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Title: Impact of Clostridium difficile infection : clinical and economic perspectives
Author: Nakamura, C. A.
ISNI:       0000 0004 7428 4907
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2017
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Clostridium difficile infection (CDI) is one of the most common causes of infective hospital-acquired diarrhoea and one of the leading causes of healthcare-associated infection (HCAI) worldwide. The emergence of hypervirulent strains has caused outbreaks in several countries, and the disease has been a challenge to healthcare workers, settings and systems mainly related to the disease heterogeneity, high rates of recurrence, antibiotic resistance and high disease-associated healthcare costs. In this thesis, a CDI cohort recruited over different time periods (2008-2012 and 2013- 2015) was used. More patients were recruited by a clinical audit (2008-2012 and 2012-2016) to increase sample size for some of my analyses, and to assess the representativeness of the cohort group. In general, the cohort and audit groups were similar, but did have some notable differences: audit patients were older [79 vs 75 years (IQR: 61-81), p<0.001 for phase I and 77 vs 66 years (IQR: 56-79), p=0.007 for phase II], and more debilitated as mortality rates were higher, considering both shortterm mortality (32% vs 7%, p<0.001, for phase I and 25% vs 4%, p<0.001, for phase II) and long-term mortality (62% vs 32%, p<0.001, for phase I and 59% vs 41%, p=0.010, for phase II). Taking all patients from 2012 to 2016 into consideration, carrier patients (GDH+/TOX- /PCR+) and CDI cases were more likely to have had longer hospitalisation [(HR=0.73, 95% CI: 0.59-0.90) and (HR=0.76, 95% CI: 0.61-0.95)], to have died within 1 year [(OR=2.34, 95% CI: 1.30-4.24) and (OR=3.02, 95% CI: 1.71-5.41)], and have incurred higher costs [(OR=1.18, 95% CI: 1.07-1.31) and (OR=1.25, 95% CI: 1.13-1.38)] compared to diarrhoea control patients. Considering only patients infected by toxigenic strains, a toxin positive test was a predictor of only CDI severity (OR=3.18, 95% CI: 1.05-9.60). The addition of a third and confirmatory diagnostic test was costsaving when considering the use of a high cost antibiotic. When procalcitonin (PCT) was measured within 72 hours after the C. difficile test in cohort patients, high levels of PCT were associated with CDI diagnosis (OR=1.76, 95% CI: 1.04-2.58), CDI severity (OR=1.56, 95% CI: 1.18-2.07), long-term mortality (OR=1.43, 95% CI: 1.15-1.77) and with increased risk of delayed discharge (HR=0.87, 95% CI: 0.80-0.95). A toxin positive result was only predictive of time to discharge when PCT was one of the covariates of the models. Cost-effective interventional measures identified by the systematic review undertaken in this thesis were screening all patients during admission, vaccination in a simulation model, treatment with fidaxomicin (FDX) and faecal microbiota transplantation (FMT) via colonoscopy. Multivariable analysis showed that costs of hospitalisation were higher for CDI cases than diarrhoea control patients in phase I (£5,761 vs £4,924 for cohort group and £6,272 vs £5,151 for audit and cohort groups). During phase II, CDI cases treated with FDX (£6,355 and £5,694) and GDH+/TOX- patients treated with FDX (£5,746 and £5,448) were more expensive than diarrhoea control patients (£4,227 and £4,251). In conclusion, this thesis has presented clinical and economic perspectives of CDI in epidemic and endemic phases in a secondary healthcare setting. CDI is associated with a number of adverse clinical outcomes, such as higher mortality rates, longer time to discharge and hospitalisation costs, which have been highlighted in this thesis. Tackling CDI requires a multifunctional approach, including prevention and control measures, and better treatment strategies to decrease the incidence rates and improve outcomes in infected patients in a cost-effective manner.
Supervisor: Pirmohamed, Munir ; Hughes, Dyfrig ; O'Brien, Sarah ; Miyajima, Fabio Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral