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Urinary tract infections (UTIs)
Epidemiology
more common in female except in age less than one
year which is more common in male (anatomical
variation)
-most UTI in children < 5y. associated with congenital
abn. of urinary tract such as VUR or obstruction.
-In 6-15y.—dysfunctional voiding.
*The morbidity & mort. great at <1y. & >65y.
DEFINITIONS
UTI is an inflammatory response of the urothelium to
bacterial invasion that is usually associated with
bacteriuria and pyuria,
clinically ranging from asymptomatic presence of
bacteria in urine to severe infection of the kidneys
with resultant sepsis.
Bacteriuria is the presence of bacteria in the urine,
which is normally free of bacteria & can be
symptomatic or asymptomatic
Pyuria, the presence of white blood cells (WBCs) in
the urine, is generally indicative of infection and an
inflammatory response of the urothelium to the
bacterium
Bacteriuria without pyuria is generally indicative of
bacterial colonization without infection of the urinary
tract.
Pyuria without bacteriuria warrants evaluation for
tuberculosis, stones, or cancer
UTIs are a result of interactions between the
uropathogen and the host & determined in part by
the virulence factors of the bacteria,
the inoculum size, and
the inadequacy of host defense mechanisms
Routes of Infection
1-Ascending Route
Most bacteria enter the urinary tract from the bowel
reservoir via ascent through the urethra into the
bladder.
2-Hematogenous Route
Infection of the kidney by the hematogenous route is
uncommon in normal individuals like Staphylococcus
aureus bacteremia originating from oral sites
3- lymphatic
4- direct extension
Urinary Pathogens
E. coli is by far the most common cause of UTIs,
accounting for 85% of community-acquired and 50%
of hospital-acquired infections
Bacterial Adhesion
E. coli expresses a number of adhesions that allow it to
attach to urinary tract tissues (piliated & nonpiliated
E.coli
Epithelial Cell Receptivity
studies established increased adherence of pathogenic
bacteria to vaginal epithelial cells is demonstrable
biologic difference that could be shown in women
susceptible to UTI
Natural Defenses of the Urinary Tract
The normal flora of the vaginal introitus, the
periurethral area, and the urethra usually contain
microorganisms such as
lactobacilli,
coagulase negative staphylococci,
corynebacteria, and
streptococci that form a barrier against uropathogenic
colonization
Alterations in Host Defense Mechanisms
-Obstruction
-Vesicoureteral Reflux
-Underlying Disease
include diabetes mellitus (renal papillary necrosis),
sickle cell disorders, analgesic abuse, sulfonamide
nephropathy, gout, heavy-metal poisoning, and aging
-Pregnancy
-Spinal Cord Injury with High-Pressure Bladders
CLINICAL MANIFESTATIONS
Symptoms and Signs
Cystitis is usually associated with dysuria, frequency,
urgency, suprapubic pain, and hematuria. Lower tract
symptoms are commonly present and usually predate
the appearance of upper tract symptoms by several
days.
Pyelonephritis is classically associated with fever,
chills, and flank pain
Diagnosis
Presumptive diagnosis of UTI is made by direct or
indirect analysis of the urine and is confirmed by
urine culture.
Assessment of the urine provides clinical information
about the status of the urinary tract. The urine and the
urinary tract are normally free of bacteria and
inflammation
GUE
Urine Collection
1- voided specimens
catheterization of a male patient for urine culture is
not indicated unless the patient cannot urinate.
The obtained voided specimens first 10 mL of urine
(representative of the urethra) and a midstream
specimen (representative of the bladder)
2- Catheterized Specimens in women catheterization
should be performed and a mid catheterized specimen
collected if contamination is suspected.
3-Suprapubic Aspiration
Macroscopic examination
1-colour &appearance:
drugs &food
*red urine does not always signify
hematuria, however hematuria must
be ruled out by microscopic examin.
*cloudy urine,
-amorphous phosphate (the most common cause
of cloudy urine) disappear by addition of acid.
-urate disappear by addition of alkali
-or pyuria
2-specific gravity.1003-1030 .
evaluate hydration.
1010 that of plasma even after overnight dehydration
due to
-lack of ADH (D.I or i.c.trauma)
-extensive acute renal tubular damage
-sickle cell anemia
~Tested by- reagent strip, hydrometer &
refractometer.
3-chemical tests
~ph –uric acid stone in ph less than 6.5
(uric acid soluble in alkaline media)
-RTA failure of kidney to acidify urine
below ph of 6.0
-UTI by urea splitting organism (proteus)
ph more than 7.0
~Protein proteinuria more than150mg/24hr
glomerulopathy electrophric to identify specific
type of protein.
~Glucose
glucose in urine if bl. Glucose more
than 180 (D.M) or low renal threshold of
glucose excretion.
