Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC): a randomised, open-label trial

Holly Fisher, Yemi Oluboyede, Thomas Chadwick, Mohamed Abdel-Fattah, Catherine Brennand, Mandy Fader, Simon Harrison, Paul Hilton, James Larcombe, Paul Little, Doreen McClurg, Elaine McColl, James N'Dow, Laura Ternent, Nikesh Thiruchelvam, Anthony Timoney, Luke Vale, Katherine Walton, Alexander von Wilamowitz-Moellendorff, Jennifer Wilkinson & 2 others Ruth Wood, Robert Pickard

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Abstract

Background: Repeated symptomatic urinary tract infections (UTIs) affect 25% of people who use clean intermittent self-catheterisation (CISC) to empty their bladder. We aimed to determine the benefits, harms, and cost-effectiveness of continuous low-dose antibiotic prophylaxis for prevention of recurrent UTIs in adult users of CISC. Methods: In this randomised, open-label, superiority trial, we enrolled participants from 51 UK National Health Service organisations. These participants were community-dwelling (as opposed to hospital inpatient) users of CISC with recurrent UTIs. We randomly allocated participants (1:1) to receive either antibiotic prophylaxis once daily (prophylaxis group) or no prophylaxis (control group) for 12 months by use of an internet-based system with permuted blocks of variable length. Trial and laboratory staff who assessed outcomes were masked to allocation but participants were aware of their treatment group. The primary outcome was the incidence of symptomatic, antibiotic-treated UTIs over 12 months. Participants who completed at least 6 months of follow-up were assumed to provide a reliable estimate of UTI incidence and were included in the analysis of the primary outcome. Change in antimicrobial resistance of urinary and faecal bacteria was monitored as a secondary outcome. The AnTIC trial is registered at ISRCTN, number 67145101; and EudraCT, number 2013-002556-32. Findings: Between Nov 25, 2013, and Jan 29, 2016, we screened 1743 adult users of CISC for eligibility, of whom 404 (23%) participants were enrolled between Nov 26, 2013, and Jan 31, 2016. Of these 404 participants, 203 (50%) were allocated to receive prophylaxis and 201 (50%) to receive no prophylaxis. 1339 participants were excluded before randomisation. The primary analysis included 181 (89%) adults allocated to the prophylaxis group and 180 (90%) adults in the no prophylaxis (control) group. 22 participants in the prophylaxis group and 21 participants in the control group were not included in the primary analysis because they were missing follow-up data before 6 months. The incidence of symptomatic antibiotic-treated UTIs over 12 months was 1·3 cases per person-year (95% CI 1·1–1·6) in the prophylaxis group and 2·6 (2·3–2·9) in the control group, giving an incidence rate ratio of 0·52 (0·44–0·61; p<0·0001), indicating a 48% reduction in UTI frequency after treatment with prophylaxis. Use of prophylaxis was well tolerated: we recorded 22 minor adverse events in the prophylaxis group related to antibiotic prophylaxis during the study, predominantly gastrointestinal disturbance (six participants), skin rash (six participants), and candidal infection (four participants). However, resistance against the antibiotics used for UTI treatment was more frequent in urinary isolates from the prophylaxis group than in those from the control group at 9–12 months of trial participation (nitrofurantoin 12 [24%] of 51 participants from the prophylaxis group vs six [9%] of 64 participants from the control group with at least one isolate; p=0·038), trimethoprim (34 [67%] of 51 vs 21 [33%] of 64; p=0·0003), and co-trimoxazole (26 [53%] of 49 vs 15 [24%] of 62; p=0·002). Interpretation: Continuous antibiotic prophylaxis is effective in reducing UTI frequency in CISC users with recurrent UTIs, and it is well tolerated in these individuals. However, increased resistance of urinary bacteria is a concern that requires surveillance if prophylaxis is started. Funding: UK National Institute for Health Research.

Original languageEnglish
Pages (from-to)957-968
Number of pages12
JournalThe Lancet Infectious Diseases
Volume18
Issue number9
Early online date28 Jun 2018
DOIs
Publication statusPublished - Sep 2018

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Antibiotic Prophylaxis
Urinary Tract Infections
Intermittent Urethral Catheterization
Control Groups
Incidence
Cost-Benefit Analysis
Anti-Bacterial Agents
Bacteria
Independent Living
Nitrofurantoin
Trimethoprim
Sulfamethoxazole Drug Combination Trimethoprim
National Institutes of Health (U.S.)
National Health Programs
Microbial Drug Resistance
Random Allocation
Exanthema
Internet
Inpatients
Urinary Bladder

