Observational Study

. 2024 Jun;52(3):1073-1085.

doi: 10.1007/s15010-023-02163-z. Epub 2024 Jan 25.

Clinical presentation and antimicrobial resistance of invasive Escherichia coli disease in hospitalized older adults: a prospective multinational observational study

Joachim Doua^{1

2}, Jesús Rodríguez-Baño^{3

4

5}, Rachel Froget⁶, Padma Puranam⁷, Oscar Go⁸, Jeroen Geurtsen⁹, Sanne van Rooij¹⁰, Tuba Vilken¹¹, Inage Minoru¹², Izumi Yasumori¹³, Bart Spiessens¹, Evelina Tacconelli¹⁴, Lena M Biehl^{15

16}, Joshua T Thaden¹⁷, Michal Sarnecki¹⁸, Herman Goossens¹¹, Jan Poolman⁹, Marc Bonten¹⁰, Miquel Ekkelenkamp¹⁹; COMBACTE-NET Consortium/EXPECT Study Group

Collaborators, Affiliations

Collaborators

COMBACTE-NET Consortium/EXPECT Study Group:
Madison Violette, Sonal Munshi, Moussa Aitabi, Christine Lammens, Sofie Van Mieghem, Sandra Van Puyvelde, Basil Britto Xavier, Anna Maria Azzini, Elda Righi, Nicola Duccio Salerno, Giuliana Lo, Cascio Eleonora Cremonini, Álvaro Pascual, Reinaldo Espíndola, Virginia Palomo, Sarah Walker, Felicia Ruffin, Michael Dagher, Andreja Varjačić

Affiliations

¹ Janssen Research and Development, Infectious Diseases and Vaccines, Janssen Pharmaceutica, Beerse, Belgium.
² European and Developing Countries Clinical Trials Partnership (EDCTP), Brussels, Belgium.
³ Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain.
⁴ Department of Medicine, University of Sevilla and Biomedicine Institute of Sevilla/CSIC, Seville, Spain.
⁵ CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain.
⁶ Inserm Clinical Investigation Center 1435, Dupuytren University Hospital, Limoges, France.
⁷ Health Sciences North Research Institute, Sudbury, ON, Canada.
⁸ Janssen Research and Development, Raritan, NJ, USA.
⁹ Bacterial Vaccines Discovery and Early Development, Janssen Vaccines & Prevention B.V., Leiden, The Netherlands.
¹⁰ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
¹¹ Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
¹² Department of Respiratory Medicine, Okitama Public General Hospital, 2000, Nishi-Otsuka, Kawanishi, Yamagata, Japan.
¹³ Department of General Internal Medicine, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan.
¹⁴ Division of Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, Verona, Italy.
¹⁵ Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50924, Cologne, Germany.
¹⁶ German Centre for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany.
¹⁷ Department of Medicine, Division of Infectious Diseases, Duke University School of Medicine, Durham, NC, USA.
¹⁸ Janssen Vaccines, Branch of Cilag GmbH International, Bern, Switzerland. sarnecki.michal@gmail.com.
¹⁹ Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.

PMID: 38267801
PMCID: PMC11142950
DOI: 10.1007/s15010-023-02163-z

Observational Study

Clinical presentation and antimicrobial resistance of invasive Escherichia coli disease in hospitalized older adults: a prospective multinational observational study

Joachim Doua et al. Infection. 2024 Jun.

. 2024 Jun;52(3):1073-1085.

doi: 10.1007/s15010-023-02163-z. Epub 2024 Jan 25.

Authors

Collaborators

COMBACTE-NET Consortium/EXPECT Study Group:
Madison Violette, Sonal Munshi, Moussa Aitabi, Christine Lammens, Sofie Van Mieghem, Sandra Van Puyvelde, Basil Britto Xavier, Anna Maria Azzini, Elda Righi, Nicola Duccio Salerno, Giuliana Lo, Cascio Eleonora Cremonini, Álvaro Pascual, Reinaldo Espíndola, Virginia Palomo, Sarah Walker, Felicia Ruffin, Michael Dagher, Andreja Varjačić

Affiliations

¹ Janssen Research and Development, Infectious Diseases and Vaccines, Janssen Pharmaceutica, Beerse, Belgium.
² European and Developing Countries Clinical Trials Partnership (EDCTP), Brussels, Belgium.
³ Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain.
⁴ Department of Medicine, University of Sevilla and Biomedicine Institute of Sevilla/CSIC, Seville, Spain.
⁵ CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain.
⁶ Inserm Clinical Investigation Center 1435, Dupuytren University Hospital, Limoges, France.
⁷ Health Sciences North Research Institute, Sudbury, ON, Canada.
⁸ Janssen Research and Development, Raritan, NJ, USA.
⁹ Bacterial Vaccines Discovery and Early Development, Janssen Vaccines & Prevention B.V., Leiden, The Netherlands.
¹⁰ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
¹¹ Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
¹² Department of Respiratory Medicine, Okitama Public General Hospital, 2000, Nishi-Otsuka, Kawanishi, Yamagata, Japan.
¹³ Department of General Internal Medicine, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan.
¹⁴ Division of Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, Verona, Italy.
¹⁵ Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50924, Cologne, Germany.
¹⁶ German Centre for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany.
¹⁷ Department of Medicine, Division of Infectious Diseases, Duke University School of Medicine, Durham, NC, USA.
¹⁸ Janssen Vaccines, Branch of Cilag GmbH International, Bern, Switzerland. sarnecki.michal@gmail.com.
¹⁹ Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.

