. The systematic review was drafted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Its protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42021258732).ResultsOur search retrieved 4,432 citations; of which five CPGs were eligible and appraised: American Academy of Pediatrics (AAP 2018) (35 and 34 weeks); Canadian Pediatric Society (CPS 2017); National Institute for Health and Care Excellence (NICE 2021); and Queensland Maternity and Neonatal Services (QH 2020). Among these, the overall assessment of two evidence-based CPGs scored > 70% (NICE and QH), which was consistent with their higher scores in the six domains of the AGREE II instrument. In domain 3 (rigor of development), NICE and QH scored 99 and 60%, respectively. In domain 5 (applicability), they scored 96 and 74%, respectively, and in domain 6 (editorial independence), they scored 90 and 71%, respectively.ConclusionThe methodological quality of the NICE CPG was superior followed by the QH CPG with relevant recommendations for use in practice.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021258732, PROSPERO (CRD42021258732).

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“…The total number of isolates in our meta-analyses from HIC (11 653) was less than for LMIC (14 588) but from half the number of studies (55 vs 90) because LMIC studies were more likely to be single-site and retrospective rather than based on multisite surveillance. Of note here are initiatives such as the Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network, which uses a standardised methodological framework to characterise Gram-negative species causing neonatal sepsis in sub-Saharan African and South Asian countries, including genotyping to identify sequence types and AMR genes 6 53 54. That multisite studies in LMICs reported a lower percentage of Gram-negatives relative to single site LMIC studies may reflect better standardisation of microbiological techniques in multisite studies that allowed for improved detection of Gram-positive organisms such as GBS.…”

Section: Discussionmentioning

confidence: 99%

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

Hallmaier‐Wacker¹,

Andrews²,

Nsonwu³

et al. 2022

Arch Dis Child

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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.

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Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study

Cited by 77 publications

References 33 publications

Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries

Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries

Quality assessment of clinical practice guidelines for neonatal sepsis using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument: A systematic review of neonatal guidelines

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

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