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Urinary tract infections

Dr. Mohamed Sakr, M.D.
Medical Microbiology and Immunology
 Urinary tract infections (UTIs)

• UTIs refer to an infection of any part of the

urinary system from kidney to bladder.

• UTIs are generally defined as the presence

of characteristic symptoms (e.g. dysuria,
frequency) and significant bacteriuria.
 Urinary tract infections (UTIs)

• Significant bacteriuria is defined as a urine

sample containing more than 105
colonies/ml of urine in pure culture using a
standard calibrated bacteriological loop.
• In the absence of symptoms, this level of
bacteriuria is termed asymptomatic
bacteriuria.
 Sterile pyuria

Pyuria is the condition of urine containing of 10 or more white blood

cells or pus per high power field of voided mid-stream urine.
Sterile pyuria, is urine which contains white blood cells while
appearing sterile by standard culturing techniques.
• Genitourinary tuberculosis
• Use of antibiotics that suppress bacterial growth or a side effect
from some medications such as paracetamol.
• Mycoplasma, ureaplasma, gonorrhea, or chlamydia
• Viruses which will not grow in bacterial cultures.
 Causes of Urinary tract infections

Bacteria
 Escherichia coli Fungi
 Klebsiella oxytoca
Candida albicans
 Proteus mirabilis
 Pseudomonas aeruginosa Candida tropicalis
 Enterococcus faecalis Viruses
 Enterococcus faecium Adenovirus
 Staphylococcus aureus (MSSA/MRSA) BKV
 Streptococcus agalactiae; GBS CMV
 Streptococcus pyogenes; GAS
 Mycobacterium tuberculosis
 categories of UTIs

Upper UTI: infection of the kidney (pyelonephritis).

Lower UTI: infection of the bladder (cystitis).

Uncomplicated UTI: if occurring in healthy non-pregnant adult

women.

Complicated UTI: the presence of factors that increase the risk of

treatment failure (e.g diabetes, structural abnormalities, catheter and
other devices).
 Risk factors of UTIs
• A condition that obstructs or blocks urinary tract, such as kidney stones
• A condition that prevents you from emptying bladder fully
• A weakened immune system, for example, diabetes, or undergoing
chemotherapy
• Female and sexually active
• Male and have an enlarged prostate gland
• A urinary catheter
• History of UTIs
• Spermicide use
• Circumcision reduces the risk of UTIs in boys.
 Pathophysiology
The normal urinary tract is a sterile environment.
The development of UTIs results from colonization and ascending spread of
microorganisms from the urethra into the bladder and kidney commonly by E.
coli, or
by hematogenous spread via the blood commonly by; Staphylococcus aureus,
Candida albicans and Mycobacterium tuberculosis.
In women, infections start with the colonization of periurethral area. It then
ascends the urethra to cause infection of the bladder.
Infections are uncommon in men for a number of reasons. They have a longer
urethra, prostatic secretions have some antimicrobial properties and their
periurethral area is generally drier.
 Keys of laboratory diagnosis of UTIs
• ‘Dip-stick’ test for leukocyte esterase and nitrite can identify patients with
infection and the need for treatment.
• Culture using a midstream urine specimen to reduce the risk of contamination.
• More than >105 colony-forming units/mL indicate UTIs.
• 104 is significant if the organism is gram + ve and only of one type.
• Chronically catheterized patients usually have ‘significant’ numbers of
organisms and multiple pathogens and may not have active infection.
• All isolates are potentially significant from a suprapubic aspirate from an
infant with suspected infection.
• Susceptibility tests should be performed on all significant isolates.
 Keys of Treatment of UTIs
• Empirical therapy is based on the known susceptibilities of
urinary pathogens.
• Most community-acquired infections respond to oral antibiotics
(e.g. cefalexin, amoxicillin, trimethoprim or nitrofurantoin).
• If septicaemia is present, ciprofloxacin or cefotaxime should be
used.
• Recurrent urinary infection may require nocturnal prophylaxis
(e.g. low-dose trimethoprim, nitrofurantoin or naladixic acid),
together with ensuring an adequate urine flow is achieved.
 E coli
E. coli is the most common cause of UTI in any age group (90% of first urinary tract
infections)
Most strains of E coli ferment lactose rapidly and produce indole. There are over 150
distinct O antigens and a large number of K and H antigens, all of which are
designated by number.
Most of the urinary tract infections that involve the bladder or kidney in an otherwise
healthy host are caused by a small number of O antigen types that have specifically
elaborated virulence factors that facilitate colonization and subsequent clinical
infections.
These organisms are designated as uropathogenic E coli. Typically, these organisms
produce hemolysin, which is cytotoxic and facilitates tissue invasion.
Strains that cause pyelonephritis express K antigen
 E. coli,
P-fimbriae and type-1 fimbriae are significant virulence determinants of uropathogenic
strains of Escherichia coli:
• E coli from the nearby rectal flora have colonized the perineum, utilizing binding by
type 1 (common) pili. E coli
• A few E coli have gained access to the bladder owing to mechanical disruptions such
as sexual intercourse or catheters. Receptors for the P pili not present on the perineal
mucosa but found on the surface of bladder mucosal cells.
• During voiding, the bladder has expelled the E coli, which have only type 1 pili. The P
pili-containing bacteria remain behind due to the strong binding to the P (Gal–Gal)
receptor.
• The remaining E coli have multiplied and are causing a UTI (cystitis) with
inflammation and hemorrhage. In some cases, the bacteria ascend the ureter to cause
pyelonephritis in the kidney where the P (Gal–Gal) receptor is most abundant.
• Over the last decade, a pandemic E. coli,
clone, E coli O25b/ST131, has
emerged as a significant
pathogen. This organism has
been successful largely as a
result of its acquisition of
plasmid-mediated resistance
factors that encode resistance to
β-lactam antibiotics (elaboration
of extended spectrum β-
lactamases), fluoroquinolones,
and aminoglycosides
 E. coli,

