Curr Infect Dis Rep (2014) 16:390 DOI 10.1007/s11908-013-0390-9
GENITOURINARY INFECTIONS (J SOBEL, SECTION EDITOR)
Urinary Tract Infections in Patients with Spinal Injuries Lindsay E. Nicolle
Published online: 21 January 2014 # Springer Science+Business Media New York 2014
Abstract Urinary tract infection remains an important problem for patients with spinal cord injury. Interventions used to promote bladder emptying and maintain low-pressure voiding have variable risks for urinary tract infection. Asymptomatic bacteriuria is common in this population and should not be treated. However, identification of symptomatic infection is compromised by difficulties in ascertainment of symptoms. Use of hydrophilic coated catheters for intermittent catheterization does not influence the frequency of symptomatic urinary tract infection. Botulinum toxin injection in the detrusor muscle or the urethral sphincter improves bladder emptying and does not influence the frequency of urinary infection. Asymptomatic bacteriuria is a common finding in pregnant women with spinal cord injury, but optimal management is not clear. Other research needs include further development and evaluation of interventions to decrease the frequency of infection, improve diagnostic precision, and limit the emergence of resistant organisms. Keywords Urinary infection . Bacteriuria . Asymptomatic bacteriuria . Spinal cord injury . Botulinum toxin . Intermittent catheter . Hydrophilic catheter
Introduction Urinary tract infection remains the most common infection occurring in patients with spinal cord injury [1•]. Renal failure and sepsis secondary to recurrent urinary infection were
previously the most common causes of death for these patients, but with advances in voiding management, urinary infection is now an infrequent cause of mortality. However, it continues to cause substantial morbidity and is a common cause of rehospitalization [1•, 2•]. Given the frequency and impact of urinary tract infection in this population, continued development and evaluation of strategies to improve prevention and treatment are necessary. Management of urinary tract infection requires differentiation of symptomatic urinary tract infection and asymptomatic bacteriuria. Impaired bladder emptying and frequent use of urologic devices in the spinal cord injury population promotes asymptomatic bacteriuria. Patients using intermittent catheterization and men with sphincterotomy and condom drainage have a prevalence of bacteriuria of 50 %. The prevalence of bacteriuria in subjects with chronic indwelling catheters is 100 % [3]. Antimicrobial treatment of asymptomatic bacteriuria is not beneficial and is associated with negative outcomes of reinfection with organisms of increasing resistance and adverse drug reactions, so only symptomatic episodes should be treated [1•, 3]. However, there are challenges in the clinical diagnosis of symptomatic urinary infection in this population [1•]. Clinical symptoms are difficult to ascertain in some spinal cord injury patients, and unique presenting symptoms such as increased spasticity and autonomic hyperreflexia must be recognized. The lack of standardization of both clinical and microbiologic definitions of urinary infection compromises the evaluation of clinical studies addressing this problem.
Bladder Management Strategies This article is part of the Topical Collection on Genitourinary Infections L. E. Nicolle (*) Health Sciences Centre, University of Manitoba, Room GG443, 820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada e-mail: [email protected]
The mechanisms leading to impaired bladder function following spinal cord injury are variable and are influenced by the time since injury, whether the injury is complete or incomplete, and the level of the injury [1•]. The goal of bladder
390, Page 2 of 7
Curr Infect Dis Rep (2014) 16:390
management is to achieve regular, complete bladder emptying to maintain a low-pressure bladder. For the initial period following injury, spinal shock is present, and urinary retention is common. Subsequently, storage failure (incontinence) may result from involuntary detrusor contraction with open distal sphincter or failure to empty (retention) with detrusor/ sphincter dysynergy or continued detrusor acontractility and a nonrelaxing sphincter. Characterization of bladder function in the individual patient requires urodynamic assessment. Management to improve voiding may require intermittent catheterization, an indwelling urethral or suprapubic catheter, timed voiding, use of external catheters for men, drug treatment, augmentation cystoplasty, or urinary