Keywords

FormalPara Objectives
  1. 1.

    Define urinary tract infection, and differentiate its presentation in men and women.

  2. 2.

    Identify causes and the presentation of pyelonephritis.

  3. 3.

    Discuss asymptomatic bacteriuria

Diagnosis and Management of Urinary Tract Infections

The purpose of this chapter is to assist nurse practitioners and physician assistants, particularly those specializing in urology, on how to recognize and manage urinary tract infections. Unfortunately, the lack of knowledge in assessing both a urine specimen correctly and the inability to correlate this information with a patient’s presenting signs and symptoms is cause for frequent misdiagnosis of urinary tract infections. In addition, the misuse and overuse of antibiotics in today’s society has made treating urinary tract infections more complicated. This chapter will review the different types of infections, the diagnostic testing required, as well as population-specific guidelines for proper management.

Definitions

Urinary tract infection (UTI) is an inflammatory response of the urothelium to bacterial invasion that is typically associated with bacteriuria and pyuria. The term acute cystitis is often used interchangeably.

Bacteriuria is the presence of bacteria in the urine and it may be symptomatic or asymptomatic.

Asymptomatic bacteriuria (ASB) is the isolation of bacteria from the urine with or without pyuria but in the absence of local or systemic urinary tract symptoms (greater than 100,000 colony forming units per milliliter CFU/mL).

Pyuria is the presence of white blood cells in the urine. This typically indicates an inflammatory response secondary to an infectious process caused from bacteria. Pyuria without bacteriuria warrants evaluation for tuberculosis, stones, or cancer. Pyuria in the presence of bacteriuria is not always indicative of an infection.

Acute pyelonephritis is the presence of bacteriuria and pyuria, in addition to the presence of specific symptoms (i.e., fever, chills, and flank pain), indicating an interstitial inflammation of the renal parenchyma.

Incidence and Epidemiology

Urinary tract infections (UTIs), also referred to as acute cystitis, are the most common bacterial infection and are responsible for between four and eight million clinic visits (Hanno 2014). Therefore, this ranks UTIs as the most common cause for ambulatory care visits in the United States. The direct costs are more than $1.6 billion per year (Hanno 2014). Medina and Castillo-Pino (2019) note that the lifetime incidence of UTI in adult women is 50–60%.

Urinary tract infections affect men, women, and children. In women, the incidence is higher in the younger population, typically at the onset of sexual activity. The risk factors relevant to the premenopausal woman are the use of spermicides and sexual frequency. The incidence will increase slowly again after menopause due to the changes in the vaginal tissues and the increased pH of the vagina as a result of estrogen deficiency. Medina and Castillo-Pino (2019) note that the lifetime incidence of UTI in adult women is 50–60%.

Of the millions of UTIs reported, women account for approximately 85% of them. Eleven percent of women will report having had a UTI during any given year (Hanno 2014). Fifty percent of all women will report having had at least one infection in their lifetime. By the age of 24, one in three women will have had a urinary tract infection. UTIs in men are less common until after the age of 50 when the incidence of enlarged prostate increases, contributing to bladder outlet obstruction and urinary retention.

Nearly 30–44% of women with a first UTI will have a recurrent UTI and 50% will have a third UTI if they have had 2 UTI’s in 6 months (Brubaker et al. 2018). Whether the infection is left untreated, or treated with short-term, long-term, or prophylactic antibiotic therapy, the risk of reoccurrence remains unchanged. Therefore, the symptomatic episodes are more of a nuisance than a health threat in the healthy population.

Asymptomatic Bacteriuria

The incidence of ASB in healthy nonpregnant adult women ranges from 1 to 8.6%. The incidence increases with age and is noted to be 10.8–16% in women in the community over age 70 and 25–50% for women in long-term care (LTC) (Nicolle et al. 2019). In men, the incidence ranges from 3.6 to 19% in the community and 15–50% for those in LTC. Women with diabetes have an incidence of 10.8–16% and men of 0.7–11%. E. coli is the most common organism isolated from patients with ASB (Zalmanovici et al. 2015). Despite current practice guidelines many patients are routinely screened and treated for ASB (Nicolle et al. 2019).

