Review of Medical Microbiology and Immunology, 13th Edition

78. Urinary Tract Infections

Contributed by Brian S. Schwartz, MD

CHAPTER CONTENTS

Introduction

Diagnostic Testing For Urinary Tract Infections

Cystitis

Pyelonephritis

Asymptomatic Bacteriuria

Prostatitis

INTRODUCTION

Urinary tract infections are a group of common diseases that occur predominantly by ascension of normal enteric flora through the urethra into the bladder. These infections more frequently affect women due to anatomic differences including a shorter urethra. Diagnosis is made by identifying related clinical symptoms in combination with an abnormal urinalysis and growth on urine culture. Antibiotics are often effective therapy, although antibiotic resistance is increasing.

DIAGNOSTIC TESTING FOR URINARY TRACT INFECTIONS

Urine microscopy is the use of a microscope to look at urine. In patients with urinary tract infections, one can often find pyuria (elevated white blood cells [WBCs] in urine) and hematuria (red blood cells in urine), and sometimes bacteria can be seen. The presence of WBC casts indicates pyelonephritis rather than cystitis. A urine sample that has abundant squamous epithelial cells suggests that it is contaminated and the results of the culture are not reliable.

Urine dipsticks use different chemicals reagents on a strip that is dipped in urine to diagnose urinary tract diseases. Certain dipstick test results are suggestive of infection, namely positive leukocyte esterase, positive nitrite, and positive hemoglobin. The positive nitrite occurs from the conversion of nitrate to nitrite by Enterobacteriaceae.

Urine culture allows identification of the organism causing infection. Urine in the bladder is normally sterile. Because contamination of samples can occur as urine passes through the outer third of the urethra, a numeric threshold of colony-forming units (CFUs) per milliliter has been established to confirm infection. In samples obtained from a midstream void, ≥1 × 105 CFU/μL is consistent with infection. In samples collected via catheterization, ≥1 × 102CFU/μL is consistent with infection.

CYSTITIS

Definition

Cystitis is an infection of the bladder. The term “cysto” refers to bladder, and “itis” refers to inflammation. Uncomplicated cystitis is defined as cystitis in otherwise healthy women, whereas complicated cystitis is defined as cystitis in all other groups such as men, pregnant women, diabetics, those with anatomic and neurologic problems, and those with recurrent urinary tract infections.

Pathophysiology

Bacteria (rarely fungi) reach the bladder via ascension through the urethra. This is much more common in women due to the short urethra and close approximation of the urethra to the vagina and anus. Preceding infection, the vagina, which is normally colonized by Lactobacillus species, will become colonized by enteric organisms such as Escherichia coli instead. E. coli are able to adhere to the urethral mucosa via pili. Once bacteria enter the bladder, they are able to reproduce and cause an inflammatory response, resulting in the symptoms of infection.

Medical conditions that cause abnormal emptying of bladder increase risk for urinary tract infections. These include anatomic abnormalities such as cystoceles, neurologic disorders such as spinal cord injuries and multiple sclerosis, and the presence of foreign bodies such as indwelling Foley catheters. In infants less than 3 months of age, uncircumcised boys are at higher risk for urinary tract infections than girls. However, after infancy, girls are at higher risk for infection than all boys.

Clinical Manifestations

The most common clinical manifestations of cystitis include dysuria (pain with urination); frequent, low-volume urination; suprapubic tenderness; and gross hematuria. Men may experience some penile discharge. Most patients with cystitis do not have fever or other systemic symptoms of infection, and when they are present, an upper urinary tract infection (pyelonephritis) should be considered.

Pathogens

E. coli is by far the most common cause of urinary tract infections. Other enteric gram-negative rods such as Klebsiella species and Proteus species are regular culprits. Pseudomonas aeruginosa can cause urinary tract infection, but this is most common in health care–associated infections, patients with anatomic/neurologic abnormalities afflicting their urinary tract, or heavily antibiotic-experienced patients. Gram-positive pathogens include Enterococcus species and Staphylococcus saprophyticusS. saprophyticus is common in younger women. Candida species can cause infection in patients who have extensive prior antibiotic use and indwelling Foley catheters. Rarely, viruses such as adenovirus, BK virus, and cytomegalovirus can cause a hemorrhagic cystitis. These viruses almost exclusively cause cystitis in immunocompromised hosts such as those who have undergone stem cell transplants.

