Gut residentEscherichia coliprofile predicts the eighteen-month probability and antimicrobial susceptibility of urinary tract infections
Authors: Tchesnokova Veronika , Larson Lydia , Basova Irina , Sledneva Yulia , Choudhury Debarati , Solyanik Thalia , Heng Jennifer , Bonilla Teresa Cristina , Pasumansky Isaac , Bowers Victoria , Pham Sophia , Madziwa Lawrence T. , Holden Erika , Tartof Sara Y. , Ralston James D. , Sokurenko Evgeni V. 
Published: April 2024

Background

Community-acquired UTI is the most common bacterial infection managed in general medical practice that can lead to life-threatening outcomes. While UTIs are primarily caused byEscherichia colicolonizing the patient’s gut, it is unclear whether the gut residentE. coliprofiles can predict the person’s risks for UTI and optimal antimicrobial treatments. Thus, we conducted an eighteen-month long community-based observational study of fecalE. colicolonization and UTI in women aged 50 years and above.

Methods and Findings

We enrolled a total of 1,804 women distributed among age groups 50-59 yo (437 participants), 60-69 yo (632), 70-79 yo (532), and above 80 yo (203), lacking antibiotic prescriptions for at least one year. The provided fecal samples were plated for the presence ofE. coliand other enterobacteria resistant to trimethoprim/sulfamethoxazole (TMP/STX), ciprofloxacin (CIP) and 3rdgeneration cephalosporins (3GC).E. coliwas also characterized as belonging to the pandemic multi-drug resistant clonal groups ST131 (subclone H30) and ST1193. Following sample collection, the women were monitored for 18 months for occurrence of UTI.

E. coliwas cultured from 90.8% fecal samples, with 24.1% containing bacteria resistant to TMP/STX, 19.4% to CIP, and 7.9% to 3GC. In 62.5% samples, only all-susceptibleE. coliwere present. Overall, there were no age-related differences in resistance prevalence. However, while the totalE. coliH30 and ST1193 carriage rates were similar (4.3% and 4.2%, respectively), there was a notable increase of H30 carriage with age (P = .001), while carriage decreased with age for ST1193 (P = .057).

Within 18 months, 184 women (10.2%) experienced at least one episode of UTI - 10.9% among the gutE. colicarriers and 3.0% among the non-carriers (P=.0013). The UTI risk among carriers ofE. coliH30 but not ST1193 was significantly above average (24.3%, P = .0004). The UTI probability increased with age, occurring in 6.4% of 50-59 yo and 19.7% of 80+ yo (P<.001), with the latter group being especially at high risk for UTI, if they were colonized byE. coliH30 (40.0%, P<.001).

E. coliwas identified in 88.1% of urine samples, with 16.1% resistant to TMP/STX, 16.1% to CIP, 4.2% to 3GC and 73.1% to none of the antibiotics. Among tested urinaryE. coliresistant to antibiotics, 86.1% matched the resistance profile ofE. coliin the fecal samples, with the clonotyping and whole genome sequencing confirming the matching strains’ identity. Positive predictive value (PPV) of using gut resistance profiles to predict UTI pathogens’ susceptibility to TMP/STX, CIP, 3GC and all three antibiotics were 98.4%, 98.3%, 96.6% and 95.3%, respectively. Corresponding negative predictive values (NPV) were 63.0%, 54.8%, 44.4% and 75.8%, respectively. The AUC ROC curve values for the accuracy of fecal diagnostic testing for the prediction of UTI resistance ranged .86-.89. The fecal test-guided drug-bug mismatch rate for empirical (pre-culture) prescription of TMP-SXT or CIP is reduced to ≤2% in 89.6% of patients and 94.8% of patients with an optional 3GC prescription.

Conclusion

The resistance profile and clonal identity of gut colonizingE. coli, along with the carrier’s age, can inform personalized prediction of a patients’ UTI risk and the UTI pathogen’s antibiotic susceptibility within an 18-month period.