#48: Perinatal Transmission of Multi-Drug Resistant Enterobacteriaceae
Authors: Mithal Leena B , Kremer Aspen , Otero Sebastian , Markuly Sotirios N , McCool Randy A , Fisher Joel , Arshad Mehreen 
Published: June 2021

Abstract

Background
There is a global rise in multi-drug resistant (MDR) Gram-negative Enterobacteriaceae. Both maternal and neonatal gut colonization with pathogenic E. coli is associated with risk of invasive infection in infancy. Infections caused by MDR strains have delayed effective therapy and higher morbidity. Additionally, extended spectrum beta-lactamase producing (ESBL) E. coli are persistent gut colonizers. Perinatal transmission of ESBL E. coli could therefore have profound impact on the infant microbiota and health.
Our aims were to 1) Determine the burden of ESBL Enterobacteriaceae (ESBL-E) colonization and rate of perinatal transmission among healthy mother-infant dyads in the Chicago area and 2) Compare rates of perinatal transmission among commensal, antibiotic-susceptible human E. coli strains versus ESBL E. coli strains in a mouse model.

Methods
This is an ongoing prospective study of healthy mothers and term infants born vaginally between 7/2020-11/2020. Maternal demographic and medical history data were collected, including age, race/ethnicity, international travel, and pregnancy/delivery information. Maternal rectal and vaginal swabs (n=62) were collected during labor. Clinical samples were initially grown in media supplemented with ampicillin and vancomycin to suppress growth of most susceptible commensal organisms. The sample was then plated on MacConkey agar (+/-ceftriaxone). We also developed a mouse model of perinatal transmission to determine the rate of transmission among ESBL E. coli compared to the commensal E. coli strain MG1655 and the pan-sensitive uropathogenic E. coli strain UTI89. Pups were sacrificed at 24–48 hours of life or 7 days of life, and presence of antibiotic resistant E. coli was noted.

Results
Human: Median maternal age was 32 years (IQR 30–35). Race was primarily white (84%), 11% Asian, and 10% were of Latina ethnicity. There were 30 (48%) female infants, and 42 (68%) infants received exclusive breastmilk. About half of the mothers reported international travel in the past 2 years (28/62, 45%), and 17/62 (27%) were born outside the USA.
Ampicillin resistant (Amp-R) Enterobacteriaceae were recovered from rectal samples of 59/62 (95%) and vaginal samples of 16/62 (26%) mothers. Ten of 62 (16%) mothers were colonized with ESBL-E. Over half of infant stool samples (27/49, 55%) grew Amp-R Enterobacteriaceae. Of 6 mother-infant dyads with maternal ESBL-E colonization and infant stool available, 2 (33%) infants grew out ESBL-E.

Murine
We tested 4 ESBL E. coli strains and 2 control strains (MG1655 and UTI89) in our perinatal transmission model. We noted that while all strains adequately colonized the gut of the dams, only 2 (ST132 and ST511) of the 4 ESBL E. coli strains and none of the control strains were transmitted efficiently to the mouse pups (Figure 1).

Conclusions
There is notable community colonization of resistant Enterobacteriaceae among healthy mothers in Chicago with significant transmission to infants. Murine model data shows that human ESBL E. coli strains can colonize pregnant dams, and some ESBL E. coli strains appear to be perinatally transmitted more efficiently than non-drug resistant and commensal E. coli strains. Persistence of colonization, genomic factors related to transmission, and impact on the developing infant microbiome are future directions of study.