High-risk Escherichia coli clones that cause neonatal meningitis and association with recrudescent infection

Abstract

Neonatal meningitis is a devasting disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis (herein NMEC) and the most common cause of meningitis in preterm neonates. Here we investigated the genomic relatedness of a collection of NMEC strains spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of strains from diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence factor was conserved in all strains; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75 and O2 were most prevalent. Antibiotic resistance genes occurred infrequently. We also monitored the infection dynamics in three patients that suffered relapsed infection caused by the original infecting strain despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggests that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.