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Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study

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Summary

Background

Patients admitted to intensive-care units are at high risk of health-care-associated infections, and many are caused by antimicrobial-resistant pathogens. We aimed to assess excess mortality and length of stay in intensive-care units from bloodstream infections and pneumonia.

Methods

We analysed data collected prospectively from intensive-care units that reported according to the European standard protocol for surveillance of health-care-associated infections. We focused on the most frequent causative microorganisms. Resistance was defined as resistance to ceftazidime (Acinetobacter baumannii or Pseudomonas aeruginosa), third-generation cephalosporins (Escherichia coli), and oxacillin (Staphylococcus aureus). We defined 20 different exposures according to infection site, microorganism, and resistance status. For every exposure, we compared outcomes between patients exposed and unexposed by use of time-dependent regression modelling. We adjusted results for patients' characteristics and time-dependency of the exposure.

Findings

We obtained data for 119 699 patients who were admitted for more than 2 days to 537 intensive-care units in ten countries between Jan 1, 2005, and Dec 31, 2008. Excess risk of death (hazard ratio) for pneumonia in the fully adjusted model ranged from 1·7 (95% CI 1·4–1·9) for drug-sensitive S aureus to 3·5 (2·9–4·2) for drug-resistant P aeruginosa. For bloodstream infections, the excess risk ranged from 2·1 (1·6–2·6) for drug-sensitive S aureus to 4·0 (2·7–5·8) for drug-resistant P aeruginosa. Risk of death associated with antimicrobial resistance (ie, additional risk of death to that of the infection) was 1·2 (1·1–1·4) for pneumonia and 1·2 (0·9–1·5) for bloodstream infections for a combination of all four microorganisms, and was highest for S aureus (pneumonia 1·3 [1·0–1·6], bloodstream infections 1·6 [1·1–2·3]). Antimicrobial resistance did not significantly increase length of stay; the hazard ratio for discharge, dead or alive, for sensitive microorganisms compared with resistant microorganisms (all four combined) was 1·05 (0·97–1·13) for pneumonia and 1·02 (0·98–1·17) for bloodstream infections. P aeruginosa had the highest burden of health-care-acquired infections because of its high prevalence and pathogenicity of both its drug-sensitive and drug-resistant strains.

Interpretation

Health-care-associated bloodstream infections and pneumonia greatly increase mortality and pneumonia increase length of stay in intensive-care units; the additional effect of the most common antimicrobial resistance patterns is comparatively low.

Funding

European Commission (DG Sanco).

Introduction

Patients in intensive-care units are at high risk of health-care-associated infections because of intrinsic (eg, severity of illness or impaired immunity) and extrinsic (eg, mechanical ventilation or central line catheterisation) risk factors. In Europe, 3·0% of patients staying more than 2 days in intensive-care units acquire bloodstream infections, and 6·2% acquire pneumonia.1 Because of their precarious clinical states, common use of antibiotics, and high prevalence of antimicrobial resistance, patients are at high risk of infection with resistant pathogens.2

Data for clinical outcomes of infections and antimicrobial resistance are conflicting.3 A key issue is the contribution of host and infection factors. Data are very dependent on methods used to address differences in patients before infection (such as underlying disease severity), type of infection, and causative pathogen.3 Large studies are needed to provide detailed information on all these factors. Furthermore, modern statistical techniques are needed to account for the timing and duration of exposure4 and the competing risks caused by informative censoring (patients leaving an intensive-care unit alive are by definition in better health than are those that stay).5

We aimed to assess the excess mortality and length of stay in intensive-care units associated with bloodstream infections and pneumonia acquired in intensive care and for infections caused by pathogens with and without some common patterns of antimicrobial resistance. We provide separate estimates for Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, because of their prevalence,1 pathogenicity, burden of antimicrobial resistance, and the availability of data for antimicrobial resistance (tracer phenotypes) in our database. This study was part of the Burden of Resistance and Disease in European Nations (BURDEN) project,6 which was financed by the European Union (EU), and followed previous EU-funded projects that developed and implemented a common protocol for the surveillance of infections associated with health care across Europe (eg, Hospitals in Europe Link for Infection Control through Surveillance and Improving Patient Safety in Europe [HELICS–IPSE]7).

Section snippets

Study design and data collection

Our prospective cohort study is reported in accordance with the strengthening the reporting of observational studies in epidemiology (STROBE) guidelines.8 We obtained data routinely collected by national intensive-care unit surveillance networks in Europe according to the European protocol for surveillance of infections in intensive-care units (HELICS-ICU).9 Participation in national surveillance networks is voluntary, and as such not all European countries have such a network and the number of

Results

We obtained data for ten European countries (Austria, Belgium, Croatia, France, Italy, Latvia, Portugal, Slovakia, Scotland, and Spain) between 2005 and 2008. The final database provided data for 537 intensive-care units that admitted 119 699 patients for more than 2 days (table 1). During their stay, 8525 (7%) patients developed health-care-associated pneumonia and 4787 (4%) had bloodstream infections (any pathogen); 7675 (90%) pneumonias were ventilator-associated.

Table 2 shows descriptive

Discussion

Health-care-associated infections cause high excess mortality in critically ill patients, although antimicrobial resistance has a comparatively low additional effect. Overall estimates (for all four microorganisms) suggest that pneumonia double the risk of death, and bloodstream infections treble the risk, with an additional effect of antimicrobial resistance of around 20% although that was significant only for pneumonia. Antimicrobial resistance had no effect on length of stay in

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