Preventing urinary tract infections in patients with neurogenic bladder
Authors: Florian M E Wagenlehner, Adrian Pilatz
Journal: The Lancet Infectious Diseases (2018)

Urological complications are very common among patients with spinal cord injury; development of neurogenic bladder leading to recurrent urinary tract infections (UTIs) and “pyelonephritis being the end condition of a paraplegic”, has determined the fate of these patients for centuries.1Donovan WH Donald Munro Lecture. Spinal cord injury—past, present, and future.J Spinal Cord Med. 2007; 30: 85-100Crossref PubMed Scopus (72) Google Scholar Antibiotic treatment and prevention of UTIs in patients who use clean intermittent self-catheterisation (CISC) have substantially improved the clinical outcomes for patients with neurogenic bladder disturbances.1Donovan WH Donald Munro Lecture. Spinal cord injury—past, present, and future.J Spinal Cord Med. 2007; 30: 85-100Crossref PubMed Scopus (72) Google Scholar, 2Biering-Sørensen F Urinary tract infection in individuals with spinal cord lesion.Curr Opin Urol. 2002; 12: 45-49Crossref PubMed Scopus (44) Google Scholar, 3Biering-Sørensen F Bagi P Høiby N Urinary tract infections in patients with spinal cord lesions: treatment and prevention.Drugs. 2001; 61: 1275-1287Crossref PubMed Scopus (91) Google Scholar, 4Binard JE Persky L Lockhart JL Kelley B Intermittent catheterization the right way! (Volume vs. time-directed).J Spinal Cord Med. 1996; 19: 194-196Crossref PubMed Scopus (20) Google Scholar However, increasing antibiotic resistance during the past decade has called into question whether long-term antibiotic prophylaxis is useful in many types of recurrent UTIs. In recurrent uncomplicated cystitis, guidelines primarily recommend non-antibiotic prophylaxis strategies to reduce the emergence of antibiotic resistance.5Kranz J Schmidt S Lebert C et al.The 2017 update of the German clinical guideline on epidemiology, diagnostics, therapy, prevention, and management of uncomplicated urinary tract infections in adult patients. Part II: therapy and prevention.Urol Int. 2018; 100: 271-278Crossref PubMed Scopus (57) Google Scholar, 6Bonkat G Pickard R Bartoletti R et al.Urological infections.http://uroweb.org/guideline/urological-infections/Date: 2018Date accessed: June 12, 2018Google Scholar Holly Fisher and colleagues7Fisher H Oluboyede Y Chadwick T et al.Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC): a randomised, open-label, superiority trial.Lancet Infect Dis. 2018; (published online June 28.)http://dx.doi.org/10.1016/S1473-3099(18)30279-2Summary Full Text Full Text PDF PubMed Scopus (55) Google Scholar studied the value of continuous antibiotic prophylaxis in patients using CISC. In their randomised, open-label study, they aimed to determine whether antibiotic prophylaxis was superior to no antibiotic prophylaxis in reducing the frequency of symptomatic, antibiotic-treated episodes of UTIs over 12 months. The incidence of symptomatic antibiotic-treated UTIs over 12 months was low: the incidence was 1·3 episodes in the antibiotic prophylaxis group versus 2·6 episodes in the no prophylaxis group. Thus, there was a 48% reduction in UTI frequency with antibiotic prophylaxis, which was significant (p<0·0001). However, the difference in incidence of febrile infections was less pronounced: febrile UTIs occurred in 15 participants in the prophylaxis group and 22 in the no prophylaxis group, but hospital treatment due to UTIs and the incidence of asymptomatic bacteriuria did not differ between groups. This reduction in episodes of symptomatic UTIs was made at the expense of increasing frequency of antibiotic resistance in urinary isolates from the prophylaxis group. This study approach has several important aspects. First, the primary aim, to assess the number of episodes of symptomatic UTIs for which antibiotic treatment was necessary, is entirely correct and substantiated by previous evidence. Earlier studies8Köves B Cai T Veeratterapillay R et al.Benefits and harms of treatment of asymptomatic bacteriuria: a systematic review and meta-analysis by the European Association of Urology Urological Infection Guidelines Panel.Eur Urol. 2017; 72: 865-868Summary Full Text Full Text PDF