Urinary Tract Infections in Neuro-Patients Urinary Tract Infections in Neuro-Patients

The majority of neurological diseases may have an impact on lower urinary tract func- tion. High intravesical pressure, post-void residual and incontinence are the main con-sequences of this dysfunction. All the mentioned conditions are inductive factors for urinary tract infections (UTIs). In addition, the potential complications of neurogenic urinary disorders (reflux, stone formation, incomplete emptying of the bladder), and the methods of urine drainage (intermittent or indwelling catheters, urinary diversion) contribute even more to UTIs. In neuro-patients, all UTIs are considered as complicated ones and there is a different microbiology as compared to the general population. In this chapter, inductive factors for UTIs in neuro-patients will be analyzed and the potential solutions will be exposed. There is a special mention in asymptomatic bacteriuria, which is correlated to neurogenic urinary dysfunction and it is clinically total different from UTI. Asymptomatic bacteriuria should not be treated as the treatment has a negative final outcome for the patient.


Introduction
The normal functioning of the urinary system is closely related to the functional integrity of the central nervous system (CNS). Neuro-urological symptoms may be caused by a variety of diseases and events affecting the nervous system controlling the lower urinary tract (LUT). The resulting neuro-urological symptoms depend predominantly on the location and the extent of the neurological lesion. There are no exact figures on the overall prevalence of neurourological disorders in the general population, but data are available on the prevalence of the underlying conditions and the relative risk of these for the development of neuro-urological Spinal cord injury (SCI) patients clinically face urinary incontinence during the bladder filling phase and incomplete emptying during the micturition phase. The main aggravating factors are the increased intravesical pressure and the residual urine. These may result in vesicoureteral reflux, bladder diverticula, and urinary stones formation. These conditions also lead to an increased risk of urinary tract infection (UTI) [7,8]. Despite improved treatment methods, UTI is considered the second leading cause of death in SCI patients [9]. It is known that UTIs are the most common hospital infections with known repercussions for the patient and the national economy. Approximately 5-10% of patients admitted to hospital are infected during their hospitalization and UTIs account for the highest (40-50%) [10,11]. In addition, SCI patients usually have asymptomatic bacteriuria. In this way, positive urine culture is not the foundation stone for the diagnosis of urinary tract infection. The clinical signs and symptoms of urinary tract infection are differentiated in these individuals as the neural sensation is affected or absent. The review of the following literature aims to highlight the specificities of urinary tract infections in people with SCI or other neurogenic conditions in order to prevent and treat the infections and recognize asymptomatic bacteriuria without treatment necessity.
The physiological function of the lower urinary tract is characterized by the central control of the urinary reflexes (inhibition or removal of reflex inhibition) from the upper cortical centers of the cortex. Urine concentration within the bladder results in an increase in intravesical pressure that causes stimulation of the thoracic-lymphatic sympathetic center (T10-L2) via transient and adductor nerve fibers. Adjacent nerve fibers transfer the stimulus to the breech centers of urination and from there to the upper centers of the cerebral cortex. Then, if there is no central depression, the urinary reflex is manifested through the contraction of the detrusor resulting in the sympathetic nerves. However, if urination is undesirable, this reflex is inhibited as cationic signals inhibit sympathetic stimulation at the level of the thoracic-lumbar sympathetic center and increase the muscular tone of the external sphincter by suture from the pelvic neural mesh formed by the S2-S4 level. From the above, it is clear that any damage at any level of SC results in disorders of lower urinary function. These disorders vary according to level [11,12], the degree (complete or incomplete) [13] and the extent of the damage.

Increased intravesical pressures
Neurogenic urinary tract dysfunction characterized by increased intravesical pressures and/ or urine residual [14]. These patients have decreased microorganism removal capacity [15]. Both incomplete emptying of the bladder [16] and high intravesical pressure [17,18] are accompanied by an increased risk of UTI. Patients who have been using Credé maneuver for a long time to empty their bladder have had severe complications in the upper urinary tract (82% pyuria, 60% ureter dilation, 35% hydronephrosis, and 16% renal failure). Men appeared more susceptible to upper urinary tract damage than to women [19]. According to Esclarin De Ruz et al [20] in patients with SCI with detrusor overactivity, the coexistence of detrusorsphincter dyssynergia duplicates the risk of urinary tract infections.

