Urinary Tract Infection

and Mikolaj Przydacz1



(1)
Department of Urology, Jewish General Hospital, McGill University, Montreal, QC, Canada

 



Keywords
Urinary tract infectionBacteriuriaLeukocyturiaPyuriaBacterial colonizationUrinalysisUrine cultureFollicular cystitisCystitis cysticaProphylaxisCranberry



Introduction


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 [25]. Because of the heterogeneity of underlying disorders causing neurogenic bladder dysfunction, each patient must be approached individually, as risk factors vary significantly among patients.


Definitions


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].


Epidemiology


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 [1215]. 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 [2224]. 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 [2932]. 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.


Diagnosis



Symptoms and Signs


Because of impaired bladder sensations, traditional symptoms and signs of UTI (urgency, frequency, dysuria) in patients with neurogenic lower urinary tract dysfunction may be replaced by distinguishing symptomatology. The most common signs and symptoms suspicious of an infection within the urinary tract in those patients are [7, 37, 38]:



  • Fever, rigors, chills


  • Discomfort or pain in back or abdomen (pain may be elicited by palpation or percussion)


  • New onset or increase in incontinence, including leakage around an indwelling catheter or between intermittent catheterizations


  • Increased need to perform catheterization


  • Cloudy urine with increased urine odor (complaint that the urine is not clear, with a distinct change in urine odor, and strong foul smell that persists on change of catheter equipment)


  • Increased urinary sediment


  • Increased spasticity (compared with the patient’s usual self-assessed baseline or on examination with increased resistance to stretch)


  • Malaise, lethargy, or sense of unease (feeling tired or unwell, different from the person’s usual state of health)


  • Nausea and vomiting


  • Sweating


  • New onset or worsening of autonomic dysreflexia

Because of these specific symptoms, patients with SCI are able to predict the presence of a UTI with an accuracy of only 61–66% [39, 40]. It has been shown that SCI patients were better able to predict the absence, rather than the presence, of UTI [39]. The highest accuracy and sensitivity in predicting the presence of UTI have been reported for cloudy urine and pyuria [9, 39]. The absence of pyuria was noted as a strong indicator for no infection [8, 36, 41]. Fever had very high specificity but very low sensitivity. In contrast, malodorous urine is not equivocal proof of infection [9, 42]. Concurrent results were demonstrated for autonomic dysreflexia , as it may be triggered by multiple causes. It has been estimated that one-third of patients with neurogenic bladder dysfunction who present with UTI experience an isolated sign, one-third experience two signs and one third experienced three signs [43]. Despite the uncertainty of symptoms, patient self-evaluation and awareness remain an important component of early detection and possible intervention [2]. Length of time of onset or increase in subjective symptom/symptoms should be carefully documented [37]. The individual would be expected to have an onset or increase of symptoms within 2 weeks.

Cystitis is the most common form of infection within the lower urinary tract in neurogenic patients [5]. In individuals with indwelling urethral catheters, urethritis may occur. It is frequently caused by Neisseria gonorrhoeae, Escherichia coli, and Chlamydia trachomatis [44]. Additional blockage of the periurethral gland by the catheter may lead to the formation of a periurethral abscess. The abscess can drain spontaneously to the penile skin, inside the urethral lumen (creating a diverticulum), or simultaneously at both sides (forming a urethrocutaneous fistula) [5]. Surgical excision needs to be performed for either diverticulum or fistula. Epididymitis is another form of catheter-related infection. Initial infection of the bladder or urethra can reach the epididymis via the vas deferens in a retrograde manner. Further involvement of testicles may also be seen and present as epididymoorchitis [12]. Acute epididymitis is a clinical syndrome consisting of pain, swelling, and inflammation of the epididymis of less than 6 weeks [5]. However, in neurologically impaired patients, pain may be absent because of impaired sensation. Therefore, the only clinical sign is often swelling and/or flare. Fever may sometimes be detected in the acute stage. Infected urine refluxing into prostatic ducts can lead to prostatitis. In neurogenic patients, high pressure voiding (due to neurogenic detrusor overactivity) or presence of a urethral catheter (due to neurogenic detrusor underactivity or detrusor sphincter dyssynergia) can significantly contribute to this condition. The most common cause of prostatitis in patients with neurogenic bladder is Escherichia coli (65–80%) [5]. Pseudomonas aeruginosa, Serratia species, Klebsiella species, and Enterobacter aerogenes are identified in a further 10–15%. In the acute phase of infection patients complain of fever, pain in the genital area and lower back, burning or painful urination, as well as urinary urgency and frequency. The prostate gland is very tender to palpation through the rectum. Chronic infection is usually asymptomatic and may affect 25–43% of patients with a history of recurrent UTIs [5, 45].

