Sequence Type 393 Associated with Increased Mortality in Escherichia coli Bloodstream Infections. (4th October 2017)

• Record Type: Journal Article
• Authors: Thaden, Joshua T; Sutton, Granger; Ruffin, Felicia; Fouts, Derrick; Fowler, Vance
• Is Part Of: Open forum infectious diseases. Volume 4(2017)Supplement 1
• Page Start: S550
• Page End: S550
• Publication Date: 2017-10-04
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofx163.1430
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: The influence of bacterial sequence type (ST) in Escherichia coli bloodstream infections (BSI) is incompletely understood. Methods: Adult inpatients with E. coli BSI at Duke University were prospectively enrolled from 2002–2015. Bacterial genotypes were determined by whole genome sequencing and multilocus sequence typing. Clinical outcomes associated with STs were evaluated using multivariate regression models adjusted for patient demographics, comorbidities, antibiotic treatment, BSI source, and BSI route (e.g., hospital-acquired). PanOCT was used to define flexible genomic islands (fGI) associated with STs. Results: 193 patients with E. coli BSI were enrolled. The most common STs were ST131 (68/193 [35%]), ST95 (19/193 [10%]), and ST69 (14/193 [7%]) (Figure 1). E. coli BSI with ST393, relative to non-ST393, was associated with increased in-hospital mortality (5/10 [50%] vs.. 35/183 [19%]; P = 0.03). ST393 was not associated with an outbreak, and patient characteristics were similar in those with ST393 vs. non-ST393 BSI. Adjusted analysis similarly revealed an association between ST393 BSI and in-hospital mortality (Odds ratio 4.99; 95% Confidence interval 1.00–24.84; P = 0.05). Genomic analysis revealed 14 fGI associated with ST393 vs. non-ST393 genomes, ranging from 5–35 putative genes. The largest fGI (present in 10/10 [100%] ST393 vs. 43/183 [23%] non-ST393) included 15 genes (15/35 [43%]) with homology to a type III secretion system (T3SS). Additional T3SS components, including genes homologous to a chaperone and two effector genes, were present on a second fGI (10/10 [100%] ST393 vs. 35/183 [19%] non-ST393). Another fGI (10/10 [100%] ST393 vs. 43/183 [23%] non-ST393) contained 8 genes encoding a type 1 CRISPR-Cas system. Conclusion: E. coli ST393 BSI was uncommon but associated with increased mortality. There were substantial genetic differences in ST393 that could account for increased mortality. Disclosures: V. Fowler Jr., Karius, Inc: Grant Investigator, Grant recipient; Pfizer, Novartis, Galderma, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Cubist, Basilea, Affinergy, Janssen, xBiotech, Contrafect: Consultant, Consulting fee; NIH, MedImmune, Cerexa/Forest/Actavis/Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Cubist/Merck; Medical Biosurfaces; Locus; Affinergy; Basilea; Contrafect; Karius: Grant Investigator, Grant recipient; Green Cross, Cubist, Cerexa, Durata, Theravance; Debiopharm: Consultant, Consulting fee; UpToDate: Royalties, Royalties