Multicenter Randomized Controlled Trial of Bacterial Interference for Prevention of Urinary Tract Infection in Patients With Neurogenic Bladder

doi:10.1016/j.urology.2011.03.062

Urology

Volume 78, Issue 2, August 2011, Pages 341-346

https://doi.org/10.1016/j.urology.2011.03.062 Get rights and content

Objectives

To compare the effectiveness of bacterial interference versus placebo in preventing urinary tract infection (UTI).

Methods

The main outcome measure was the numbers of episodes of UTI/patient-year. Randomization was computer generated, with allocation concealment by visibly indistinguishable products distributed from a core facility. The healthcare providers and those assessing the outcomes were unaware of the group allocation. Adult patients (n = 65) with neurogenic bladder after spinal cord injury and a history of recurrent UTI were randomized in a 3:1 ratio to receive either Escherichia coli HU2117 or sterile saline. Urine cultures were obtained weekly during the first month and then monthly for 1 year. The patients were evaluable if they remained colonized with E. coli HU2117 for >4 weeks (experimental group). The trial is closed to follow-up.

Results

Of the 59 patients who received bladder inoculations, 27 were evaluable (17 in the experimental group and 10 in the placebo group). The 2 study groups had comparable clinical characteristics. Of 17 patients colonized with E. coli HU2117 and the 10 control patients, 5 (29%, 95% confidence interval 0.11-0.56) and 7 (70%, 95% confidence interval 0.35-0.92) developed >1 episode of UTI (P = .049; 1-sided Fisher's exact test), respectively. The average number of episodes of UTI/patient-year was also lower (P = .02, Wilcoxon rank sum test) in the experimental (0.50) than in the control group (1.68). E. coli HU2117 did not cause symptomatic UTI.

Conclusions

Bladder colonization with E. coli HU2117 safely reduces the risk of symptomatic UTI in patients with spinal cord injury. Effective, but less complex, methods for achieving bladder colonization with E. coli HU2117 are under investigation.

Section snippets

Study Design

A randomized, placebo-controlled, double-blind, multicenter clinical trial was conducted at 6 medical centers across the United States. The institutional review boards at the respective institutions approved the present research. All participants provided written informed consent. The patients who had consented were randomly assigned, in a 3:1 ratio, to receive bladder inoculation with either E. coli HU2117 (experimental group) or sterile normal saline (control group). Neither the patients nor

Study Flow

The disposition of the enrolled subjects is listed in Table 1. Bladder colonization with E. coli HU2117 for ≥1 month was achieved in 17 (38%) of 45 subjects who received >1 cycle of bladder inoculation with this organism. The clinical characteristics of 27 evaluable patients (including 17 in the experimental group whose bladder became colonized with E. coli HU2117 and 10 control patients who completed the study) are listed in Table 2. The 2 study groups had comparable clinical characteristics,

Comment

The limited clinical success of antimicrobial preventive measures has generated an escalating interest in exploring innovative nonantimicrobial-based approaches, including bacterial interference using nonpathogenic strains of E. coli.13, 21, 23 Intentional colonization of the neurogenic bladder with a nonpathogenic strain of E. coli 83972 has been reported in both prospective nonrandomized²¹ and randomized²³ pilot trials to be safe and protective against development of UTI. The purpose of the

Conclusions

The use of antibiotics or antiseptics for prophylaxis in patients with SCI could decrease the rate of UTI due to organisms susceptible to the administered antimicrobial agents. However, the overall incidence of infection caused by all organisms (susceptible or not to the used antimicrobial agent) was not significantly altered. Because of the lack of overall efficacy, potential drug adverse events, and possible emergence of antimicrobial resistance, the prophylactic use of systemic or local

Acknowledgment

To Sarah Riosa and Dr. Barbara Trautner, with thanks for their assistance.

