THIS EVIDENCE REPORT IS OUTDATED AND IS NO LONGER VIEWED AS GUIDANCE FOR CURRENT MEDICAL PRACTICE. IT IS MAINTAINED FOR ARCHIVAL PURPOSES ONLY.

Evidence Report/Technology Assessment

Number 6

Prepared for:
Agency for Health Care Policy and Research

U.S. Department of Health and Human Services
2101 East Jefferson Street
Rockville, MD 20852
http://www.ahcpr.gov

Contract No. 290-97-0001

Prepared by:
Southern California Evidence-Based Practice Center/RAND
Barbara G. Vickrey, MD, MPH
Project Director

Paul Shekelle, MD,PhD
Sally Morton, PhD
Ken Clark, MD
Mayank Pathak, MD
Caren Kamberg, MSPH
Investigators

AHCPR Publication No. 99-E008

February 1999

The Agency for Health Care Policy and Research (AHCPR), through its Evidence-based Practice Centers (EPCs), sponsors the development of evidence reports and technology assessments to assist public- and private-sector organizations in their efforts to improve the quality of health care in the United States. The reports and assessments provide organizations with comprehensive, science-based information on common, costly medical conditions and new health care technologies. The EPCs systematically review the relevant scientific literature on topics assigned to them by AHCPR and conduct additional analyses when appropriate prior to developing their reports and assessments.

To bring the broadest range of experts into the development of evidence reports and health technology assessments, AHCPR encourages the EPCs to form partnerships and enter into collaborations with other medical and research organizations. The EPCs work with these partner organizations to ensure that the evidence reports and technology assessments they produce will become building blocks for health care quality improvement projects throughout the Nation. The reports undergo peer review prior to their release.

AHCPR expects that the EPC evidence reports and technology assessments will inform individual health plans, providers, and purchasers as well as the health care system as a whole by providing important information to help improve health care quality.

We welcome written comments on this evidence report. They may be sent to: Director, Center for Practice and Technology Assessment, Agency for Health Care Policy and Research, 6010 Executive Blvd., Suite 300, Rockville, MD 20852.

John M. Eisenberg, M.D.		Douglas B. Kamerow, M.D.
Administrator		Director, Center for Practice and Technology Assessment
Agency for Health Care Policy and Research		Agency for Health Care Policy and Research

The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Health Care Policy and Research or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.

The objective was to analyze the evidence on aspects of the prevention and management of urinary tract infections in paralyzed persons. The two most common conditions affected are spinal cord injury (SCI) and multiple sclerosis (MS). Both conditions have a predilection for onset in young adulthood. Eighty percent of persons with SCI experience a urinary tract infection (UTI) by their 16th year post-injury, and diseases of the urinary system are the 5th most common cause of death. Over 70 percent of persons with MS develop bladder dysfunction over the course of their disease.

Specific questions addressed were (1) what combination of signs, symptoms, and laboratory findings are associated with risks to this population, (2) what are risk factors for recurrent UTIs, and (3) what are the risks and benefits of antibiotic prophylaxis.

An expert and consumer panel was convened to focus the literature review. A research librarian performed a search of MEDLINE (1966-January 1998) and EMBASE (1974-January 1998) databases, using the terms urinary tract, urinary tract infections, bacteriuria, paraplegia, quadriplegia, spinal cord injuries, multiple sclerosis, neurogenic bladder, and neuropathic bladder. CINAHL (1982-July 1998) was also searched. Some articles were identified by panel members and by review of reference lists.

All titles were reviewed, then abstracts of non-rejected titles, where available. Full-length articles were reviewed for accepted abstracts and for titles with no abstract. Selection criteria included human studies of adults and adolescents with neurogenic bladder due to spinal cord dysfunction and relevant to a key question, and non-acute SCI patients. Excluded were case reports, reviews, editorials, and letters, and studies published before 1979 on risk factors for recurrent UTI. For prophylaxis of UTI, only randomized controlled trials were included, as were studies of acute SCI.

As articles were reviewed they were designated as addressing one of the key questions. Project investigators reviewed full-length articles and excluded those having insufficient data or not otherwise addressing a question. Data from remaining articles were extracted into evidence tables. Quality of controlled trials and of cohort studies was formally assessed. A formal meta-analysis was undertaken on prophylaxis of UTI. A draft evidence report was critiqued by 22 experts and consumers.

