Journal
CLINICAL INFECTIOUS DISEASES
Volume 60, Issue 4, Pages 539-548Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciu866
Keywords
type III secretion system; multidrug resistance; virulence; bloodstream infections; Pseudomonas aeruginosa
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Funding
- Ministerio de Economia y Competitividad of Spain, Instituto de Salud Carlos III
- European Regional Development Fund A way to achieve Europe through the Spanish Network for the Research in Infectious Diseases [RD06/0008, RD12/0015]
- Direccio General d'Universitats, Recerca i Transferencia del Coneixement del Govern de les Illes Balears
- [08/0276]
- [PS09/00033]
- [11/00164]
- [PI12/00103]
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Background. The type III secretion system (TTSS) is a major virulence determinant of Pseudomonas aeruginosa. The objective of this study was to determine whether the TTSS genotype is a useful prognostic marker of P. aeruginosa bacteremia mortality. We also studied the potential association between TTSS genotypes and multidrugresistant (MDR) profiles, and how this interaction impacts the outcome of bloodstream infections. Methods. We performed a post hoc analysis of a published prospective multicenter cohort of P. aeruginosa bloodstream infections. The impact in mortality of TTSS genotypes (exoS, exoT, exoU, and exoY genes) and resistance profiles was investigated. Cox regression analysis was used to control for confounding variables. Results. Among 590 patients, the 30-day mortality rate was 30% (175 patients), and 53% of them died in the first 5 days (early mortality). The unadjusted probabilities of survival until 5 days was 31.4% (95% confidence interval [CI], 17.4%-49.4%) for the patients with exoU-positive isolates and 53.2% (95% CI, 44.6%-61.5%) for exoU-negative isolates (log rank P = .005). After adjustment for confounders, exoU genotype (adjusted hazard ratio [aHR], 1.90 [95% CI, 1.15-3.14]; P = .01) showed association with early mortality. In contrast, late (30-day) mortality was not influenced by TTSS genotype but was independently associated with MDR profiles (aHR, 1.40 [95% CI, 1.01-1.94]; P = .04). Moreover, the exoU genotype (21% of all isolates) was significantly less frequent (13%) among MDR strains (particularly among extensively drug-resistant isolates, 5%), but was positively linked to moderately resistant (1-2 antipseudomonals) phenotypes (34%). Conclusions. Our results indicate that the exoU genotype, which is associated with specific susceptibility profiles, is a relevant independent marker of early mortality in P. aeruginosa bacteremia.
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