Bacterial Infections of the Urinary System

Urinary tract infections (UTIs) include infections of the urethra, bladder, and kidneys, and are common causes of urethritis, cystitis, pyelonephritis, and glomerulonephritis. Bacteria are the most common causes of UTIs, especially in the urethra and bladder.

Cystitis

Cystitis is most often caused by a bacterial infection of the bladder, but it can also occur as a reaction to certain treatments or irritants such as radiation treatment, hygiene sprays, or spermicides. Common symptoms of cystitis include dysuria (urination accompanied by burning, discomfort, or pain), pyuria (pus in the urine), hematuria (blood in the urine), and bladder pain.

In females, bladder infections are more common because the urethra is short and located in close proximity to the anus, which can result in infections of the urinary tract by fecal bacteria. Bladder infections are also more common in the elderly because the bladder may not empty fully, causing urine to pool; the elderly may also have weaker immune systems that make them more vulnerable to infection. Conditions such as prostatitis in males or kidney stones in males and females can impact proper drainage of urine and increase risk of bladder infections. Catheterization can also increase the risk of bladder infection (see the Case in Point below).

Gram-negative bacteria such as Escherichia coli (most commonly), Proteus vulgaris, Pseudomonas aeruginosa, and Klebsiella pneumoniae cause most bladder infections. Gram-positive pathogens associated with cystitis include the coagulase-negative Staphylococcus saprophyticus, Enterococcus faecalis, and Streptococcus agalactiae. Routine manual urinalysis using a urine dipstick or test strip can be used for rapid screening of infection. These test strips (see the figure below) are either held in a urine stream or dipped in a sample of urine to test for the presence of nitrites, leukocyte esterase, protein, or blood that can indicate an active bacterial infection. The presence of nitrite may indicate the presence of E. coli or K. pneumoniae; these bacteria produce nitrate reductase, which converts nitrate to nitrite. The leukocyte esterase (LE) test detects the presence of neutrophils as an indication of active infection.

Low specificity, sensitivity, or both, associated with these rapid screening tests require that care be taken in interpretation of results and in their use in diagnosis of urinary tract infections. Therefore, positive LE or nitrite results are followed by a urine culture to confirm a bladder infection. Urine culture is generally accomplished using blood agar and MacConkey agar, and it is important to culture a clean catch of urine to minimize contamination with normal microbiota of the penis and vagina. A clean catch of urine is accomplished by first washing the labia and urethral opening of female patients or the penis of male patients. The patient then releases a small amount of urine into the toilet bowl before stopping the flow of urine. Finally, the patient resumes urination, this time filling the container used to collect the specimen.

Bacterial cystitis is commonly treated with fluoroquinolones, nitrofurantoin, cephalosporins, or a combination of trimethoprim and sulfamethoxazole. Pain medications may provide relief for patients with dysuria. Treatment is more difficult in elderly patients, who experience a higher rate of complications such as sepsis and kidney infections.

Kidney Infections (Pyelonephritis and Glomerulonephritis)

Pyelonephritis, an inflammation of the kidney, can be caused by bacteria that have spread from other parts of the urinary tract (such as the bladder). In addition, pyelonephritis can develop from bacteria that travel through the bloodstream to the kidney. When the infection spreads from the lower urinary tract, the causative agents are typically fecal bacteria such as E. coli. Common signs and symptoms include back pain (due to the location of the kidneys), fever, and nausea or vomiting. Gross hematuria (visible blood in the urine) occurs in 30–40% of females but is rare in males (Tibor Fulop. “Acute Pyelonephritis” Medscape, 2015.). The infection can become serious, potentially leading to bacteremia and systemic effects that can become life-threatening. Scarring of the kidney can occur and persist after the infection has cleared, which may lead to dysfunction.