~Hb dip strip not specific for erythrocyte
use for screening only
~Bacteria &leukocyte.
some bacteria like enterobacter reduce dietary nitrate
to nitrite,
so nitrite level+ leukocyte estarase from w.b.c. used
to diagnose infection.
Microscopic examination
Is essential if -urinary symptoms
-abn. Macroscopic exam.
*early morning urine is the best specimen if it can be
examined within a few minutes of collection.
1-centerfuge 10ml 2000 rpm for 5min.
2-decant the supernatant
3-resuspend the sediment in the
remaining 1ml,by tapping the tube gently
4-place one drop of the mixture on slide &
cover with coverslip & examin 1st with low power
(10) then high power (40)
~staining with methylen blue or gram stain may be
helpful to distinguish bact. & differentiate wbc.
Interpretation:
A-bacteria.
the significance of bact. depend on:
1-method of collection.
2-specific gravity (dilutional effect.)
3-staining.
B-leukocytes
just as the presence of bact.is not an absolute
indication of infection neither is the finding of pyuria.
Also it depend on-method of collection.
-state of hydration.
Pyuria :
is the presence of 5-8 leukocytes/hpf (msu in m. or
catheterized f.)
~symptom of uti+pyuria+bacteruria=diagnoses of
infection& initiating emperic therapy.
One can verify the diagnoses by bacterial culture.
-estimate the number of bact.,
-identify the exact organism, &
-predict the drug will be effective in treating
infection.
*renal tb. Should be considered in any pt. with sterile
pyuria
(persistent pyuria+-ve result on routine culture).
Ziehl-neelsen stain for AFB can be diagnostic in
-50% of spot specimen
-70-80% of 24hr.specimen.
*urolithiases & malignancy can also cause sterile
pyuria.
C- Erythrocytes.
the presence of even few RBCs in urine (hematuria)
is abn. &require further investigation.
3-container method of collection (micro.)
Initial10-15ml. =urethra.
middle30-40ml.=upper tract (total)
final 5-10ml.=prostate &bladder neck
dysmorphic RBCs indicate active glomerular disease
result from extreme changes in osmolality affecting
RBC during their passage through renal tubules
D-epithelial cells
Sequamous cells-indicate contamination
Transitional cells-of no significance unless abnormal
histologically.
E- Casts
formed in the distal tubules & collecting ducts,
commonly signify intrinsic renal disease
-leukocyte casts suggest p.n. (not absolute)
-erythrocyte casts =underlying vasculitis or
glomerulitis.
-epithelial casts of little significance be differentiated
from leukocyte casts.
-hyaline casts (mixture of mucus + globulin) of no
significance.
-granular casts disintegrated WBC and epithelial cells
=intrinsic renal disease
-crystals of varying importance
(cystine, leucine, tyrosine ) can be helpful in some
instance
IMAGING TECHNIQUES
Radiologic studies are unnecessary for evaluation of
most women with genitourinary infections.
Indication including
1-high-risk patients, women with febrile infections and
most men,
2-acute infectious processes that require further
intervention or may find the cause of complicated
infections with possible UT obstruction
3-bacteriuria fails to resolve after appropriate
antimicrobial therapy or who have rapid recurrence of
infection, abnormalities that cause bacterial persistence
should be sought.
*The renal ultrasound is an important technique
because it is noninvasive, easy to perform, and rapid,
and offers no radiation or contrast agent risk to the
patient.
It is particularly useful in identifying calculi and
hydronephrosis, pyonephrosis, and perirenal abscesses
PRINCIPLES OF ANTIMICROBIAL THERAPY
Factors important in aiding selection of empirical
therapy include whether
-the infection is complicated or uncomplicated;
-the spectrum of activity of the drug against the
probable pathogen;
-a history of hypersensitivity;
-potential side effects, including renal and hepatic
toxicity; and
-cost
-The concentration of the antimicrobial agent
achieved in blood is not important in treatment of
uncomplicated UTIs.
-Blood levels are critical in patients with bacteremia
and febrile urinary infections consistent with
parenchymal involvement of the kidney and prostate
-prophylactic to keep the urine sterile
-Suppressive, to prevent already present bact.
infecting ut.
Trimethoprim/Sulfamethoxazole
The combination of TMP-SMX has been the most
widely used antimicrobial agent for the treatment of
acute UTIs
-Antagonism of bacterial folate metabolism
-inexpensive and have minimal effects on the bowel
flora.
-relatively common adverse effects, consisting
primarily of rashes and gastrointestinal complaints
C.I, folic acid def, G6PD def, pregnancy
Nitrofurantoin
Nitrofurantoin is effective against common
uropathogens, but it is not effective against
Pseudomonas & proteus species
-Inhibition of several bacterial enzyme systems
-It is rapidly excreted from the urine but does not
obtain therapeutic levels in most body tissues,
-it is not useful for upper tract and complicated
infections
-It has minimal effects on the resident bowel and
vaginal flora and has been used effectively in
prophylactic regimens for more than 40 years
Cephalosporins
-Inhibition of bacterial cell wall synthesis
-First generation against gram positive organisms &
common uropathogens such as E. coli, proteus &
Klebsiella pneumoniae
-second generation against anaerobes & h.influenza
-Third generation against gram negative organisms
-should limited to complicated infections and
situations in which parenteral therapy is required and
resistance to standard antimicrobial agents is likely.
