Outcomes of Appropriate Empiric Combination versus Monotherapy for Pseudomonas aeruginosa Bacteremia

Abstract

e Pseudomonas aeruginosa bacteremia is associated with high hospital mortality. Empirical combination therapy is commonly used to increase the likelihood of appropriate therapy, but the benefits of employing >1 active agent have yet to be established. The purpose of this study was to compare outcomes of patients receiving appropriate empirical combination versus monotherapy for P. aeruginosa bacteremia. This was a retrospective, multicenter, cohort study of hospitalized adult patients with P. aeruginosa bacteremia from 2002 to 2011. The primary endpoint (30-day mortality) was assessed using multivariate logistic regression, adjusting for underlying confounding variables. Secondary endpoints of hospital mortality and time to mortality were assessed by Fisher's exact test and the Cox proportional hazards model, respectively. A total of 384 patients were analyzed. Thirtyday mortality was higher for patients receiving inappropriate therapy than for those receiving appropriate empirical therapy (43.8% versus 21.5%; P ‫؍‬ 0.03). However, there were no statistical differences in 30-day mortality following appropriate empirical combination versus monotherapy after adjusting for baseline APACHE II scores and lengths of hospital stay prior to the onset of bacteremia (P ‫؍‬ 0.55). Observed hospital mortality was 36.6% for patients administered combination therapy, compared with 28.7% for monotherapy patients (P ‫؍‬ 0.17). After adjusting for baseline APACHE II scores, the relationship between time to mortality and combination therapy was not statistically significant (P ‫؍‬ 0.59). Overall, no significant differences were observed for 30-day mortality, hospital mortality, and time to mortality between combination and monotherapy for P. aeruginosa bacteremia. Empirical combination therapy did not appear to offer an additional benefit, as long as the isolate was susceptible to at least one antimicrobial agent.

Empiric Combination Therapy for Gram-Negative Bacteremia

“…29,30 These studies further support our conclusion that if a sufficiently broad-spectrum b-lactam agent is selected, in the absence of risk factors for MDRGN organisms, b-lactam monotherapy should be adequate.…”

Phenotypic and Genotypic Diversity of Multidrug-Resistant Pseudomonas aeruginosa Isolates from Bloodstream Infections Recovered in the Hospitals of Belo Horizonte, Brazil

“…P. aeruginosa bacteremia, in particular, is associated with high mortality. Reported mortality rates exceed 50% in some series and are even higher within certain populations, such as in patients with severe underlying comorbid conditions or those with immunosuppression [5]. …”

Bacterial sepsis

“…Delayed treatment of the source infection was also associated with an increase in mortality of 1% per hour [106]. Diverse other studies were also able to prove the association of a delayed first application with increased mortality [6,[107][108][109][110][111] and worsening of secondary endpoints (e. g., acute kidney damage; development of acute respiratory distress syndrome, ARDS; increase of the SOFA score; [112][113][114]) among the investigated patient collective. It is therefore not surprising that rash initiation of a calculated antibiotic therapy is one of the most important cornerstones of sepsis treatment [1,7,76,[115][116][117][118][119] and a central element of current guidelines [7].…”