PMID: 38267801
PMCID: PMC11142950
DOI: 10.1007/s15010-023-02163-z

Abstract

Background: Clinical data characterizing invasive Escherichia coli disease (IED) are limited. We assessed the clinical presentation of IED and antimicrobial resistance (AMR) patterns of causative E. coli isolates in older adults.

Methods: EXPECT-2 (NCT04117113) was a prospective, observational, multinational, hospital-based study conducted in patients with IED aged ≥ 60 years. IED was determined by the microbiological confirmation of E. coli from blood; or by the microbiological confirmation of E. coli from urine or an otherwise sterile body site in the presence of requisite criteria of systemic inflammatory response syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), or quick SOFA (qSOFA). The primary outcomes were the clinical presentation of IED and AMR rates of E. coli isolates to clinically relevant antibiotics. Complications and in-hospital mortality were assessed through 28 days following IED diagnosis.

Results: Of 240 enrolled patients, 80.4% had bacteremic and 19.6% had non-bacteremic IED. One-half of infections (50.4%) were community-acquired. The most common source of infection was the urinary tract (62.9%). Of 240 patients, 65.8% fulfilled ≥ 2 SIRS criteria, and 60.4% had a total SOFA score of ≥ 2. Investigator-diagnosed sepsis and septic shock were reported in 72.1% and 10.0% of patients, respectively. The most common complication was kidney dysfunction (12.9%). The overall in-hospital mortality was 4.6%. Of 299 E. coli isolates tested, the resistance rates were: 30.4% for trimethoprim-sulfamethoxazole, 24.1% for ciprofloxacin, 22.1% for levofloxacin, 16.4% for ceftriaxone, 5.7% for cefepime, and 4.3% for ceftazidime.

Conclusions: The clinical profile of identified IED cases was characterized by high rates of sepsis. IED was associated with high rates of AMR to clinically relevant antibiotics. The identification of IED can be optimized by using a combination of clinical criteria (SIRS, SOFA, or qSOFA) and culture results.

Keywords: Antimicrobial resistance; Bacteremia; Bloodstream infection; Elderly; Extraintestinal pathogenic E. coli; Invasive E. coli disease; Sepsis.

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Conflict of interest statement

JD: Employee and stock option owner of Janssen Research & Development, a pharmaceutical company of Johnson & Johnson. OG: Employee of Janssen Research & Development, a pharmaceutical company of Johnson & Johnson and a shareholder of Johnson & Johnson. JG: Employee and stock (option) owner of Janssen Vaccines & Prevention, a pharmaceutical company of Johnson & Johnson. BS: Employee and share owner of Johnson & Johnson. MS: Employee and unrestricted share owner of Janssen Vaccines, Branch of Cilag GmbH International, a Johnson & Johnson company. JP: Employee and stock option owner of Janssen Research & Development, a pharmaceutical company of Johnson & Johnson. MB: Grants paid to University Medical Center Utrecht (UMCU) from CureVac, Janssen Vaccines, Merck, and Novartis; honoraria payments to MJMB from Takeda; participation on a Data Safety Monitoring Board supported by AstraZeneca, Merck, Novartis, Pfizer, Sanofi, and Spherecydes. JRB, RF, PP, SvR, TV, IM, IY, ET, LMB, JTT, HG, ME: The authors declare that they have no competing interests. Author(s) JD, OG, JG, BS, MS, and JP belong to EFPIA (European Federation of Pharmaceutical Industries and Association) member companies in the Innovative Medicines Initiative Joint Undertaking (IMI JU), and costs related to their part in the research were carried by the respective company as in kind contribution under the IMI JU scheme.

Figures

**Fig. 1**
Study flow diagram. ^aE. coli isolates that were sent to the central laboratory were available in 238 patients: one sample was discarded accidentally, and another was removed after an absence of *E. coli* was discovered upon whole genome sequencing

See this image and copyright information in PMC

References

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Clinical presentation and antimicrobial resistance of invasive Escherichia coli disease in hospitalized older adults: a prospective multinational observational study

Collaborators

Affiliations

Clinical presentation and antimicrobial resistance of invasive Escherichia coli disease in hospitalized older adults: a prospective multinational observational study

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Affiliations

Abstract

Conflict of interest statement

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