Study samples in most of the published literature were patients with SCI. Bacteriuria is a common occurrence; pyuria with bacteriuria may be associated with symptomatic infections, but these findings are also common in asymptomatic patients. The occurrence of febrile episodes in prior years is associated with upper urinary tract complications or abnormalities; bladder calculi are associated with prior cultures of certain bacterial species and of multiple organisms. Other evidence regarding the significance of signs, symptoms, and laboratory findings is sparse or inconclusive due to study design limitations. Indwelling catheterization is associated with more frequent infections than bladder management methods not involving a catheter. The literature does not support firm conclusions regarding most other risk factors. Antibiotic prophylaxis reduces bacteriuria but is not associated with a reduced number of symptomatic infections in the populations studied and results in two-fold increases in the occurrence of antibiotic-resistant bacteria.

Febrile episodes are associated with the later occurrence of upper tract complications. Intermittent catheterization is associated with a lower risk of urinary tract infections. The regular use of antibiotic prophylaxis for most patients with spinal cord dysfunction cannot be supported. Future research should focus in the areas of (1) prospective cohort studies to assess the short-term and long-term significance of signs, symptoms, and laboratory findings (level of bacteriuria and type of organism, pyuria, others); (2) large, multicenter prospective studies of risk factors - potentially modifiable risk factors, in particular - for urinary tract infection; and (3) randomized controlled trials in the subgroup of patients who have frequent, recurrent urinary tract infections that limit their functioning. Studies should include both SCI and MS patients, where feasible, and state-of-the-art methods for maximizing the quality of the study designs should be employed.

This document is in the public domain and may be used and reprinted without permission, except for those copyrighted materials noted for which further reproduction is prohibited without the specific permission of copyright holders.

Vickrey BG, Shekelle P, Morton S, et al. Prevention and Management of Urinary Tract Infections in Paralyzed Persons. Evidence Report/Technology Assessment No. 6. (Prepared by Southern California Evidence-Based Practice Center/RAND under Contract No. 290-97-0001.) AHCPR Publication No. 99-E008. Rockville, MD: Agency for Health Care Policy and Research. February 1999.

The objective was to analyze the evidence on selected aspects of the prevention and management of urinary tract infections in paralyzed persons. The two populations most commonly affected are persons having spinal cord injury (SCI) and people with multiple sclerosis (MS). Both of these conditions have a predilection for onset in young adulthood. Eighty percent of persons with SCI experience a urinary tract infection (UTI) by their 16th year post-injury, and diseases of the urinary system are overall the 5th most common primary or secondary cause of death in this population. Between 70 to 90 percent of persons with MS develop bladder dysfunction over the course of their disease, placing them at increased risk for UTIs. Urinary complications are responsible for a large proportion of hospitalization-related episodes in these patient populations. UTI is the most frequent secondary medical complication reported by the federally designated Model Spinal Cord Injury Systems during acute care and rehabilitation, and UTI was the primary or secondary diagnosis for nearly one-third of hospitalizations of MS patients over the age of 65, according to 1989 Medicare data.

The specific questions addressed in this report are (1) what combination of signs, symptoms, and laboratory findings are associated with risks to persons with paralysis due to neurogenic bladder, (2) what are risk factors for recurrent UTIs, and (3) what are the risks and benefits of antibiotic prophylaxis.

The literature review for the first key question was broad and included studies of both short-term and long-term risks as related to episodes of various combinations of signs, symptoms, and laboratory findings, for example, the presence of fever, the level of bacteriuria, the type or organism, the presence of varying levels of pyuria, or some combination. For the literature search on risk factors for UTI, types of risk factors examined were socioeconomic status, insurance status, behavioral factors, personal hygiene, sex, and domicile, as well as intermediate risk factors of bladder management method (or drainage), time since injury, and level of functioning (or injury). Regarding prophylaxis, the efficacy of any oral antibiotic therapy and the efficacy of specific oral antibiotics were examined. All analyses were further stratified by acute versus non-acute SCI patients and by asymptomatic and symptomatic UTIs.

Study populations included adults and adolescents (13 years and older). In studies that had patient samples with spinal cord injury, the review focused on non-acute patients (defined as more than 90 days out from their injury) for all key questions, with the additional inclusion of studies of acute SCI patients for the analysis of antibiotic prophylaxis.