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Citation Excerpt :
These reviews urged for randomized controlled trials (RCT) to estimate the role of the probiotics in UTI [10,11]. Two RCT's included in one of these reviews evaluated the role of intravesical instillation of non-pathogenic E. coli for evaluation of risk reduction of recurrent UTI in patients of the neuropathic bladder, and these trials concluded that such instillation is generally safe [12,13]. This systemic review failed to find any encouraging evidence to support the belief that this route of administration of non non-virulent E. coli reduced the risk of recurrent UTI in case of spinal bladder [12].
The role of microbiome milieu in the urinary tract, their interplay in diverse urological conditions and their therapeutic implications are not completely understood. The microbiome has contributed towards urinary tract infections, urolithiasis and urological cancers. The possibility of manipulating microbiome for diagnosis and treatment is evolving. Probiotics might help in overcoming the problems of recurrent infection and antibiotic resistance. Novel applications like stents and catheters coated with non-pathogenic organisms are being developed. Research in the urinary microbiome has progressed from using mouse models to the presently available three- dimensional cultured organoids, thus making it more feasible. As our knowledge regarding the urinary microbiome increases, justice can be done to many patients in whom the advancements can be used for prophylaxis, diagnosis, treatment and even in improving their quality of life. The growing amount of antibiotic resistance is also a matter of concern and probiotics might be the answer to this upcoming calamity. In this review, we have discussed the role of the urinary microbiome in pathogenesis, diagnosis and treatment of urological conditions and pondered upon its future prospects.
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Citation Excerpt :
Eventually, 27 patients could be evaluated (17 in the experimental group and 10 in the placebo group). The average number of episodes of UTI/patient-year in the experimental group was lower than in the control group (0.50 versus 1.68 respectively, P = 0.02, Wilcoxon rank-sum test) [74]. In another prospective clinical trial, adult inpatients, diagnosed with SCI for more than one year, with neurogenic bladder that required indwelling (transurethral or suprapubic) catheter drainage and who had had at least one UTI in the past, were enrolled [76].
Urinary tract infections (UTIs) in patients with neurogenic bladder are a major public health issue due to their high incidence and major consequences. Despite their frequency and potential severity, their physiopathology and management are poorly known. We provide a narrative literature review on the epidemiology, physiopathology, diagnostic criteria, microbiology, antimicrobial management, and prevention. UTIs among patients with neurogenic bladder are associated with high morbidity and healthcare utilization. Risk factors for UTI among this population are: indwelling catheter, urinary stasis, high bladder pressure, and bladder stones. Their diagnosis is a major challenge as clinical signs are often non-specific and rare. A urinary sample should be analyzed in appropriate conditions before any antibiotic prescription. According to most guidelines, a bacterial threshold ≥ 103 CFU/ml associated with symptoms is acceptable to define UTI in patients with neurogenic bladder. The management of acute symptomatic UTI is not evidence-based. A management with a single agent and a short antibiotic treatment of 10 days or less seems effective. Antibiotic selection should be based on the patient's resistance patterns. Asymptomatic bacteriuria should not be treated to avoid the emergence of bacterial resistance. Regarding preventive measures, use of clean intermittent catheterization, intravesical botulinum toxin injection, and prevention using antibiotic cycling are effective. Bacterial interference is promising but randomized controlled trials are needed. Large ongoing cohorts and randomized controlled trials should soon provide more evidence-based data.
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: Funding support: This study was funded by the National Institutes of Health (grant HD043943).

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Infectious DiseaseMulticenter Randomized Controlled Trial of Bacterial Interference for Prevention of Urinary Tract Infection in Patients With Neurogenic Bladder

Objectives

Methods

Results

Conclusions

Section snippets

Study Design

Study Flow

Comment

Conclusions

Acknowledgment

Arch Phys Med Rehabil

Am J Infect Control

J Urol

J Urol

J Urol

Urology

J Urol

Urology

Spinal Cord Injury: facts and figures at a glance

A prospective, randomized trial of 3 or 14 days of ciprofloxacin treatment for acute urinary tract infection in patients with spinal cord injury

Clin Infect Dis

Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 international clinical practice guidelines from the Infectious Diseases Society of America

Clin Infect Dis

Epidemiology and risk factors for urinary tract infection in patients with spinal cord injury

J Urol

Prevention of urinary tract infection in spinal cord-injured patients: safety and efficacy of a weekly oral cyclic antibiotic (WOCA) programme with a 2 year follow-up—an observational prospective study

J Antimicrob Chemother

Catheter-associated bacteriuria: failure to reduce attack rates using periodic instillations of a disinfectant into urinary drainage systems

JAMA

Randomized trial of meatal care with silver sulfadiazine cream for the prevention of catheter-associated bacteriuria

J Infect Dis

Infectious Disease
Multicenter Randomized Controlled Trial of Bacterial Interference for Prevention of Urinary Tract Infection in Patients With Neurogenic Bladder