Vesicoureteral reflux
Under normal circumstances, the ureterovesical junction allows urine to enter the bladder but prevents urine from regurgitating into the ureter and the kidney. This results in the kidney being protected from high pressure in the bladder and from contamination by vesical bacteria. In this way, vesicoureteral reflux is considered to be an important factor in urinary tract infection [20]. It occurs in 10% of patients over 4 years of SCI [21]. Although the reflux is the result of high intravesical pressure, it must be controlled by another neurological mechanism since patients with a T10-L2 lesion exhibit more regressive effects than patients who have a level of damage above or below this level [22]. The damage at this level is probably related to the ureteral peristaltic mechanisms.

Intermittent catheterization
Intermittent catheterization (IC) during the recovery period appears to reduce the rate of urinary tract infections and substantially eliminate many of the complications associated with the use of an indwelling catheter [23,24]. However, IC may also present certain complications, such as traumatic urethral injury (immediate) or urethral restenosis and recurrent epididymitis (late). In one study, SCI patients, using pure intermittent catheterization for more than 5 years, showed urine stasis at 19% and epididymitis at 28.5% [23]. The appearance of the above complications appears to be increased according to the number of years of pure IC performed [23]. Research supports the use of sterile IC technique in the acute phase of the neurogenic bladder [25] and agrees with a study in which few cases of bacteriuria and urinary tract infection were observed using sterile intermittent catheterization as compared to using a non-sterile procedure [26]. On the other hand, Shekelle et al. reported contradictory results in the value of sterile techniques or techniques without direct catheter contact compared to pure intermittent catheterization, as there is insufficient evidence of risk associated with psychological, behavioral and hygienic factors [27]. Hydrophilic catheters for clean intermittent catheterization are associated with lower rates of long-term complications (urethral stenosis) and may cause a lower degree of bacteriuria [28]. Another type of catheter, with an insertion sheath, which bypasses the first 1.5 cm of the urethra, appears to reduce the incidence of urinary tract infections in hospitalized men with SC damage [29].

Permanent indwelling catheters
Permanent indwelling catheters are the greatest risk factor for complicated UTIs [30]. They are responsible for most in-hospital UTIs, 3-10% per day and with 100% bacteriuria in their long-term use [31]. Silver-coated catheters are more effective in preventing urinary tract infections in patients who require short-term catheterization and reduce the incidence of symptomatic urinary tract infection and bacteriemia compared to simple catheters [32,33]. For short-term catheters not exceeding 2-3 weeks, the use of nitrofurazone, minocycline, and rifampin-impeded catheters reduce the risk of urinary tract infection [34,35] due to antibiotic overlap.

Suprapubic catheters
The use of a permanent suprapubic catheter is an effective way of draining the bladder in SCI patients with a low rate of urinary tract infection [36,37]. Suprapubic catheterization may be an alternative drainage method for female patients who cannot perform self-IC [38]. The disadvantage is the continuous presence of the catheter (foreign material) within the bladder associated with the formation of urinary lithiasis as compared to intermittent catheterization at rates of 9 and 4%, respectively, over a period of more than 9 years [39]. On the other hand, this chronic irritation from the catheter is accompanied by an increased incidence of bladder cancer as compared to intermittent catheterization [40]. Nomura et al. [41] reported that 25% of patients with long-term use of suprapubic catheter showed bladder stone formation, which was accompanied by a 7.24 urine pH. Suprapubic drainage in patients with neurogenic urinary disorders is preferred (against urethral catheterization) as it appears to reduce the risk of urethritis, orchiepididymitis, testicular abscess and urethral erosion as compared to permanent catheterization [42].