diversion. However, a Cochrane review [4•] identified no randomized or quasi-randomized controlled trials that compared methods for managing urinary voiding in patients with neurogenic bladders. Thus, interventions to promote bladder emptying are individualized and are not based on clinical trial evidence. The high frequency of urinary infection in spinal cord injured patients and the variation of infection rates with different voiding methods are consistent in recent global reports (Table 1). A retrospective record review describes the evolution of bladder management strategies following discharge from rehabilitation after spinal cord injury in 164 patients in Turkey [5]. While bladder management at discharge was usually clean intermittent catheterization (63.4 %), 42 % of patients changed their bladder emptying method during 5- to 84-month follow-up, including 21.4 % who reverted to an indwelling urethral catheter. The frequency and proportion of subjects experiencing urinary tract infection was highest with a chronic indwelling catheter. Reports from China [6] describing patients with injury at least 1 year previously and from Korea [7] also describe the highest frequency of infection with an indwelling catheter. There is a wide variability in reported infection with other bladder emptying methods, likely
reflecting differences in definitions, patient populations, and follow-up. These studies also highlight the variable definitions used to identify urinary infection: One reports only symptomatic episodes, another reports bacteriuria, and the third reports both symptomatic and asymptomatic infection. In addition, the quantitative count for confirming bacteriuria is different for each study. Current evidence relevant to urinary tract infection in patients using clean intermittent catheterization was summarized in a systematic review [8••]. Urinary tract infection remains an important clinical problem for these patients, and the problem of inconsistent criteria for diagnosis of symptomatic infection was recognized. Priority research questions identified by the review included the impact of types of catheter on infection, the impact of frequency of intermittent catheterization on symptomatic infection, the role of prophylactic antibiotics, and exploration of methods for preserving natural defense mechanisms of the lower urinary tract to limit urinary infection. The frequency or severity of urinary infection following augmentation cystoplasty for patients who cannot be effectively managed with other modalities is not well characterized. A case series of 61 patients describes long-term functional results following supratrigonal cystectomy and Hautmann pouch created from the distal ileum for treatment of neurogenic bladder in spinal cord injury [9•]. All patients had refractory neurogenic detrusor overactivity as an indication for surgery, and all continued using intermittent catheterization following the procedure. The goal of incontinence management was achieved in 74 % of subjects. While urinary tract infection was experienced by 68.8 % of subjects before the procedure, only 13.8 % had infection after the procedure (mean follow-up, 5.84 years; range, 1–20.5). However, these patients also received a “cyclical antibiotic protocol,” and the definition of urinary infection was unclear. Another report
Table 1 Rates of urinary tract infection or bacteriuria for spinal cord injured subjects stratified by voiding method Reference (Number of Subjects)
Follow-up from injury Bladder management (% infected) Spontaneous voiding Intermittent catheter Chronic indwelling catheter Reflex voiding/Crede
Asfar [5]1 (164)
Shen [6]2 (67)
Ryu [7]3 (112)
53.9±27.7 months
18.6 (2–42) years
n.s.
0 67.6 %/year 93.3 %/year
42.9 %/2 years 66.7 %/2 years 100 %/2 years
71.1 % (includes condom) 69.8 % suprapubic 82.3 % urethral 77.6 %
4.2 % /year
100 %/2 years
NR
Definitions for urinary infection: 1
>104 cfu/ml and one or more clinical signs and symptoms
2
Based on monthly screening for asymptomatic bacteriuria; IC≥102 cfu/ml, voided≥104 cfu/ml
3
72.7 % of specimens from symptomatic patients; 27.3 % screening at regular follow-up; ≥ 103 cfu/ml
Curr Infect Dis Rep (2014) 16:390
described outcomes following insertion of a dual flange metallic urethral stent in 28 male patients with high spinal cord injury [10]. Urinary tract infection, undefined, occurred in 22 patients prior to stenting and only 7 after stenting, with a mean poststenting follow-up of 18 months. However, 45 % of the stents were removed during the follow-up period. Stone formation, in 47 % of patients, was the most common reason for removal.
