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

Abstract

SummaryBackgroundRepeated 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.MethodsIn 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.FindingsBetween 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...

Duration of antibiotic treatment for common infections in English primary care: cross sectional analysis and comparison with guidelines

“…Many countries, including the United Kingdom, are trying to tackle antibiotic resistance by reducing unnecessary or inappropriate prescribing. 1 2 3 The clear link between antibiotic prescribing and resistance at the individual 4 5 and population level 6 indicates that reducing antibiotic prescribing might decrease—or should at least stabilise—levels of antibiotic resistance. 7 8 9 Previous work has reported substantial over-prescribing of antibiotics in primary care in the UK 1 10 11 and elsewhere.…”

How can we improve investigation, prevention and treatment for recurrent urinary tract infections – ICI‐RS 2018

“…As a result of these discussions there are several research priorities which have emerged The definition of what constitutes a UTI needs consensus. Many studies use the pragmatic definition of symptoms plus the taking of a treatment course of antibiotic, whereas others define a UTI based on microbiological tests. Laboratory UTI diagnosis requires refinement and further research is required on point of care testing.…”

“…The definition of what constitutes a UTI needs consensus. Many studies use the pragmatic definition of symptoms plus the taking of a treatment course of antibiotic, whereas others define a UTI based on microbiological tests.…”

“…This information would help clinicians when counselling patients regarding the risks to the individual of long‐term antibiotic use. For example, the recently published ANTIC study demonstrated that prophylactic antibiotics were superior to placebo in reducing rUTI rates for ISC patients, but those treated with antibiotics showed higher rates of antimicrobial resistance . Further exploration of this “trade‐off” is required to improve patient counselling, specifically regarding the risks of antibiotic treatment.…”

Preventing urinary tract infections in patients with neurogenic bladder

“…The International Spinal Cord Injury Urinary Tract Infection Basic Data Set 11 has, therefore, defined a list of symptoms, if new or increasing in severity, that might be present in individuals with spinal cord lesions who have a UTI. Fisher and colleagues 7 have used these signs and symptoms in their study. However, it would have been preferable to have also required a visit to the doctor by patients reporting symptomatic UTI, to provide validation of this important primary outcome criterion.…”