Condom catheter drainage
Condom catheters are used in male patients to manage incontinence but not bladder emptying. Their application is accompanied by the same degree of urinary tract infection as in the use of intermittent catheterization. However, condom catheters do not ensure complete bladder drainage and can (in cases of poor application) be considered a cause of occlusion [43]. It is recommended that the condom catheter is applied daily, although no increase in infections has been reported in non-daily applications [44]. In addition, although condom catheters are external, they appear to be related to colonization of the urethra by pathogenic microbes. They are accompanied by Pseudomonas [45] and Klebsiella [46] infections due to the colonization of the regions of the urethra, perineum, penis, and rectum by the above microorganisms. In addition, the urine trap is a very good reservoir of microorganisms. In male patients using condom catheter, urine culture was 73% positive for Pseudomonas, although the degree of bacteriuria was much lower [47,48]. Also, the colonization of the urethra with Pseudomonas is combined with the presence of the condom catheter [49]. From the above, it can be seen that the chronic use of a condom catheter drainage and urine collector predisposes to the colonization of the patient and the upward introduction of microorganisms into the anterior urethra.

Biofilm (biomembranes)
According to their initial description, microorganisms are referred to as non-adherent "planktonic" cells [50] based on their developmental characteristics in enriched liquids and solids. Today, it is now known that bacteria in their natural environment are typically attached to some biological or non-surface area. It is also known that adhering microorganisms under suitable conditions form complex structures, biofilms (bio-membranes). These structures are formed as the microorganisms are surrounded by an extracellular exopolysaccharide (EPS) layer which themselves produce [50,51]. Bacteria are the best-studied microorganisms regarding surface colonization and subsequent biofilm formation.
Fungi, protozoa, viruses, and algae have also been isolated from corresponding extracellular material in direct contact with organic or inorganic surfaces [52]. Stable microbial attachment to the underlying surfaces and the formation of biofilms creates significant and often insoluble problems both in the medical community and in the industry [53]. Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Pseudomonas aeruginosa often colonize implanted medical devices [54] (such as pacemakers, intravenous catheters, urinary catheters, prosthetic implants, and heart valves) as well as pathological tissue structures (such as respiratory epithelium in patients with cystic fibrosis or cystic fibrosis mucosal in patients with neurogenic bladder) and create biofilms, thus causing chronic and often resistant to treatment infections.
Bacterial biomembranes are observed in 73% [55] patients with SCI using IC, and no relationship has been found between the presence of bio-membrane and symptoms [56]. However, the presence of at least 20 bacterial adherence in each bladder cell appears to be related to the symptomatology of the infection [57]. Bacterial cells are detached individually or in groups from the upper layers of the biofilm circulating in the fluid medium, urine in this case, and attempting to adhere to a new substrate which is more conducive to their growth. These detachable bacteria can cause systemic infection [53,58].

Clinical symptoms
The specificity of individuals with SCI is that asymptomatic bacteriuria is usually present and the sensory disorder results in the lack of a clear symptom of urinary tract infection. The clinician should carefully evaluate the patient to decide whether a positive urine culture reveals infection or is an asymptomatic bacteriuria. Additionally, fever should not be attributed to urinary tract infection if the only positive point is bacteriuria unless other possible causes of fever are excluded. Approximately 45% of feverish conditions in these patients are thought to be due to urinary tract infections [59]. Other causes are respiratory infections as well as thromboembolic events. The septic condition in quadriplegic patients may also occur as hypothermia [60]. Approximately 10% of febrile episodes may be the result of a temperature control malfunction and not an infection [61]. The coexistence of elevated CRP and routine serum test values should be considered. UTI is accompanied by a specimen of urine blisters with microbes above 10 5 CFU/ml, and symptoms such as fever, back pain in the lumbar region of the kidney, upper urinary tract infection, and if the patient has a sensation at this level, urinary urgency and increased spasticity. A characteristic symptom is the reduction of cystic functional capacity and the aggravation of overactive bladder syndrome, in the case of a neurogenic overactive detrusor, or the discontinuation of response to previously well-regulated treatment for increased extravasation activity. The incidence of urinary tract infections in SCI patients is 2.5 episodes per patient per year. Bacteremia and sepsis occur in 1% of SCI patients [62]. The urinary system is considered to be the most common source of bacteremia [62,63]. Bacteremia in SCI patients is accompanied by 90% fever, 17% hypotension, and death rate of about 15%. [62,63]. Approximately 20-25% of episodes are characterized by polymicrobial infections. Bacteriemia is more common in quadriplegic patients and in patients with complete SCI [64]. Urogenital tube manipulations are considered as risk factors for bacteremia [65].

