NIHR DC Discover

NIHR Signal Daily low-dose antibiotics halve urinary tract infections in people who self-catheterise

Published on 14 August 2018

doi: 10.3310/signal-000634

People who perform clean intermittent self-catheterisation can reduce symptomatic urinary tract infections from two per year to one by taking daily low-dose antibiotics.

This NIHR-funded trial randomised 404 adults in the UK who perform the procedure for a variety of reasons to either daily oral low-dose antibiotics or no prophylaxis. All had a recent history of urinary tract infection.

Although prophylactic antibiotics halved infection rates, it increased antimicrobial resistance compared with the control group who took short courses of antibiotics for each infection. This has implications for the individual and wider population. As overall reported health status was similar between the two groups, it is unclear if this reduction in infection is sufficient to justify wider use of prophylactic antibiotics.

Share your views on the research.

Why was this study needed?

People with bladder obstruction or who have problems with muscle contraction due to neurological disorders may be unable to empty their bladders normally.

Inserting catheters to drain their bladder 3 to 5 times a day is one option. The number of people performing self-catheterisation in the UK is unknown, but approximately 66 million catheters for self-use were prescribed in 2015, costing £103 million.

Up to 88% of people who carry out self-catheterisation experience repeated urinary tract infections (UTIs). The evidence base for daily use of low-dose antibiotics to prevent UTIs in this group of people is currently lacking.

What did this study do?

The AnTIC open-label trial randomised 404 adults from 51 NHS sites to receive either low dose daily antibiotics or no prophylaxis. All participants undertook self-catheterisation and were expected to continue doing so for at least 12 months, and had a previous history of UTIs associated with self-catheterisation. Participants had long-term underlying conditions such as multiple sclerosis, spina bifida or spinal injury.

The prophylaxis group received nitrofurantoin, trimethoprim or cephalexin according to individual suitability. Switching was possible if telephone assessments throughout the study indicated a clinical need.

Study assessors were blinded to treatment allocation, but participants and clinicians were not which may have affected the threshold that each group used for reporting or seeking treatment for UTIs.

What did it find?

  • People who took daily low-dose antibiotics had one UTI over 12 months (interquartile range [IQR] 0 to 2) on average compared with two UTIs in the no prophylaxis group (IQR 1 to 4).
  • Low-dose antibiotics reduced the risk of symptomatic UTI by 48% (incidence rate ratio [IRR] 0.52, 95% confidence interval [CI] 0.44 to 0.6). For microbiologically confirmed UTIs, the result was similar (IRR 0.49, 95% CI 0.39 to 0.60).
  • An increase in resistance to most of the antibiotics used was found in the prophylaxis group from asymptomatic samples taken from three months onwards, but there was no evidence of an increase in resistance in the control group. By 9 to 12 months, resistance to nitrofurantoin, trimethoprim and co-trimoxazole had significantly increased in the prophylaxis group.
  • Health status did not differ between the groups at 12 months according to the Short Form questionnaire-36, in terms of their physical component summary score or mental component summary score.
  • The added cost of preventing one UTI was £99. This did not factor in costs associated with increased antibiotic resistance.

What does current guidance say on this issue?

NICE 2017 guidelines focus on the question of antibiotic prophylaxis for long-term indwelling urinary catheters and in this situation recommend that prophylactic antibiotics should not be routinely given. However, they may be considered for people who have either a history of symptomatic UTIs after catheter change, or who experience trauma during catheter changes.

Current NICE guidelines make no recommendation on the use of antibiotic prophylaxis in intermittent self-catheterisation.

What are the implications?

For people carrying out self-catheterisation, recurrent UTIs add to the difficulties they face with their pre-existing conditions. Though this trial found that low-dose prophylactic antibiotics reduces the risk of UTI, and maybe a useful reduction for some people, it comes at a personal inconvenience of increased pill burden. This potential benefit must be balanced against the potential harm of antimicrobial resistance.

Interestingly, the rate of infection in both groups was much lower than the average of five infections in the year before the study commenced. It may be that the study conditions, such as increased clinical contact or improved technique, reduced the infection risk.

Citation and Funding

Pickard R, Chadwick T, Oluboyede Y, et al. Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT. Health Technol Assess. 2018;22(24):1-102.

This project was funded by the National Institute for Health Research Health Technology Assessment programme (project number 11/72/01).

Bibliography

NICE. Healthcare-associated infections: prevention and control in primary and community care. CG139. London: National Institute for Health and Care Excellence; 2017.

Why was this study needed?

People with bladder obstruction or who have problems with muscle contraction due to neurological disorders may be unable to empty their bladders normally.

Inserting catheters to drain their bladder 3 to 5 times a day is one option. The number of people performing self-catheterisation in the UK is unknown, but approximately 66 million catheters for self-use were prescribed in 2015, costing £103 million.

Up to 88% of people who carry out self-catheterisation experience repeated urinary tract infections (UTIs). The evidence base for daily use of low-dose antibiotics to prevent UTIs in this group of people is currently lacking.