Catheterized Urinary Tract Infections (CAUTI)

Catheter-associated urinary tract infection (CAUTI) has also become of great concern over the past several years. They are the most common cause of nosocomial infection (Stamm and Norrby 2001). The end result is an increased risk for falls, delirium, and immobility in the older population and an increased financial burden on the health care system. Most of the uropathogens responsible for CAUTIs gain access by extraluminal (direct inoculation when inserted) or intraluminal (reflux of uropathogens from failure to maintain a closed system). As soon as the catheter is inserted, bacteria will start to develop colonies known as biofilms (living layers). These biofilms are collections of microorganisms with altered phenotypes that adhere to a medical device, such as the catheter and/or collection bag. The biofilm is protective against antimicrobials and the host–immune response. The risk of colonization increases in relation to the duration of catheterization and reaches nearly 100% at 30 days (Hanno 2014).

Risk factors for UTIs include:

  • Sexual intercourse;

  • A new sex partner within the past year;

  • Use of spermicides;

  • Use of diaphragm/cervical cap;

  • Estrogen deficiency;

  • Previous UTI;

  • History of UTI in first-degree female relative;

  • Urinary retention;

  • Benign prostatic hyperplasia;

  • and steroid use.

Subpopulations at increased risk for UTIs:

  • Pregnant women;

  • Elderly;

  • Spinal cord injury;

  • Indwelling catheters;

  • Diabetes;

  • Muscular sclerosis;

  • Acquired immunodeficiency disease;

  • and those with underlying urological abnormalities.

Pathophysiology

The model for uncomplicated UTIS is that bacterial virulence is crucial for overcoming normal host defenses (Hanno 2014). However, in complicated UTIs the paradigm is reversed; the bacterial virulence is not as critical as the host factors. UTIs are typically initiated by a potential urinary pathogen migrating from the bowel. In some cases the pathogens arise from the vaginal flora, as a direct result of inoculation during sexual activity. These pathogens then begin to colonize the vagina and perineum with enteric organisms. As the organisms move to the periurethral mucosa, they ascend through the urethra into the bladder (urethritis and/or cystitis) and in some cases through the ureter to the kidney (pyelonephritis).

Most infections in women represent an ascending infection, and this process of infection is related to the relatively short length of the female urethra. UTIs are less common in the younger male, with the incidence increasing in the aging male. The male urethra is considerably longer than the female, which makes ascending infections less common. Most UTIs in older men are typically related to a voiding dysfunction that puts them at risk for acquiring an infection (i.e., urinary retention secondary to an enlarged prostate), or they may acquire it after some form of instrumentation.

Classification

Urinary tract infections may be classified by several different categories: complicated or uncomplicated, upper tract or lower tract, and first infection, unresolved bacteriuria, or recurrent infection. Recurrent infections can be separated into two separate classifications of “reinfection” or “bacterial persistence.” On occasion, UTIs may be classified by the type of organism.

Uncomplicated UTIs may be defined as a UTI in the setting of a functionally and structurally normal urinary tract, in a patient that is typically afebrile. This type of infection typically occurs in women, and the uropathogen is one that is susceptible to and eradicated by a short course of an inexpensive oral antimicrobial therapy. Complicated UTIs are typically defined as pyelonephritis and/or a structural or functional abnormality that decreases the efficacy of antimicrobial therapy. In most cases, complicated UTIs are caused by bacteria that are resistant to many antimicrobials. CAUTIs are classified as complicated and the rate of innoculation of bacteria averages about 5% per day (Nicolle et al. 2019).

The diagnosis of upper UTI refers to an infection of the kidney (pyelonephritis). The lower urinary tract (LUT) refers to infections of the bladder (cystitis) or urethra (urethritis). As for the organism responsible for the infection, it may be caused by bacterial, fungal, viral, or parasitic organisms.

The majority of uncomplicated UTI’s (95%) are monobacterial (only one organism) and typically caused by a gram-positive organism. It is estimated that 75–95% of uncomplicated UTIs are caused by E. coli, followed by Klebsiella pneumoniae, Staphylococcus saprophyticus, Enterococcus faecalis, group B streptococci and Proteus mirabilis. E. coli can cause both complicated and uncomplicated UTI’s. Pseudomonas aeruginosa, Enterococcus, and P. mirabilis are typically seen in complicated UTIs. Corynebacterium urealyticum is a nosocomial infection typically associated with catheter use.

UTIs categorized as first infections are typically new or an isolated infection that is separated by a previous infection of at least 6 months, such as the “honeymooners’ UTI.” Unresolved bacteriuria occurs during therapy and implies that the urinary tract is not sterilized during the treatment period. Recurrent UTIs are defined as two episodes of acute bacterial cystitis within a 6 month period or three infections in a 12 month period. This definition includes episodes that are different in nature with resolution of symptoms in between. The definition does not include those that require more than one treatment or multiple antibiotic courses as a result of inappropriate initial or empiric treatment (Anger et al. 2019).