Microbiology-urine culture
Urinary tract colonization often follows colonization of the urogenital tract, perineum or urethra with enteropathogenic microorganisms [66,67]. In a study of 15 adult men with SCI and other neurogenic urinary dysfunctions, the normal flora of the perineum, penis and urethra regions was compared with the flora of 10 control men without neurogenic urinary disorders [68]. The predominant microorganisms with respect to the control group were Grampositive granules and diphtheroids. In the individuals with the neurogenic urinary disorder, the microorganisms isolated from the skin flora include species such as Enterobacteriaceae, Pseudomonas, Acinetobacter, and Enterococcus [68]. In addition, other studies of individuals with SCI as compared to non-injured patients, the presence of E.coli microorganisms and Klebsiella spp. are less, and have a higher frequency of infections than Pseudomonas, Proteus, and Serratia. Esclarin De Ruz et al. [20] reported that E. coli, 36% enterobacteria, 15% Pseudomonas aeruginosa, 15% Acinetobacter spp., 12% Enterococcus, 6% other microorganisms, and 26% multiple strains were isolated in 45%. In another study in 43 of 50 individuals with SCI, the same types of microorganisms as those from various areas of the skin, including perineal, peripubic, and perinatal regions, were isolated in urine [69]. In 50% of the cases, the same microorganism was isolated from the anterior urethra and from the bladder [70]. Also, the catheter insertion mode is also considered to be significant, which appears to cause an increase of approximately 10 times the number of bladder colonies [70]. The above results demonstrate the important role of bacterial colonization of the skin and urethra as a source of vaccination, through the catheters, of the bladder with microorganisms.
When a UTI is suspected, it is important that the urine specimen is obtained in an appropriate manner in order to prevent contamination and a potential false-positive result. For patients with indwelling catheters (either the urethral catheter or suprapubic), the indwelling catheter should be changed to a new catheter, and the specimen should be obtained from the new catheter after capping the catheter for a few minutes to allow a small amount of urine to collect in the bladder. The urine specimen should then be collected by uncapping the catheter. For patients with external catheters or those who perform IC, the specimen should be collected by catheterization with a new sterile catheter.

Pyuria
The significance of pyuria in neurogenic patients in combination with the use of intermittent catheterization or permanent catheter is often difficult to assess. Changing the Foley catheter in symptomatic patients causes an increase in the leucocytes without affecting the microbial strain or the number of colonies [71]. Positive urine culture (10 5 CFU/ml colonies), with the presence of >50 leucocytes per field of vision, is associated with an increased risk of fever. In addition, Gram-positive microorganisms such as Staphylococcus epidermidis and Streptococcus faecalis are accompanied by a small number of leukocytes despite the occurrence of a large number of colonies, while Gram-negative microorganisms are accompanied by significant pyuria [72]. According to the above significant pyuria is associated with the presence of catheters, infection with Gram-negative microorganisms, as well as bacterial tissue filtration.

Bacteriuria
Comparative studies are difficult to perform in these patient groups due to different definitions of bacteriuria and urinary tract infection, different urinary tract drainage methods, as well as the severity of acute, subacute, chronic, or total and partial lesions. In 1992, according to the National Institute on Disability Rehabilitation Research, severe bacteriuria is defined as the number of colony counts of 10 2 CFU uropathogenic micro granules per ml of urine in samples taken by catheterization, 10 4 CFU/ml urine samples under pure micturition and any detectable uropathogenic concentration in samples from permanent catheter or supraventricular puncture. Other researchers continue to regard the concentration of 10 5 CFU/ml in urine as a criterion for significant bacteriuria even in samples after catheterization [73]. Waites et al. reported that patients with 10 CFU/ml in urine have a 10% risk of a febrile episode, while the presence of pyuria is more associated with fever and shivering [73]. In patients receiving 40% IC, the source of bacteriuria was the upper urinary tract, while in 60%, the source was the lower urinary tract [74]. Pyuria was much higher in patients with upper urinary tract infection [75].

