EARLY ACQUISITION AND CARRIAGE OF GENETICALLY DIVERSE MULTI-DRUG RESISTANT GRAM-NEGATIVE BACILLI IN HOSPITALISED SMALL VULNERABLE NEWBORNS IN THE GAMBIA

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Abstract
Aim: This detailed genomic study aimed to characterise multi-drug resistant-gram negative bacilli (MDR-GNB) intestinal and skin carriage in small vulnerable newborns and their paired mothers at a low-resource African hospital. Methods: This cross-sectional cohort study was conducted at the only neonatal referral unit in The Gambia with genomic analysis at MRC Unit The Gambia at LSHTM. Neonates K. pneumoniae and E. coli , with heterogeneous strain diversity, no evidence of clonality and 111 distinct antibiotic resistance genes, mostly Beta-Lactams ( Bla -AMPH, Bla- PBP, CTX-M-15, Bla- TEM-105). 76% (16/21) and 62% (13/21) of mothers had recto-vaginal carriage of at least 1 MDR-GNB and ESBL-GNB respectively, most commonly MDR- E. coli ( 76%, 16/21) and MDR- K. pneumoniae (24%, 5/21). Of 21 neonate-mother dyads only one had genetically identical isolates ( E. coli ST131 and K. pneumoniae ST3476). Conclusion: Gambian hospitalised small vulnerable neonates exhibit high MDR and ESBL-GNB carriage prevalence with acquisition between birth and 7 days. The heterogeneous strain diversity and lack of matching isolates between mothers and newborns suggests multiple environmental sources may be important in transmission. Larger genomic studies to confirm these findings in similar resource limited settings is foundational to inform targeted surveillance and infection prevention control policies. What is known: - MDR-GNB, especially Klebsiella pneumoniae and Escherichia coli , are important causes of neonatal invasive infections and mortality in Africa, classified by WHO as pathogens of high priority for research - Neonatal MDR-GNB carriage is a pre-curser for invasive infection, with preterm, low-birth weight neonates (“Small Vulnerable Newborns”) at greatest risk - Maternal MDR-GNB carriage is a risk factor for neonatal pathogen acquisition in Europe and other well-resourced settings, but a priority evidence gap exists for transmission pathways for small vulnerable African newborns What this study adds: - Hospitalised Gambian small vulnerable neonates have high carriage prevalence of MDR- and ESBL-GNB with acquisition occurring between birth and 7 days - Heterogeneous diversity of K. pneumoniae and E. coli strains suggests multiple environmental sources with no evidence of clonal outbreak - Beta-lactamase genes were most commonly identified with high rates of ESBL- and AMP-C gene production - Despite high maternal MDR-GNB carriage prevalence there is no genomic evidence indicating widespread transmission from mother to newborn

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