Prevalence of Antibiotic Tolerance and Risk for Reinfection Among Escherichia coli Bloodstream Isolates: A Prospective Cohort Study

BACKGROUND: Tolerance is the ability of bacteria to survive transient exposure to high concentrations of a bactericidal antibiotic without a change in the MIC, thereby limiting the efficacy of antimicrobials. The study sought to determine the prevalence of tolerance in a prospective cohort of E. coli bloodstream infection, and to explore the association of tolerance with reinfection risk.

METHODS: Tolerance, determined by the Tolerance Disk Test (TDtest), was tested in a prospective cohort of consecutive patient-unique E. coli bloodstream isolates, and a collection of strains from patients who had recurrent blood cultures with E. coli (Cohorts 1 and 2, respectively) Selected isolates were further analyzed using time-dependent killing and typed using whole genome sequencing. Covariate data were retrieved from electronic medical records. The association between tolerance and reinfection was assessed by the Cox Proportional-Hazards regression and a Poisson regression models.

RESULTS: In cohort 1, 8/94 isolates (8.5%) were tolerant. Using multivariate analysis, it was determined that the risk for reinfection in the patients with tolerant index bacteremia was significantly higher than for patients with non-tolerant strain, Hazard Ratio (HR) of 3.98 (95% CI: 1.32-12.01). The prevalence of tolerance among cohort 2 was higher than in cohort 1, 6/21(28.6%) vs. 8/94 (8.5%), respectively (P = 0.02).

CONCLUSIONS: Tolerant E. coli are frequently encountered among bloodstream isolates, and are associated with an increased risk of reinfection. The TDtest appears to be a practicable approach for tolerance detection and could improve future patient management.