Urinary tract infection (UTI) is the most common complication observed among patients suffering from neurogenic lower urinary tract dysfunction. The risk of UTI depends mainly on underlying urodynamic pathology and the bladder-emptying technique used. UTI risk increases with indwelling catheterization, incorrectly performed intermittent catheterization, and with application of external appliances [1]. Other risk factors include high bladder pressures, low bladder compliance, impaired voiding with poor bladder emptying, urine stasis, bladder overdistension, bladder outflow obstruction, altered intrinsic defense mechanisms, urinary tract stones, bladder diverticula, vesicoureteral reflux, instrumentation of the urinary tract, catheter composition, medications, immunosuppression secondary to medical therapy, decreased fluid intake, poor hygiene, perineal colonization, decubiti/other evidence of local tissue trauma, and reduced host defense associated with chronic illness [2–5]. Because of the heterogeneity of underlying disorders causing neurogenic bladder dysfunction, each patient must be approached individually, as risk factors vary significantly among patients.

UTI is the onset of signs and/or symptoms accompanied by laboratory findings (bacteriuria, leukocyturia, positive urine culture) [6]. The specific cut-off values for the quantification of laboratory findings vary and remain a matter of dispute.

Currently available guidelines propose that a significant bacteriuria can be diagnosed with >10² colony-forming units per milliliter of urine (CFU/mL) in persons performing intermittent catheterization, >10⁴ CFU/mL from clean-void specimens, and any detectable concentration from suprapubic aspirates [7, 8]. Insufficient data exist to recommend a standardized level of significant bacteriuria in individuals managed with chronic indwelling catheterization [9]. It has been generally proposed that in catheterized patients (intermittent, indwelling urethral, indwelling suprapubic, condom) concentration of >10³ CFU/mL of ≥1 bacterial species in a single catheter urine specimen can be classified as a significant bacteriuria [9]. Of note, bacteriuria does not necessarily signify a UTI. Clinicians should remember that only symptomatic bacteriuria allows diagnosing UTI. The standard of care among clinicians is not to treat asymptomatic bacteriuria—traditionally defined as 10⁵ CFU/mL of 1 or more organisms in an appropriately collected specimen in an asymptomatic person—with antibiotics [9].

Leukocyturia (pyuria) refers to the presence of leukocytes in the urine. There is disagreement regarding a threshold for significant leukocyturia. It has been proposed that ten or more leukocytes in centrifuged urine samples per microscopic field (400×) can be considered as significant [7]. Similarly to bacteriuria, pyuria alone is not diagnostic of infection, as it may result from irritative effects from a urinary catheter, particularly at a low level of less than or equal to 30 white blood cells per high-power field (WBC/HPF) [5]. More than 50 WBC/HPF is an indicator of high-level pyuria and has been associated with increased morbidity [5].

Bacterial colonization is differentiated from UTI by the absence of an inflammatory response and the associated symptoms and signs that result from bacterial invasion. Bacterial colonization of the bladder in neurogenic patients suffering from neurogenic lower urinary tract dysfunction is the norm, regardless of bladder-emptying technique, including indwelling or intermittent catheterization [10]. Because of the risk of developing more invasive and resistant organisms, bladder colonization with asymptomatic bacteriuria should not be routinely treated [10].

The incidence of UTI in the population of neurogenic bladder patients is high and may vary in cause of underlying pathology. It has been estimated that the overall rate of UTI in these patients is 2.5 episodes per patient per year [11]. The incidence of febrile UTI has been gauged as 1.8 per patient per year [3]. The rate of bacteriuria following the introduction of a catheter is 5–8% for each day of catheterization, with a 100% incidence of bacteriuria with long-term indwelling catheters within 4 weeks [12–15]. Prevalence of bacteriuria in those performing clean intermittent catheterization varies from 23–89% [16]. A retrospective study of 46,271 patients with neurogenic lower urinary tract dysfunction showed that more than one-third (29.2–36.4%) of patients were diagnosed with a UTI within the first year of diagnosis of bladder dysfunction [17]. Importantly, 20% of these patients required hospitalization. The study noted that spinal cord injury (SCI) patients required more hospitalizations due to UTI than patients with multiple sclerosis. Prospective cohort studies of SCI individuals have shown concurrent results and revealed that hospitalized patients required an average length of hospital stay of 15.5 days [18]. The outcomes of a recently published large cohort study of SCI patients are of the utmost importance for daily clinical practice. Authors demonstrated that 51.2% of the emergency department visits in the aftermath of UTI could potentially be prevented [19]. UTI is the most common type of all infections and the most common cause of fever in the SCI patient [20, 21]. As neurologically impaired individuals are more susceptible to developing UTI, virtually all kinds of procedures within the urinary tract have higher risk of infection. For instance, the incidence of post-urodynamic UTI has been estimated as 16%, significantly higher compared to the non-neurogenic population [22–24]. Some experts proposed that sterilization of urine before urodynamics can reduce the risk of UTI by half [22]. In male patients who empty their bladders by increasing intravesical pressure, either by Valsalva or Crede maneuvers, reflux of urine into the prostate and seminal vesicles occurs in more than 50% of patients and can lead to other complications such as epididymoorchitis [12]. Seminal vesiculitis, prostatitis, epididymitis, and orchitis may all be seen in patients with long-term urethral catheterization with blockage of the ejaculatory and prostatic ducts [12].

