Review
Long-term morbidity and mortality following bloodstream infection: A systematic literature review

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Summary

Objectives

Bloodstream infection results in significant short-term morbidity and mortality. No literature review has studied the long-term outcome following a bloodstream infection. This PROSPERO registered systematic review evaluated studies, which measured the association of a bloodstream infection with long-term morbidity and mortality.

Methods

Databases were systematically searched for studies of adult patients reporting morbidity and/or mortality one year or more following a bloodstream infection in comparison to a matched cohort without a bloodstream infection.

Results

Ten observational studies were included in the final analysis. Five studies assessed only mortality, two assessed morbidity and mortality and three studies assessed morbidity only. The one year mortality ranged from between 8 and 48% for patients with bloodstream infection. The pooled risk ratio of death at one year was significantly higher for patients with bloodstream infection when compared to the matched cohort (RR 4.04 [95% CI 1.84-8.87]).

Conclusions

Bloodstream infection was associated with poor long-term outcome measured at one year when compared to matched controls. More evidence is needed to determine if this association is causative.

Introduction

Bloodstream infections (BSI) are a significant cause of morbidity and mortality worldwide.1 The practice of measuring mortality at one month following a BSI is well established2, 3. A recent review of clinical trials of antibiotics for patients with bloodstream infection in the last 10 years demonstrated all outcomes were measured at 90 days or less.4

BSI have been associated with high long-term mortality, subsequent cardiovascular disease5, 6, 7 and increased risk of recurrent bloodstream infection.8 The interpretation of the impact of BSI in many of these studies is limited by the absence of a suitable comparator group.5, 6, 7 The measurement of outcome following a serious infection beyond the short term is potentially confounded by co-morbid disease as BSI often occurs in patients with pre-disposing disorders, which carry a high risk of increased morbidity and premature death when compared to the general population. Risk factors that have been associated with acquisition of a bloodstream infection include: diabetes, HIV infection, chronic liver disease, previous and repeated hospitalisation, corticosteroid therapy use, chronic renal failure, presence of a solid tumour and overall degree of co-morbid disease.9

The long-term sequelae from other serious infections have been well described.10 Sepsis has been evaluated in multiple studies using outcome measurements such as: quality of life adjusted years, subsequent cardiovascular risk and mortality beyond one year.11 Patients with sepsis have ongoing mortality beyond the usual short-term outcome time point with survivors consistently demonstrating impaired quality of life.11

Understanding the long-term impact of a BSI on mortality and morbidity is important to adequately establish disease burden, define when to measure endpoints for clinical trials and to guide allocation of healthcare and research resources.

The objectives of this systematic review were to (i) identify studies that assessed the outcome (either morbidity or mortality) following a bloodstream infection at one year or greater (ii) where morbidity was assessed, describe the methods used to assess and describe associated morbidities, (iii) include studies which included a matched cohort of patients without bloodstream infection as a comparator.

Section snippets

Methods

This study has been reported in accordance with the PRISMA guidelines on reporting systematic reviews12 and was registered with the PROSPERO international prospective register of systematic reviews (PROSPERO 2016:CRD42016052052) on 8th December 2016, http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016052052.

We searched the following electronic bibliographic databases: EMBASE, PubMed, The Cochrane Library, Scopus and references from included articles. The search strategy included

Study characteristics

The search strategy identified 10,135 citations using the described search strategy as shown in Fig. 1. Two hundred and forty-one abstracts and 39 full-text publications were chosen for full review. Ten studies met our inclusion criteria. Six studies were multicentre studies and four were single centre studies. Study characteristics as shown in Table 2. There were no international multicentre matched studies of long term outcome following a bloodstream infection. JFM and HW completed assessment

Discussion

This systematic review identified ten studies that measured long-term mortality or morbidity as an outcome following a bloodstream infection in comparison to a non-BSI cohort. These were all observational studies, which included different pathogens and included community, health-care associated and hospital acquired infections. Some heterogeneity was expected as studies of this type define different criteria for the included pathogen, the selection of the matched population and the degree and

Funding source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest disclosure

The authors declare no conflicts of interest.

Acknowledgement

The authors would like to thank Mary-Elena McNamara for editing services during the drafting process.

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