Microbial Diseases of the Urinary

System

By:
Yemane Weldu (MSc., Assistant professor)
 Microbial Diseases of the Urinary System
Learning objectives
• Describe the normal microbiota of the urinary system.
• Describe the features of urethritis, cystitis, and
pyelonephritis.
• Describe the features of leptospirosis

• Describe the manifestations and cause of streptococcal

acute glomerulonephritis
 Normal Microbiota of the Urinary System
• The urethra normally supports the growth of some
microbiota such as:
– Species of Lactobacillus, Staphylococcus and
Streptococcus.
– Occasionally other bacteria such as species of
Mycobacterium, Bacteroides, Fusobacterium, and
Peptostreptococcus colonize the distal end of a
urethra.
• T
• In both males and females, the rest of the urinary
organs and the urine in them are axenic (lacking in
microbial contaminants).
– due to the acidic pH of urine and the flushing action
of urination.
• Microbiota of a urethra do contaminate urine during
urination; for this reason, normally voided urine contains
some bacteria,
– whereas urine collected directly from a urinary
bladder via a catheter is typically sterile.
• In both males and females, microorganisms infecting the
urethra can move into the bladder, up the ureters, and
infect the kidneys.
• In addition to the ascending infection, systemic diseases
can also affect the urinary system.
Urinary Tract Infections
Terms
• Urethritis: Inflammation of the urethra, usually caused by
infection.
• Cystitis: Inflammation of the urinary bladder, often caused
by infection.
• Pyelonephritis: Inflammation of the kidney (both the
urine-forming and urine-collecting parts).
• Prostatitis: Inflammation of the prostate gland.

• Dysuria: Pain or difficulty in urinating

• Bactriuria: Presence of bacteria in the urine
 Urinary Tract Infections
• Bacterial colonization of the urine within this tract
(bacteriuria) is common and can, at times, result in
microbial invasion of the tissues responsible for the
manufacture, transport, and storage of urine.
• Bacteria may trigger inflammation and pain in any or all
of the urinary tract.
– Infection of the upper urinary tract, consisting of the
kidney and its pelvis, is known as pyelonephritis.
 – Infection of the lower tract may involve the bladder
(cystitis), urethra (urethritis), or prostate (prostatitis),
the genital organ that surrounds and communicates
with the first segment of the male urethra.
• Because all portions of the urinary tract are joined by a
fluid medium, infection at any site may spread to involve
other areas of the system.
Clinical Manifestations
• The clinical manifestations of UTI are variable.
• Approximately 50% of infections do not produce
recognizable illness and are discovered incidentally
during a general medical examination.
• Infections in infants produce symptoms of a nonspecific
nature, including fever, vomiting, and failure to thrive.
• Manifestations in older children and adults, when
present, often suggest the diagnosis and sometimes the
localization of the infection within the urinary tract.
Urethritis
• Symptoms may be mild or absent in either sex,
particularly women.
• Men have urethritis usually with yellow, creamy pus and
painful urination.
– Purulent urethral discharge and dysuria develop
– Approximately 95% of all infected men have acute
symptoms.
– Although complications are rare, epididymitis,
prostatitis, and periurethral abscesses may occur.
• Is mainly caused by Neisseria gonorrhoeae, Chlamydia
trachomatis, Ureaplasma urealyticum
– Up to 50% of nongonococcal urethritis (men) or the
urethral syndrome (women) is attributed to chlamydia
trachomatis and produces dysuria, nonpurulent
discharge, and frequency of urination.
– Dual infections with both C. trachomatis and Neisseria
gonorrhoeae are not uncommon.
– Studies suggest that approximately one half of cases
of nongonococcal, nonchlamydial urethritis in men
may be caused by U. urealyticum.
• Although there is less purulent exudate in patients with
chlamydial urethral infections, such infections cannot be
differentiated reliably from urethritis caused by Neisseria
gonorrhoeae.
• Gonococcal urethritis is a more acute disease than
nongonococcal urethritis, overlap in the symptoms
mandates laboratory confirmation.
– So specific diagnostic tests for both organisms should
be performed.
Urethritis

Purulent urethral discharge in man with urethritis.