UTI may also aggravate underlying neurological pathology , in particular, multiple sclerosis. Available data suggest that bacterial infection within the urinary tract may be a significant trigger factor of disease exacerbation [25]. Up to 30% of patients with multiple sclerosis may experience disease exacerbation as a consequence of UTI [26]. Furthermore, patients with documented bacterial infection have shown little response to steroid therapy until appropriate antibiotics are co-administered [26]. Recurrent UTI may result in overall disease progression, and individuals suffering from multiple sclerosis have a more pressing need for rapid diagnosis and prompt treatment [2]. Thus, it has been proposed that in these patients diagnosis can be made with urine dipstick followed by treatment based on dipstick results [27]. When urine culture results are available, treatment may be discontinued or modified (if required), with emphasis on avoiding treatment delay for the primary illness of multiple sclerosis [2, 27, 28].

The Enterobacteriaceae family represents the most commonly isolated organisms in the neurogenic population [29–32]. Escherichia coli and Klebsiella species dominate with E. coli comprising 50% of all isolated strains. However, patients with neurogenic bladder tend to have an increased rate of infection with other organisms such as Pseudomonas (8.7–15%), Acinetobacter (6–15%), Enterococcus (6–12%), and multiorganismic infections (26%) [31, 33]. The incidence of polymicrobial infections represents the greatest difference between infections in the neurogenic bladder as opposed to a healthy bladder [2]. Individuals with neurogenic lower urinary tract dysfunction are also prone to develop fungal infections. Possible risk factors of fungal infection include recent antibiotic use and indwelling catheterization. A prospective study of SCI patients has found that candiduria may be present in up to 17% of these patients. Those managed with indwelling catheterization (both urethral and suprapubic) are ten-fold more likely to develop candiduria compared to individuals who performed clean intermittent catheterization [34]. To make matters worse, multiple antibiotic treatment for recurrent UTIs contributes to rising multi-drug resistance. It has been shown that up to 50% of SCI patients may complain of UTI caused by multi-drug resistant strains [30]. More than 50% of these strains are resistant to ampicillin, levofloxacin, cefazolin, and clavulin [31]. This issue affects both inpatient and outpatient individuals.

With the increased frequency and severity of UTI, there is higher risk of morbidity and mortality secondary to urosepsis and end-stage renal disease compared to the general population [35]. Although advances in diagnostic procedures and medical care have significantly improved during past decades and have reduced the morbidity and mortality of UTI in patients with neurogenic bladders , currently up to 10–15% of these patients may die from sepsis of urinary origin [36]. Importantly, UTI in neurogenic patients may also indicate change or evolution of bladder dysfunction, thus requiring new urodynamic assessment in some cases.

In individuals with neurogenic bladder, asymptomatic bacteriuria of varying degrees is the norm. Thus, asymptomatic bacteriuria should not be screened or treated unless there is suspicion of UTI [7, 9]. Treatment of asymptomatic bacteriuria may result in significantly more resistant bacterial strains without improving the outcome [62]. Exceptions include pregnant women and patients before urological procedures within the urinary tract. In those on immunosuppression (e.g., individuals with multiple sclerosis), treatment of asymptomatic bacteriuria may be considered [63, 64]. Antibiotic therapy can be given simultaneously with corticosteroid treatment [63].

UTI in patients with neurogenic lower urinary tract dysfunction is categorized as complicated [7]. Treatment duration has not been well established and depends on infection severity and location (cystitis, urethritis, prostatitis, epididymitis, pyelonephritis). It has been generally proposed that a 5- to 7-day course of antibiotic therapy should be employed [7, 62]. This time interval can be extended up to 14 days, according to the extent of the infection. In patients with indwelling catheters, initial treatment course of 7–10 days is recommended [9, 65]. Patients presenting with UTI and fever (infection within the upper urinary tract) should be treated for 14 days [62]. Antibiotic therapy should be chosen based on the results of urine culture and sensitivity. The urine specimen for testing should be obtained before the initiation of antimicrobial therapy. Once treatment is initiated, all catheters should be changed. In patients performing intermittent catheterization, frequent complete emptying is required. If immediate therapy is mandatory (e.g., patients with fever, sepsis, or risk of deterioration of other concomitant disorders), the choice of treatment should be based on local and individual resistance profiles [21]. Clinicians should be aware that bacterial isolates may vary in outpatient and inpatient settings and higher rates of resistance to commonly prescribed antibiotics are not rare, making broad-spectrum antibiotics mandatory in severe cases [31, 64]. When immediate treatment is necessary, it usually involves fluoroquinolones, trimethoprim/sulfamethoxazole (if there is a suspicion of methicillin-resistant Staphylococcus aureus in outpatient settings) or vancomycin (if there is a suspicion of methicillin-resistant S. aureus in inpatient settings) [29]. In patients with upper urinary tract infection, double intravenous antibiotics (ampicillin–gentamicin) should be started until the results of cultures appear [5]. On the third day, appropriate oral antibiotic therapy may be introduced. If symptoms persist beyond 72 h, the possibility of perinephric or intrarenal abscesses or obstruction should be considered and radiologic investigation with ultrasound or computed tomography should be performed. Urine and blood cultures should be repeated at appropriate intervals and antimicrobial therapy should be adjusted, if necessary [5]. Figure 10.9 presents an algorithm of UTI diagnosis and management [62, 64] (Fig. 10.9).