138 CHAPTER 5 Infections and inflammatory conditions

Urinary tract infection: microbiology

Most UTIs are caused by fecal-derived bacteria that are facultative anaerobes (i.e., they can grow under both anaerobic and nonanaerobic conditions)—see Table 5.3.

Uncomplicated UTI

Most UTIs are bacterial in origin. The most common cause is Escherichia coli (E. coli), a gram-negative bacillus, which accounts for 85% of communityacquired and 50% of hospital-acquired infection.

Other common causative organisms include Staphylococcus saprophyticus and Enterococcus faecalis (also known as Streptococcus faecalis—gram positive), Proteus mirabilis, Klebsiella, and other gram-negative Enterobacteriaceae.

Complicated UTI

E. coli is responsible for up to 50% of cases. Other causes include

Enterococci (e.g., Streptococcus faecalis), Staph. aureus, Staph. epidermidis

(gram positive) and Pseudomonas aeruginosa (gram negative).

Route of infection

Ascending

The vast majority of UTIs result from ascending or retrograde infections up the urethra. The bacteria, derived from the large bowel, colonize the perineum, vagina, and distal urethra. They ascend along the urethra to the bladder (risk is increased in females as the urethra is shorter), causing cystitis, and from the bladder they may ascend, via the ureters, to involve the kidneys (pyelonephritis).

Reflux is not necessary for infection to ascend to the kidneys, but the presence of reflux facilitates ascending infection, as will any process that impairs ureteric peristalsis (e.g., ureteric obstruction, gram-negative organisms and endotoxins, pregnancy).

Infection that ascends to involve the kidneys is also more likely where the infecting organism has P pili (filamentous protein appendages—also known as fimbriae—which allow binding of bacteria to the surface of epithelial cells).

Hematogenous is uncommon, but is seen with Staph. aureus, Candida fungemia, and TB.

Infection via lymphatics is seen rarely in inflammatory bowel disease and retroperitoneal abscess.

Factors increasing bacterial virulence

Adhesion factors

Many gram-negative bacteria contain pili on their surface, which aid attachment to urothelial cells of the host. A typical piliated cell may contain 100–400 pili. Pili are 5–10 nm in diameter and up to 2 µm long.

E. coli produces a number of antigenically and functionally different types of pili on the same cell; other strains may produce only a single type, and, in some isolates, no pili are seen.

Pili are defined functionally by their ability to mediate hemagglutination (HA) of specific types of erythrocytes. Mannose-sensitive (type 1) pili are

URINARY TRACT INFECTION: MICROBIOLOGY 139

Table 5.3 Bacterial classification: uropathogens

Cocci	Gram-positive
	Staphylococcus, Enterococcus faecalis (also known as Streptococcus
	faecalis) e.g., S. saprophyticus causes approximately 10% of
	symptomatic lower UTIs in young, sexually active women
	Gram-negative
	Aerobes: Neisseria
Bacilli (rods)	Gram-positive
	Anaerobes*: Clostridium, Lactobacillus (usually a vaginal
	commensal)
	Gram-negative
	Aerobes: Enterobacteria (Escherichia, Klebsiella, Proteus),
	Pseudomonas
	Anaerobes*: Bacteroides
Others	Filamentous bacteria: Mycobacterium (M. tuberculosis—acid-fast,
	aerobic, gram-positive)
	Chlamydiae: Chlamydia trachomatis Fungi: Candida albicans
	Mycoplasma: Mycoplasma species, Ureaplasma urealyticum
	(cause UTI in patients with indwelling catheters)

*Anaerobic infections of the bladder and kidney are uncommon—anaerobes are normal commensals of the perineum, vagina, and distal urethra. However, infections of the urinary system that produce pus (pyogenic) (e.g., scrotal, prostatic, or perinephric abscesses) are often caused by anaerobic organisms (e.g., Bacteroides species such as Bacteroides fragilis,

Fusobacterium species, anaerobic cocci, and Clostridium perfringens).

produced by all strains of E. coli. Certain pathogenic types of E. coli also produce mannose-resistant (P) pili (associated with pyelonephritis).

Avoidance of host defense mechanisms:

An extracellular capsule reduces immunogenicity and resists phagocytosis (E. coli). M. tuberculosis resists phagocytosis by preventing phagolysosome fusion.

