Tracing Carriage, Acquisition, and Transmission of ESBL-Producing Escherichia coli Over Two Years in a Tertiary Care Hospital

Infectious Diseases Medicine Environmental and Public Health Life Sciences Microbiology
ESBL-producing Escherichia coli nosocomial acquisition antibiotic selective pressure community setting hospital setting ST131 clade

Report on a Study of the Dynamics of Carriage, Acquisition, and Transmission of ESBL-Producing E. coli (ESBL-EC) in Non-ICU Hospital Wards Over Two Years

Antimicrobial resistance is an increasingly significant global public health issue, with the rapid dissemination of extended-spectrum beta-lactamase-producing (ESBL) Enterobacterales, such as Klebsiella pneumoniae and Escherichia coli, being particularly concerning. These bacteria not only contribute to hospital-acquired infections but also have a substantial impact on community infections. Global surveillance data shows significant geographic variability in the prevalence of ESBL-E strains in Europe, the Middle East, Africa, and the United States, reflecting the complex influence of regional antimicrobial usage policies and resistance transmission patterns.

To investigate the epidemiology of ESBL-E strains in hospitals more deeply and inform effective infection control strategies, this study focused on the carriage, hospital acquisition, transmission, and infection dynamics of ESBL-producing E. coli (ESBL-EC) in non-ICU wards of the highly regarded tertiary care “Università Cattolica Sacro Cuore” hospital in Rome, Italy. Conducted as a two-year prospective study, the findings were published in Genome Medicine (2024, Volume 16, Article 151) by a multidisciplinary international research team including Minh Ngoc Nguyen, Evelina Tacconelli, and Surbhi Malhotra-Kumar.

Why This Study Is Important

Over the past 20 years, endogenous infections—those caused by strains from the patient’s own gut microbiota—have emerged as a critical challenge. Data shows that global intestinal ESBL carriage rates have surged from 7% in 2001-2005 to over 25% in 2016-2020. Simultaneously, Italy has borne one of the highest antimicrobial resistance-related death rates and disease burdens in Europe, particularly for invasive third-generation cephalosporin-resistant E. coli and Klebsiella strains. While previous studies have identified the gut as a key reservoir for hospital infections, gaps in understanding the dynamics of intra-host persistence, inter-patient transmission chains, and horizontal gene transfer have hindered the development of effective infection control measures.

Methods and Study Design

This retrospective analysis examined data and biobank samples from 3,703 patients admitted between 2010 and 2013 to Rome’s “Policlinico A. Gemelli” hospital, focusing on ESBL-EC epidemiology and genomic characteristics.

  1. Patient Classification and Sampling: As part of a larger prospective study, rectal swabs were collected from all admitted patients within 48 hours to screen for ESBL-producing Enterobacterales (ESBL-E).

    • Patients colonized at admission were classified as “positive-at-admission” (PA-ESBL).
    • Previously negative patients who acquired ESBL-E during hospitalization were classified as “hospital-acquired” (HA-ESBL).
    • Non-colonized patients throughout were categorized as “ESBL-free.”

  2. Strain Isolation and Confirmation: Samples were cultured on selective chromogenic media (Brilliance ESBL Agar), and the production of ESBL was confirmed using the double disc diffusion synergy test.

  3. Genome Sequencing and Analysis:

    • Whole-genome sequencing (WGS) of 366 ESBL-EC isolates was performed using Illumina MiSeq to analyze phenotypic resistance, multilocus sequence typing (MLST), and functional pathways of antimicrobial resistance genes.
    • Long-read sequencing was utilized for ST131 isolates, facilitating identification of key pathogenic genes such as fimH, iss, and others.

  4. Transmission and Genomic Relationships:

    • A single nucleotide polymorphism (SNP) analysis, combined with epidemiological data, was conducted to determine clusters of patient-to-patient transmissions. A cut-off of 10 SNPs was used to delineate clonal transmission events.

Key Findings

1. Prevalence and Risk Factors of ESBL in Patients

Among the 3,703 screened patients: - 12.3% (456 patients) were colonized with ESBL-E at admission. - Of those initially negative, 10.6% acquired ESBL-E during hospitalization, resulting in an acquisition density of 7.96 cases per 1,000 patient-days. - Patients treated with antibiotics during their stay showed significantly higher acquisition risks (p < 0.001).

Among the isolates, 71.9% were ESBL-EC, with the globally dominant, multidrug-resistant clonal lineage ST131 being the most frequent sequence type (48.6%).

2. Infection and Transmission Pathways

In 30 patients with confirmed infections, 60% were caused by the patient’s own colonizing strain (endogenous infection), highlighting the critical role of the intestinal reservoir. Patient-to-patient transmission was relatively rare, occurring in 19.2% of cases, across 21 identified clusters involving 48 patients.

3. Characterization of ESBL-EC Strains

  • Genomic analysis revealed that ST131 isolates showed a high degree of resistance and carried virulence genes associated with extraintestinal infections (e.g., iss, iha, and sat). These strains had genetic overlaps with ESBL-EC strains from multiple European countries, indicating transnational spread.
  • The shared profiles of ESBL-EC in PA-ESBL and HA-ESBL cohorts suggest similar clonal diversity and virulence across community and hospital settings.

Academic Significance and Practical Implications

This study provides critical insights into ESBL-EC transmission and infection dynamics in hospital settings:

1. Scientific Contribution

This is the first in-depth characterization of ESBL-EC epidemiology and genomic diversity in non-outbreak hospital conditions, offering a clearer understanding of the role of endogenous gut reservoirs as a primary source of infections.

2. Practical Applications

  • Risk-based Screening: The study highlights high-risk patient groups for ESBL-EC colonization, including patients ≥80 years old, those with prior colonization, recent hospitalizations, residence in long-term care facilities, or those undergoing antibiotic therapy. Targeted screening could reduce unnecessary use of resources while focusing on high-risk cases.
  • Antimicrobial Stewardship: Evidence supports strengthening stewardship programs to reduce unnecessary use of broad-spectrum antibiotics and subsequent colonization risks.

3. Patient Care and Infection Control

Findings suggest most infections stem from endogenous reservoirs rather than cross-patient transmission, emphasizing the need to manage gut microbiota through interventions like optimizing antibiotic prescribing practices. Additionally, hospital environments and healthcare equipment use should be monitored as potential transmission vectors.

Conclusion

This study sheds light on the dynamics of ESBL-E colonization and the trajectories of ESBL-EC infections in a non-outbreak, non-ICU hospital context. Genomic analyses underline the critical role of the gut as an endogenous reservoir of ESBL-E and its involvement in infections among patients colonized prior to or during hospitalization. These findings reinforce the urgency of widespread implementation of antibiotic stewardship programs to relieve antibiotic pressure, thereby reducing ESBL-E incidence and improving healthcare outcomes.