Molecular Epidemiology Of Esbl-Producing E. Coli And K. Pneumoniae: Establishing Virulence Clusters

Objective: To genetically characterize clusters of virulence factors (VFs) among extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and assess whether these clusters are associated with genetic determinants or clinical outcomes.Methods: One hundred forty-eight E. coli and 82 K. pneumoniae clinical isolates were obtained from 213 patients in Paris, France. Isolates underwent ESBL characterization, MultiLocus Sequence Typing (MLST) typing and phylogenetic group identification. Detection of ten E. coli and seven K. pneumoniae VF-encoding genes were assessed, from which a k-medians partition algorithm with Jaccard similarity measure was used to construct clusters.Results: CTX-M was the predominant ESBL and susceptibility to trimethoprim-sulfamethoxa-zole (32%), ciprofloxacin (22%) and aminoglycosides (32%) was low. In E. coli, there were five identified clusters, with significantly different distributions of ESBL-sequence type (P<0.001), ST131 (P<0.001) and phylogenetic group (P=0.001) between clusters. "Siderophore exclusive", "siderophore exclusive with iroN" and "adhesin sfa/papGIII-rich" clusters had higher 12-month mortality rates compared to others (49% vs 22%, respectively, P=0.02). In K. pneumoniae, three different clusters, with significantly different distributions of aminoglycoside-sensitivity (P<0.004), MLST-type (P<0.001) and relaxase plasmids (P=0.001) were described.Conclusion: Distinct clusters of E. coli and K. pneumoniae VFs are observed within ESBL-producing isolates and are strongly associated with several genetic determinants. Their association with overall morbidity and mortality requires further evidence.