Project Details

Unraveling Colonization, Transmission Dynamics, and Resistance Determinants of Pantoea species in a Neonatology Unit in a Tertiary Care Children’s Hospital in Bamako, Mali

Sumanth Cherukumilli, MD

Summary

BACKGROUND: Pantoea species are environmental pathogens which are emerging causes of neonatal sepsis (NS). Preliminary data from a neonatal sepsis study in Mali reveal a high culture positivity rate (24%), with Pantoea species accounting for 60% of this burden. GAP: Given the high prevalence of Pantoea in our cohort, we have a novel opportunity to investigate transmission dynamics of this emerging pathogen. HYPOTHESIS: Aim 1: To identify the source of early onset NS (EONS) and late onset NS (LONS) caused by Pantoea species among hospitalized neonates by comparing clinical isolates to environmental and maternal isolates using whole genome sequencing (WGS). Hypothesis A: Both EONS and LONS caused by Pantoea are primarily horizontally acquired. Aim 2: To identify genes associated with third generation cephalosporin resistance (3GC-R) in clinical Pantoea isolates. Hypothesis B: blaOXA-1 and blaCTX-M-15 will be most the most prevalent genes conferring 3GC-R. Aim 3: To identify colonization rates with Pantoea among hospitalized neonates at admission, 24 hours, 48 hours, and one week, and to identify risk factors for Pantoea colonization. Hypothesis C: Pantoea colonization will be <20% on admission but will exceed 80% after two weeks. Hypothesis D: Neonates colonized within 24 hours are likely to have acquired colonization vertically; neonates colonized >24 hours are likely to have acquired colonization horizontally. Hypothesis E: Neonates with prolonged hospitalizations, prior antibiotic exposure, and low birthweight will have higher colonization odds. METHODS: This is a prospective observational study. Neonates with clinical illness will have blood cultures collected (as currently done). All neonates will have rectal cultures collected on admission, at 48 hours, and weekly thereafter. Mothers admitted in labor will have rectovaginal cultures collected, with processing occurring if the baby is admitted. Standard techniques will be utilized for Pantoea isolation and susceptibility testing; WGS will occur on site. For Hypothesis A, the primary outcome is the percentage of horizontally vs. vertically transmitted isolates, with strain relatedness being defined as <5 single nucleotide polymorphisms. For Hypothesis B, the primary outcome will be the percentage of isolates with genes conferring 3GC-R, with the secondary outcome being the percentage of isolates with genes conferring resistance to other antibiotics. For Hypothesis C, the primary outcome will be the percentage of Pantoea colonized neonates by time. For Hypothesis D, the primary outcome will be percentage of horizontally colonized vs. vertically colonized neonates. For Hypothesis E, we will utilize logistic regression to determine risk factors for Pantoea colonization. RESULTS: Pending. IMPACT: This will also be a critical study due to the knowledge it will generate on Pantoea transmission in particular and NS transmission in general. Similar studies of this magnitude are rare in under-resourced LMIC environments, making the knowledge generated from this effort critical for regional stewardship and infection control efforts.