Upper urinary tract infection (pyelonephritis) may also affect patients with neurogenic bladder. The main risk factors for this complication include impaired antireflux mechanism (leading to vesicoureteral reflux) and detrusor-sphincter dyssynergia (leading to urine stasis and high intravesical pressure during voiding with retrograde urine flow into the kidneys) [5]. The main clinical symptom of acute pyelonephritis is high fever, up to 40 °C. Patients may also report abdominal pain that radiates along the flank towards the back, vomiting, malaise, decreased appetite, and the whole spectrum of lower urinary tract symptoms (LUTS) . Chronic pyelonephritis implies recurrent kidney infections and can result in scarring of the renal parenchyma, resulting in impaired renal function (see Chap. 13, “Renal Failure”).


Laboratory Testing


Neurourology Guidelines of the European Association of Urology indicate urine culture and urinalysis as the gold standard for UTI diagnosis [7]. The dipstick test alone seems to be useful in excluding the presence of infection if the results for both nitrites and leukocyte esterase are negative [46]. The usefulness of the dipstick test alone to rule in infection is uncertain [46, 47]. Urine culture remains the definitive proof of infection. Microbiologic testing in persons with neurourological disorders is mandatory, as bacterial strains and resistance patterns may differ from those of able-bodied patients [7, 48]. In addition, an antibiogram providing a sensitivity pattern of relevant antimicrobials is highly recommended [37]. Multiresistance has been defined as the resistance to three or more different antimicrobial agents to which the microorganism would normally be susceptible [49, 50]. Colonization with multiresistant organisms may be especially suspected in individuals with neurogenic bladder dysfunction who have been managed with indwelling catheterization, multiple antibiotics, mechanical ventilation, and for pressure ulcers [37, 49, 5153]. The antibiogram can also be used in revealing reinfection (infection by different type/strain of organism), relapse (infection by the same organism), or chronic/biofilm infection [54]. Discovery of a chronic/biofilm infection can justify prolonged antibiotic treatment and may initiate additional examination [41]. In patients with epididymitis and prostatitis, urinalysis or even urine culture may not reveal any abnormalities.

The interpretation of the results obtained should include analysis of bladder-emptying technique and account for the presence of an indwelling catheter [1]. The results should also be interpreted in the context of previous urological history and treatment, as well as presence of confounding diseases and/or comorbidities. Appropriate urine samples include clean-catch midstream samples, samples taken from a freshly inserted intermittent sterile catheter, and samples taken from a catheter port [55]. In patients already treated with indwelling catheter (urethral or suprapubic), the urine specimen should be obtained from a new freshly inserted catheter [5]. The external urethral meatus must be exposed and cleaned with antiseptic solution. The first 50 mL urine is passed without collection. Afterward, approximately 50 mL midstream urine is collected in a sterile container. In patients who wear a condom catheter, a fresh condom catheter should be applied with subsequent urine collection [9]. The urine should be analyzed/cultured as soon as possible or kept refrigerated and cultured within 24 h [56]. It is not acceptable to collect a urine culture from a pre-existing catheter, from a collection bag, or from a container [37].

In patients with generalized infection (pyelonephritis, urosepsis), blood tests may show a polymorphonuclear leukocytosis, increased erythrocyte sedimentation rate, elevated C-reactive protein concentration, as well as elevated creatinine levels if renal impairment developed [5].