Cystitis
• The symptoms of cystitis are dysuria (painful urination),
frequency (frequent voiding), and urgency (an imperative
“call to toilet”).
• These findings are similar to those of urethritis

• The cystitis complex is, in fact, produced by irritation of

the mucosal surface of the urethra as well as the bladder.
• It is clinically distinguished from pure urethritis by a more
acute onset, more severe symptoms, the presence of
significant bacteriuria, and in approximately 50% of
cases, hematuria.
• The urine is often cloudy and malodorous and
occasionally frankly bloody.
• Cystitis patients also experience pain and tenderness in
the suprapubic area.
• Fever and systemic manifestations of illness are usually
absent unless the infection spreads to involve the
kidney.
Pyelonephritis
• The typical presentation of upper urinary infection
consists of flank pain and fever that exceeds 38.5°C.
• These findings may be preceded or accompanied by
manifestations of cystitis.
• Rigors, vomiting, diarrhea, and tachycardia are present
in more severely ill patients.
• Physical examination reveals tenderness over the
costovertebral areas of the back and, occasionally,
evidence of septic shock.
• In the absence of obstruction, the clinical manifestations
usually abate within a few days, leaving the kidneys
functionally intact.
– It has been estimated, however, that 20 to 50% of pregnant
women with acute pyelonephritis give birth to premature
infants, one of the most serious consequences of UTI.
• In the presence of obstruction, a neurogenic bladder, or
vesicoureteral reflux, clinical manifestations are more
persistent, occasionally leading to:
• Necrosis of the renal papillae and progressive impairment of
kidney function with chronic bacteriuria.
• If a renal calculus or necrotic renal papilla impacts in the
ureter, severe flank pain with radiation to the groin
occurs.
• The term chronic pyelonephritis is used to describe
inflamed, scarred, contracted kidneys often in
association with compromised renal function.
Prostatitis
• Infection of the prostate is typically manifested as pain in the
lower back, perirectal area, and testicles.
• In acute infection, the pain may be severe and accompanied
by high fever, chills, and the signs and symptoms of cystitis.
• Inflammatory swelling can lead to obstruction of the
neighboring urethra and urinary retention.
• On rectal palpation, the prostate is boggy and exquisitely
tender.
• Occasionally abscess formation, epididymitis, and seminal
vesiculitis or chronic infection may develop.
• Typically, acute prostatitis develops in young adults;
however, it can also follow placement of an indwelling
catheter in an older man.
• Patients with chronic prostatitis seldom give a history of
an acute episode.
– Many are totally without symptoms; others
experience low grade pain and dysuria.
• Periodic spread of prostatic organisms to the urine in the
bladder produces recurrent bouts of cystitis.
• In fact, chronic prostatitis is probably the major cause of
recurrent bacteriuria in men.
• The etiologic agents are the same as in cystitis and
pyelonephritis.
Epidemiology
• Urinary tract infection (UTI) is among the most common
of infectious diseases particularly among women.
• Prevalence is age and sex dependent.
– UTIs are more common in females than males
because female urethras are shorter and closer to the
anus.
• Millions of girls and women in the world suffer
bacterial urinary tract infections (UTIs) each year.
– It is estimated that 20% or more of the female
population suffers some form of UTI in their lifetime.
– In young girls, UTIs are most common around age
three, because of contamination during the toilet
training period.
– In boys, UTIs are rare except in cases of urinary tract
abnormalities that restrict the flow of urine.
– UTIs are more common in uncircumcised males than
in circumcised males.
– Approximately 1% of children, many of whom
demonstrate functional or anatomic abnormalities of
the urinary tract, develop infection during the
neonatal period.
– Infection in the male population remains uncommon
through the fifth decade of life, when enlargement of
the prostate begins to interfere with emptying of the
bladder.
– In the elderly of both sexes, gynecologic or prostatic
surgery, incontinence, instrumentation, and chronic
urethral catheterization push UTI rates to 30 to 40%.
• Diabetics, nursing home patients, elderly men who
have trouble emptying their bladders due to prostate
enlargement, patients with urinary catheters, women
who use diaphragms for birth control, and people who
do not drink adequate fluids are at risk for UTIs.
• A single bladder catheterization carries an infectious
risk of 1%, and at least 10% of individuals with
indwelling catheters become infected.
Pathogenesis
• The urine produced in the kidney and delivered through
the renal pelvis and ureters to the urinary bladder is
sterile in health.
• Infection results when bacteria gain access to this
environment and are able to persist.
• Access primarily follows an ascending route for bacteria
that are resident or transient members of the perineal
flora.
• These organisms are derived from the large intestinal
flora, which is uncomfortably nearby.
– Patients with urinary tract infections often inoculate
their own urethras by introducing fecal bacteria.
• Conditions that create access are varied, but the most
important is sexual intercourse, which has been shown to
transiently displace bacteria into the bladder.
– This puts the female partner is at risk because of the
short urethral distance.
• Other manipulations of the urethra carry risk as well,
particularly medical ones such as catheterization.
• Bacteria may also reach the urinary tract from the
bloodstream.
– This is obviously much less common, because it
requires an uncontrolled infection at another site.
• For bacteria that reach the urinary tract, the major
competing forces are the rich nutrient content of the
urine itself and the flushing action of bladder voiding.
• Persistence is favored by host factors that interrupt or
retard the urinary flow such as instrumentation,
obstruction, or structural abnormalities.
• In youth, factors are congenital malformations, and with
age these include changes that alter the mechanics of
outflow, such as prostatic hypertrophy.
• Bacterial factors include the ability to adhere to the
perineal and uroepithelial mucosa and to produce other
classical virulence factors like exotoxins.
– Important virulence factors are the adhesive factors
and ability to produce toxins by the causative agents.
Etiologic agents
• Most urinary infections are caused by bacteria from the
intestinal flora.
– Enteric bacteria (members of Enterobacteriaceae)—
Gram-negative bacteria that are part of the intestinal
microbiota—are the most common cause of urinary
tract infections.
• Nonintestinal bacteria, such as Pseudomonas and
Staphylococcus, occasionally cause urinary tract
infections.
• Yeasts, particularly species of Candida, may be isolated
from catheterized patients receiving antibacterial therapy
and from diabetic individuals, but they seldom produce
symptomatic disease.
• Neisseria gonorrhoeae and C trachomatis and
Ureaplasma urealyticum account for most cases of
urethritis.
– Less common agents isolated from nongonococcal
urethritis include herpes simplex virus and
Trichomonas vaginalis.
Urinary tract infection Pathogen
Escherichia coli
• Is by far the most common and potent UTI pathogen.
– Escherichia coli causes about 70-80% of UTI cases.