Diagnosis

The diagnosis of cystitis requires identifying a combination of pyuria (by seeing WBCs on microscopy or positive leukocyte esterase on urine dipstick) often accompanied by positive nitrite and evidence of red blood cells in the urine plus positive urine cultures plus consistent clinical symptoms of infection.

Treatment

Treatment of cystitis requires antibiotic therapy. Empiric therapy is directed against E. coli in cases of uncomplicated cystitis and is accomplished with either trimethoprim-sulfamethoxazole or nitrofurantoin. Empiric therapy for complicated cystitis is usually with a fluoroquinolone (ciprofloxacin or levofloxacin). Symptomatic relief of the dysuria can be accomplished using phenazopyridine.

Prevention

There is no known method for primary prevention of cystitis. However, prevention of cystitis in patients with a history of recurrent cystitis may be accomplished with several strategies. These include ways to enhance growth of the normal vaginal flora (Lactobacillus species) to prevent colonization with enteric gram-negative rods, such as E. coli, intravaginal estrogen in postmenopausal women and avoidance of spermicide as a form of contraception. In women who frequently have cystitis following sexual intercourse, postcoital antibiotics can be beneficial.

PYELONEPHRITIS

Definition

Pyelonephritis is an infection of the kidney(s). “Pyelo” refers to the renal pelvis, and “nephritis” means inflammation of the kidney. Uncomplicated pyelonephritis is defined as pyelonephritis in otherwise healthy women, whereas complicated pyelonephritis is pyelonephritis in all other patients.

Pathophysiology

Pyelonephritis may occur either by ascension of bacteria from the urethra to the bladder and then to the kidney(s) or, less commonly, through hematogenous spread from other sites of infection such as endocarditis. Kidney stones predispose to pyelonephritis (Figure 78–1). Urinary tract infections in children can be associated with anatomic abnormalities, and additional workup for diseases such as vesicoureteral reflex should be considered.

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Figure 78–1 Pyelonephritis. Note enlarged right kidney (left side of image) caused by a stone at the ureteropelvic junction. (Reproduced with permission from McKean SC et al. Principles and Practice of Hospital Medicine. New York: McGraw-Hill, 2012. Copyright © 2012 by The McGraw-Hill Companies, Inc.)

Clinical Manifestations

Patients with pyelonephritis typically present with fever, flank pain, nausea, and vomiting. They may or may not have signs and symptoms of lower tract infection (dysuria, frequency, hematuria, suprapubic tenderness).

Pathogens

E. coli is the most common pathogen causing pyelonephritis. Other enteric gram-negative rods such as Klebsiella and Proteus species are also involved. P. aeruginosa can cause urinary tract infection, but this is most common in health care–associated infections, patients with anatomic/neurologic abnormalities afflicting their urinary tract, or heavily antibiotic-experienced patients. Patients with recurrent Proteus pyelonephritis should be evaluated for struvite stones. Infection of the kidney following hematogenous spread of infection can occur with essentially any organism but is seen most commonly with Staphylococcus aureus. Hematogenous spread also occurs with Mycobacterium tuberculosis and can been seen in disseminated fungal infection as well.

Diagnosis

Urine test findings are similar to those seen in cystitis, but urinary WBC casts can be seen (Figure 78–2). Blood WBC counts are frequently elevated, and occasionally blood cultures can be positive. Ultrasound and computed tomography scans can reveal inflammation and can occasionally reveal obstruction or perinephric abscess (see Figure 78–1). Radiographic imaging is not routinely recommended in patients who respond quickly to antibiotics and in whom there is no clinical concern for associated nephrolithiasis or obstruction. Patients with renal tuberculosis may have pyuria in the absence of positive cultures (sterile pyuria) because M. tuberculosis does not grow in routine culture media.

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Figure 78–2 White blood cell casts. Note cylindrical-shaped casts containing round, refractile white blood cells (arrow). (Used with permission from Longo DL et al [eds]: Harrison’s Principles of Internal Medicine, 18th ed. New York: McGraw-Hill, 2009. Copyright © 2012 by The McGraw-Hill Companies, Inc.)