Asymptomatic bacteriuria
Asymptomatic bacteriuria is defined as the presence of a significant number of urine microbes (10 5 CFU/ml) in patients without clinical symptoms or signs of infection. The incidence varies depending on the age of the patients, the sex and the presence or absence of functional or anatomical urinary tract abnormalities. Bladder catheterization is the most important predisposing factor for asymptomatic microbial growth. In hospitalized catheterized patients with an open urine collection system, the incidence of the asymptomatic microbial disease is 100% of the patients within 3-4 days.
Microorganisms most commonly isolated in bladder catheterized patients are Escherichia coli, Klebsiella, Proteus, Enterococcus, Enterobacter, Pseudomonas, Serratia, and Candida. Most are part of the microbial flora of the bowel colonizing the anterior part of the urethra. In patients with a bladder catheter for a short or long period of time, urine specimen collection should be taken by catheter puncture after meticulous antisepsis of the puncture site and not through the catheter's mouth. The presence of leucocytes with or without hematuria is taken into account but does not necessarily require the diagnosis of active infection. Asymptomatic bacteriuria in individuals with SCI requires treatment only in cases where symptomatic urinary tract infection develops [76,77].

Skin colonization
As mentioned, bacterial colonization of the skin and the urethra is an important source of bladder infection using catheters. Differences in microbial species and their presence in normal skin flora of SCI patients and other neurogenic urinary disorders in relation to individuals without neurogenic disorders may result from the use of antibiotic therapy, use of condom catheters, pH and skin temperature in the area, personal hygiene, or fecal contamination. Pseudomonas colonizes the perineum, in addition to the high pH of the skin of the area appears to contribute positively to the high risk of colonization [78,79]. The meticulous soap wash of the perineum area only has temporary effects in reducing its colonization by Gram-negative microorganisms, whereas the use of antiseptics, such as chlorhexidine and povidone-iodine, has no effect [80,81].

Bladder catheterization
Efforts to eliminate bacteriuria due to the use of permanent or intermittent catheterization have no effect. Intensive or continuous catheterization is a frequent but not documented method of treatment to prevent sedimentation, bacteriuria, urinary tract infection and/or bacteremia. Intravenous administration with neomycin/polymyxin has no effect. Spinal hygiene, perineal wash, and frequent catheter changes have found ineffective methods in reducing urinary tract infection due to catheterization [82]. In addition, it is important for both coating and catheter composition. Prevention of P. aeruginosa biofilm formation is observed using silver-coated catheters [83].

Biofilm management
As mentioned above, a general feature of the microorganisms that form the bio-membranes is their resistance to various antimicrobial substances, as opposed to free-flowing cells. The main objective should prevent biofilm formation by the prophylactic administration of antibiotics and strict adherence to antisepsis rules when attaching any prosthetic material and in this case a catheter. It is also proposed to incorporate antimicrobial agents into the material to be implanted and to modify the physical or chemical properties of the material so as not to favor biofilm formation.
To achieve satisfactory penetration of antimicrobial drugs into the bio-membrane, experimentally liposomal forms of drugs have been tested with encouraging results. Reid et al. claimed that the daily use of cranberry helmet juice drastically reduced the formation of biofilm and reduced the adhesion of Gram-negative and -positive microorganisms to bladder cells [84]. Respectively, in more recent studies and post-analysis, the clinical benefit of using cranberry juice to reduce urinary tract infections appears to be limited to recurrent urothelial infections in women without neurogenic urinary disorders of young and middle age [85,86].
The use of antimicrobial drugs for the prevention of UTIs in people who have intermittent catheterization or carry an indwelling bladder catheter has some positive results. In some studies, prophylactic antibiotics are reported to be effective. The use of methenamine orally and intake of acidic substances contributes to the reduction of urinary tract infection in the case of intermittent catheterization [87]. A low dose of ciprofloxacin appears to be more effective than placebo in preventing urinary tract infection [88]. In a study, administration of the 500 mg twice daily dose for 10 days reduced the incidence of Gram-negative organisms in the perineum and urethra but ciprofloxacin-susceptible microorganisms were replaced by resistant microorganisms such as staphylococci, including methicillin-resistant S. aureus, Enterococci and Acinetobacter spp. [89]. In contrast to the above, comparative studies of prophylactic administration of ascorbic acid, TMP-SMX, nalidixic acid, methenamine hippurate, or nitrofurantoin microcrystals to prevent urinary tract infection in patients with SCI did not provide statistically significant results. In a daily use of TMP-SMX study compared to placebo as a prophylaxis for urinary tract infections in SCI patients, the use of TMP-SMX did not reduce the incidence of symptomatic bacteremia while there was an increase in TMP-SMX resistance in asymptomatic patients [90].