Toxins

E. coli releases cytokines with direct effect on host tissues.

Enzyme production

Proteus species produce ureases, which causes breakdown of urea in the urine to ammonia. This contributes to disease processes (struvite stone formation).

Host defenses

Factors protecting against UTI are the following:

•Mechanical flushing effect of urine through the urinary tract (i.e., antegrade flow of urine)

•A mucopolysaccharide coating of the bladder (Tamm–Horsfall protein, glucose amino glycan [GAG layer]) helps prevent bacterial adherence.

•Low urine pH and high osmolarity reduce bacterial growth.

•Urinary immunoglobulin (IgA) inhibits bacterial adherence.

140 CHAPTER 5 Infections and inflammatory conditions

Lower urinary tract infection

Cystitis

Cystitis is infection and/or inflammation of the bladder.

Presentation

There is frequent voiding of small volumes, dysuria, urgency, offensive urine, suprapubic pain, hematuria, fever (uncommon), and incontinence. Up to 33% of women experience an episode of bacterial cystitis by age 24, and 50% of women will have an episode in their lifetime. Bacterial cystitis in healthy men is rare.

Investigation

Dipstick of midstream specimen of urine (MSU)

Not all patients with bacteriuria have significant pyuria (sensitivity of 75–95% for detection of infection, that is, 5–25% of patients with infection will have a negative leukocyte esterase test suggesting, erroneously, that they have no infection). Cloudy urine that is positive for WBCs on dipstick and is nitrite positive is very likely infected.

Microscopy of midstream specimen of urine (MSU)

•False negatives: Low bacterial counts may make it very difficult to identify bacteria, and the specimen of urine may therefore be deemed negative for bacteriuria, when in fact there is active infection.

•False positives: Bacteria may be seen in the MSU in the absence of infection. This is most often due to contamination of the MSU with commensals from the distal urethra and perineum (urine from a woman may contain thousands of lactobacilli and corynebacteria,

and these organisms are derived from the vagina). These bacteria are readily seen under the microscope, and although they are grampositive, they often appear gram-negative (gram-variable) if stained.

The finding of pyuria and red blood cells suggests the presence of active infection.

Noninfective hemorrhagic cystitis

While bacterial cystitis can result in hemorrhagic cystitis, pelvic radiotherapy (radiation cystitis—bladder capacity is reduced and multiple areas of mucosal telangiectasia are seen cystoscopically) and drug-induced cystitis (e.g., cyclophosphamide treatment) are types of noninfectious hemorrhagic cystitis.

Urethritis

Urethritis is inflammation of the urethra. Urethritis in men is a sexually transmitted disease, which presents with dysuria and urethral discharge.

Gonococcal urethritis (GU)

GU is caused by the gram-negative diplococcus Neisseria gonorrhoea (incubation 3–10 days) and commonly associated with concomitant infection with Chlamydia trachomatis. Diagnosis is based on cultures from urethral swab.

LOWER URINARY TRACT INFECTION 141

Treatment involves ceftriaxone 125 mg IM in a single dose or cefixime 400 mg orally in a single dose or 400 mg by suspension (200 mg/ 5 mL) plus treatment for chlamydia if chlamydial infection is not ruled out. Quinolones are no longer recommended in the United States because of resistant strains).1

Sexual contacts must be informed and treated.

Nongonococcal urethritis (NGU)

NGU is mainly caused by Chlamydia trachomatis (incubation 1–5 weeks). Treat with azithromycin, 1 g as a single oral dose; or doxycycline, 100 mg orally twice a day for 7 days.

Transmission to females results in increased risk of pelvic inflammatory disease, abdominal pain, ectopic pregnancy, infertility, and perinatal infection.

Urethral syndrome

Urethral syndrome is a condition of uncertain etiology that only affects women. It manifests as dysuria, frequency, and urgency without evidence of infection, although some cases improve with antibiotics.2

Further reading

Foster RT Sr (2008). Uncomplicated urinary tract infections in women [review]. Obstet Gynecol Clin North Am 35(2):235–248, viii.

1 MMWR Morbid Mortal Wkly Rep April 13, 2007; 56(14);332–336.

2 Kaur H, Arunkalaivanan AS (2007). Urethral pain syndrome and its management. Obstet Gynecol Surv 62(5):348–351.