What did this study do?

The AnTIC open-label trial randomised 404 adults from 51 NHS sites to receive either low dose daily antibiotics or no prophylaxis. All participants undertook self-catheterisation and were expected to continue doing so for at least 12 months, and had a previous history of UTIs associated with self-catheterisation. Participants had long-term underlying conditions such as multiple sclerosis, spina bifida or spinal injury.

The prophylaxis group received nitrofurantoin, trimethoprim or cephalexin according to individual suitability. Switching was possible if telephone assessments throughout the study indicated a clinical need.

Study assessors were blinded to treatment allocation, but participants and clinicians were not which may have affected the threshold that each group used for reporting or seeking treatment for UTIs.

What did it find?

  • People who took daily low-dose antibiotics had one UTI over 12 months (interquartile range [IQR] 0 to 2) on average compared with two UTIs in the no prophylaxis group (IQR 1 to 4).
  • Low-dose antibiotics reduced the risk of symptomatic UTI by 48% (incidence rate ratio [IRR] 0.52, 95% confidence interval [CI] 0.44 to 0.6). For microbiologically confirmed UTIs, the result was similar (IRR 0.49, 95% CI 0.39 to 0.60).
  • An increase in resistance to most of the antibiotics used was found in the prophylaxis group from asymptomatic samples taken from three months onwards, but there was no evidence of an increase in resistance in the control group. By 9 to 12 months, resistance to nitrofurantoin, trimethoprim and co-trimoxazole had significantly increased in the prophylaxis group.
  • Health status did not differ between the groups at 12 months according to the Short Form questionnaire-36, in terms of their physical component summary score or mental component summary score.
  • The added cost of preventing one UTI was £99. This did not factor in costs associated with increased antibiotic resistance.

What does current guidance say on this issue?

NICE 2017 guidelines focus on the question of antibiotic prophylaxis for long-term indwelling urinary catheters and in this situation recommend that prophylactic antibiotics should not be routinely given. However, they may be considered for people who have either a history of symptomatic UTIs after catheter change, or who experience trauma during catheter changes.

Current NICE guidelines make no recommendation on the use of antibiotic prophylaxis in intermittent self-catheterisation.

What are the implications?

For people carrying out self-catheterisation, recurrent UTIs add to the difficulties they face with their pre-existing conditions. Though this trial found that low-dose prophylactic antibiotics reduces the risk of UTI, and maybe a useful reduction for some people, it comes at a personal inconvenience of increased pill burden. This potential benefit must be balanced against the potential harm of antimicrobial resistance.

Interestingly, the rate of infection in both groups was much lower than the average of five infections in the year before the study commenced. It may be that the study conditions, such as increased clinical contact or improved technique, reduced the infection risk.

Citation and Funding

Pickard R, Chadwick T, Oluboyede Y, et al. Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT. Health Technol Assess. 2018;22(24):1-102.

This project was funded by the National Institute for Health Research Health Technology Assessment programme (project number 11/72/01).

Bibliography

NICE. Healthcare-associated infections: prevention and control in primary and community care. CG139. London: National Institute for Health and Care Excellence; 2017.

Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT

Published on 16 May 2018

Pickard R, Chadwick T, Oluboyede Y, Brennand C, von Wilamowitz-Moellendorff A, McClurg D, Wilkinson J, Ternent L, Fisher H, Walton K, McColl E, Vale L, Wood R, Abdel-Fattah M, Hilton P, Fader M, Harrison S, Larcombe J, Little P, Timoney A, N’Dow J, Armstrong H, Morris N, Walker K & Thiruchelvam N.

Health Technology Assessment Volume 22 Issue 24 , 2018

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. 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.

Expert commentary

For patients worldwide, clean intermittent self-catheterisation to ensure adequate bladder drainage has transformed the lives of many who otherwise suffered from renal failure and high rates of infection.

Despite clean intermittent self-catheterisation, infections remain a recurring theme for patients, and this important study provides compelling evidence that continuous low-dose antibiotic prophylaxis prevents urinary tract infection.

Concerns about longer-term antibiotic resistance were highlighted, but in the short-term clinicians can now start balancing risks and benefits for patients and further work on the longer terms risk can be established.

Rakesh Heer, Senior Lecturer and Honorary Consultant Urologist, Newcastle University

Expert commentary

Recurrent urinary tract infections (UTIs) are more prevalent in those patients who catheterise themselves regularly, and these episodes are associated with a significant symptom burden.

This trial illustrates the efficacy of daily low dose antibiotics in reducing the incidence of UTI in patients who self-catheterise. The health economic analysis shows that this treatment appears to be cost-effective.

This could now become standard of care, but clinicians should be mindful of the increased levels of antimicrobial resistance found in those given daily antibiotics compared with the placebo group.

Chris Harding, Chairman – British Association of Urological Surgeons Subsection of Female, Neurological and Urodynamic Urology; Consultant Urological Surgeon, Freeman Hospital