Prospective Multicenter Study of the Impact of Carbapenem Resistance on Mortality in Pseudomonas aeruginosa Bloodstream Infections

Abstract

The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities. Pseudomonas aeruginosa is a leading cause of nosocomial infections, which are often severe (26, 43) and difficult to treat because of their limited susceptibility to antimicrobial agents (35) and the frequent emergence of antibiotic-resistant mutants during therapy (8). Factors related to the host, the organism, and the treatment may increase mortality. With regard to the host, the severity of the underlying disease may be synergistic with infection due to resistant organisms; concomitantly, increased virulence could explain the adverse impact of resistant pathogens on clinical outcomes, although this association has not been demonstrated to date. In addition, factors such as decreased antibiotic effectiveness or a delay in the initiation of therapy may contribute to adverse outcomes in patients infected by resistant pathogens (17).The problem of antibiotic-resistant organisms is increasing (18), and the impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations (2, 5, 9, 15, 25-28, 32, 33, 40, 41, 43), although its contribution to mortality remains uncertain. Measurements of its impact on patients are, by necessity, derived essentially from observational studies, and therefore, an adequate control of confound...

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