External sphincterotomy
The efficacy of the sphincterotomy has been well documented since Emmett JL and Dunn JH described the trans-urethral resection of the bladder neck and prostate in SCI patients with outlet obstruction. Ross JC introduced the resection of the external urinary sphincter. Large series have shown that sphincterotomy is successful in the treatment of vesical outlet obstruction in certain male patients with quadriplegia, in order to reduce detrusor leak point pressure, followed by condom catheter drainage. Patients who develop UTIs after sphincterotomy are should undergo assessment of PVR to ensure adequate bladder emptying. Urodynamic testing should also be considered to assess the efficacy of the sphincterotomy. If there is evidence of urethral obstruction, repeat sphincterotomy may be indicated. Sphincterotomy can also be indicated when patients use Credé or Valsalva to empty their bladder, but first, surgeons must have assessed that the lower urinary tract is urodynamically safe and that the upper urinary tract is not damaged [91].

Bladder augmentation
The aim of bladder augmentation is to reduce detrusor overactivity (DO), improve bladder compliance and reduce the pressure effect of DO [92,93]. Complications associated with these procedures are recurrent infection, stone formation, perforation or diverticula, possible malignant changes, metabolic abnormality, mucus production and impaired bowel function [94][95][96]. Special attention should be paid to patients with preoperative renal scars since metabolic acidosis can develop [97]. Several different techniques have been published [98][99][100][101][102][103][104][105][106]. Bladder substitution, even by performing a supratrigonal cystectomy [93], is also indicated in patients with a severely fibrotic bladder wall. IC may become necessary after this procedure.

Urinary diversion
Following supravesical urinary diversion, pyelonephritis may occur, usually accompanied by fever, chills, leukocytosis, nausea and vomiting. Upper tract imaging should be performed, due to possible urinary obstruction. If there is an obstruction, the system should be drained via percutaneous nephrostomy. In this case, urine culture should be obtained from the nephrostomy tube.

Continent diversion
It is the first choice for urinary diversion. The continent urinary reservoir is indicated when the native bladder and urethra are severely devastated functionally or anatomically, as well as bladder neck closure and ureteral re-implantation are not avoidable. All of the different techniques have complications such as leakage or stenosis. The short-term continence rates are >80% and good protection of the UUT is achieved [107][108][109][110][111][112][113][114][115][116][117][118][119].

Incontinent diversion
If catheterization is impossible, incontinent diversion is indicated. The ileal conduit is the most common form of incontinent urinary diversion used. It could be considered in patients who show intractable and untreatable incontinence, in patients with LUT dysfunction, when the upper urinary tract is severely compromised and in patients who refuse other therapy [119]. An ileal segment is used for the deviation in most cases [120][121][122][123][124] and patients gain better functional status and quality of life [125]. Incontinent diversion has also an acceptable rate of complications. Especially in children, there are concerns about long-term effects on renal function, and while conduit diversion may be considered in this population, alternative methods may be preferable.

Undiversion
Long-standing diversions may be successfully undiverted or an incontinent diversion changed to a continent one with the cause of better techniques for control of detrusor pressure and incontinence [120]. The patient must be carefully counseled and must comply with the instructions [120]. Only then successful undiversion can be performed [126].