Diagnosis of pyelonephritis is made using microscopic examination of urine, culture of urine, testing for leukocyte esterase and nitrite levels, and examination of the urine for blood or protein. It is also important to use blood cultures to evaluate the spread of the pathogen into the bloodstream. Imaging of the kidneys may be performed in high-risk patients with diabetes or immunosuppression, the elderly, patients with previous renal damage, or to rule out an obstruction in the kidney. Pyelonephritis can be treated with either oral or intravenous antibiotics, including penicillins, cephalosporins, vancomycin, fluoroquinolones, carbapenems, and aminoglycosides.

Glomerulonephritis occurs when the glomeruli of the nephrons are damaged from inflammation. Whereas pyelonephritis is usually acute, glomerulonephritis may be acute or chronic. The most well-characterized mechanism of glomerulonephritis is the post-streptococcal sequelae associated with Streptococcus pyogenes throat and skin infections. Although S. pyogenes does not directly infect the glomeruli of the kidney, immune complexes that form in blood between S. pyogenes antigens and antibodies lodge in the capillary endothelial cell junctions of the glomeruli and trigger a damaging inflammatory response. Glomerulonephritis can also occur in patients with bacterial endocarditis (infection and inflammation of heart tissue); however, it is currently unknown whether glomerulonephritis associated with endocarditis is also immune-mediated.

Leptospirosis

Leptospira are generally harmless spirochetes that are commonly found in the soil. However, some pathogenic species can cause an infection called leptospirosis in the kidneys and other organs (see the figure below). Leptospirosis can produce fever, headache, chills, vomiting, diarrhea, and rash with severe muscular pain. If the disease continues to progress, infection of the kidney, meninges, or liver may occur and may lead to organ failure or meningitis. When the kidney and liver become seriously infected, it is called Weil’s disease. Pulmonary hemorrhagic syndrome can also develop in the lungs, and jaundice may occur.

Leptospira spp. are found widely in animals such as dogs, horses, cattle, pigs, and rodents, and are excreted in their urine. Humans generally become infected by coming in contact with contaminated soil or water, often while swimming or during flooding; infection can also occur through contact with body fluids containing the bacteria. The bacteria may enter the body through mucous membranes, skin injuries, or by ingestion. The mechanism of pathogenicity is not well understood.

Leptospirosis is extremely rare in the United States, although it is endemic in Hawaii; 50% of all cases in the United States come from Hawaii (Centers for Disease Control and Prevention. “Leptospirosis.” 2015.). It is more common in tropical than in temperate climates, and individuals who work with animals or animal products are most at risk. The bacteria can also be cultivated in specialized media, with growth observed in broth in a few days to four weeks; however, diagnosis of leptospirosis is generally made using faster methods, such as detection of antibodies to Leptospira spp. in patient samples using serologic testing. Polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), slide agglutination, and indirect immunofluorescence tests may all be used for diagnosis. Treatment for leptospirosis involves broad-spectrum antibiotics such as penicillin and doxycycline. For more serious cases of leptospirosis, antibiotics may be given intravenously.

Check Your Understanding

Nongonococcal Urethritis (NGU)

There are two main categories of bacterial urethritis: gonorrheal and nongonococcal. Gonorrheal urethritis is caused by Neisseria gonorrhoeae and is associated with gonorrhea, a common STI. This cause of urethritis will be discussed in Bacterial Infections of the Reproductive System. The term nongonococcal urethritis (NGU) refers to inflammation of the urethra that is unrelated to N. gonorrhoeae. In females, NGU is often asymptomatic. In males, NGU is typically a mild disease, but can lead to purulent discharge and dysuria. Because the symptoms are often mild or nonexistent, most infected individuals do not know that they are infected, yet they are carriers of the disease. Asymptomatic patients also have no reason to seek treatment, and although not common, untreated NGU can spread to the reproductive organs, causing pelvic inflammatory disease and salpingitis in females and epididymitis and prostatitis in males. Important bacterial pathogens that cause nongonococcal urethritis include Chlamydia trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, and Mycoplasma hominis.