• Strains of E. coli that infect the bladder have attachment

fimbriae (sometimes called pili) that bind specifically to
epithelial cells lining the urinary bladder.
• Using fimbriae, these strains of E. coli move into
bladder and form biofilm-like aggregations within a
bladder cell’s cytosol.
• In this way, E. coli avoids the body’s defensive cells.
– Uropathogenic E. coli is the strain that causes 90% of
the urinary tract infections.
– The bacteria colonize the vagina & periurethral
region from the feces or perineal region and ascend
the urinary tract to the bladder or kidney causing
cystitis or pyelonephritis.
Proteus species
• Proteus species are relatively common causes of
uncomplicated as well as nosocomial UTIs.
• Urease-producing members of the genus Proteus are
associated with urinary stones, which themselves are
predisposing factors for infection.
• P. mirabilis : is a common cause of urinary infection in
the elderly and young males and often following
catheterization or cystoscopy.
 – P. mirabilis produces large quantities of urease,
which splits urea into carbon dioxide and ammonia.
• This process raises the urine pH, precipitating
magnesium and calcium in the form of crystals
and results in the formation of renal stones (renal
calculi).
• The increased alkalinity of the urine is also toxic
to the uroepithelium.
• Proteus vulgaris : is also Commonly isolated from
nosocomial urinary tract infection.
• Staphylococcus saprophyticus
– It is a 2nd most common cause of UTI, after E. coli in
sexually active young women accounting for 10-20%.
• Enterococcus faecalis, Staphylococcus
epidermidis, S. aureus, Pseudomonas aeruginosa
and Klebsiella spp (Klebsiella pneumoniae, K.
Oxytoca )
– Are among the leading cause of hospital-acquired
UTIs.
Others
• Enterobacter spp (E. aerogenes)
• Citrobacter spps (C. freundii, C. koseri

• Serratia spp (Serratia marscesens)