A 13-member panel of experts, consumers, and a managed care organization representative was convened to focus the literature review on a set of key questions and to develop potential causal pathways for each question. Subsequently, a research librarian performed searches of MEDLINE (1966-January 1998) and EMBASE (1974-January 1998) databases, using the terms urinary tract, urinary tract infections, bacteriuria, paraplegia, quadriplegia, spinal cord injuries, multiple sclerosis, neurogenic bladder, and neuropathic bladder; case reports and animal studies were excluded. CINAHL (1982-July 1998) was also searched. Foreign language articles were not excluded from any searches. Some additional articles were identified by panel members and by review of citations of articles obtained from searches.

All titles were reviewed by two physicians, then abstracts of non-rejected titles, where available. Full-length articles were reviewed for accepted abstracts and for titles with no abstract. Twelve translators assisted in the screening and evaluation of articles in 14 different foreign languages.

Selection criteria included human studies of adults and adolescents with neurogenic bladder due to spinal cord dysfunction and relevant to a key question and inclusion of a potentially relevant outcome measure, such as bacteriuria or UTI. For the first two key questions, studies of acute SCI patients (i.e., limited to within the first 90 days following injury) were excluded. For prophylaxis of UTI, only randomized controlled trials were included; both acute and non-acute SCI study samples were included for this key question. Rejection criteria for all key questions were case reports, reviews, editorials, and letters; studies published before 1979 on risk factors for recurrent UTI were also excluded, because bladder management methods and their associated risks changed greatly with the introduction of intermittent catheterization at that time. As articles were reviewed, they were designated as addressing one of the key questions. Project investigators reviewed full-length articles and excluded those having insufficient data or not otherwise addressing a question. Data from remaining articles were extracted into evidence tables, and results summarized. Quality of controlled trials and of cohort studies was formally assessed.

A meta-analysis was conducted for the key question on benefits and harms of long-term use of antibiotic prophylaxis for UTI in people with neurogenic bladder due to spinal cord dysfunction. Steps included obtaining any additional information needed from authors of studies, identification of the outcomes and subgroups for analyses, formal assessment of evidence for publication bias, selection of an appropriate statistical pooling method, assessment and incorporation of heterogeneity, combination of data across studies, and execution of sensitivity analyses.

A draft evidence report was circulated for critique by the 13-member panel previously convened and by 7 additional content experts, methodologists, and a managed care organization representative. The meta-analysis was additionally reviewed by two outside experts in meta-analysis.

• Study samples in most of the published literature were patients with SCI.
• Bacteriuria is a common occurrence; pyuria with bacteriuria may be associated with symptomatic infections, but these findings are also relatively common in asymptomatic patients.
• There is convergent data from several large cohort and case-control studies that the occurrence of febrile episodes in prior years is associated with a higher occurrence of upper urinary tract complications or abnormalities at long-term followup.
• The presence of certain bacteria or of multiple organisms early after spinal cord injury is associated with an approximately 3@@@frac12@@@-fold increased odds for developing bladder calculi at 2 years, but the presence of other signs and symptoms and treatment status were not included in the single study of this issue that was identified.
• Other evidence regarding the significance of signs, symptoms, and laboratory findings either is sparse or is inconclusive due to study design limitations.
• Indwelling catheterization is associated with more frequent infections than that involving intermittent catheterization, which in turn is associated with more frequent infections than methods not involving a catheter. (However, severity of disease affects choice of method, particularly the alternatives involving use of a catheter versus no catheter.)
• The literature does not support firm conclusions regarding most other risk factors.
• Antibiotic prophylaxis significantly reduces bacteriuria among acute spinal cord injury patients (p <0.05), and there is a trend for reduction in bacteriuria among non-acute spinal cord patients (p = 0.06). However, antibiotic prophylaxis is not associated with a reduced number of symptomatic infections in the populations studied.
• Antibiotic prophylaxis results in two-fold increases in the occurrence of antibiotic-resistant bacteria.

Future research should focus in the areas of (1) prospective cohort studies to assess the short-term and long-term significance of signs, symptoms, and laboratory findings (level of bacteriuria and type of organism, pyuria, others); (2) large, multi-center, prospective cohort or randomized trial studies of risk factors for UTIs, particularly targeting potentially modifiable risk factors like behavioral factors and catheterization techniques; and (3) randomized controlled trials in the subgroup of patients who have frequent, recurrent urinary tract infections that limit their daily functioning and well-being. These studies should include both SCI and MS patients, where feasible, and should enroll a sufficient number of patients for adequate statistical power to detect meaningful clinical differences. In addition to traditional clinical measures, these studies should also measure quality-of-life outcomes and costs. State-of-the-art methods for maximizing the quality of the study designs and the rigor with which they are executed should be employed.