C. trachomatis is a difficult-to-stain, gram-negative bacterium with an ovoid shape. An intracellular pathogen, C. trachomatis causes the most frequently reported STI in the United States, chlamydia. Although most persons infected with C. trachomatis are asymptomatic, some patients can present with NGU. C. trachomatis can also cause non-urogenital infections such as the ocular disease trachoma (see Bacterial Infections of the Skin and Eyes). The life cycle of C. trachomatis is illustrated in a figure of Nonproteobacteria Gram-Negative Bacteria and Phototrophic Bacteria.

C. trachomatis has multiple possible virulence factors that are currently being studied to evaluate their roles in causing disease. These include polymorphic outer-membrane autotransporter proteins, stress response proteins, and type III secretion effectors. The type III secretion effectors have been identified in gram-negative pathogens, including C. trachomatis. This virulence factor is an assembly of more than 20 proteins that form what is called an injectisome for the transfer of other effector proteins that target the infected host cells. The outer-membrane autotransporter proteins are also an effective mechanism of delivering virulence factors involved in colonization, disease progression, and immune system evasion.

Other species associated with NGU include Mycoplasma genitalium, Ureaplasma urealyticum, and Mycoplasma hominis. These bacteria are commonly found in the normal microbiota of healthy individuals, who may acquire them during birth or through sexual contact, but they can sometimes cause infections leading to urethritis (in males and females) or vaginitis and cervicitis (in females).

M. genitalium is a more common cause of urethritis in most settings than N. gonorrhoeae, although it is less common than C. trachomatis. It is responsible for approximately 30% of recurrent or persistent infections, 20–25% of nonchlamydial NGU cases, and 15%–20% of NGU cases. M. genitalium attaches to epithelial cells and has substantial antigenic variation that helps it evade host immune responses. It has lipid-associated membrane proteins that are involved in causing inflammation.

Several possible virulence factors have been implicated in the pathogenesis of U. urealyticum (see the figure below). These include the ureaplasma proteins phospholipase A, phospholipase C, multiple banded antigen (MBA), urease, and immunoglobulin α protease. The phospholipases are virulence factors that damage the cytoplasmic membrane of target cells. The immunoglobulin α protease is an important defense against antibodies. U. urealyticum can also generate hydrogen peroxide, which may adversely affect host cell membranes through the production of reactive oxygen species.

Source note: the source attributes hydrogen-peroxide generation to the immunoglobulin α protease itself (“It can generate hydrogen peroxide…”); in the Ureaplasma virulence-factor literature, IgA protease activity and hydrogen-peroxide production are documented as separate factors of the organism, not one enzyme performing both — corrected here.

Treatments differ for gonorrheal and nongonococcal urethritis. However, N. gonorrhoeae and C. trachomatis are often simultaneously present, which is an important consideration for treatment. NGU is most commonly treated using tetracyclines (such as doxycycline) and azithromycin; erythromycin is an alternative option. Tetracyclines and fluoroquinolones are most commonly used to treat U. urealyticum, but resistance to tetracyclines is becoming an increasing problem (Ken B Waites. “Ureaplasma Infection Medication.” Medscape, 2015.). While tetracyclines have been the treatment of choice for M. hominis, increasing resistance means that other options must be used. Clindamycin and fluoroquinolones are alternatives. M. genitalium is generally susceptible to doxycycline, azithromycin, and moxifloxacin. Like other mycoplasma, M. genitalium does not have a cell wall and therefore β-lactams (including penicillins and cephalosporins) are not effective treatments.

Check Your Understanding

Summary

• Bacterial cystitis is commonly caused by fecal bacteria such as E. coli.
• Pyelonephritis is a serious kidney infection that is often caused by bacteria that travel from infections elsewhere in the urinary tract and may cause systemic complications.
• Leptospirosis is a bacterial infection of the kidney that can be transmitted by exposure to infected animal urine, especially in contaminated water. It is more common in tropical than in temperate climates.
• Nongonococcal urethritis (NGU) is commonly caused by C. trachomatis, M. genitalium, Ureaplasma urealyticum, and M. hominis.
• Diagnosis and treatment for bacterial urinary tract infections varies. Urinalysis (e.g., for leukocyte esterase levels, nitrite levels, microscopic evaluation, and culture of urine) is an important component in most cases. Broad-spectrum antibiotics are typically used.

