Pathophysiology of Escherichia coli ventilator-associated pneumonia: implication of highly virulent extraintestinal pathogenic strains.
OBJECTIVE
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 × 10(8) 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.
Institut National de la Santé et de la Recherche Médicale, Paris, France.
Jonathan
J
Messika
Fatma
F
Magdoud
Olivier
O
Clermont
Dimitri
D
Margetis
Stéphane
S
Gaudry
Damien
D
Roux
Catherine
C
Branger
Didier
D
Dreyfuss
Erick
E
Denamur
Jean-Damien
JD
Ricard
D000328:Adult; D000368:Aged; D000818:Animals; D002353:Carrier State / Q000453:epidemiology / Q000382:microbiology / Q000503:physiopathology; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000145:classification / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000382:microbiology / Q000503:physiopathology*; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D058889:Molecular Typing; D053717:Pneumonia, Ventilator-Associated / Q000453:epidemiology / Q000382:microbiology / Q000503:physiopathology*; D011446:Prospective Studies; D037521:Virulence Factors / Q000235:genetics*
D037521:Virulence Factors