Complications of Urinary Infection Renal calculi have been reported in 1.3 %–28 % of patients with spinal cord injury, with reports of 38 % by 45 years after injury and 9.4 % by 20 years [11]. Urinary tract infection is one risk factor for urolithiasis in these patients. Renal stones are usually composed of either magnesium ammonium phosphate (struvite) resulting from bacterial infection with ureaseproducing organisms or calcium phosphate (apatite), which may be secondarily colonized with bacteria in biofilm. Reports from the 1970s characterized stone composition as over 90 % struvite, but recent studies report that 18 % of stones are struvite and 50 % calcium apatite. Thus, progress in management of voiding and urinary infection in this population has altered stone disease from being primarily an infectious to primarily a metabolic complication. Recurrent urinary infection is common with spinal cord injury. Repeated courses of antimicrobial therapy promote emergence of organisms of increasing antimicrobial resistance. Antimicrobial resistance in Enterobacteriaceae is a particular concern, which may limit options for treatment. A cross-sectional prevalence study of 38 Brazilian outpatients with chronic spinal cord injury, 71 % using intermittent catheterization, who had at least two symptomatic urinary infections in the previous 2 years, reported a prevalence of bacteriuria of 65.7 % [12]. E. coli was isolated from 15 (60 %), and 36 % of these strains were resistant to three or more oral antibiotics—usually ampicillin, trimethoprim/ sulfamethoxazole, and fluoroquinolones. A report from a French rehabilitation center describes the epidemiology of extended spectrum beta-lactamase (ESBL) producing Proteus mirabilis isolated from urine specimens of spinal cord injured patients [13]. During a 3-year period, 43 distinct strains were identified, concurrently or sequentially, in 16 patients. Twelve (38 %) of 32 penicillin-resistant strains expressed ESBL, and nosocomial dissemination of two ESBL clones was recognized.
Monitoring for Infection Spinal cord injured patients with voiding dysfunction are at risk for renal functional impairment and urinary infection.
Page 3 of 7, 390
Urologic monitoring is recommended to prevent these complications, but there is no consensus regarding the optimal frequency or type of monitoring. A survey of urologists in Saudi Arabia [14] reported that urinalysis monitoring of spinal cord injured patients was highly variable—every 3 months (20 % of respondents), 6 months (14 %), 1 year (56 %), and 2 years (10 %). In addition, 40 % said that they would treat asymptomatic bacteriuria, in contrast to surveys of Dutch and Canadian urologists, who reported that they rarely treated bacteriuria. A systematic review of reports describing urological follow-up after spinal cord injury evaluated evidence supporting different monitoring strategies [15•]. Twelve articles were relevant to urinary tract infection screening, but there was no standardization of definitions, and most studies did not distinguish symptomatic or asymptomatic infection. In three reports, the absence of pyuria was a reasonable negative predictor for bacteriuria or urinary infection. Two studies evaluated the utility of routine urine cultures to screen for bacteriuria. In one, bacteria isolated from weekly urinescreening cultures of asymptomatic patients did not predict optimal antimicrobial therapy when symptomatic urinary infection occurred in the patient. The second report concluded that urine-screening cultures were unlikely to be positive if there was
GENITOURINARY INFECTIONS (J SOBEL, SECTION EDITOR)
Urinary Tract Infections in Patients with Spinal Injuries Lindsay E. Nicolle
Published online: 21 January 2014 # Springer Science+Business Media New York 2014
Abstract Urinary tract infection remains an important problem for patients with spinal cord injury. Interventions used to promote bladder emptying and maintain low-pressure voiding have variable risks for urinary tract infection. Asymptomatic bacteriuria is common in this population and should not be treated. However, identification of symptomatic infection is compromised by difficulties in ascertainment of symptoms. Use of hydrophilic coated catheters for intermittent catheterization does not influence the frequency of symptomatic urinary tract infection. Botulinum toxin injection in the detrusor muscle or the urethral sphincter improves bladder emptying and does not influence the frequency of urinary infection. Asymptomatic bacteriuria is a common finding in pregnant women with spinal cord injury, but optimal management is not clear. Other research needs include further development and evaluation of interventions to decrease the frequency of infection, improve diagnostic precision, and limit the emergence of resistant organisms. Keywords Urinary infection . Bacteriuria . Asymptomatic bacteriuria . Spinal cord injury . Botulinum toxin . Intermittent catheter . Hydrophilic catheter
Introduction Urinary tract infection remains the most common infection occurring in patients with spinal cord injury [1•]. Renal failure and sepsis secondary to recurrent urinary infection were
previously the most common causes of death for these patients, but with advances in voiding management, urinary infection is now an infrequent cause of mortality. However, it continues to cause substantial morbidity and is a common cause of rehospitalization [1•, 2•]. Given the frequency and impact of urinary tract infection in this population, continued development and evaluation of strategies to improve prevention and treatment are necessary. Management of urinary tract infection requires differentiation of symptomatic urinary tract infection and asymptomatic bacteriuria. Impaired bladder emptying and frequent use of urologic devices in the spinal cord injury population promotes asymptomatic bacteriuria. Patients using intermittent catheterization and men with sphincterotomy and condom drainage have a prevalence of bacteriuria of 50 %. The prevalence of bacteriuria in subjects with chronic indwelling catheters is 100 % [3]. Antimicrobial treatment of asymptomatic bacteriuria is not beneficial and is associated with negative outcomes of reinfection with organisms of increasing resistance and adverse drug reactions, so only symptomatic episodes should be treated [1•, 3]. However, there are challenges in the clinical diagnosis of symptomatic urinary infection in this population [1•]. Clinical symptoms are difficult to ascertain in some spinal cord injury patients, and unique presenting symptoms such as increased spasticity and autonomic hyperreflexia must be recognized. The lack of standardization of both clinical and microbiologic definitions of urinary infection compromises the evaluation of clinical studies addressing this problem.