Presentation

In most patients, the presenting signs and symptoms may include dysuria (pain with urination), frequency, urgency, nocturia (nighttime voiding), suprapubic pain, gross hematuria, and low back pain. Fever with an uncomplicated UTI is unusual (see Table 11.1). Therefore, acute pyelonephritis should be considered when fever, tachycardia, and/or costovertebral angle pain are present. Cloudy urine and foul smelling urine can be indicative of many other conditions (dehydration, food intake) and are not considered indicative of a UTI by itself. A UTI’s number one symptom is burning with urination and is key to diagnosis (Anger et al. 2019). In addition, patients with suspected pyelonephritis may present as ill appearing and seem uncomfortable.

Table 11.1 Signs and symptoms
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History and Physical Examination

The patient’s history is the most important tool for diagnosing an uncomplicated UTI. Always include an evaluation of the patient’s current urinary tract symptoms, past history of urinary tract infections, and any other urinary tract problems or conditions include episodes of dysuria, frequency, urgency, nocturia, incontinence hematuria and constipation, diarrhea, or bowel incontinence. Use and frequency of antibiotics should be obtained. Vaginal discharge and irritative symptoms should be assessed. Follow that with a routine family history and social history (specifically looking at smoking history) prolapse, rectocele or atrophic vaginitis. In addition, one should also inquire into the patient’s sexual history, with a special focus on any known history of sexually transmitted infections (STIs). Finally, one should support the detailed history with a focused physical exam and urinalysis.

Female Examination

  • Temperature

  • Check post void residual

  • Evaluate the possibility of pregnancy and history of reproductive issues

  • Include pelvic exam, assessing for and if symptoms indicate a possible pelvic infection or urethritis

  • Examine low back, abdomen, and suprapubic area for tenderness, pain, or abnormalities

Male Examination

  • Temperature

  • Check postvoid residual

  • Evaluate any history of prostate problems

  • Examine genitals, low back, and abdomen for tenderness, pain, or abnormalities

  • Examine rectum and prostate for prostate enlargement, growths, inflammation, or pain

Abnormal Findings

  • Pain or discomfort in response to pressure on the lower back, abdomen, or the area above the pelvic bone (10–20% of patients have suprapubic tenderness in uncomplicated UTIs)

  • Costovertebral angle tenderness is typically indicative of pyelonephritis

  • Growths or abnormalities detected during the pelvic or rectal exam

  • Enlarged or tender prostate gland (men only)

  • Discharge from the urethra

Differential Diagnosis

Among the female population, interstitial cystitis (IC) and sexually transmitted infections (STIs) are the most common diagnoses that present with similar symptoms. Dysuria is common with cystitis, urethritis, and vaginitis. However, cystitis is more likely when the signs and symptoms also include frequency, urgency, and/or hematuria. If the symptoms are of severe or sudden onset and in the absence of vaginal irritation and/or discharge, then cystitis is also more likely. The probability of acute UTI is greater than 50%, in women with any one of the signs or symptoms. It increases to more than 90% when there is a combination of symptoms, such as dysuria and frequency, without vaginal irritation or discharge. A urine culture is typically positive with bacterial cystitis.

Urethritis is typically caused by Chlamydia trachomatis, Neisseria gonorrhoeae, or the herpes simplex virus. Vaginitis is caused by Candida species or Trichomonas vaginalis. Pyuria is commonly seen in cystitis and urethritis but is less likely in vaginitis. The symptoms of urethritis also tend to be mild, gradual in onset, and include vaginal discharge. Vaginal irritation or discharge, if present, is a symptom suggestive of vaginitis and reduce the likelihood of the diagnosis of bacterial cystitis by 20%. In a patient that has a documented history of bacterial cystitis, as evidenced by a positive urine culture, and they present again, with similar symptoms, the likelihood of true infection approaches 90% (Hanno 2014).

