Review
Clinical and economic burden of Clostridium difficile infection in Europe: a systematic review of healthcare-facility-acquired infection

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Summary

PubMed, EMBASE and conference abstracts were reviewed systematically to determine the clinical and economic burden associated with Clostridium difficile infection (CDI) acquired and treated in European healthcare facilities. Inclusion criteria were: published in the English language between 2000 and 2010, and study population of at least 20 patients with documented CDI acquired/treated in European healthcare facilities. Data collection was completed by three unblinded reviewers using the Cochrane Handbook and PRISMA statement. The primary outcomes were mortality, recurrence, length of hospital stay (LOS) and cost related to CDI. In total, 1138 primary articles and conference abstracts were identified, and this was narrowed to 39 and 30 studies, respectively. Data were available from 14 countries, with 47% of studies from UK institutions. CDI mortality at 30 days ranged from 2% (France) to 42% (UK). Mortality rates more than doubled from 1999 to 2004, and continued to rise until 2007 when reductions were noted in the UK. Recurrent CDI varied from 1% (France) to 36% (Ireland); however, recurrence definitions varied between studies. Median LOS ranged from eight days (Belgium) to 27 days (UK). The incremental cost of CDI was £4577 in Ireland and £8843 in Germany, after standardization to 2010 prices. Country-specific estimates, weighted by sample size, ranged from 2.8% to 29.8% for 30-day mortality and from 16 to 37 days for LOS. CDI burden in Europe was most commonly described using 30-day mortality, recurrence, LOS and cost data. The continued spread of CDI and resultant healthcare burden underscores the need for judicious use of antibiotics.

Introduction

Clostridium difficile infection (CDI) is a bacterial infection that can cause symptoms ranging from diarrhoea to life-threatening inflammation of the colon (toxic megacolon). Illness from CDI most commonly occurs after use of antibiotics, and affects elderly patients in healthcare facilities including regional and academic hospitals, long-term care facilities and ambulatory centres. In recent years, CDI has become more frequent, more severe and more difficult to treat. This is primarily due to the emergence of the epidemic C. difficile ribotype 027 clone.1 Whilst it is anticipated that the current epidemic due to this ribotype will decrease over the next decade, it is likely to be replaced by other strains, combined with the continuing evolution of healthcare delivery, thereby maintaining the CDI burden.1

Describing the burden of CDI in Europe is hampered by differential reporting requirements and variability in CDI testing. For example, a Europe-wide hospital-based survey of CDI found that consensus on preferred testing methods is lacking, diagnostic methods are not uniform, and the frequency of testing varies up to 47-fold between countries.2 CDI reporting by hospitals in the National Health Service (NHS) in England became mandatory in 2004, and currently captures CDI data from 167 hospital trusts. While the CDI reporting programme in the UK represents the most extensive of its kind, France and Germany have implemented mandatory reporting for severe cases of CDI, and systematic surveillance is slowly emerging in Spain, Poland and Nordic countries.3, 4

Despite the testing and reporting limitations identified in the study by Bauer et al., their findings provide a valuable insight into the current state of clinical practice and burden of CDI across the European continent.2 In conjunction with the European Centre for Disease Prevention and Control, CDI data were captured from 97 hospitals in 34 European countries. In each country, one to six hospitals were recruited and 509 patients were included. While CDI rates varied considerably, the aggregate rate of CDI in Europe was 4.1 cases out of every 10,000 patient-days, and 18% of the captured CDI cases were recurrent. By Day 90, 22% of patients had died; CDI was the primary or contributive cause of death in 2% and 7% of patients, respectively.2

The clinical burden of CDI is intuitively tied to a commensurate economic burden; however, there is a paucity of data on this topic. Reviews of the available literature reported significant variability in study designs, cost methods and patient populations evaluated, with the majority of studies completed in the USA.5 Drivers of economic outcomes at the hospital level include length of hospital stay (LOS), laboratory tests and antibiotic treatment.6 Population-level economic studies are hindered by limited data on total LOS and use of diagnostics, laboratory tests and treatment for CDI.2 Cost estimates may be derived from hospital records, national formularies or expert opinion.6, 7, 8 Furthermore, most studies are from a hospital or provider perspective, and have little information in relation to third party and societal costs or perspectives. Indeed, a recently published economic computer simulation model aimed to determine the costs of hospital-acquired CDI attributable from all three perspectives, but only in relation to US practice.9 Overall, few studies have made a full evaluation of the cost burden of CDI despite the commonly held assumption that the treatment and management of CDI are extremely costly.5

Inherent obstacles are present in clinical practice and research methodology that have made it difficult to describe the clinical and economic burden of CDI in Europe. The possibility of undertaking economic simulations in relation to European practice would be fraught with difficulties due to the differing natures of the healthcare systems, compounded by the many inherent limitations of economic modelling outlined in the analysis by McGlone et al.9 Therefore, one step towards a co-ordinated and streamlined approach to capturing, evaluating and reporting data on the CDI burden in Europe is to systematically review the current state of understanding around this topic.

Section snippets

Methods

A systematic review of primary articles and conference abstracts was conducted to address the clinical and economic burden of CDI acquired and treated in European healthcare facilities. The Cochrane Handbook and PRISMA statement were used to guide the initial planning and subsequent reporting of the methods capturing literature for this systematic review.10, 11 The criteria outlined in these documents were modified (available on request) to account for the nature (outcomes vs clinical trial)

Overview

In total, 678 primary articles and 460 abstracts addressing the clinical and/or economic burden of CDI were identified. Figure 1 describes the identification, screening, eligibility and inclusion process. Upon further screening and application of eligibility criteria, the literature field was reduced to 39 primary articles and 30 abstracts (Table Ia, Table Ib). The primary CDI outcomes identified in this report are mortality, recurrence, LOS and cost associated with CDI.

Discussion

A clearer understanding of the clinical and economic burden of CDI is of value to a range of key clinical decision makers. Hospital administrators, infection prevention teams and antimicrobial stewardship programmes can use the information to determine appropriate investment scales for these measures compared with use of resources in other priority areas.68 These data are also valuable to diagnostic and pharmaceutical companies in planning to develop, test and price new diagnostics and

Acknowledgements

The authors would like to acknowledge Wendy Wan, a senior research analyst with Pharmerit, and Isaac Foley, who was a research analyst with Pharmerit, for their assistance and significant contributions towards the data collection for the project. The study sponsor did not contribute to the data collection or provide funds for manuscript development.

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