• Acinetobacter spp (Acinetobacter baumannii)
• Mycoplasma spp (Mycoplasma hominis, Mycoplasma
genitalium.
• Mumps virus
• Cytomegalovirus
DIAGNOSIS
Specimen Collection
• The diagnosis of UTI is based on examination of the
urine for evidence of bacteria or an accompanying
inflammatory reaction.
• Urine is most easily obtained by spontaneous micturition.
• Unfortunately, voided urine is invariably contaminated
with urethral flora and, in female patients, perineal and
vaginal flora, which can confound the results of
laboratory testing.
• Although the contaminants can never be completely
eliminated, their quantity may be diminished by carefully
cleansing the periurethrum before voiding and allowing
the initial part of the stream to flush the urethra before
collecting a specimen for examination.
– Use of appropriate techniques for specimen collection
is critical for examination.
• Clean-voided midstream urine collection procedure is
preferred to catheterization for routine purposes
because it avoids the risk of introducing organisms into
the bladder.
• When the laboratory examination of such a specimen
produces equivocal results or the patient cannot comply
with the requirements of the clean-voided technique,
catheterization or suprapubic aspiration from the
distended bladder may be necessary.
• For the diagnosis of prostatitis, urine is collected in three
segments by interrupting a single bladder excavation.
– The first voiding is considered a urethral washout.

– The midstream specimen that follows is used to

assess cystitis.
• The prostate is then massaged, and the final urine is a
prostatic secretions washout.
• The quantitative culture results are then compared.
– In prostatitis, it is expected that the third specimen
contains the largest numbers of the pathogen.
• Whenever possible, the first urine passed by the patient
at the beginning of the day should be sent for
examination.
– This specimen is the most concentrated and therefore
the most suitable for culture, microscopy, and
biochemical analysis.
• Explain to the patient the need to collect the urine with
as little contamination as possible, i.e. a ‘clean-catch’
specimen.
Female patients:
• Wash the hands. Cleanse the area around the urethral
opening with clean water, dry the area with a sterile
gauze pad, and collect the urine with the labia held
apart.
Male patients:
• Wash the hands before collecting a specimen (middle of
the urine flow).
NB: As soon as possible, deliver the specimen to the
laboratory.
1. Microscopic Examination

Wet mount /direct examination

– Approximately 90% of patients with acute symptomatic
UTI have pyuria (> 10 white cells/mm3 of urine).
• Presumptive diagnosis can be made by demonstrating
pyuria.
• This finding is also common, however, in a number of
noninfectious diseases.

– More specific is the presence of white cell casts,

which occur primarily in patients with acute
pyelonephritis.
Gram stain
• A more sensitive and specific microscopic procedure is a
Gram-stained smear of uncentrifuged urine.
– The presence of at least one organism per field is
almost always indicative of bacterial infection.
– The absence of white cells and bacteria in several
fields makes the diagnosis of UTI unlikely.
• However, this finding does not rule it out,
especially in young women with acute,
symptomatic infection who may be infected with
smaller numbers of organisms.
Gram stain of an uncentrifuged clean voided urine specimen from a patient
with an acute Escherichia coli urinary tract infection. Some degenerating
polymorphonuclear leukocytes and numerous Gram-negative rods are
present.
2. Chemical Screening Tests
• A number of urinary screening tests are commercially
available.
• The most successful detects:

– Leukocyte esterase from inflammatory cells and

– Nitrite produced from urinary nitrates by bacterial

metabolism.
• Although technically simpler, the sensitivity and specificity of
these products are similar to that of microscopic examination.
• Like microscopic examination, they do not reliably detect
bacteriuria below the level of 105 organisms/mL.
Urine Culture
• Is considered as a gold diagnostic standard for UTI.
• Quantitative urine culture is essential for diagnosis.

– In general, above 105 bacteria/mL of urine is

considered as UTI, Whereas below is contamination.
• Properly submitted urine that contains >105
organisms/ml indicates significant infection.
– However it is possible to void more than 105 of
contaminants and to have a genuine UTI with less
than 105 bacteria.
– For example: with acute cystitis, bacterial counts
may be lower.
• Fully one third of women with UTI limited to the
bladder demonstrate counts less than 105
bacteria/mL
• Given the overlap, application of these findings to clinical
practice requires linking the epidemiologic probability to
the clinical findings.
– If a woman has symptoms of cystitis and a culture
positive for a urinary pathogen, the probability she
has a UTI is 90%, even if the count is as low as 105
bacteria/mL.
– If the woman is asymptomatic, the probability drops
to 80% even if the count is more than 105/mL.
Treatment
• Mild UTIs resolve on their own without treatment

