Incidence of Nitrofurantoin Drug Induced Liver Injury
Research type
Research Study
Full title
The incidence and clinical characteristics of Nitrofurantoin drug induced liver injury
IRAS ID
168552
Contact name
Stephen Barclay
Contact email
Duration of Study in the UK
3 years, 10 months, 28 days
Research summary
Nitrofurantoin is a commonly prescribed antibiotic that can cause drug induced liver injury (DILI). Its local use has increased in due to a change in its status, becoming a first line antibiotic for uncomplicated urinary tract infection.
The mechanism of liver damage relates to activation of the host immune system. As patients may have repeated courses of antibiotics over time, or receive the drug prophylactically, the risk of DILI may increase with repeated exposure.
We intend to analyse the incidence of significant Nitrofurantoin DILI at 2 time points, in 2007 (prior to alteration of antimicrobial prescribing guidelines) and in 2013. Prescribing data shows an increase from 134,409 daily dispensed doses/1000 population in 2007, to 472,777/1000 population in 2014. Anecdotally nitrofurantoin DILI has increased over this time.
Significant nitrofurantoin DILI will be defined as that which was significant enough to warrant liver biopsy. Cases will be identified by an electronic pathology search, with screening of reports to include or exclude potential cases by two independent pathologists. For potential cases, case note review will be performed to identify those cases felt to be secondary to nitrofurantoin at the time.
Cases that were histologically compatible with nitrofurantoin DILI but not identified as such, will have a prescription search performed to identify any nitrofurantoin prescriptions in the preceding 3 months. The pattern of nitrofurantoin prescription (acute versus prophylactic) for each case will be recorded. For each year the incidence of nitrofurantoin DILI relative to daily dispensed doses will be calculated to establish if this has increased.
Demographic data (age, sex) and relevant medical history (concurrent medication, past medical history of autoimmune disesase) will be recorded to give a descriptive summary of patients affected. The outcome of nitrofurantoin DILI in terms of liver dysfunction, mortality, liver transplantation, and need for long term immunosupression will be described.REC name
West Midlands - Black Country Research Ethics Committee
REC reference
15/WM/0321
Date of REC Opinion
28 Aug 2015
REC opinion
Favourable Opinion