E coli is readily isolated in

culture. In UTIs, the bacteria
typically reach high numbers
(> 105 /mL), which makes
them readily detectable by
Gram stain even in an unspun
urine specimen.
E. Coli grows on MacConkey
agar and ferments lactose.
 Klebsiella oxytoca
Gram-negative, rod-shaped bacteria
The most distinctive bacteriologic features
of the genus Klebsiella are the absence of
motility and the presence of a
polysaccharide capsule. This gives
colonies a glistening, mucoid character
and forms the basis of a serotyping system.
they usually give positive test results for
lysine decarboxylase and citrate.
Over 70 capsular types have
been defined.
 Klebsiella oxytoca

Klebsiella oxytoca is closely related to K.

pneumoniae, from which it is distinguished
by being indole-positive
Klebsiella oxytoca is characterized by
negative methyl red, positive VP, positive
citrate, urea and TSI gas production
Klebsiella species are resistant to
antimicrobial agents
 Proteus

Proteus found with varying

frequencies in the normal intestinal Strains of Proteus vary greatly in antibiotic
flora. susceptibility.

Proteus mirabilis, the most commonly

isolated member of the group, is
susceptible to ampicillin and the
cephalosporins and is indole negative.
Proteus Vulgaris are regularly resistant
to ampicillin and the cephalosporins and
is indole positive.
 Proteus

Proteus mirabilis and Proteus

vulgaris share the ability to
swarm over the surface of
media, rather than remaining
confined to discrete colonies.
Swarming along with motility
could facilitate the production of
UTIs by movement of Proteus
up urinary catheters.
 Proteus

Proteus differ from other

Enterobacteriaceae in the production of a
very potent urease, which aids their rapid
identification.
Urease breaks down urea, releasing
ammonia that, when converted to
ammonium, raises the urine pH.
It also contributes to the formation of
urinary stones and produces alkalinity and
an ammoniac odor to the urine.
 Proteus typing
Dienes phenomenon, when two
identical Proteus cultures are
inoculated at different points on
the same medium, the resulting
swarming of growth coalesce
without signs of demarcation.

