Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT
Background: People carrying out clean intermittent self-catheterisation (CISC) to empty their bladder often suffer repeated urinary tract infections (UTIs). Continuous once-daily, low-dose antibiotic treatment (antibiotic prophylaxis) is commonly advised but knowledge of its effectiveness is lacking...
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| Format: | Article |
| Language: | English |
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NIHR Journals Library
2018-05-01
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| Series: | Health Technology Assessment |
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| Online Access: | https://doi.org/10.3310/hta22240 |
| _version_ | 1818477827712876544 |
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| author | Robert Pickard Thomas Chadwick Yemi Oluboyede Catherine Brennand Alexander von Wilamowitz-Moellendorff Doreen McClurg Jennifer Wilkinson Laura Ternent Holly Fisher Katherine Walton Elaine McColl Luke Vale Ruth Wood Mohamed Abdel-Fattah Paul Hilton Mandy Fader Simon Harrison James Larcombe Paul Little Anthony Timoney James N’Dow Heather Armstrong Nicola Morris Kerry Walker Nikesh Thiruchelvam |
| author_facet | Robert Pickard Thomas Chadwick Yemi Oluboyede Catherine Brennand Alexander von Wilamowitz-Moellendorff Doreen McClurg Jennifer Wilkinson Laura Ternent Holly Fisher Katherine Walton Elaine McColl Luke Vale Ruth Wood Mohamed Abdel-Fattah Paul Hilton Mandy Fader Simon Harrison James Larcombe Paul Little Anthony Timoney James N’Dow Heather Armstrong Nicola Morris Kerry Walker Nikesh Thiruchelvam |
| author_sort | Robert Pickard |
| collection | DOAJ |
| description | Background: People carrying out clean intermittent self-catheterisation (CISC) to empty their bladder often suffer repeated urinary tract infections (UTIs). Continuous once-daily, low-dose antibiotic treatment (antibiotic prophylaxis) is commonly advised but knowledge of its effectiveness is lacking. Objective: To assess the benefit, harms and cost-effectiveness of antibiotic prophylaxis to prevent UTIs in people who perform CISC. Design: Parallel-group, open-label, patient-randomised 12-month trial of allocated intervention with 3-monthly follow-up. Outcome assessors were blind to allocation. Setting: UK NHS, with recruitment of patients from 51 sites. Participants: Four hundred and four adults performing CISC and predicted to continue for ≥ 12 months who had suffered at least two UTIs in the previous year or had been hospitalised for a UTI in the previous year. Interventions: A central randomisation system using random block allocation set by an independent statistician allocated participants to the experimental group [once-daily oral antibiotic prophylaxis using either 50 mg of nitrofurantoin, 100 mg of trimethoprim (Kent Pharmaceuticals, Ashford, UK) or 250 mg of cefalexin (Sandoz Ltd, Holzkirchen, Germany); n = 203] or the control group of no prophylaxis (n = 201), both for 12 months. Main outcome measures: The primary clinical outcome was relative frequency of symptomatic, antibiotic-treated UTI. Cost-effectiveness was assessed by cost per UTI avoided. The secondary measures were microbiologically proven UTI, antimicrobial resistance, health status and participants’ attitudes to antibiotic use. Results: The frequency of symptomatic antibiotic-treated UTI was reduced by 48% using prophylaxis [incidence rate ratio (IRR) 0.52, 95% confidence interval (CI) 0.44 to 0.61; n = 361]. Reduction in microbiologically proven UTI was similar (IRR 0.49, 95% CI 0.39 to 0.60; n = 361). Absolute reduction in UTI episodes over 12 months was from a median (interquartile range) of 2 (1–4) in the no-prophylaxis group (n = 180) to 1 (0–2) in the prophylaxis group (n = 181). The results were unchanged by adjustment for days at risk of UTI and the presence of factors giving higher risk of UTI. Development of antimicrobial resistance was seen more frequently in pathogens isolated from urine and Escherichia coli from perianal swabs in participants allocated to antibiotic prophylaxis. The use of prophylaxis incurred an extra cost of £99 to prevent one UTI (not including costs related to increased antimicrobial resistance). The emotional and practical burden of CISC and UTI influenced well-being, but health status measured over 12 months was similar between groups and did not deteriorate significantly during UTI. Participants were generally unconcerned about using antibiotics, including the possible development of antimicrobial resistance. Limitations: Lack of blinding may have led participants in each group to use different