Continent catheterizable channel
Some patients with spinal cord injury have difficulty or are unable to perform IC through a native urethra. In such cases, the creation of an abdominal stoma using a continent catheterizable channel (CCC) should be considered. A CCC is particularly helpful in women because their ability to access their urethra is more difficult than in men [127][128][129]. A concomitant bladder neck closure with a CCC becomes an option when urethral dysfunction or destruction does not result in acceptable continence over anti-incontinence surgeries.
The majority of patients with bladder augmentation or continent urinary diversion will have mucus production that can act as an incubation material for infection. Irrigation of the bladder or pouch at regular intervals with normal saline decrease the incidence of symptomatic urinary tract infection.

Treatment
Generally, asymptomatic bacteriuria does not require treatment because the microorganism cannot be eliminated or will recur after the treatment is complete. In addition, antimicrobial therapy will lead to resistant strains of microorganisms [130,131]. Therefore, there is no indication that treatment reduces virulence or mortality. Systemic antimicrobial therapy for asymptomatic bacteriuria is recommended only in special cases such as: • patients who undergo urological surgery or prosthetic graft • treatment may be a part of the control of a hospital infection due to a particular prevalent virulent microorganism • patients belonging to high-risk groups (immunosuppressed) • strains of microorganisms suspected of bacteremia such as Serratia marcescens [132][133][134][135].
Symptomatic UTI in the neurogenic patient is defined as a urinary culture with ≥10 2 CFU bacteria/mL and symptoms including, but not limited, to LUTS, urinary incontinence, increased spasticity, autonomic dysreflexia, pelvic discomfort, fever, and decreased energy level. Moreover, it has not been shown that the type of microbe isolated in urine culture of an asymptomatic patient is the cause of infection when a symptomatic episode occurs. In 30-50% of cases, urinary catheter removal is accompanied by urinary tract purification by the microorganism [40,134]. People with symptomatic bacteriuria-UTI should be treated with the most specific antibiotic treatment for the shortest but sufficient period. Since the urinary catheter surface, due to biofilm formation becomes a source of bacterial growth, it is justified and important to remove it and replace it with a new one before treatment of symptomatic infection [40,[136][137][138][139]. The guidelines for choosing the right antimicrobial treatment are the same as those of the general population. They include the identification of the microorganism, antimicrobial susceptibility, the location of the infection, its complexity, and the risk factors.
Although there are insufficient clinical studies on the duration of treatment for urinary tract infections in neurogenic patients, the duration of treatment varies from 3 to 21 days depending on the microorganism, the accompanying factors of infection and the condition of the patient [138,140,141]. When oral treatment is sufficient, it is usually given for a period of 5-7 days, and when intravenous treatment is required, it remains from 7 to 14 days depending on the clinical and laboratory findings [142]. In the appearance of fungi in urethral cultures, treatment is unnecessary. In this case, either local (intravesical) or systemic antifungal treatment [143,144] is not recommended, and it is recommended to replace the catheter with a new one. If the infection is accompanied by symptoms of the urinary tract or the presence of fungus is a symptom of systemic infection, then antifungal treatment is necessary [145].

Conclusion
Urinary tract infections are a grade issue for medical doctors and patients. It is even more difficult to diagnose and treat neurogenic patients rather than general population. The higher frequency of recurrent infections in these patients and resistant microorganisms remain the main problems as for this specific population. In summary, based on the criteria of evidencebased medicine, there is currently no preventive measure for recurrent urinary tract infections in neurogenic patients that can be recommended without limitations. Individualized concepts, including immunostimulation, phytotherapy, and complementary medicine, should be taken into consideration [146]. Prophylaxis is important to pursue, but there are no data favoring one approach over another. In this case, prophylaxis is essentially a trial and error approach.
Nowadays, the quality of life of the neurogenic patients is the primary concern. Antibiotics, catheterization techniques and urinary diversions are the main features of treatment applied. The medical community contributes in this direction with the proper diagnosis of the diseases in this group of patients. Personalized physician and patient collaboration and the timely recognition of symptoms by the patient remain the cutting edge of early symptoms relief. The proper and efficient control of the "neurogenic bladder" is essential for the prevention and the management of the UTIs. The controlled bladder pressure and its complete periodical evacuation under a low-pressure environment can ensure that the UTIs will be less frequent and less severe.