In the male population, prostatitis, epididymitis, and STIs are the most common diagnoses that present with similar symptoms when compared to acute cystitis. However, with acute bacterial prostatitis, in addition to the typical dysuria, frequency, urgency, and nocturia, additional constitutional symptoms, such as fever, chills, and malaise, may also occur. Patients may also report complaints of perineal and/or low back pain. On exam, the prostate may feel enlarged and boggy, with acute tenderness. Epididymitis occurs more commonly in the adolescent and elderly male population but can affect men of all ages. In the population of men under the age of 35, the form of transmission is sexual and is typically caused by C. trachomatis and N. gonorrhoeae pathogens. In the elderly population, E. coli and Pseudomonas are the most common offending pathogens. Indwelling catheters, in the elderly population, are also responsible for the development of epididymitis, through a retrograde mechanism. In patients, with epididymitis, the presenting symptoms may include a tender hemiscrotum, in addition to a swollen epididymis. The scrotum may be warm, erythematous, and swollen. Fever, chills, voiding symptoms, and pain that radiates to the ipsilateral flank may also occur.

Diagnostic Testing

Commercially available dipsticks that test for leukocyte esterase (an enzyme released by leukocytes), and for nitrites (which is reduced from nitrates by some bacteria), are an appropriate alternative to urinalysis and urine microscopy, to diagnose cases of acute uncomplicated cystitis. When obtaining a urine specimen for evaluation, it is recommended that in order to avoid contamination, with skin flora the patient should obtain a midstream, clean-catch urine specimen. Since nitrites and leukocyte esterase are the most accurate indicators of uncomplicated cystitis in symptomatic patients, the urine dipsticks are convenient and cost effective. However, critical evaluation of each individual patient’s case needs to be evaluated cautiously since even negative results for both tests do not reliably rule out the presence of infection.

An urinalysis is often used to detect UTI’s and a clean-catch dipstick leukocyte esterace is a rapid screening test for detecting pyuria, however, the presence of pyuria is nonspecific and does not always indicate clinical UTI. And the presence of bacteriuria alone without symptoms is nonspecific and should not be treated (Nicolle et al. 2019).

The only true diagnosis of a UTI is symptoms associated with a positive urine culture.

Imaging

Typically, no further studies beyond urinalysis and urine cultures are needed to diagnose acute uncomplicated cystitis. In those patients that present with atypical symptoms of acute uncomplicated cystitis, those who do not respond to initial antimicrobial therapy, those with a history of recurrent UTIs, or those with suspected pyelonephritis may need imaging studies to rule out complications and other disorders (see Table 11.2).

Ultrasound (U/S) Ultrasonography is the recommended initial screening tool if testing is indicated. It is noninvasive, is cost effective, has no risk of contrast reaction, and has no risk of radiation exposure. Ultrasonography is able to identify calculi, obstruction of the upper urinary tracts, abscess, and other congenital abnormalities. Renal ultrasounds are the most cost-effective treatment option.

Intravenous Pyelogram (IVP) IVP is useful for visualizing the ureters, the details of calyceal anatomic structures and the presence of calyceal dilatation, and the presence of stricture, stones, or obstruction. The calyceal details are necessary for diagnosis of reflux nephropathy as well as papillary necrosis.

An IVP is usually done in the operating room and requires anesthesia.

Table 11.2 Imaging Considerations
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Computed Tomography (CT Scan) CT scan offers the best anatomic detail but its cost prevents it from being used for screening. It is more sensitive than ultrasound in the diagnosis of acute focal bacterial nephritis and renal and perirenal abscess (it may demonstrate stones or obstruction).

It is useful if a patient has an abnormal ultrasound.

Patients with known pyelonephritis should have a CT scan with contrast or a U/S to assess the presence of foci of pyelonephritis in the renal cortex or cortical or perinephric abscesses. Immediately after a CT scan with contrast, it is possible to obtain the equivalent of an IVP by taking a KUB (X-ray of kidney, ureter, and bladder) film of the patient in the prone position and observe the anatomic structures of the collecting system and ureters, as the contrast is cleared into the bladder.

Magnetic Resonance Imaging (MRI) MRI provides much greater contrast between different soft tissues than a CT scan. It relies on obtaining a radiofrequency (RF) signal from alignment and subsequent relaxation of protons in hydrogen atoms in water in the body. It should never be utilized in routine practice or as a first-line diagnostic test. It is typically used in follow-up when the ultrasound has already been performed and has been unable to fully answer the diagnostic question. The CT and magnetic resonance imaging (MRI) provide the best anatomic data as well as the cause and extent of the infection.

Risk Factors

Some of the risk factors for UTIs, along with the causes of bacterial persistence, and the factors that increase the risk of complications from UTIs are shown in tables below Table 11.3.

