Antibiotics to Prevent Infections in Stroke

The clinical primary outcome measure is the incidence of chest infections in the first 14 days after stroke onset. This will be defined as a temperature greater than 37.5°C on two consecutive measurements or a single measurement of greater than 38.0°C with chest symptoms and one or more of the following:
1. White cell count greater than 11,000/mL
2. Pulmonary infiltrate on chest x-rays
3. Positive microbiology cultures

The primary cost outcome measure will be the total hospital costs (acute and rehabilitation) for the initial episode of care, calculated as a product of costs per day for type of care (standardised NHS tariff) and number of days spent in each care setting.

Current secondary outcome measures as of 30/06/2014:
1. C. difficile diarrhoea, concordance with protocol treatment, discontinuation of prophylaxis or use of additional antibiotics
2. New onset of MRSA infection
3. Adverse Event (AE), Adverse Reaction (AR), Serious Adverse Event / Reaction (SAE / SAR), and Suspected Unexpected Serious Adverse Reactions (SUSAR) as defined per protocol. (Protocol KCH-STR-INF v7.0, 27th July 2011 (2007-004298-24)
4. Death, or chest infection at 14 days of stroke onset
5. National Institute of Health Stroke Scale (NIHSS) at 14 days of stroke onset or at discharge if sooner
6. Change in NIHSS from baseline at 14 days of stroke onset or at discharge if sooner
7. Modified Rankin Scale at 90 (± 14) days post-stroke
8. Patients achieving dichotomised modified Rankin Scale score (mRS 0-2) at 90 (± 14) days post-stroke
9. Ordinal regression analysis of mRS at 90 (± 14) days post stroke
10. Mortality, institutionalisation and mortality or institutionalisation at 90 (± 14) days post stroke
11. EuroqUROQOL EQ-5D-3L and EQ-VAS -5D VAS scores as a whole and comparisons of the domains in the scale at 90 (± 14) days post stroke.
12. Discontinuation of antibiotic prophylaxis in the intervention group (< 4 days of treatment)
13. Antibiotic use in the control group within 7 days of stroke onset
14. Duration of hospital stay
15. Participation in programmed assessment or therapy activities, measured as the number and duration of supervised rehabilitation during hospital stay.
16. Incremental cost-effectiveness ratios (ICERs) if either the intervention or control approach involves an additional cost alongside an improvement in outcome (ICERs will then represent the cost per 1% reduction in incidence of chest infection and/or cost per quality-adjusted life-year (QALY) gained).

Previous secondary outcome measures:
1. Adverse events related to antibiotic use including:
1.1. Antibiotic related side-effects
1.2. New onset of Methicillin Resistant Staphylococcus Aureus (MRSA) infection
1.3. C. difficile diarrhoea
2. Mortality, institutionalisation and measures of activity (Functional Independence Measure), participation (Rankin Scale), mood (Hospital Anxiety and Depression Scale) and quality of life (Euroqol 5D and Visual Analogue Scale [VAS]) at three months
3. Total duration of hospital stay

Secondary economic outcome measures will include Incremental Cost-Effectiveness Ratios (ICERs) and Quality-Adjusted Life-Years (QALY) gained by the intervention.