Bladder Management Strategies This article is part of the Topical Collection on Genitourinary Infections L. E. Nicolle (*) Health Sciences Centre, University of Manitoba, Room GG443, 820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada e-mail: [email protected]
The mechanisms leading to impaired bladder function following spinal cord injury are variable and are influenced by the time since injury, whether the injury is complete or incomplete, and the level of the injury [1•]. The goal of bladder
390, Page 2 of 7
Curr Infect Dis Rep (2014) 16:390
management is to achieve regular, complete bladder emptying to maintain a low-pressure bladder. For the initial period following injury, spinal shock is present, and urinary retention is common. Subsequently, storage failure (incontinence) may result from involuntary detrusor contraction with open distal sphincter or failure to empty (retention) with detrusor/ sphincter dysynergy or continued detrusor acontractility and a nonrelaxing sphincter. Characterization of bladder function in the individual patient requires urodynamic assessment. Management to improve voiding may require intermittent catheterization, an indwelling urethral or suprapubic catheter, timed voiding, use of external catheters for men, drug treatment, augmentation cystoplasty, or urinary diversion. However, a Cochrane review [4•] identified no randomized or quasi-randomized controlled trials that compared methods for managing urinary voiding in patients with neurogenic bladders. Thus, interventions to promote bladder emptying are individualized and are not based on clinical trial evidence. The high frequency of urinary infection in spinal cord injured patients and the variation of infection rates with different voiding methods are consistent in recent global reports (Table 1). A retrospective record review describes the evolution of bladder management strategies following discharge from rehabilitation after spinal cord injury in 164 patients in Turkey [5]. While bladder management at discharge was usually clean intermittent catheterization (63.4 %), 42 % of patients changed their bladder emptying method during 5- to 84-month follow-up, including 21.4 % who reverted to an indwelling urethral catheter. The frequency and proportion of subjects experiencing urinary tract infection was highest with a chronic indwelling catheter. Reports from China [6] describing patients with injury at least 1 year previously and from Korea [7] also describe the highest frequency of infection with an indwelling catheter. There is a wide variability in reported infection with other bladder emptying methods, likely
reflecting differences in definitions, patient populations, and follow-up. These studies also highlight the variable definitions used to identify urinary infection: One reports only symptomatic episodes, another reports bacteriuria, and the third reports both symptomatic and asymptomatic infection. In addition, the quantitative count for confirming bacteriuria is different for each study. Current evidence relevant to urinary tract infection in patients using clean intermittent catheterization was summarized in a systematic review [8••]. Urinary tract infection remains an important clinical problem for these patients, and the problem of inconsistent criteria for diagnosis of symptomatic infection was recognized. Priority research questions identified by the review included the impact of types of catheter on infection, the impact of frequency of intermittent catheterization on symptomatic infection, the role of prophylactic antibiotics, and exploration of methods for preserving natural defense mechanisms of the lower urinary tract to limit urinary infection. The frequency or severity of urinary infection following augmentation cystoplasty for patients who cannot be effectively managed with other modalities is not well characterized. A case series of 61 patients describes long-term functional results following supratrigonal cystectomy and Hautmann pouch created from the distal ileum for treatment of neurogenic bladder in spinal cord injury [9•]. All patients had refractory neurogenic detrusor overactivity as an indication for surgery, and all continued using intermittent catheterization following the procedure. The goal of incontinence management was achieved in 74 % of subjects. While urinary tract infection was experienced by 68.8 % of subjects before the procedure, only 13.8 % had infection after the procedure (mean follow-up, 5.84 years; range, 1–20.5). However, these patients also received a “cyclical antibiotic protocol,” and the definition of urinary infection was unclear. Another report
Table 1 Rates of urinary tract infection or bacteriuria for spinal cord injured subjects stratified by voiding method Reference (Number of Subjects)
Follow-up from injury Bladder management (% infected) Spontaneous voiding Intermittent catheter Chronic indwelling catheter Reflex voiding/Crede
Asfar [5]1 (164)
Shen [6]2 (67)
Ryu [7]3 (112)
53.9±27.7 months
18.6 (2–42) years
n.s.