Table 11.3 Causes of bacterial resistance
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Management of Urinary Tract Infections

Behavioral Modifications

The majority of behavioral interventions are aimed at prevention. Based on a meta-analysis by Smith et al. (2018), there are few recommended behavioral interventions that have shown to reduce recurrent UTIs. These include voiding before or after sexual relations, delaying voiding, wiping from front to back, frequency of urination, douching, tampons, use of hot tubs or bubble baths, body mass index, use of tight clothing, type of clothing, bicycle riding, and volume of fluid consumed. The meta-analysis did find a correlation between spermicide use with or without a contraceptive diaphragm and recurrent UTI among sexually active women. Smith et al. (2018) found that certain prevention strategies were supported by indirect data; patients with diabetes having good glucose control, normal vaginal pH by avoiding harsh cleaners, limit antibiotic use to under five days, and avoiding broad spectrum or unnecessary antibiotics. The authors felt that though not supported in the literature preventing recurrent UTI through the following practices are advised, maintaining adequate hydration, voiding after intercourse, avoiding delayed voiding, and avoiding sequential anal and vaginal intercourse.

Oral Supplements

There have been several studies looking at the use of cranberry juice to prevent urinary tract infections. Cranberry juice does inhibit bacterial attachment to and pills epithelial cells. Based on a meta-analysis done in 2012, it was concluded that adults that consumed cranberry juice or pills on a regular basis were 38% less likely to develop symptoms of UTI. In addition, the cranberry may reduce the symptoms of UTI by suppressing the inflammatory response. A Cochrane review in 2012 found no evidence of cranberry being effective in the prevention of UTI. It remains unclear which ingredients in cranberry products may be responsible for the overall benefit. Cranberry is essentially safe and inexpensive and is recommended for the prevention of UTI. However, it is not currently recommended as a treatment for acute cystitis.

Pharmacological Treatment

The management of UTIs has become quite complicated due to the increasing prevalence of antibiotic-resistant uropathogens. Symptomatic relief is a high priority in the majority of patients with UTIs. With appropriate antibiotic treatment relief should be obtained within 24 h for an uncomplicated cystitis. Complicated nosocomial UTIs were primarily responsible for antibiotic resistance in the past. However, as things change the resistance has spread to uncomplicated community-acquired UTIs. It is important to try and understand the antibiotic resistance rates within the area that one is practicing (see Table 11.4). Urine levels are more important than serum levels in relation to the efficacy of antibiotics treating UTIs.

Current guidelines in the treatment of acute uncomplicated cystitis with antibiotics recommend nitrofurantoin, fosfomycin, trime thoprim sulfamethoxazole and fluoroquinolones as first-line antibiotics. However, fluoroquinolones have become more of a second-line treatment in the past 10 years due to resistance patterns as well as side-effect profiles (Brubaker et al. 2018). At the writing of this publication the Infectious Disease Society of American was updating their 2010 guidelines.

Table 11.4 Antibiotic Stewardship
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When treating with nitrofurantoin, or sulfamethoxazole patients with renal impairment especially the elderly must be monitored carefully (see Table 11.5). Although nitrofurantoin is on the BEERS criteria short-term usage has not been shown to be detrimental to patients. Although nitrofurantoin is on the BEERS criteria short term usage has not been shown to be detrimental to patients. Routine monitoring of patient’s renal function is recommended in all patients over 65 years of age. Nitrofurantoin is well tolerated, has good efficacy, and does tend to be effective against Pseudomonas and Proteus species. If symptoms persist after 2–3 days of therapy, one can always consider changing the antibiotic to a more expensive, broad-spectrum antibiotic. However, the recurrence of symptoms after the initial short-course therapy would indicate the need for culture and sensitivity testing, and retreatment should be for a 7–10-day period.

Fluoroquinolones have a very broad spectrum of activity against the majority of uropathogens, including Pseudomonas. However, it is not recommended to use this drug class in treating uncomplicated UTIs. This class has limited gram-positive activity and is not effective in treating Enterococcus. Fluoroquinolones are very expensive agents and should be reserved for the treatment of complicated UTI, pseudomonal infections, or treatment of resistant organisms.

Table 11.5 Antimicrobial Agents for the Management of Uncomplicated UTI
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Recurrent Bacterial Cystitis

Women with recurrent UTIs need a complete history that includes symptoms of dysuria, frequency, urgency, nocturia, incontinence, and hematuria. Include any bowel symptoms such as diarrhea, bowel incontinence, or constipation. Note previous or current antibiotic use, allergies, and prior antibiotic-related problems such as Clostridium difficle.

