Predictors of Mortality in Bloodstream Infections Caused by Pseudomonas aeruginosa and Impact of Antimicrobial Resistance and Bacterial Virulence

Abstract

Whether multidrug resistance (MDR) is associated with mortality in patients with Pseudomonas aeruginosa bloodstream infections (BSI) remains controversial. Here, we explored the prognostic factors of P. aeruginosa BSI with emphasis on antimicrobial resistance and virulence. All P. aeruginosa BSI episodes in a 5-year period were retrospectively analyzed. The impact in early (5-day) and late (30-day) crude mortality of host, antibiotic treatment, and pathogen factors was assessed by multivariate logistic regression analysis. Of 243 episodes, 93 (38.3%) were caused by MDR-PA. Crude 5-day (20%) and 30-day (33%) mortality was more frequent in patients with MDR-PA (34.4% versus 11.3%, P < 0.001 and 52.7% versus 21.3%, P < 0.001, respectively). Early mortality was associated with neutropenia (adjusted odds ratio [aOR], 9.21; 95% confidence interval [CI], 3.40 to 24.9; P < 0.001), increased Pitt score (aOR, 2.42; 95% CI, 1.34 to 4.36; P = 0.003), respiratory source (aOR, 3.23; 95% CI,2.01 to 5.16; P < 0.001), inadequate empirical therapy (aOR, 4.57; 95% CI, 1.59 to 13.1; P = 0.005), shorter time to positivity of blood culture (aOR, 0.88; 95% CI, 0.80 to 0.97; P = 0.010), an exoU-positive genotype (aOR, 3.58; 95% CI, 1.31 to 9.79; P = 0.013), and the O11 serotype (aOR, 3.64; 95% CI, 1.20 to 11.1; P = 0.022). These risk factors were similarly identified for late mortality, along with an MDR phenotype (aOR, 2.18; 95% CI, 1.04 to 4.58; P = 0.040). Moreover, the O11 serotype (15.2%, 37/243) was common among MDR (78.4%, 29/37) and exoU-positive (89.2%, 33/37) strains. Besides relevant clinical variables and inadequate empirical therapy, pathogen-related factors such as an MDR phenotype, an exoU-positive genotype, and the O11 serotype adversely affect the outcome of P. aeruginosa BSI.

Keywords: Pseudomonas aeruginosa; antimicrobial resistance; bloodstream infections; mortality; virulence.

FIG 1

Study flow diagram. Non-duplicated clinical isolates from P. aeruginosa bloodstream infection patients between 2013 and 2017. Only the first episode of bacteremia recorded for each individual patient was included. MDR, multidrug resistant; PA, P. aeruginosa; BSI, bloodstream infections.

FIG 2

Clinical and pathogen factors in P. aeruginosa isolates from bloodstream infection patients according to O-antigen serotype. The proportion of isolates for each variable is indicated in the bar chart. Statistical significance (P ≤ 0.05) by χ² or Fisher test is represented by colored bars (black, more prevalent; white, less prevalent). MDR, multidrug resistant; NT, nontypeable.

FIG 3

Kaplan-Meier curves showing the crude impact of exoU genotype (A, B, and C) and O11 serotype (D, E, and F) on 30-day mortality in patients with P. aeruginosa bloodstream infections according to the resistance phenotype. Statistical significance was determined by the log-rank test.