Original

Intensive Care Medicine

, Volume 38, Issue 12, pp 2007-2016

Pathophysiology of Escherichia coli ventilator-associated pneumonia: implication of highly virulent extraintestinal pathogenic strains

  • Jonathan MessikaAffiliated withInstitut National de la Santé et de la Recherche Médicale, INSERM U722Univ Paris Diderot, Sorbonne Paris Cité, UMR 722AP-HP, Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier
  • , Fatma MagdoudAffiliated withAP-HP, Laboratoire de Microbiologie et Hygiène, Hôpital Louis Mourier
  • , Olivier ClermontAffiliated withInstitut National de la Santé et de la Recherche Médicale, INSERM U722Univ Paris Diderot, Sorbonne Paris Cité, UMR 722
  • , Dimitri MargetisAffiliated withInstitut National de la Santé et de la Recherche Médicale, INSERM U722Univ Paris Diderot, Sorbonne Paris Cité, UMR 722AP-HP, Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier
  • , Stéphane GaudryAffiliated withInstitut National de la Santé et de la Recherche Médicale, INSERM U722Univ Paris Diderot, Sorbonne Paris Cité, UMR 722AP-HP, Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier
  • , Damien RouxAffiliated withInstitut National de la Santé et de la Recherche Médicale, INSERM U722Univ Paris Diderot, Sorbonne Paris Cité, UMR 722AP-HP, Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier
  • , Catherine BrangerAffiliated withInstitut National de la Santé et de la Recherche Médicale, INSERM U722Univ Paris Diderot, Sorbonne Paris Cité, UMR 722AP-HP, Laboratoire de Microbiologie et Hygiène, Hôpital Louis Mourier
  • , Didier DreyfussAffiliated withInstitut National de la Santé et de la Recherche Médicale, INSERM U722Univ Paris Diderot, Sorbonne Paris Cité, UMR 722AP-HP, Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier
  • , Erick DenamurAffiliated withInstitut National de la Santé et de la Recherche Médicale, INSERM U722Univ Paris Diderot, Sorbonne Paris Cité, UMR 722
    • , Jean-Damien RicardAffiliated withInstitut National de la Santé et de la Recherche Médicale, INSERM U722Univ Paris Diderot, Sorbonne Paris Cité, UMR 722AP-HP, Service de Réanimation Médico-Chirurgicale, Hôpital Louis MourierService de Réanimation Médico-Chirurgicale, CHU Louis Mourier Email author 

Abstract

Purpose

To characterize Escherichia coli ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients by determining antibioresistance and genotypic characteristics of E. coli isolates responsible for VAP or lung colonization, by comparing them with their oropharyngeal and rectal counterparts and by assessing representative isolates’ virulence in a pneumonia mouse model.

Methods

Patients under mechanical ventilation for more than 72 h were screened for simultaneous presence of E. coli in rectal, oropharyngeal, and respiratory samples (colonization or VAP). If present, E. coli isolates were characterized by antimicrobial susceptibility, phylogenetic grouping, and virulence factor (VF) gene content determination. BALB/c mice were challenged intranasally with 3.6 × 108 colony-forming units (CFU) of patients’ E. coli isolates.

Results

Multisite E. coli colonization was observed in 19 % of patients (25 patients, 12 with E. coli VAP). One hundred fifteen distinct E. coli isolates were analyzed. B2 phylogenetic group was predominant, with high VF gene content and low antimicrobial resistance. Antimicrobial resistance diversity was observed in four patients with VAP. E. coli isolates from VAP patients were more frequently B2 isolates, with significantly greater VF gene content than lung colonization isolates. Among screened VF genes, iroN and sfa appeared important for lung infection. A very strong correlation (R 2 = 0.99) was found between VF gene content and mortality in the mouse model.

Conclusions

This is the first study establishing antibioresistance and genotypic characteristics of E. coli isolates responsible for VAP in adult ICU patients. These isolates are highly virulent specific extraintestinal pathogenic E. coli strains expressing virulence factors, representing potential targets for new therapies.

Keywords

Nosocomial infection Ventilator-associated pneumonia Escherichia coli Virulence factor genes Antibiotic resistance Animal model