Any vaginal symptoms such as discharge or irritation should be noted. Note the frequency of UTI’s and any associations with the UTI such as intercourse or menses. Menopausal status and use of localized estrogens or spermicides should be noted. Obtain surgical history of any previous urinary tract or pelvic surgery. Note urgency, frequency, nocturia, and incontinence between episodes of infection. Document what the patient considers symptoms of a UTI, and relationships of acute triggers to episodes.

Physical exam should include an abdominal and detailed pelvic examination.

Document culture proven symptomatic uncomplicated acute cystitis episodes in the last year. As discussed in uncomplicated cystitis rule out, interstitial cystitis, OAB, kidney or bladder calculi, pelvic floor hypertonicity, bacterial or fungal vaginitis, and dermatitis.

Each recurrent episode must have a urine culture prior to treatment. Obtain a repeat culture when contamination is suspected. Consider a catheterized specimen if unable to get a clean catch. The vaginal flora of a women contains many bacterial species that are considered pathogens in urine (S. aureus, S. viridans, Enterococci, and Group B Streptococci).

Routine screening of patients should not be initiated. Only screen when a patient is symptomatic. Do not treat ASB.

Over the years, patients have also been treated with long-term prophylactic use of antibiotics. This therapy may have been utilizing nitrofurantoin (50–100 mg every night) or TMP-SMZ (1/2 tab every other night). Typically after 6–12 months, the therapy could be stopped in the hopes that the colonization with uropathogenic gram-negative organisms has resolved. Over the next 6 months, if a patient develops 2–3 episodes of UTI, then another course of prophylaxis would be initiated (Anger et al. 2019).

The current goal in treating UTIs is to decrease the overall use of antibiotics while maintaining a quality of life. Several studies have looked at different strategies that can be used to achieve this goal. One of these strategies is the “self-start” strategy. This relies on the patient to make the clinical diagnosis of UTI, which is typically not difficult for these patients, when the previous infections have been confirmed by a positive culture. These patients are given a prescription for an antibiotic (i.e., TMP-SMZ, cephalexin, or nitrofurantoin), to be taken for 2–3 days at the onset of symptoms. If symptoms persist or reoccur beyond this initial therapy, then an office visit is recommended for culture and sensitivity testing. Self-start therapy works very well in the patient who has been well educated.

Special Situations

There are certain populations in which an otherwise uncomplicated UTI requires more attention. There are physiologic changes that take place during pregnancy that have important implications in regard to ASB and the progression of infection. During pregnancy there is an increased renal size, altered renal function, hydroure-teronephrosis, and anterosuperior displacement of the bladder. The rate of pyelonephritis in pregnant females is much higher than that of the nonpregnant female and a 20–40% increase in acute pyelonephritis if ASB is left untreated in the pregnant population (Nicolle et al. 2019). In turn, it is associated with higher rates of prematurity and perinatal mortality. In a pregnant woman with acute uncomplicated UTI, one could consider treating with amoxicillin (250 mg every 8 h), ampicillin (250 mg every 6 h), nitrofurantoin (100 mg every 6 h), or even an oral cephalosporin. As previously noted, amoxicillin and ampicillin are no longer first-line recommendations due to their ability to interfere with the fecal flora.

Young healthy men with no complicating risk factors may be treated with a 7–10-day course of antibiotics. The recommended course of treatment is TMP-SMZ (double strength every 12 h), trimethoprim (100–200 mg every 12 h), or a fluoroquinolone, and a pretreatment culture and sensitivity is recommended in this population. In the middle-aged and elderly population, who are sexually active, no further workup is needed if the infection is eradicated with antibiotic therapy. However, in the younger, nonsexually active, population or when there is a high clinical suspicion, then further workup can be done to look for an abnormality of the urinary tract. One might obtain imaging studies to assess the kidneys, ureters, and bladder, a cystoscopy, and a post-void residual.

Patients with indwelling catheters, whether short term or long term, pose a risk for infection. It should be noted that for every day that a catheter is left indwelling, the risk of colonization is 5–10% per day (Nicolle et al. 2019). The Center for Disease Control (CDC) has completed studies evaluating the majority of circumstances where an indwelling catheter may be utilized. The recommendations can be reviewed at http://www.cdc.gov/hicpac/pdf/CAUTI/CAUTIguideline2009final.pdf and a brief summary of the recommendations are as follows:

  • Limit long-term use, especially for the treatment of incontinence, unless the patient has a stage 3 decubitus.