0 67.6 %/year 93.3 %/year
42.9 %/2 years 66.7 %/2 years 100 %/2 years
71.1 % (includes condom) 69.8 % suprapubic 82.3 % urethral 77.6 %
4.2 % /year
100 %/2 years
NR
Definitions for urinary infection: 1
>104 cfu/ml and one or more clinical signs and symptoms
2
Based on monthly screening for asymptomatic bacteriuria; IC≥102 cfu/ml, voided≥104 cfu/ml
3
72.7 % of specimens from symptomatic patients; 27.3 % screening at regular follow-up; ≥ 103 cfu/ml
Curr Infect Dis Rep (2014) 16:390
described outcomes following insertion of a dual flange metallic urethral stent in 28 male patients with high spinal cord injury [10]. Urinary tract infection, undefined, occurred in 22 patients prior to stenting and only 7 after stenting, with a mean poststenting follow-up of 18 months. However, 45 % of the stents were removed during the follow-up period. Stone formation, in 47 % of patients, was the most common reason for removal.
Complications of Urinary Infection Renal calculi have been reported in 1.3 %–28 % of patients with spinal cord injury, with reports of 38 % by 45 years after injury and 9.4 % by 20 years [11]. Urinary tract infection is one risk factor for urolithiasis in these patients. Renal stones are usually composed of either magnesium ammonium phosphate (struvite) resulting from bacterial infection with ureaseproducing organisms or calcium phosphate (apatite), which may be secondarily colonized with bacteria in biofilm. Reports from the 1970s characterized stone composition as over 90 % struvite, but recent studies report that 18 % of stones are struvite and 50 % calcium apatite. Thus, progress in management of voiding and urinary infection in this population has altered stone disease from being primarily an infectious to primarily a metabolic complication. Recurrent urinary infection is common with spinal cord injury. Repeated courses of antimicrobial therapy promote emergence of organisms of increasing antimicrobial resistance. Antimicrobial resistance in Enterobacteriaceae is a particular concern, which may limit options for treatment. A cross-sectional prevalence study of 38 Brazilian outpatients with chronic spinal cord injury, 71 % using intermittent catheterization, who had at least two symptomatic urinary infections in the previous 2 years, reported a prevalence of bacteriuria of 65.7 % [12]. E. coli was isolated from 15 (60 %), and 36 % of these strains were resistant to three or more oral antibiotics—usually ampicillin, trimethoprim/ sulfamethoxazole, and fluoroquinolones. A report from a French rehabilitation center describes the epidemiology of extended spectrum beta-lactamase (ESBL) producing Proteus mirabilis isolated from urine specimens of spinal cord injured patients [13]. During a 3-year period, 43 distinct strains were identified, concurrently or sequentially, in 16 patients. Twelve (38 %) of 32 penicillin-resistant strains expressed ESBL, and nosocomial dissemination of two ESBL clones was recognized.
Monitoring for Infection Spinal cord injured patients with voiding dysfunction are at risk for renal functional impairment and urinary infection.
Page 3 of 7, 390
Urologic monitoring is recommended to prevent these complications, but there is no consensus regarding the optimal frequency or type of monitoring. A survey of urologists in Saudi Arabia [14] reported that urinalysis monitoring of spinal cord injured patients was highly variable—every 3 months (20 % of respondents), 6 months (14 %), 1 year (56 %), and 2 years (10 %). In addition, 40 % said that they would treat asymptomatic bacteriuria, in contrast to surveys of Dutch and Canadian urologists, who reported that they rarely treated bacteriuria. A systematic review of reports describing urological follow-up after spinal cord injury evaluated evidence supporting different monitoring strategies [15•]. Twelve articles were relevant to urinary tract infection screening, but there was no standardization of definitions, and most studies did not distinguish symptomatic or asymptomatic infection. In three reports, the absence of pyuria was a reasonable negative predictor for bacteriuria or urinary infection. Two studies evaluated the utility of routine urine cultures to screen for bacteriuria. In one, bacteria isolated from weekly urinescreening cultures of asymptomatic patients did not predict optimal antimicrobial therapy when symptomatic urinary infection occurred in the patient. The second report concluded that urine-screening cultures were unlikely to be positive if there was