thresholds to trigger reporting and treatment-seeking for UTI. Conclusions: The results of this large randomised trial, conducted in accordance with best practice, demonstrate clear benefit for antibiotic prophylaxis in terms of reducing the frequency of UTI for people carrying out CISC. Antibiotic prophylaxis use appears safe for individuals over 12 months, but the emergence of resistant urinary pathogens may prejudice longer-term management of recurrent UTI and is a public health concern. Future work includes longer-term studies of antimicrobial resistance and studies of non-antibiotic preventative strategies. Trial registration: Current Controlled Trials ISRCTN67145101 and EudraCT 2013-002556-32. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 22, No. 24. See the NIHR Journals Library website for further project information. |
| first_indexed | 2024-12-10T09:41:39Z |
| format | Article |
| id | doaj.art-cf98cf6d5e344324bedcb36272ff61ef |
| institution | Directory Open Access Journal |
| issn | 1366-5278 2046-4924 |
| language | English |
| last_indexed | 2024-12-10T09:41:39Z |
| publishDate | 2018-05-01 |
| publisher | NIHR Journals Library |
| record_format | Article |
| series | Health Technology Assessment |
| spelling | doaj.art-cf98cf6d5e344324bedcb36272ff61ef2022-12-22T01:53:58ZengNIHR Journals LibraryHealth Technology Assessment1366-52782046-49242018-05-01222410.3310/hta2224011/72/01Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCTRobert Pickard0Thomas Chadwick1Yemi Oluboyede2Catherine Brennand3Alexander von Wilamowitz-Moellendorff4Doreen McClurg5Jennifer Wilkinson6Laura Ternent7Holly Fisher8Katherine Walton9Elaine McColl10Luke Vale11Ruth Wood12Mohamed Abdel-Fattah13Paul Hilton14Mandy Fader15Simon Harrison16James Larcombe17Paul Little18Anthony Timoney19James N’Dow20Heather Armstrong21Nicola Morris22Kerry Walker23Nikesh Thiruchelvam24Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UKInstitute of Health and Society, Newcastle University, Newcastle upon Tyne, UKInstitute of Health and Society, Newcastle University, Newcastle upon Tyne, UKNewcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UKNewcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UKNursing, Midwifery and Allied Health Professions Research Unit, Glasgow Caledonian University, Glasgow, UKNewcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UKInstitute of Health and Society, Newcastle University, Newcastle upon Tyne, UKInstitute of Health and Society, Newcastle University, Newcastle upon Tyne, UKDepartment of Microbiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UKInstitute of Health and Society, Newcastle University, Newcastle upon Tyne, UKInstitute of Health and Society, Newcastle University, Newcastle upon Tyne, UKNewcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UKInstitute of Applied Health Sciences, University of Aberdeen, Aberdeen, UKFaculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UKHealth Sciences, University of Southampton, Southampton, UKDepartment of Urology, Mid-Yorkshire Hospitals NHS Trust, Pinderfields Hospital, Wakefield, UKSkerne Medical Centre, Sedgefield, UKPrimary Care and Population Sciences, University of Southampton, Southampton, UKBristol Urological Institute, North Bristol NHS Trust, Bristol, UKInstitute of Applied Health Sciences, University of Aberdeen, Aberdeen, UKPatient representative, no affiliationBristol Urological Institute, North Bristol NHS Trust, Bristol, UKNursing, Midwifery and Allied Health Professions Research Unit, Glasgow Caledonian University, Glasgow, UKDepartment of Urology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UKBackground: People carrying out clean intermittent self-catheterisation (CISC) to empty their bladder often suffer repeated urinary tract infections (UTIs). Continuous once-daily, low-dose antibiotic treatment (antibiotic prophylaxis) is commonly advised but knowledge of its effectiveness is lacking. Objective: To assess the benefit, harms and cost-effectiveness of antibiotic prophylaxis to prevent UTIs in people who perform CISC. Design: Parallel-group, open-label, patient-randomised 12-month trial of allocated intervention with 3-monthly follow-up. Outcome assessors were blind to allocation. Setting: UK NHS, with recruitment of patients from 51 sites. Participants: Four hundred and four adults performing CISC and predicted to continue for ≥ 12 months who had suffered at least two UTIs in the previous year or had been hospitalised for a UTI in the previous year. Interventions: A central randomisation system using random block allocation set by an independent statistician allocated participants to the