Influence of virulence genotype and resistance profile in the mortality of Pseudomonas aeruginosa bloodstream infections.
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 multidrug-resistant (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.
Servicio de Enfermedades Infecciosas, Hospital Universitario de Bellvitge-IDIBELL, Barcelona.
Carmen
C
Peña
Unidad de Investigación, Servicio de Microbiología y Servicio de Medicina Interna, Hospital Universitario de Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca.
Gabriel
G
Cabot
Servicio de Enfermedades Infecciosas, Hospital Universitario de Bellvitge-IDIBELL, Barcelona.
Silvia
S
Gómez-Zorrilla
Unidad de Investigación, Servicio de Microbiología y Servicio de Medicina Interna, Hospital Universitario de Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca.
Laura
L
Zamorano
Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander.
Alain
A
Ocampo-Sosa
Unidad de Investigación, Servicio de Microbiología y Servicio de Medicina Interna, Hospital Universitario de Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca.
Javier
J
Murillas
Servicio de Enfermedades Infecciosas, Hospital Universitario Vall d'Hebrón.
Benito
B
Almirante
Unidad de Enfermedades Infecciosas, Hospital Santa Creu i Sant Pau, Barcelona.
Virginia
V
Pomar
Servicio de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocío, Sevilla.
Manuela
M
Aguilar
Sección de Enfermedades Infecciosas, Consorci Hospitalari Parc Taulí, Sabadell.
Ana
A
Granados
Sección de Enfermedades Infecciosas, Hospital Mutua de Terrasa.
Esther
E
Calbo
Sección de Enfermedades Infecciosas, Hospital Universitario Virgen Macarena, Sevilla.
Jesús
J
Rodríguez-Baño
Servicio de Microbiología Infecciosas, Hospital Universitario Reina Sofía-IMIBIC, Córdoba.
Fernando
F
Rodríguez-López
Servicio de Enfermedades Infecciosas, Hospital Universitario de Bellvitge-IDIBELL, Barcelona.
Fe
F
Tubau
Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
Luis
L
Martínez-Martínez
Unidad de Investigación, Servicio de Microbiología y Servicio de Medicina Interna, Hospital Universitario de Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca.
Antonio
A
Oliver
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000382:microbiology* / Q000401:mortality*; D001426:Bacterial Proteins / Q000235:genetics; D058947:Bacterial Secretion Systems / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D010641:Phenotype; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000382:microbiology* / Q000401:mortality*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D012044:Regression Analysis; D013030:Spain; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D037521:Virulence Factors
Pseudomonas aeruginosa; bloodstream infections; multidrug resistance; type III secretion system; virulence