Additional Testing


In patients with relapsing or persistent infections and recurrent catheter blockage, a search for the source of infection must be undertaken. This may include a cystoscopy (to rule out a stone); upper tract imaging (to rule out stasis, stone, renal abscess, or hydronephrosis); intravenous urogram (to rule out stasis, stone, hydronephrosis, or vesicoureteral reflux); and ensuring that the patient has changed all of his/her reusable catheters and is not reinfecting himself/herself [12]. Common findings in patients with recurrent UTIs are follicular cystitis and cystitis cystica et glandularis, which may be considered within the spectrum of normal bladder as an immunological response to infection (Figs. 10.1 and 10.2) [57]. Computed tomography imaging is commonly used in patients suspected of acute pyelonephritis or renal abscess (Figs. 10.3 and 10.4) [58]. Nevertheless, it may also be used in patients with chronic pyelonephritis (Fig. 10.5) [59]. Those suspected of epididymis or epididymoorchitis are typically examined with ultrasound (Fig. 10.6 and see Fig. 10.7) [60].

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Fig. 10.1
Follicular cystitis . (a) Multiple discrete small mucosal irregularities are present. They do not significantly obscure the vasculature beneath them. (b) Lamina propria contains lymphoid follicles, often with a germinal center (From MacLennan et al. [57], with permission)


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Fig. 10.2
Cystitis cystica . (a) The mucosal surface is studded with innumerable bleb-like lesions that appear to contain straw-colored fluid. The remainder of the mucosa looks normal. (b) Normal urothelial cells often have eosinophilic secretions. The lumens of some cells are lined by taller columnar-type cells, consistent with cystitis glandularis of the typical type. The cystic spaces lined by goblet cells comprise cystitis glandularis of the intestinal type, also sometimes designated intestinal metaplasia (From MacLennan et al. [57], with permission)


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Fig. 10.3
Findings of acute pyelonephritis on delayed CT. (a, b) Contrast-enhanced CT scans show enlarged right kidney with multiple, wedge-shaped lesions of low attenuation (arrows). (c, d) Delayed CT scans taken 6 h later without further injection of contrast material show retained contrast material (arrows) in the area of poor enhancement at initial CT (From Cho [58], with permission)


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Fig. 10.4
Renal abscess . (a, b) Contrast-enhanced CT scans show a low-attenuated, nonenhancing lesion (arrow) in the left kidney. Note thickened renal fascia (small arrows) (From Cho [58], with permission)


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Fig. 10.5
Chronic pyelonephritis . Multidetector CT urography. Coronal reformations. (a, b) Right kidney. Calyceal distortion and clubbing (arrows) due to the underlying renal parenchymal damage with renal parenchymal scarring and focal reduction of renal parenchymal thickness. (c, d) Left kidney. Diffuse reduction of the renal parenchymal thickness with calyceal distortion (arrows) (From Quaia et al. [59], with permission)


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Fig. 10.6
Acute epididymoorchitis . (a) Longitudinal ultrasound (US) of the right scrotum shows heterogeneous hypoechogenicity (arrows) of right epididymal tail and reactive thickening of the adjacent scrotal wall. (b) Spectral Doppler US along the left epididymis shows hypervascularity and high-resistance waveforms. (c) Transverse color Doppler US of the scrotum shows markedly increased vascularity in the right testis, suggesting associated orchitis (From Lee and Kim [60], with permission)


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Fig. 10.7
Acute epididymoorchitis . (a) Longitudinal ultrasound (US) of the right scrotum shows enlarged heterogeneous right testis (T) and epididymis (E) with reactive hydrocele (H). Note intratesticular cyst (arrow). (b) Transverse color Doppler US of right scrotum shows markedly increased vascularity in the enlarged epididymis at the tail portion with diffuse thickening of the scrotal wall (From Lee and Kim [60], with permission)

A basic data set for UTI (International SCI UTI Basic Data Set) has been developed to standardize collection and reporting of the minimal amount of information required to define a possible UTI (Fig. 10.8) [37, 61]. Although the data set has been designed primarily for SCI individuals, it may also be used for other neurologically impaired patients.

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Fig. 10.8
Urinary Tract Infection Basic Data Set (Version 1.0) (Courtesy of the International Spinal Cord Society (ISCoS) [61], with permission)


Treatment


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).
Jan 13, 2018 | Posted by in NEUROLOGY | Comments Off on Urinary Tract Infection

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