  • Limit use in nursing home patients and consider intermittent or external catheter if possible.

  • Only use for specific surgical procedures when necessary, not as a routine surgical intervention and remove the catheter within 24 h or as soon as possible.

  • Only treat patients with symptoms.

  • Do not do routine urine cultures.

In addition, the CDC guidelines support the use of indwelling catheters when attempting to promote comfort and quality of life for the terminal patient and those patients whom will be experiencing prolonged immobilization (i.e., spinal surgery or traumatic injuries, such as pelvic fractures).

Pyelonephritis

Incidence

Acute uncomplicated pyelonephritis is much less common than cystitis. There is an estimated ratio of 1:28 cases of pyelonephritis to that of cystitis, with an annual incidence of 25 cases per 10,000 women between the ages of 15 and 34 years (Hooten 2012).

Presentation

As previously shown in table below Table 11.6, the classic symptoms of pyelonephritis are any combination of cystitis symptoms, accompanied by bacteriuria, pyuria, fever, chills, flank pain, and/or nausea and vomiting. One should remember that patients with flank pain and UTI do not necessarily have pyelonephritis, and the reverse is true in that patients may actually have a case of pyelonephritis in the absence of local and systemic symptoms. The majority of patients with acute pyelonephritis will be ill appearing and may have additional symptoms such as malaise or hypotension. It should create a high level of suspicion if a patient has any of the known risks factors, listed in the table below.

Table 11.6 Risk factors for pyelonephritis
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Classification

Pyelonephritis may be caused by several different routes:

  1. 1.

    Ascending: Bacteria reach the renal pelvis through the collecting ducts at the papillary tips and then ascend through the collecting tubules. The presence of urinary reflux from the bladder or increased intrapelvic pressures caused by lower urinary tract obstruction can also cause upper urinary tract infection.

  2. 2.

    Hematogenous: This tends to be the result of Staphylococcus aureus septicemia or Candida in the blood stream. Hematogenous causes are uncommon.

  3. 3.

    Lymphatic: This is an intraperitoneal infection (i.e., abscess) caused by an unusual form of extension to the renal parenchyma.

The majority of acute uncomplicated pyelonephritis cases can be managed in the outpatient setting. However, if one has diabetes, a renal stone, hemodynamic instability, or is pregnant, then they should be hospitalized for the initial 2–3 days of parenteral therapy. Pyelonephritis can lead to sepsis, hypotension, and even death, especially if the infection is caused by an unrecognized upper tract obstruction.

Flank tenderness is a prominent finding on physical exam. In addition, an infected urine with large amounts of granular or leukocyte casts in the sediment is also indicative for the diagnosis. Eighty percent of the cases of pyelonephritis are caused by E. coli. In patients who have undergone a form of urinary tract instrumentation, who have had a previous indwelling catheter, or those that have developed a nosocomial infection, the microorganism responsible for the infection in these situations is typically Pseudomonas, Serratia, Enterobacter, and Citrobacter. In patients with stone disease, one should suspect Proteus or Klebsiella. Both of these microorganisms contain the enzyme urease, which has the ability to split urea with the production of ammonia and an alkaline environment. This leads to the precipitation of the salt struvite (magnesium ammonium phosphate), which form branched calculi. These calculi harbor bacteria in the interstices of the renal calculi. These types of stones are referred to as staghorn calculi, which can lead to chronic renal infection.

Diagnostic Testing

Laboratory testing and radiology studies can assist in differentiating the cause. One should order both urine and blood cultures to rule out sepsis. An intravenous urogram may demonstrate normal results or it may show renal enlargement secondary to edema. It is necessary to distinguish whether focal enlargement is a result of a renal mass or abscess. A delayed appearance of the pyelogram or a diminished nephrogram may be caused by inflammation. When assessing an imaging study, the most important thing to rule out is the presence of obstruction and/or urolithiasis. Both of which could lead to a life-threatening situation if left undiagnosed and untreated. Ultrasound is useful in some cases; however, CT may demonstrate the patchy decreased enhancements that suggest focal renal involvement.

Complications

Abnormal findings and complications associated with pyelonephritis are:

  1. (a)

    Xanthogranulomatous pyelonephritis (XGP)—severe and chronic renal infection that destroys the kidneys.

  2. (b)

    Chronic pyelonephritis—rare in the absence of an underlying functional or structural abnormality of the urinary tract.

