Complicated UTIs with the neurogenic bladder
Authors
Bill Tak Hing WONG (Pedder Clinic, Central, Hong Kong)
Stanley Chi Fai KAN (Division of Urology, Department of Surgery, Queen Elizabeth Hospital, Kowloon, Hong Kong)
Alex Hak Keung LO (Department of Urology, St. Paul's Hospital, Hong Kong)
Lap Yin HO (Division of Urology, Department of Surgery, Queen Elizabeth Hospital, Kowloon, Hong Kong)
Raymond Wai Man KAN (Division of Urology, Department of Surgery, Queen Elizabeth Hospital, Kowloon, Hong Kong)
Christopher LAI (Department of Microbiology, Chinese University of Hong Kong, Hong Kong)
Summary of recommendations & findings
Epidemiology and pathogenesis
1. Urinary tract infection (UTI) in patients with neurogenic bladder causes significant morbidity and mortality.
Diagnosis
1. UTI in neurogenic bladder causes atypical symptomatology. Urine tests are pivotal in confirming or excluding UTI, and in guiding appropriate antibiotic treatment.
Treatment
1. Symptomatic UTI warrants appropriate antibiotic treatment with reference to culture results and local antibiotic resistance patterns. Asymptomatic bacteriuria should not be treated, and antibiotic prophylaxis is generally not recommended.
2. Adequate bladder drainage is essential in reducing the occurrence of urinary tract infections.
3. Recurrent UTI in neurogenic bladder may necessitate the treatment of neurogenic detrusor overactivity and the restoration of low bladder pressure during bladder storage and voiding by drugs or surgery.
Introduction
Urinary tract infection in patients with neurogenic bladder causes high morbidity, impaired quality of life, and still significant mortality[1].
Diagnosis
UTI in patients with neurogenic bladder is characterized by clinical symptoms and laboratory findings of leukocyturia, bacteriuria, and positive urine culture[2][3][4](LE: 4; GR: B).
Signs and symptoms of UTI in neurogenic bladder are different from those in non-neurogenic bladder. They include cloudy urine, foul smelling urine, fever, malaise and lethargy, new or increased urine leakage, increased spasticity, autonomic dysreflexia, loin pain, suprapubic pain, and dysuria [2][5]. One has to beware that catheter-associated UTI can be asymptomatic[6].
Urine specimen may be obtained by clean-catch midstream technique, from a newly inserted catheter or bladder puncture[2][4][7]. Microscopic analysis of urine, particularly for bacteria and white cells, is very helpful in evaluating presence of bacteriuria and quantitatively the degree of pyuria. Leukocyturia is deemed significant when there are 10 or more white cells per high-power microscopic field (400x) in centrifuged urine sediment, or 10 or more white cells per uL in unspun urine using counting chamber[3][7]. Pyuria however has low specificity as diagnostic test for UTI. Yet lack of pyuria generally indicates absence of UTI [6][8](LE: 2b; GR: B).
Quantitative criteria of significant bacteriuria as defined by urine culture are clean-void urine with>104 cfu/ml, urine from intermittent catheterization with >102 cfu/ml, and any detectable concentration in suprapubic aspirate or urine specimen from indwelling catheter[3].
The usefulness of urine dipstick test alone to diagnose UTI is still not proven. Yet urine dipstick test is useful to exclude UTI, if results of both nitrites and leukocyte esterase are negative[2][9](LE: 2a; GR B).
Treatment
Spectrum of pathogens causing UTI in patients with neurogenic bladder is similar to other complicated UTIs (i.e. pregnant and immunocompromised, urinary tract abnormalities, and previous antibiotics exposure) and differs from that in patients with normal bladder function and is much broader.
Majority of UTIs are caused by members of the Enterobacteriaceae family and is predominated by Escherichia coli and Klebsiella species. Organisms that are classically seen in hospitalized patients including Pseudomonas, Serratia, Proteus, Acinetobacter, Enterococcus are also seen[10-13]. They are commensal organisms of bowel and perineum, and exogenous bacteria from hospital environment. Spinal cord injury patients with an indwelling catheter and suprapubic catheter were ten times more likely to develop candiduria compared to patients who used CIC[10][14]. UTIs are often polymicrobial. Urine culture and sensitivity testing must be performed before initiating antibiotic therapy[8](LE 3; GR: B).
Symptomatic UTI warrants antibiotic treatment. Optimal duration of therapy has not been established[8]. It ranges generally from five to maximum fourteen days depending on severity. Seven days of therapy is most commonly used[3][8][15](LE: 3, GR: B). There is no definite superiority of one agent or class of antimicrobials, and regional differences in antibiotic resistance patterns need to be taken into consideration[16](LE: 3, GR: B).
Asymptomatic bacteriuria should not be treated[8], even in cases of intermittent catheterization[3], because it has not been shown to be beneficial and it increases the risk of developing antimicrobial resistance[17](LE: 3, GR: B).
Also, antibiotic prophylaxis is generally not recommended, because its benefit is unproven, and it is associated with development of antimicrobial resistance[8][17](LE: 3, GR: B).
Prevention of recurrent UTI
Patients with neurogenic bladder dysfunction have increased risk of developing urinary tract infections[18]. Adequate bladder drainage is an important prophylactic measure against recurrent urinary tract infections[19][20](LE: 2b, GR: B).
