Elsevier

Journal of Infection

Volume 74, Issue 2, February 2017, Pages 131-141
Journal of Infection

Attributable mortality of ICU-acquired bloodstream infections: Impact of the source, causative micro-organism, resistance profile and antimicrobial therapy

https://doi.org/10.1016/j.jinf.2016.11.001Get rights and content

Highlights

  • Bloodstream Infection acquired in ICU was associated with an increase in the risk mortality.

  • Early adequate antimicrobial therapy was associated with a better outcome.

  • This was true whatever the susceptibility of the causative bacteria.

  • Fluoroquinolone use, but not aminoglycoside use, was associated with an improved outcome.

Summary

Objectives

ICU-acquired bloodstream infection (ICUsingle bondBSI) in Intensive Care unit (ICU) is still associated with a high mortality rate. The increase of antimicrobial drug resistance makes its treatment increasingly challenging.

Methods

We analyzed 571 ICU–BSI occurring amongst 10,734 patients who were prospectively included in the Outcomerea Database and who stayed at least 4 days in ICU. The hazard ratio of death associated with ICU–BSI was estimated using a multivariate Cox model adjusted on case mix, patient severity and daily SOFA.

Results

ICU–BSI was associated with increased mortality (HR, 1.40; 95% CI, 1.16–1.69; p = 0.0004). The relative increase in the risk of death was 130% (HR, 2.3; 95% CI, 1.8–3.0) when initial antimicrobial agents within a day of ICU–BSI onset were not adequate, versus only 20% (HR, 1.2; 95% CI, 0.9–1.5) when an adequate therapy was started within a day. The adjusted hazard ratio of death was significant overall, and even higher when the ICU–BSI source was pneumonia or unknown origin. When treated with appropriate antimicrobial agents, the death risk increase was similar for ICU–BSI due to multidrug resistant pathogens or susceptible ones. Interestingly, combination therapy with a fluoroquinolone was associated with more favorable outcome than monotherapy, whereas combination with aminoglycoside was associated with similar mortality than monotherapy.

Conclusions

ICU–BSI was associated with a 40% increase in the risk of 30-day mortality, particularly if the early antimicrobial therapy was not adequate. Adequacy of antimicrobial therapy, but not pathogen resistance pattern, impacted attributable mortality.

Introduction

Intensive Care Unit (ICU)-acquired bloodstream infection (ICUsingle bondBSI) is defined by bloodstream infection occurring in patients 72 h after their ICU admission. It occurs within approximately 5% of all ICU patients,1, 2 and remains a frequent cause of severe sepsis associated with increased cost and burden.3 In large cohorts, ICU–BSI was an independent factor for higher mortality when adjusted to severity of illness.4 Conflicting results have been reported regarding the potential influence on the mortality related to ICU–BSI of factors such as the source of infection, the illness severity, the existence of superinfection risk factors, and finally on the pathogen and its susceptibility profile. These discrepancies were likely related to the case-mix: limited cohorts, studies focusing on specific pathogens,5, 6, 7, 8 or on catheter-related ICU–BSI,9 to the definition used for catheter-related ICU–BSI, and to the adjustment for confounding factors. For instance, after the third day in ICU, the capability of many severity scores at admission in predicting the mortality hazard became poor.10, 11 In addition, although its impact on mortality is still debated,4 the increase of antimicrobial resistance, particularly amongst Gram-negative pathogens, may lead to inappropriate initial therapy.12 Not only assessing ICU–BSI impact on mortality is clinically important, but ICU–BSI rate is also an indicator for quality care when benchmarking ICUs. Therefore, determining its exact impact on outcome is critical for an accurate evaluation of ICU care by critical car team.

In the present study, we analyzed the epidemiology, characteristics, risk factors, and microorganism resistance pattern associated with the 30-day mortality of ICU–BSI in a large cohort of patients admitted in the ICUs of the Outcomerea Network. We also evaluated the importance of the antimicrobial treatment according to the drug resistance pattern of the causative pathogen.

Section snippets

Data collection

In participating ICUs, data were collected daily by study monitors helped by senior physicians. For each patient, the data were entered into an electronic case-report form using VIGIREA® and RHEA® data-capture softwares, and then loaded into the OutcomeRea® data warehouse. All codes and definitions were established prior to study initiation. For each patient, age, sex, McCabe score, severity of illness on the first ICU day using the Simplified Acute Physiology Score (SAPS II), Sequential Organ

Results

Out of the 17,014 adult patients included in the database, we restricted the analysis to 10,734 patients who stayed more than 72 h in the ICU as they were susceptible to develop nosocomial infection according to the usual definition. Then we excluded 337 patients who were re-admitted in ICU, and 356 patients with therapeutic limitation. Overall, 4819 (48%) patients were followed up to 30 days or died before; the event-free survival at Day 30 was hypothesized for 1696 (17%) patients who were

Discussion

In this large cohort patients, ICU–BSI was independently associated with a higher risk of mortality, particularly for those not receiving an early initial adequate therapy, regardless of the antimicrobial susceptibility profile of the causative pathogen. This was particularly true in Gram-negative bacilli (non-fermenting ones excluded). An initial combination with fluoroquinolone appeared to be associated with an improved outcome. We worked on a large and high quality database, and used a Cox

Conflict of interest

None.

Financial/nonfinancial disclosures

The study was entirely funded by the Outcomerea Research Network and was supported in part by a research grant on ICU-acquired bloodstream infections from 3M company.

Acknowledgment

The authors thank Celine Feger, MD (EMIBiotech), for her editorial support.

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