Key terms

• dysuria — urination accompanied by burning, discomfort, or pain.
• pyuria — pus or white blood cells in the urine.
• hematuria — condition in which there is blood in the urine.
• leptospirosis — bacterial infection of the kidney caused by Leptospira spp.; may spread to the liver, lungs, brain, and other organs.
• Weil’s disease — advanced stage of leptospirosis in which the kidney and liver become seriously infected.
• nongonococcal urethritis (NGU) — a nonspecific infection of the urethra that is not caused by Neisseria gonorrhoeae.

Practice

Identify the most common bacterial pathogens that can cause urinary tract infections

Compare the major characteristics of specific bacterial diseases affecting the urinary tract

This section is adapted from Microbiology, Section 23.2: Bacterial Infections of the Urinary System by Nina Parker, Mark Schneegurt, Anh-Hue Thi Tu, Philip Lister, Brian M. Forster, and OpenStax, © OpenStax, licensed under CC BY-NC-SA 4.0. Access the original for free at openstax.org. Changes: all three photographic and micrograph figures re-encoded as WebP and rendered as mediafigures with kind="photo" after image inspection; the Dipstick figure carries eager="true" as the page’s first figure; the Disease Profile table image (OSC_Microbio_23_02_BlaKidTbl) is transcribed as a Markdown table from the pinned CNXML alt (checked against the PDF) rather than vendored, per this book’s Disease Profile rule — the NGU row’s Transmission cell follows the pinned alt (“Transmitted sexually or from a pregnant person to neonate during birth”), where the printed table image reads “from mother to neonate during birth”; the Cystitis and Pyelonephritis/glomerulonephritis rows’ Antimicrobial Drugs cells follow the pinned alt’s “cephalosporins,” where the printed table image misspells it “cephalosprins” in both rows; feature boxes rendered as callouts; the three footnote citations are rendered as inline parenthetical citations, bare access URLs dropped; the cross-reference to Section 23.3 (Bacterial Infections of the Reproductive System) and the cross-references to Bacterial Infections of the Skin and Eyes (Section 21.2) and to a figure of Nonproteobacteria Gram-Negative Bacteria and Phototrophic Bacteria (Section 4.3) are links to those pages; the two source Multiple Choice items and the one Fill in the Blank item are adapted into Practice unchanged with their source keys; the unkeyed Short Answer question (“What is pyuria?”) is graded as a textin from this module’s own defining sentence; the unkeyed Critical Thinking question (leptospirosis risk factors) remains a self-check with a model answer assembled from this module’s own two risk-factor sentences, since no single sentence states them both; of this section’s four body Check Your Understanding bullets, one (the most common cause of a kidney infection) is graded as a textin from a single fixing sentence, and three remain self-checks whose model answers are assembled from this module’s own text, because each needs more than one sentence to answer honestly — the “three most common causes of urethritis” self-check’s model answer states only the two categories and their causative species the module gives, since the module does not name exactly three; three key-term recall textin items (dysuria, leptospirosis, nongonococcal urethritis) fill out the Practice groups against this module’s thin exercise bank. One one-word source typo is corrected: “K. pneumonia” to “K. pneumoniae” in the Cystitis subsection. A claim correction in the Nongonococcal Urethritis subsection replaces the source’s “It can generate hydrogen peroxide” (attributing hydrogen-peroxide production to the immunoglobulin α protease) with “U. urealyticum can also generate hydrogen peroxide,” with a visible Source note beside the passage, because the Ureaplasma virulence-factor literature documents IgA protease activity and hydrogen-peroxide production as separate factors of the organism, not one enzyme performing both.