Initial bladder management during the period of spinal or cerebral shock in acute neurological lesions thus consists of proper bladder drainage. Bladder emptying in acute phase can be achieved by aseptic intermittent catheterization, or by indwelling suprapubic or urethral catheters[21-23](LE: 3, GR: B).
In the long-term management of neurogenic bladder dysfunction, the most important issue is the method of bladder emptying. This can be achieved by long-term indwelling catheters or by intermittent catheterization[24]. Chronic indwelling catheters can either be suprapubic catheter cystostomy or urethral catheter[25]. Intermittent catheterization can either be clean intermittent catheterization (CIC) by carer, or clean intermittent self-catheterization (CISC)[26].
Suprapubic catheterization may have comparable risk of UTI to intermittent catheterization, but has significant long-term morbidity from suprapubic tube complications[13][27]. Intermittent catheterization has lower UTI rate and less complications than indwelling urethral catheterization; CIC or CISC are the best voiding methods for reducing bacteriuria and urinary tract infections in neurogenic bladders[26][28][29]. CIC and CISC are generally deemed effective, safe, practical and cost-effective methods of bladder emptying. Clean intermittent catheterization - whenever possible self catheterization - should be used as a standard routine treatment for patients who are unable to empty their bladders (LE: 2b, GR: B).
Urinary catheter-coating technologies have been introduced to prevent the development of biofilm on both the internal and external surfaces of the catheter. Common strategies to inhibit biofilm formation included bactericidal coatings, contact-killing coatings, antifouling coatings, disruption of biofilm architecture, and bacterial inference[30]. Both antibiotic and silver-coated catheters have been studied for the prevention of UTIs[31]. The silver-alloy hydrogel coated catheters are possible the most well-studied. It has been demonstrated in multiple clinical trials to reduce the incidence of CAUTI compared to non–silver-coated catheters and are well tolerated in long term usage[32-34](LE: 2a, GR: B). Antibiotic coated catheter has been studied for CAUTI prevention. Nitrofural-impregnated catheter is most studied antibiotic coated catheter. However it fails to show clinically significant reduction in CAUTI and is associated with more discomfort[35][36](LE: 1b, GR: A). Combination of silver-based products and antibiotics, or coating materials which as nitric oxide, chlorhexidine, antimicrobial peptides and surface acoustic wave technology showed promising in-vitro and in-vivo studies. They are investigational options to prevent CAUTI[37].
There is no convincing clinical evidence to date that cranberry[38](LE: 1a, GR: A). Lactobacillus rhamnosus GG (LGG®) instilled intravesically is safe for self-management of inflammatory urinary symptoms in adults and children with NLUTD due to spinal cord injury or disease and who use intermittent catheterization[39]. In a large multicenter prospective randomized double-blind factorial-design placebo-controlled trial. Researchers did not show probiotic therapy with Lactobacillus alone and/or Lactobacillus bifidobacterium combination are effective in preventing UTI in people with spinal cord injury[40]. Bacterial interference using a non-pathogenic strain of Escherichia coli HU2117 has initially shown to be safe and were able to significant lower the number of UTI but long-term data are lacking[41][42]. A more recent study showed colonization with Escherichia coli HU2117 did not prevent UTI in patients with chronic indwelling catheters[43].
Bowel dysfunction affects almost all patients with neurogenic bladder, with chronic constipation being the commonest symptom, followed by fecal incontinence[44]. Rectal distension caused by chronic constipation markedly affects bladder capacity, contractility and sensation[45]. Standard bowel care should be advocated for all patients, which includes adjustment of diet and fluid intake, general lifestyle alteration, stool softener, laxatives or suppositories, and digital stimulation[46](LE: 2a, GR: B). In addition to standard bowel care, transanal irrigation or enema was able to reduce the incidence of urinary tract infection in both adult[46][47] and pediatric[48-50] population, and hence the cost associated with it[51](LE: 1b, GR: A).
Neuro-urological management
Prime objective in preventing recurrent UTI in neurogenic bladder is to treat neurogenic detrusor overactivity and to restore low bladder pressure during bladder storage and voiding[52].
Oral anticholinergic medications are widely used as first-line treatment for patients with neurogenic detrusor overactivity. However they need to be taken long-term, are ineffective in some patients, or can cause troublesome side-effects such as dry mouth, constipation, drowsiness and blurred vision[53].
Injection of botulinum neurotoxin (Botox) into bladder wall is effective in treating neurogenic detrusor overactivity, and is indicated in patients refractory to or experiencing side effects from anticholinergics[54-58](LE: 1a, GR: A). Botox injection is effective in achieving continence, reducing incontinence episodes, improving urodynamic parameters and health-related quality of life. Significant adverse effects of Botox injection are asymptomatic urinary infection, urinary retention, and de novo intermittent catheterization.
Neurogenic bladder with low compliance may eventually necessitate surgical intervention to convert the high-pressure bladder into a low-pressure storage reservoir[59-61]. Bladder augmentation in itself, or when combined with simultaneous procedures[62] (like surgery on bladder outlet, and/or construction of a continent abdominal stoma by applying the Mitrofanoff principle), can produce sustainable improvements in bladder capacity, continence, urinary infection rate and preserve renal function in the long term. (LE: 3, GR: B)
Abbreviations
UTI: urinary tract infection, CIC: clean intermittent catheterization, CISC: clean intermittent self catheterization, CAUTI: catheter-associated urinary tract infection, NLUTS: neurogenic lower urinary tract dysfunction
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