Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality

Abstract

Introduction: To estimate the incidence of intensive care unit (ICU)-acquired bloodstream infection (BSI) and its independent effect on hospital mortality.

Methods: We retrospectively studied acquisition of BSI during admissions of >72 hours to adult ICUs from two university-affiliated hospitals. We obtained demographics, illness severity and co-morbidity data from ICU databases and microbiological diagnoses from departmental electronic records. We assessed survival at hospital discharge or at 90 days if still hospitalized.

Results: We identified 6339 ICU admissions, 330 of which were complicated by BSI (5.2%). Median time to first positive culture was 7 days (IQR 5-12). Overall mortality was 23.5%, 41.2% in patients with BSI and 22.5% in those without. Patients who developed BSI had higher illness severity at ICU admission (median APACHE III score: 79 vs. 68, P < 0.001). After controlling for illness severity and baseline demographics by Cox proportional-hazard model, BSI remained independently associated with risk of death (hazard ratio from diagnosis 2.89; 95% confidence interval 2.41-3.46; P < 0.001). However, only 5% of the deaths in this model could be attributed to acquired-BSI, equivalent to an absolute decrease in survival of 1% of the total population. When analyzed by microbiological classification, Candida, Staphylococcus aureus and gram-negative bacilli infections were independently associated with increased risk of death. In a sub-group analysis intravascular catheter associated BSI remained associated with significant risk of death (hazard ratio 2.64; 95% confidence interval 1.44-4.83; P = 0.002).

Conclusions: ICU-acquired BSI is associated with greater in-hospital mortality, but complicates only 5% of ICU admissions and its absolute effect on population mortality is limited. These findings have implications for the design and interpretation of clinical trials.

Figure 1

Histogram of time of diagnosis of ICU-acquired BSI. Due to uncertainty over the exact time at which blood cultures were taken, some taken in the fourth calendar day in the ICU (first column) might have in fact been taken between 48 and 72 hours after ICU admission. At the most 29 patients may have been miss-attributed. Conversely, use of a later cut-off might exclude a similar number of genuine ICU-acquired BSI. Analysis was designed to err on the side of maximal inclusion. BSI, bloodstream Infection.

Figure 2

Year on year trend in incidence of BSI (Panel a), mortality in patients with BSI (Panel b) and all ICU admissions of longer than 72 hours (Panel c) showing no significant trend in change in these variables over the study period. BSI, bloodstream Infection.

Figure 3

The independent effect of acquired BSI on hospital mortality in a Cox-proportional model of survival after ICU admission of 72 hours or longer. Plots show predicted survival in the absence of acquired bloodstream Infection (BSI) and with BSI occurring at the median time (day 7) and the lower and upper quartiles for time of acquisition (days 5 and 12). All other covariates fixed at population means. Dotted lines show 95% confidence limits.

Figure 4

Plot of scaled Schoenfeld residuals versus transformed time (based on Kaplan-Meir estimate of survival function) demonstrating acceptable linearity for the proportional hazard for the covariate Acquired BSI. Beta(t) is the exponential associated with the covariate, equivalent to the natural logarithm of the hazard ratio. The solid black line is a smoothing-spline fit to the plot, with the broken lines representing a ± 2-standard-error band around the fit. Grey line represents a completely proportional (time-invariant) hazard ratio of 2.89. BSI, bloodstream Infection.

Figure 5

Survival in the Cox-proportional hazard model in the absence of acquired BSI and in the whole population of ICU admissions lasting 72 hours or longer. In this model, at the observed incidence of acquired bloodstream Infection (BSI) in the whole population, only a 1% increase in total hospital mortality can be associated with BSI. All other covariates fixed at population means. Dotted lines show 95% confidence limits.