ASJC Scopus subject areas

  • Infectious Diseases

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Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC) : a randomised, open-label trial. / Fisher, Holly; Oluboyede, Yemi; Chadwick, Thomas; Abdel-Fattah, Mohamed; Brennand, Catherine; Fader, Mandy; Harrison, Simon; Hilton, Paul; Larcombe, James; Little, Paul; McClurg, Doreen; McColl, Elaine; N'Dow, James; Ternent, Laura; Thiruchelvam, Nikesh; Timoney, Anthony; Vale, Luke; Walton, Katherine; von Wilamowitz-Moellendorff, Alexander; Wilkinson, Jennifer; Wood, Ruth; Pickard, Robert.

In: The Lancet Infectious Diseases, Vol. 18, No. 9, 09.2018, p. 957-968.

Research output: Contribution to journalArticle

Fisher, H, Oluboyede, Y, Chadwick, T, Abdel-Fattah, M, Brennand, C, Fader, M, Harrison, S, Hilton, P, Larcombe, J, Little, P, McClurg, D, McColl, E, N'Dow, J, Ternent, L, Thiruchelvam, N, Timoney, A, Vale, L, Walton, K, von Wilamowitz-Moellendorff, A, Wilkinson, J, Wood, R & Pickard, R 2018, 'Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC): a randomised, open-label trial' The Lancet Infectious Diseases, vol. 18, no. 9, pp. 957-968. https://doi.org/10.1016/S1473-3099(18)30279-2
Fisher, Holly ; Oluboyede, Yemi ; Chadwick, Thomas ; Abdel-Fattah, Mohamed ; Brennand, Catherine ; Fader, Mandy ; Harrison, Simon ; Hilton, Paul ; Larcombe, James ; Little, Paul ; McClurg, Doreen ; McColl, Elaine ; N'Dow, James ; Ternent, Laura ; Thiruchelvam, Nikesh ; Timoney, Anthony ; Vale, Luke ; Walton, Katherine ; von Wilamowitz-Moellendorff, Alexander ; Wilkinson, Jennifer ; Wood, Ruth ; Pickard, Robert. / Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC) : a randomised, open-label trial. In: The Lancet Infectious Diseases. 2018 ; Vol. 18, No. 9. pp. 957-968.
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abstract = "Background: Repeated symptomatic urinary tract infections (UTIs) affect 25{\%} of people who use clean intermittent self-catheterisation (CISC) to empty their bladder. We aimed to determine the benefits, harms, and cost-effectiveness of continuous low-dose antibiotic prophylaxis for prevention of recurrent UTIs in adult users of CISC. Methods: In this randomised, open-label, superiority trial, we enrolled participants from 51 UK National Health Service organisations. These participants were community-dwelling (as opposed to hospital inpatient) users of CISC with recurrent UTIs. We randomly allocated participants (1:1) to receive either antibiotic prophylaxis once daily (prophylaxis group) or no prophylaxis (control group) for 12 months by use of an internet-based system with permuted blocks of variable length. Trial and laboratory staff who assessed outcomes were masked to allocation but participants were aware of their treatment group. The primary outcome was the incidence of symptomatic, antibiotic-treated UTIs over 12 months. Participants who completed at least 6 months of follow-up were assumed to provide a reliable estimate of UTI incidence and were included in the analysis of the primary outcome. Change in antimicrobial resistance of urinary and faecal bacteria was monitored as a secondary outcome. The AnTIC trial is registered at ISRCTN, number 67145101; and EudraCT, number 2013-002556-32. Findings: Between Nov 25, 2013, and Jan 29, 2016, we screened 1743 adult users of CISC for eligibility, of whom 404 (23{\%}) participants were enrolled between Nov 26, 2013, and Jan 31, 2016. Of these 404 participants, 203 (50{\%}) were allocated to receive prophylaxis and 201 (50{\%}) to receive no prophylaxis. 1339 participants were excluded before randomisation. The primary analysis included 181 (89{\%}) adults allocated to the prophylaxis group and 180 (90{\%}) adults in the no prophylaxis (control) group. 22 participants in the prophylaxis group and 21 participants in the control group were not included in the primary analysis because they were missing follow-up data before 6 months. The incidence of symptomatic antibiotic-treated UTIs over 12 months was 1·3 cases per person-year (95{\%} CI 1·1–1·6) in the prophylaxis group and 2·6 (2·3–2·9) in the control group, giving an incidence rate ratio of 0·52 (0·44–0·61; p<0·0001), indicating a 48{\%} reduction in UTI frequency after treatment with prophylaxis. Use of prophylaxis was well tolerated: we recorded 22 minor adverse events in the prophylaxis group related to antibiotic prophylaxis during the study, predominantly gastrointestinal disturbance (six participants), skin rash (six participants), and candidal infection (four participants). However, resistance against the antibiotics used for UTI treatment was more frequent in urinary isolates from the prophylaxis group than in those from the control group at 9–12 months of trial participation (nitrofurantoin 12 [24{\%}] of 51 participants from the prophylaxis group vs six [9{\%}] of 64 participants from the control group with at least one isolate; p=0·038), trimethoprim (34 [67{\%}] of 51 vs 21 [33{\%}] of 64; p=0·0003), and co-trimoxazole (26 [53{\%}] of 49 vs 15 [24{\%}] of 62; p=0·002). Interpretation: Continuous antibiotic prophylaxis is effective in reducing UTI frequency in CISC users with recurrent UTIs, and it is well tolerated in these individuals. However, increased resistance of urinary bacteria is a concern that requires surveillance if prophylaxis is started. Funding: UK National Institute for Health Research.",
author = "Holly Fisher and Yemi Oluboyede and Thomas Chadwick and Mohamed Abdel-Fattah and Catherine Brennand and Mandy Fader and Simon Harrison and Paul Hilton and James Larcombe and Paul Little and Doreen McClurg and Elaine McColl and James N'Dow and Laura Ternent and Nikesh Thiruchelvam and Anthony Timoney and Luke Vale and Katherine Walton and {von Wilamowitz-Moellendorff}, Alexander and Jennifer Wilkinson and Ruth Wood and Robert Pickard",
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TY - JOUR