experimental group [once-daily oral antibiotic prophylaxis using either 50 mg of nitrofurantoin, 100 mg of trimethoprim (Kent Pharmaceuticals, Ashford, UK) or 250 mg of cefalexin (Sandoz Ltd, Holzkirchen, Germany); n = 203] or the control group of no prophylaxis (n = 201), both for 12 months. Main outcome measures: The primary clinical outcome was relative frequency of symptomatic, antibiotic-treated UTI. Cost-effectiveness was assessed by cost per UTI avoided. The secondary measures were microbiologically proven UTI, antimicrobial resistance, health status and participants’ attitudes to antibiotic use. Results: The frequency of symptomatic antibiotic-treated UTI was reduced by 48% using prophylaxis [incidence rate ratio (IRR) 0.52, 95% confidence interval (CI) 0.44 to 0.61; n = 361]. Reduction in microbiologically proven UTI was similar (IRR 0.49, 95% CI 0.39 to 0.60; n = 361). Absolute reduction in UTI episodes over 12 months was from a median (interquartile range) of 2 (1–4) in the no-prophylaxis group (n = 180) to 1 (0–2) in the prophylaxis group (n = 181). The results were unchanged by adjustment for days at risk of UTI and the presence of factors giving higher risk of UTI. Development of antimicrobial resistance was seen more frequently in pathogens isolated from urine and Escherichia coli from perianal swabs in participants allocated to antibiotic prophylaxis. The use of prophylaxis incurred an extra cost of £99 to prevent one UTI (not including costs related to increased antimicrobial resistance). The emotional and practical burden of CISC and UTI influenced well-being, but health status measured over 12 months was similar between groups and did not deteriorate significantly during UTI. Participants were generally unconcerned about using antibiotics, including the possible development of antimicrobial resistance. Limitations: Lack of blinding may have led participants in each group to use different thresholds to trigger reporting and treatment-seeking for UTI. Conclusions: The results of this large randomised trial, conducted in accordance with best practice, demonstrate clear benefit for antibiotic prophylaxis in terms of reducing the frequency of UTI for people carrying out CISC. Antibiotic prophylaxis use appears safe for individuals over 12 months, but the emergence of resistant urinary pathogens may prejudice longer-term management of recurrent UTI and is a public health concern. Future work includes longer-term studies of antimicrobial resistance and studies of non-antibiotic preventative strategies. Trial registration: Current Controlled Trials ISRCTN67145101 and EudraCT 2013-002556-32. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 22, No. 24. See the NIHR Journals Library website for further project information.https://doi.org/10.3310/hta22240randomised controlled trialintermittent catheterisationrecurrent urinary tract infectionanti-bacterial agentsantibiotic prophylaxisurinary pathogensescherichia colioutcome assessmenthealth statusurinary bladdercost-benefit analysisbacterial resistance |
| spellingShingle | Robert Pickard Thomas Chadwick Yemi Oluboyede Catherine Brennand Alexander von Wilamowitz-Moellendorff Doreen McClurg Jennifer Wilkinson Laura Ternent Holly Fisher Katherine Walton Elaine McColl Luke Vale Ruth Wood Mohamed Abdel-Fattah Paul Hilton Mandy Fader Simon Harrison James Larcombe Paul Little Anthony Timoney James N’Dow Heather Armstrong Nicola Morris Kerry Walker Nikesh Thiruchelvam Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT Health Technology Assessment randomised controlled trial intermittent catheterisation recurrent urinary tract infection anti-bacterial agents antibiotic prophylaxis urinary pathogens escherichia coli outcome assessment health status urinary bladder cost-benefit analysis bacterial resistance |
| title | Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT |
| title_full | Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT |
| title_fullStr | Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT |
| title_full_unstemmed | Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT |
| title_short | Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT |
| title_sort | continuous low dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self catheterisation the antic rct |
| topic | randomised controlled trial intermittent catheterisation recurrent urinary tract infection anti-bacterial agents antibiotic prophylaxis urinary pathogens escherichia coli outcome assessment health status urinary bladder cost-benefit analysis bacterial resistance |
| url | https://doi.org/10.3310/hta22240 |
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