-They are also useful during pregnancy
Aminopenicillins
-Inhibition of bacterial cell wall synthesis
-the emergence of resistance in 40% to 60% of
common urinary isolates has lessened the usefulness
of these drugs
-addition of B-lactamase inhibiter. (Glavulinic acid)
makes aminopenicillin more effective against G-ve
-The extended-spectrum penicillin derivatives (e.g.,
piperacillin, mezlocillin, azlocillin) retain ampicillin's
activity against enterococci and offer activity against
many ampicillin-resistant gram-negative bacilli
Aminoglycosides
-Inhibition of ribosomal protein synthesis
-Their nephrotoxicity and ototoxicity are well
recognized;
-Once-daily aminoglycoside regimens have been
instituted to maximize bacterial killing and reduce
potential for toxicity
-When combined with TMP-SMX or ampicillin,
aminoglycosides are the first drugs of choice for
febrile UTIs
Fluoroquinolones
-Inhibition of bacterial DNA gyrase
-have a broad spectrum of activity that makes them
ideal for the empirical treatment of UTIs
- C.I-children, pregnant & lactating F.
-highly effective against Enterobacteriaceae, as well
as P. aeruginosa, S. saprophyticus & S.aureus.
but, in general, antistreptococcal coverage is marginal
-not nephrotoxic, but renal insufficiency prolongs the
serum half-life, requiring adjusted dosing in patients
with creatinine clearances of less than 30 mL/min
Urethritis
Usually STD
Either GC uethritis
Or NGC urethritis
the most important is chlamydia trichomatis but
others like ureaplasma urealyticum & trichomonas
vaginalis not uncommon
prostatitis
BLADDER INFECTIONS
Most cases of uncomplicated cystitis occur in women.
more than 50% of all women have at least one such
infection in their lifetime.
Although it is much less common, young men may
also experience acute cystitis without underlying
structural or functional abnormalities of the urinary
tract
UTIs in most men should be considered complicated
until proven otherwise
Clinical Presentation
The presenting symptoms of cystitis are variable but
usually include dysuria, frequency or urgency, and
suprapubic pain
Hematuria or foul-smelling urine may develop
E. Coli is the causative organism in 75% to 90% of
cases of acute cystitis in young women
S. saprophyticus a commensal organism of the skin, is
the second most common cause
Laboratory Diagnosis
The presumptive laboratory diagnosis of acute
cystitis is based on microscopic urinalysis, which
indicates microscopic pyuria, bacteriuria, and
hematuria
However, routine urine cultures are often not
necessary it remains the definitive test;
and in symptomatic patients, the presence of 100
cfu/mL or more of urine usually indicates infection
Acute Pyelonephritis
pyelonephritis is defined as inflammation of the
kidney and renal pelvis,
-the diagnosis is clinical.
The classic presentation is an abrupt onset of chills,
fever, and unilateral or bilateral flank or
costovertebral angle pain and/or tenderness. These
so-called upper tract signs are often accompanied by
dysuria, increased urinary frequency, and urgency
Variations of this clinical presentation have been
recognized
On physical examination, there often is tenderness to
deep palpation in the costovertebral angle.
Urinalysis usually reveals numerous WBCs, often in
clumps, and bacterial rods or chains of cocci
The presence of large amounts of granular or
leukocyte casts in the urinary sediment is suggestive
of acute pyelonephritis
Excretory Urogram most patients with pyelonephritis
have a normal excretory urogram
Renal Ultrasonography to rule out urinary tract
obstruction
Computed Tomography
commonly used to evaluate patients initially with
complicated UTIs factors or reevaluate patients who
do not respond after 72 hours of therapy
Differential Diagnosis
Acute appendicitis, diverticulitis, and pancreatitis can
cause a similar degree of pain, but the location of the
pain often is different
Management
Depend on severity of infection
~not severely ill out pt. treatment
TMP-SMX or fluoroquinolones for 14 days.
~pt. with physiological or anatomical abnormalities
toxic pt.& sepses.
Hospitalization, initially with complete bed rest,
intravenous fluids, and antipyretics.
Antibiotics either ampicillin & aminoglycosides or
3rd generation cephalosporin until fever subside.
or additional 7-10 days if bacteremia is present.
Then oral therapy 10-14 days.
In patients with fever lasting longer than 72 hours,
Radiologic investigation (CT) is indicated to
identify unsuspected obstructive uropathy,
urolithiasis, or underlying anatomic abnormalities
prevented a rapid therapeutic response, or caused
complications of the infectious process, such as renal
or perinephric abscess