T1 - Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC)

T2 - a randomised, open-label trial

AU - Fisher, Holly

AU - Oluboyede, Yemi

AU - Chadwick, Thomas

AU - Abdel-Fattah, Mohamed

AU - Brennand, Catherine

AU - Fader, Mandy

AU - Harrison, Simon

AU - Hilton, Paul

AU - Larcombe, James

AU - Little, Paul

AU - McClurg, Doreen

AU - McColl, Elaine

AU - N'Dow, James

AU - Ternent, Laura

AU - Thiruchelvam, Nikesh

AU - Timoney, Anthony

AU - Vale, Luke

AU - Walton, Katherine

AU - von Wilamowitz-Moellendorff, Alexander

AU - Wilkinson, Jennifer

AU - Wood, Ruth

AU - Pickard, Robert

N1 - Funder: UK National Institute for Health Research. Open Access funded by Department of Health UK

PY - 2018/9

Y1 - 2018/9

N2 - Background: Repeated symptomatic urinary tract infections (UTIs) affect 25% of people who use clean intermittent self-catheterisation (CISC) to empty their bladder. We aimed to determine the benefits, harms, and cost-effectiveness of continuous low-dose antibiotic prophylaxis for prevention of recurrent UTIs in adult users of CISC. Methods: In this randomised, open-label, superiority trial, we enrolled participants from 51 UK National Health Service organisations. These participants were community-dwelling (as opposed to hospital inpatient) users of CISC with recurrent UTIs. We randomly allocated participants (1:1) to receive either antibiotic prophylaxis once daily (prophylaxis group) or no prophylaxis (control group) for 12 months by use of an internet-based system with permuted blocks of variable length. Trial and laboratory staff who assessed outcomes were masked to allocation but participants were aware of their treatment group. The primary outcome was the incidence of symptomatic, antibiotic-treated UTIs over 12 months. Participants who completed at least 6 months of follow-up were assumed to provide a reliable estimate of UTI incidence and were included in the analysis of the primary outcome. Change in antimicrobial resistance of urinary and faecal bacteria was monitored as a secondary outcome. The AnTIC trial is registered at ISRCTN, number 67145101; and EudraCT, number 2013-002556-32. Findings: Between Nov 25, 2013, and Jan 29, 2016, we screened 1743 adult users of CISC for eligibility, of whom 404 (23%) participants were enrolled between Nov 26, 2013, and Jan 31, 2016. Of these 404 participants, 203 (50%) were allocated to receive prophylaxis and 201 (50%) to receive no prophylaxis. 1339 participants were excluded before randomisation. The primary analysis included 181 (89%) adults allocated to the prophylaxis group and 180 (90%) adults in the no prophylaxis (control) group. 22 participants in the prophylaxis group and 21 participants in the control group were not included in the primary analysis because they were missing follow-up data before 6 months. The incidence of symptomatic antibiotic-treated UTIs over 12 months was 1·3 cases per person-year (95% CI 1·1–1·6) in the prophylaxis group and 2·6 (2·3–2·9) in the control group, giving an incidence rate ratio of 0·52 (0·44–0·61; p<0·0001), indicating a 48% reduction in UTI frequency after treatment with prophylaxis. Use of prophylaxis was well tolerated: we recorded 22 minor adverse events in the prophylaxis group related to antibiotic prophylaxis during the study, predominantly gastrointestinal disturbance (six participants), skin rash (six participants), and candidal infection (four participants). However, resistance against the antibiotics used for UTI treatment was more frequent in urinary isolates from the prophylaxis group than in those from the control group at 9–12 months of trial participation (nitrofurantoin 12 [24%] of 51 participants from the prophylaxis group vs six [9%] of 64 participants from the control group with at least one isolate; p=0·038), trimethoprim (34 [67%] of 51 vs 21 [33%] of 64; p=0·0003), and co-trimoxazole (26 [53%] of 49 vs 15 [24%] of 62; p=0·002). Interpretation: Continuous antibiotic prophylaxis is effective in reducing UTI frequency in CISC users with recurrent UTIs, and it is well tolerated in these individuals. However, increased resistance of urinary bacteria is a concern that requires surveillance if prophylaxis is started. Funding: UK National Institute for Health Research.