Treatment

Antibiotics that are able to obtain high concentrations in the renal parenchyma and have activity against common pathogens are required to treat pyelonephritis. Empiric regimens for community-onset infection include a fluoroquinolone (ciprofloxacin or levofloxacin) or a third-generation cephalosporin such as ceftriaxone. Patients with heavy exposure to prior antibiotics, anatomic abnormalities, or exposure to the health care setting should be treated with antibiotics with reliable activity against Pseudomonas, such as cefepime, piperacillin, or meropenem. Antibiotic therapy should be narrowed once antibiotic susceptibilities become available.

Prevention

Patients who have bladder dysfunction that predisposes them to pyelonephritis may require frequent catheterization to allow proper urinary tract drainage. Pregnant women with asymptomatic bacteriuria (see next section) may benefit from antibiotic therapy to prevent pyelonephritis.

ASYMPTOMATIC BACTERIURIA

Definition

Asymptomatic bacteriuria is when bacteria colonize the urinary bladder in the absence of signs or symptoms of upper or lower urinary tract infection.

Pathophysiology

Asymptomatic bacteriuria is common in many populations including persons with diabetes, patients with anatomic and neurologic abnormalities of the urinary tract, patients with indwelling Foley catheters, and elderly patients. The bacteria reach the bladder via ascension through the urethra, not from hematogenous dissemination.

Clinical Manifestations

Patients with asymptomatic bacteriuria have no signs or symptoms of upper or lower tract infection.

Pathogens

The same organisms that commonly cause cystitis also cause asymptomatic bacteriuria. Asymptomatic candiduria can occur as well.

Diagnosis

The diagnosis of asymptomatic bacteriuria requires the identification of positive urine cultures. Patients have pyuria present in about 50% cases of asymptomatic bacteriuria.

Treatment

Treatment of asymptomatic bacteriuria is indicated in select populations who have been identified to be at risk for subsequent severe infection from presence of bacteriuria. These high-risk groups include (1) pregnant women, (2) adults scheduled to undergo urinary tract procedures that could cause mucosal bleeding and translocation of bacteria into the blood, and (3) neutropenic patients.

Prevention

Strategies to prevent asymptomatic bacteriuria are not routinely used.

PROSTATITIS

Definition

Prostatitis is inflammation of the prostate, which can be due to infection or other causes. Prostatitis is also discussed in Chapter 74 on Pelvic Infections.

Pathophysiology

Infection most frequently occurs via the urethra then into to the prostatic ducts. However, hematogenous seeding of the prostate can occur as well. Microabscesses may develop within the prostate (Figure 78–3).

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Figure 78–3 Prostatitis. Note yellow-green areas of pus (arrow) forming multiple abscesses in prostate gland. (Used with permission from Kemp WL, Burns DK, Brown TG. Pathology: The Big Picture. New York: McGraw-Hill, 2008. Copyright © 2008 by The McGraw-Hill Companies, Inc.)

Clinical manifestations

Acute prostatitis may present with acute onset of fever, dysuria, urinary frequency, and severe pain with palpation of the prostate. Patients may be very ill and can present with severe sepsis. In contrast, chronic prostatitis presents with more subacute onset of dysuria, frequency, urinary hesitancy, and pelvic discomfort.

Pathogens

In younger patients, Neisseria gonorrhoeae and Chlamydia trachomatis are the most common causes of prostatitis. However, in older patients, enteric bacteria, such as E. coli, are the predominant pathogens. When hematologic seeding occurs, S. aureus is a common cause.

Diagnosis

The diagnosis of acute bacterial prostatitis is often confirmed by the finding of an acutely tender prostate on digital rectal exam. Recovery of an organism, when possible, is from urine or blood cultures. Prostatic massage is contraindicated in acute prostatitis. However, in chronic prostatitis, prostate massage following collection of prostatic secretion is recommended to obtain a microbiologic diagnosis.

Treatment

Antimicrobial therapy with excellent penetration to the prostatic tissues is recommended for treatment of prostatitis. Fluoroquinolones and trimethoprim-sulfamethoxazole both achieve high levels in the prostate. Antibiotic susceptibility testing should be used to guide treatment of infecting pathogens.

Prevention

Prompt treatment of acute prostatitis may reduce the risk of development of chronic prostatitis.