PubMed Scopus (73) Google Scholar, 9Pannek J Wöllner J Management of urinary tract infections in patients with neurogenic bladder: challenges and solutions.Res Rep Urol. 2017; 9: 121-127PubMed Google Scholar regarding this topic have frequently included onset of bacteriuria as a primary outcome variable. Bacteriuria is not clinically meaningful; asymptomatic bacteriuria, for example, should only rarely be treated. For most people, including patients with neurogenic bladder, treatment of asymptomatic bacteriuria is not beneficial and could even be harmful. This primary aim, to evaluate symptomatic UTIs that require antibiotic treatment, has already been successfully implemented in another trial10Pickard R Lam T MacLennan G et al.Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial.Lancet. 2012; 380: 1927-1935Summary Full Text Full Text PDF PubMed Scopus (183) Google Scholar by the authors, in which different urinary catheter materials were studied. Second, the study was not placebo-controlled and the primary outcome was determined on the basis of patient-reported outcomes. Diagnosis of symptomatic UTIs in patients with neurogenic lower-urinary tract dysfunction can be challenging,11Goetz LL Cardenas DD Kennelly M et al.International spinal cord injury urinary tract infection basic data set.Spinal Cord. 2013; 51: 700-704Crossref PubMed Scopus (64) Google Scholar and symptoms could have been caused by the underlying neurogenic disorder. The International Spinal Cord Injury Urinary Tract Infection Basic Data Set11Goetz LL Cardenas DD Kennelly M et al.International spinal cord injury urinary tract infection basic data set.Spinal Cord. 2013; 51: 700-704Crossref PubMed Scopus (64) Google Scholar 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 colleagues7Fisher H Oluboyede Y Chadwick T et al.Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC): a randomised, open-label, superiority trial.Lancet Infect Dis. 2018; (published online June 28.)http://dx.doi.org/10.1016/S1473-3099(18)30279-2Summary Full Text Full Text PDF PubMed Scopus (55) Google Scholar 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. This validation is especially important because patients in the control group who did not receive placebo were not blinded to the treatment, and knowing that they did not receive antibiotics could have caused them to overestimate when they self-reported their UTIs. The treating physician was also aware of the patient's treatment group, introducing some bias when judging whether the reported symptoms are due to an infection that is dependent on whether the physician believes that prophylaxis will be efficacious. Third, the emergence of antibiotic resistance was carefully assessed from urine and perianal isolates, which is one of the most important ways to evaluate the collateral effects of antibiotic prophylaxis. Resistance against nitrofurantoin, trimethoprim, and co-trimoxazole increased significantly in patients receiving prophylaxis, whereas there was no evidence of increasing frequency of resistance in the no prophylaxis group. Finally, the economic evaluation revealed a slight cost-effectiveness of the antibiotic prophylaxis strategy, although the true expense of antibiotic resistance is difficult to calculate. In summary, this study gathers important evidence in a specific patient population. However, the slight advantages to antibiotic prophylaxis that were found by Fisher and colleagues7Fisher H Oluboyede Y Chadwick T et al.Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC): a randomised, open-label, superiority trial.Lancet Infect Dis. 2018; (published online June 28.)http://dx.doi.org/10.1016/S1473-3099(18)30279-2Summary Full Text Full Text PDF PubMed Scopus (55) Google Scholar might not be transferable to other health-care systems. FMEW serves as a scientific adviser for Achaogen, AstraZeneca, Bionorica, Enteris BioPharma, Helperby Therapeutics, Janssen, LEO Pharma, MERLION, MSD, OM Pharma, Pfizer, Rosen Pharma, Shionogi, and VenatoRx Pharmaceuticals. AP declares no competing interests. Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC): a randomised, open-label trialContinuous 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. Full-Text PDF Open Access