AB - Background: Repeated symptomatic urinary tract infections (UTIs) affect 25% of people who use clean intermittent self-catheterisation (CISC) to empty their bladder. We aimed to determine the benefits, harms, and cost-effectiveness of continuous low-dose antibiotic prophylaxis for prevention of recurrent UTIs in adult users of CISC. Methods: In this randomised, open-label, superiority trial, we enrolled participants from 51 UK National Health Service organisations. These participants were community-dwelling (as opposed to hospital inpatient) users of CISC with recurrent UTIs. We randomly allocated participants (1:1) to receive either antibiotic prophylaxis once daily (prophylaxis group) or no prophylaxis (control group) for 12 months by use of an internet-based system with permuted blocks of variable length. Trial and laboratory staff who assessed outcomes were masked to allocation but participants were aware of their treatment group. The primary outcome was the incidence of symptomatic, antibiotic-treated UTIs over 12 months. Participants who completed at least 6 months of follow-up were assumed to provide a reliable estimate of UTI incidence and were included in the analysis of the primary outcome. Change in antimicrobial resistance of urinary and faecal bacteria was monitored as a secondary outcome. The AnTIC trial is registered at ISRCTN, number 67145101; and EudraCT, number 2013-002556-32. Findings: Between Nov 25, 2013, and Jan 29, 2016, we screened 1743 adult users of CISC for eligibility, of whom 404 (23%) participants were enrolled between Nov 26, 2013, and Jan 31, 2016. Of these 404 participants, 203 (50%) were allocated to receive prophylaxis and 201 (50%) to receive no prophylaxis. 1339 participants were excluded before randomisation. The primary analysis included 181 (89%) adults allocated to the prophylaxis group and 180 (90%) adults in the no prophylaxis (control) group. 22 participants in the prophylaxis group and 21 participants in the control group were not included in the primary analysis because they were missing follow-up data before 6 months. The incidence of symptomatic antibiotic-treated UTIs over 12 months was 1·3 cases per person-year (95% CI 1·1–1·6) in the prophylaxis group and 2·6 (2·3–2·9) in the control group, giving an incidence rate ratio of 0·52 (0·44–0·61; p<0·0001), indicating a 48% reduction in UTI frequency after treatment with prophylaxis. Use of prophylaxis was well tolerated: we recorded 22 minor adverse events in the prophylaxis group related to antibiotic prophylaxis during the study, predominantly gastrointestinal disturbance (six participants), skin rash (six participants), and candidal infection (four participants). However, resistance against the antibiotics used for UTI treatment was more frequent in urinary isolates from the prophylaxis group than in those from the control group at 9–12 months of trial participation (nitrofurantoin 12 [24%] of 51 participants from the prophylaxis group vs six [9%] of 64 participants from the control group with at least one isolate; p=0·038), trimethoprim (34 [67%] of 51 vs 21 [33%] of 64; p=0·0003), and co-trimoxazole (26 [53%] of 49 vs 15 [24%] of 62; p=0·002). Interpretation: Continuous antibiotic prophylaxis is effective in reducing UTI frequency in CISC users with recurrent UTIs, and it is well tolerated in these individuals. However, increased resistance of urinary bacteria is a concern that requires surveillance if prophylaxis is started. Funding: UK National Institute for Health Research.

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