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

Abstract

AbstractAimThis 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.MethodsThis 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 <2kg underwent skin and peri-anal carriage swab sampling weekly with paired maternal rectovaginal swabs. Prospective bacteriological culture used MacConkey agar with species identification by API20E and API20NE. All GNB isolates underwent whole genome sequencing on Illumina Miseq platform. Multi-Locus Sequence Typing and SNP-distance analysis were used to identify strain type and infer relatedness.Findings135 carriage swabs were obtained from 34 neonates and 21 paired mothers (21 neonate-mother dyads), yielding 137 GNB isolates of which 112 were high quality de novo assemblies. Neonatal MDR-GNB skin or intestinal carriage prevalence was 41% (14/34) at admission with 85% (11/13) new acquisition occurring by 7 days. Multiple MDR and ESBL - GNB species were carried by neonates at different timepoints, most frequentlyK. pneumoniaeandE. 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 1MDR-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. coliST131 andK. pneumoniaeST3476).ConclusionGambian 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, especiallyKlebsiella pneumoniaeandEscherichia 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 newbornsWhat 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 ofK. pneumoniaeandE. colistrains 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