– antimicrobial drugs, such as cephalosporins,

sulfonamides, and semisynthetic penicillins, can prevent
the spread of infection to the kidneys and blood.
• The antimicrobials may be selected empirically based on
knowledge of the susceptibility of local strains.
– Sulfonamides and trimethoprim alone or in combination with
sulfamethoxazole, a fluoroquinolone, and nitrofurantoin are
the agents most commonly used if the etiology is assumed
to be E. coli.
• In most areas, the use of ampicillin is precluded by
resistance rates exceeding 25%.
• However, the treatment of UTI is best guided by the
results of cultures and antimicrobial susceptibility
tests.
– For children and patients with risk factors or recurrent
infections, empiric therapy should always be
confirmed by culture and susceptibility testing.
• Likewise, the duration of therapy depends on the
severity of the infection and the risk status of the
patient.
– Some cases of chronic cystitis require antimicrobials
for six months to two years.
– Physicians prescribe 10–14 days of antimicrobial
drugs to treat acute pyelonephritis.
– Intravenous administration is used when an infection
is severe.
Prevention
• Prevention of UTIs includes:
– Drinking 2–4 liters of fluids per day to increase the
volume of urine and the cleansing action of urination,
– Urinating following sexual intercourse to flush out
bacteria that may have been introduced into the
urethra,
– Refraining from vaginal douching (which eliminates
normal, protective microbiota),
– Using a form of birth control other than diaphragms.
– Continual low doses of antimicrobials can be
prescribed to prevent recurrent infections in at-risk
patients.
• Those with several symptomatic episodes annually may
be helped with long-term, low dose chemoprophylaxis.

– Wiping from front to back after defecation so as not

to drag bacteria from the anus into the urethra is the
most important thing females can do to prevent UTIs.
– Surgery is necessary to repair anatomical
abnormalities that restrict the flow of urine.
Leptospirosis
• Leptospirosis is a zoonosis disease primarily seen in
animals that spreads to humans.
• Leptospira interrogans, a Gram-negative spirochete
cause leptospirosis.
• The causative agent enters the body through breaks in
the skin or mucous membranes and spreads to the
urinary system from the blood.
• L. interrogans normally lives in many wild and domestic
animals—in particular, rats, raccoons, foxes, dogs,
horses, cattle, and pigs—in which it grows
asymptomatically in the kidney tubules.
• The spirochete can also survive in streams, rivers, and
lakes.
• Humans develop leptospirosis 2–26 days following direct
contact with the urine of infected animals or with the
spirochetes in animal-urine-contaminated streams, lakes,
or moist soil.
Signs and Symptoms
• An abrupt fever, myalgia (muscle pain), muscle stiffness,
and headache characterize leptospirosis.
• Half of patients develop nausea, vomiting, and diarrhea;
one-third have a dry cough.
• Leptospirosis is rarely fatal, but when it is, mortality is
due to kidney and liver failure, meningitis, or respiratory
distress.
Diagnosis, Treatment, and Prevention
• Leptospira does not stain well with Gram stain.

• A specific antibody test revealing the presence of the

spirochete in blood or urine specimens is the preferred
method of diagnosis.
• Intravenous ampicillin treats severe infections;
• oral doxycycline, chloramphenicol, or erythromycin are
drugs of choice for less severe cases.
Diagnosis, Treatment, and Prevention
• The most effective way to limit the spread of Leptospira
is to refrain from swimming in, or consuming water
contaminated with animal urine.
• Rodent control is also important, but eradication is
impractical because the spirochete has many animal
reservoirs.
• An effective vaccine is available for livestock and pets.
Streptococcal Acute Glomerulonephritis
• Is a post-streptococcal disease that may occur 1- 4 weeks
following a primary inadequately treated group A
streptococcal infection of the skin & throat infections
(pharyngitis).
• Develops 3 weeks after infection with a nephritogenic
strain of streptococci (types 12, 4, 2 & 49).
• For an undetermined reason, when there is infection by
some strains of group A Streptococcus (Streptococcus
pyogenes), the body does not remove from circulation
antibodies bound to the antigens of the pathogen.
• Instead, antibody-antigen complexes accumulate in
the glomeruli of the kidneys.
• The condition is due to Ag-Ab complex deposition on
the glomerular basement membrane (GBM).

• This triggers inflammation of the glomeruli and nephrons,

a condition called glomerulonephritis.
• Disease is characterized by fever, edema, elevated BUN
(azotemia), hematuria, high BP, low serum complement
levels. Blood, albumin, granular casts present in urine.
• The majority of patients recover completely. However few
may die or pass to chronic GN & renal failure.
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