Sánchez-Diener I1, Zamorano L2, Peña C3, Ocampo-Sosa A4, Cabot G1, Gómez-Zorrilla S5, Almirante B6, Aguilar M7, Granados A8, Calbo E9, Baño JR10, Rodríguez-López F11, Tubau F12, Martínez-Martínez L11, Navas A13, and Oliver A14.

1Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de les Illes Balears (IdISBa), Palma de Mallorca, Spain.
2Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de les Illes Balears (IdISBa), Palma de Mallorca, Spain. Electronic address: laura.zamorano@ssib.es.
3Servicio de Medicina Interna, Hospital Virgen de los Lirios, Alcoy, Spain.
4Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander.
5Hospital del mar, Servicio de Enfermedades Infecciosas, Instituto Hospital del mar de Investigaciones Médicas (IMIM).
6Servicio de Enfermedades Infecciosas, Hospital Universitario Vall d’Hebrón.
7Servicio de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocío, Sevilla.
8Sección de Enfermedades Infecciosas, Consorci Hospitalari Parc Taulí, Sabadell.
9Sección de Enfermedades Infecciosas Hospital Mutua de Terrasa.
10Unidad de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla-IBiS, Sevilla, Spain.
11Unidad de Gestión Clínica de Microbiología, Hospital Universitario Reina Sofía, Córdoba, Spain; Departamento de Microbiología, Universidad de Córdoba, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.
12Hospital de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Universidad de Barcelona L’Hospitalet de Llobregat, Barcelona, Spain; CIBER de Enfermedades Respiratorias (CIBERes), Instituto de Salud Carlos III, Madrid, Spain.
13 Departamento de Biodiversidad y Biología Evolutiva, Museo Nacional de Ciencias Naturales, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
14Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de les Illes Balears (IdISBa), Palma de Mallorca, Spain. Electronic address: antonio.oliver@ssib.es.

Abstract:

OBJECTIVES: We assessed the association between the lethality of Pseudomonas aeruginosa in a Caenorhabditis elegans model and outcomes of P. aeruginosa bloodstream infections.

METHODS: A total of 593 P. aeruginosa bloodstream isolates recovered from a prospective Spanish multicenter study were analyzed. Clinical variables, susceptibility profiles and Type III Secretion System (TTSS) genotypes (exoU/exoS genes) were available from previous studies. A C. elegans virulence score (CEVS) was used, classifying the isolates into high (CEVS 4-5), intermediate (CEVS 3) and low-virulence (CEVS 1-2). The main outcome analyzed was 30-days mortality.

RESULTS: Up to 75% (446/593) of the isolates showed a high-virulence phenotype, and 17% (101/593) a low-virulence one. No association between virulence phenotype and the main outcome variable (30-days) mortality was evidenced (29/101(28.7%) vs 127/446 (28.5%), p=1. However, an inverse association between C. elegans virulence and MDR and XDR profiles was documented (O.R=0.655 (0.571-0.751)) and O.R=0.523 (0.436-0.627), p˂0.001, respectively), whereas the exoU genotype was significantly more frequent among isolates showing high-virulence (10/101 (9.9%)vs 112/446 (25.1%), p˂0.001). Moreover, although significance was not reached, strains showing a high-virulence phenotype tended to be associated with community acquired infections (1/101 (1%) vs 25/446 (5.6%), p=0.065), whereas low-virulence phenotypes tended to be associated with a higher illness severity [such as higher median Pitt Score (2(1-4) vs 1(0-3), p=0.036) or initial multiorgan disfuction (17/101(16.8%) vs 41/446 (9.2%), p=0.024)], with some underlying conditions (such as chronic renal failure 24/101 (23.8%)vs 59/446 (13.2%), p=0.013) and with the respiratory source of infections (17/101 (16.8%) vs 45/446 (10.1%), p=0.058).

CONCLUSIONS: Our results indicate that P. aeruginosa virulence phenotype in C. elegans model correlates with virulence genotype (TTSS) and resistance profile, but it is a poor prognostic marker of mortality in bloodstream infections.

Clin Microbiol Infect. 2019 Jul 6. pii: S1198-743X(19)30389-1. doi: 10.1016/j.cmi.2019.06.034. [Epub ahead of print]

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