  3. (c)

    Renal insufficiency—rare complication.

  4. (d)

    Hypertension—is noted in over 50% of patients.

  5. (e)

    Renal abscess—collection of purulent material confined to the renal parenchyma.

  6. (f)

    Infected hydronephrosis—bacterial infection of a hydronephrotic kidney and can often be associated with destruction of the renal parenchyma.

  7. (g)

    Perinephric abscess—typically results from a rupture of a cortical abscess or hematogenous seeding from another infection site.

  8. (h)

    Emphysematous pyelonephritis—acute necrotizing parenchyma and perirenal infection caused by gas-forming uropathogens.

Management

In the majority of cases, acute uncomplicated pyelonephritis can be treated on an outpatient basis. However, the patient should be hospitalized in the following situations:

  • Nausea or vomiting.

  • Dehydrated.

  • Pregnant.

  • History of non-adherence to medical therapies.

  • Evidence of septicemia.

Urine cultures should be obtained on all suspected cases of pyelonephritis. On all hospitalized patients, one should obtain blood cultures and baseline labs to check renal functioning. The results of the blood cultures tend to be positive in approximately 15–20% of patients (Bastani 2001).

Initial treatment for uncomplicated pyelonephritis should be started using a fluoroquinolone pending cultures results. It is becoming a more common practice to administer a single parenteral dose of ceftriaxone (1 g), a consolidated 24 h dose of an aminoglycoside (i.e., gentamicin), or a fluoroquinolone before initiating oral antibiotics (Hanno 2014).

In the outpatient setting, it is recommended to treat with a 10-day course of antibiotics using a fluoroquinolone or trimethoprim-sulfamethoxazole. In the presence of sepsis, it is recommended to treat for 14 days. According to the Infectious Disease Society of America (IDSA), the recommendation is to treat with ciprofloxacin 500 mg BID for 7 days or levofloxacin 750 mg QD × 5 days (2011). If the patient demonstrates improvement within 72 h, then continue the oral antibiotic therapy and obtain a repeat urine culture at 4 days on and 10 days off of the medication. If no improvement is noted, then the patient should be hospitalized and one should review the culture and sensitivity results. In the presence of an obstruction or abscess, treatment and/or drainage of the causative factor would be recommended. Complicated cases of pyelonephritis requiring hospitalization or a procedure may also require up to 3 weeks of antibiotic therapy.

Clinical Pearls

  • In uncomplicated UTIs, there is no association between recurrent infections and renal scarring, hypertension, or renal failure.

    • Methenamine or hexamine hippurate are used as urinary antiseptics for chronic therapy, which reduces the risk of antibiotic resistance and efficacy may be increased if used as adjuvant therapy to cranberry supplements. Asymptomatic bacteriuria, in the elderly population, should not be treated.

  • In uncomplicated UTIs, there is no association between recurrent infections and renal scarring, hypertension, or renal failure.

  • Methenamine or hexamine hippurate are used as urinary antiseptics for chronic therapy, which reduces the risk of antibiotic resistance and efficacy may be increased if used as adjuvant therapy to cranberry supplements.

  • Asymptomatic bacteriuria, in the elderly population, may be unjustified and is typically ineffective.

  • It is a challenge clinically to differentiate between upper and lower UTI; however, it is most often not necessary because management and treatment are similar.

  • Recurrent UTI tends to be biological in nature and not necessarily related to personal hygiene.

  • When investigating UTIs, the best overall screening tool remains the retro-peritoneal ultrasonography.

  • Due to the risk of pulmonary fibrosis with nitrofurantoin use, it is not recommended as a long-term prophylactic antibiotic of choice. However, it remains an excellent option for short-course treatment of recurrent UTI.

  • If a male patient has no culture documented history of a UTI, then it is unlikely that he will have a diagnosis of chronic bacterial prostatitis.

References for Clinicians

AUA Guidelines (https://auanet.org/guidelines)

  • Recurrent uncomplicated urinary tract infections in women

    AUA White papers (https://auanet.org/whitepapers)

  • Beers criteria

  • Catheter-associated urinary tract infections

Infectious Disease Society of America Clinical practice guideline for the management of Asymptomatic Bacteriuria retrieved from: https://www.idsociety.org/practice-guideline/asymptomatic-bacteriuria/

Resources for Patients

Urology Care Foundation https://www.urologyhealth.org/educational-materials?product_format=466|&language=1122|

NIDDK https://www.niddk.nih.gov/search?s=all&q=uti