However, When, two different

strains of Proteus are inoculated,
the spreading films of growth fail
to coalesce and remain separated
by a narrow easily visible area.
 Pseudomonas aeruginosa

• This organism is widespread in the environment, but rare in the flora of

healthy individuals. Its carriage increases with hospitalization. Moist places
such as sink-traps, drains and flower vases can harbour Pseudomonas.
• Its most striking bacteriologic feature is the production of colorful water-
soluble pigments. Its production of blue, yellow or rust-colored or green
pigments differentiates it from most other Gram-negative bacteria.
• Pseudomonas aeruginosa also demonstrates the most consistent resistance
to antimicrobial agents of all the medically important bacteria.
 Pseudomonas aeruginosa
Virulence
• Outer membrane protein porins are relatively impermeable antibiotics.
• Pili attach to host tissues.
• A single polar flagellum rapidly propels the organism.
• A mucoid exopolysaccharide slime layer is present outside the cell wall in
some strains. This layer is created by secretion of alginate, Most strains of P
aeruginosa produce multiple extracellular products allow biofilm formation.
• Enzymes with phospholipase, collagenase, adenylate cyclase, or elastase
activity.
• The elastase acts on biologically important substrates, including elastin,
human IgA and IgG, complement components, and some collagens.
 Pseudomonas aeruginosa

• Exotoxin A (ExoA) is a secreted protein that inactivates

eukaryotic elongation factor 2 (EF-2). This arrests translation
leading to shutdown of protein synthesis and cell death.
Although this action is the same as diphtheria toxin, the two
toxins are unrelated.
• Exoenzyme S (ExoS) and a number of other proteins (ExoT,
ExoY, ExoU) are transported directly into host cells inducing
apoptosis.
 Pseudomonas aeruginosa
Laboratory diagnosis
Smears: Gram-negative rods.
Culture: grape like smell –wide temp range:5-42 °C
Nutrient agar: greenish exopigment
MacConkey agar: pale yellow non lactose fermenting
Blood agar: often hemolytic
Biochemical production
Pyocin typing
Typing by pulse-field gel electrophoresis or multilocus sequence
typing (MLST).
 Organisms are often
resistant; therefore,
treatment is guided
Pseudomonas by susceptibilities..
aeruginosa
Treatment Acombiantion
therapy: B-lactam
as pipracillin with
an aminoglycosides
• Enterococci are gram-positive cocci that often occur in pairs or
short chains. Enterococci
• Enterococci are part of the normal intestinal flora of humans and
animals.
• The genus Enterococcus includes more than 17 species.
• Enterococcus faecalis and Enterococcus faecium can cause
UTIs
• Enterococcus species are
 facultative anaerobic organisms
 can survive temperatures of 60°C for short periods
 grow in high salt concentrations.
• In the laboratory, enterococci are distinguished by their
morphologic appearance on Gram stain and culture and their
ability to hydrolyze esculin in the presence of bile.
 Enterococci
• Bile-esculin test is based on the ability of certain
bacteria, as Enterococcus species, to hydrolyze
esculin in the presence of bile.
• Hydrolysis of the esculin in the medium results in
the formation of glucose and a compound called
esculetin.
• Esculetin, in turn, reacts with ferric ions to form a
black diffusible complex.
 Enterococci
• Enterococci are innately resistant to cephalosporins as this group of
antibiotics cannot bind to enterococcal penicillin-binding proteins.
• Enterococci are able to utilize folic acid in their environment and are
thus insensitive to Trimethoprim/sulfamethoxazole .
• Although ampicillin plus an aminoglycoside is often used to treat
enterococcal UTIs, these organisms show intrinsic resistance to
aminoglycosides alone.
• Vancomycin resistance is the most alarming form of resistance among
strains of enterococci.
• Vancomycin resistance Enterococci are treated by linezolid
• Adenoviruses are naked capsid, icosahedral, and
double-stranded DNA viruses. There are 57 Adenovirus
different serotypes of adenoviruses that infect
humans, which are classified into one of six
subgroups (A-F) based on multiple biologic
properties of the virus.
• Adenovirus is an important cause of hemorrhagic
cystitis in which hematuria and dysuria are
prominent findings.
• Adenovirus is an important cause of infections in
immunocompromised patients. In particular,
adenovirus infection is one of the most severe viral
infection in renal transplant recipients and can
cause graft loss because of adenovirus induced
nephritis.