Urinary Tract

Infections
Debre Berhan University
Collage of health sciences
Department of pharmacy
Integrated therapeutics IV
 DEFINITION
Urinary tract infection (UTI)
• is defined as the presence of microorganisms in the
urinary tract that cannot be accounted for by
contamination.
• Infections of the urinary tract represent a wide variety
of clinical syndromes, including:
— urethritis,
― cystitis,
― prostatitis, and
― pyelonephritis
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 Definition. . .
 Lower Vs. Upper UTIs
• Lower tract infections include
• cystitis (bladder), urethritis (urethra), prostatitis
(prostate gland), and epididymitis.
• Upper tract infections involve
−Infections involving the kidney and are
referred to as pyelonephritis.

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 Definition. . .
 Uncomplicated Vs. Complicated UTIs. . . .
• Uncomplicated UTIs when an individuals who lack
structural or functional abnormalities of the urinary tract that
interfere with the normal flow of urine or voiding mechanism.
―are not associated with structural or neurologic
abnormalities.
• Complicated UTIs are usually the result of a predisposing
lesion of the urinary tract, such as a congenital abnormality or
distortion of the urinary tract, a stone, indwelling catheter,
prostatic hypertrophy, obstruction, or neurologic deficit that
interferes with the normal flow of urine and urinary tract
defenses.
• Complicated infections occur in both genders and frequently
involve the upper and lower urinary tract.
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 Definition. . .
Recurrent UTIs are characterized by:
• Two or more UTIs occurring within 6 months or three or
more UTIs within 1 year. These infections are either due to
reinfection or to relapse.
• Reinfections are caused by a different organism and
account for the majority of recurrent UTIs. It usually
happens more than 2 weeks after the last UTI and is
treated as a new uncomplicated UTI.
• Relapse represents the development of repeated
infections caused by the same initial organism. It
usually happens within 2 weeks of the original
infection.

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 Defin…
• Asymptomatic bacteriuria when there is
significant bacteriuria (more than 105
bacteria/mL [108/L] of urine) in the absence of
symptoms.
• Symptomatic abacteriuria or acute urethral
syndrome consists of symptoms of frequency
and dysuria in the absence of significant
bacteriuria.
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 EPIDEMIOLOGY

• The prevalence of UTIs varies with age and

gender.
• The overall incidence of UTI increases in the
elderly.

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 ETIOLOGY
• The most common cause of uncomplicated UTIs is
E. coli , accounting for more than 80-90% of
community-acquired infections,
• Followed by: Staphylococcus saprophyticus (coagulase-
negative staphylococcus), accounting for 5% to 15%.
• Additional causative organisms in uncomplicated
infections include Klebsiella pneumoniae, Proteus
spp., Pseudomonas aeruginosa, and Enterococcus
spp.

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 ETIOLOGY. . .
The urinary pathogens in complicated or nosocomial
infections may include:
• E. coli , which accounts for less than 50% of these
infections, Proteus spp., Klebsiella pneumoniae ,
Enterobacter spp., Pseudomonas aeruginosa ,
staphylococci, and enterococci.
• Candida spp. have become common causes of
urinary infection in the critically ill and chronically
catheterized patient.

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 ETIOLOGY. . .
• The majority of UTIs are caused by a single
organism.
• However, in patients with stones, indwelling urinary
catheters, or chronic renal abscesses, multiple
organisms may be isolated.

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 Pathophysiology
• The bacteria causing UTIs usually originate from
bowel flora of the host.
• UTIs can be acquired via three possible routes of
infection:
– the ascending,
– hematogenous(descending), or
– lymphatic pathways.

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 Pathophysiology. . .
In females,
• the short length of the urethra and proximity to the
perirectal area make colonization of the urethra likely.
• Bacteria are then believed to enter the bladder from the
urethra.
• Once in the bladder, the organisms multiply quickly and
can ascend the ureters to the kidney.
• UTIs are more common in females than in males because
the anatomic differences in location and length of the
urethra tend to support the ascending route of infections
as the primary acquisition route.

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 Pathophysiology. . .
Three factors determine the development of UTI:
• the size of the inoculum,
• virulence of the microorganism, and
• competency of the natural host defense mechanisms.

 Patients who are unable to void urine completely are

at greater risk of developing UTIs and frequently
have recurrent infections.

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 Pathophysiology. . .
An important virulence factor of bacteria is
• Their ability to adhere to urinary epithelial cells by
fimbriae.
Other virulence factors include:
• Hemolysin, a cytotoxic protein produced by bacteria
that lyses a wide range of cell and
• Aerobactin, which facilitates the binding and uptake
of iron by Escherichia coli
E. coli and other gram negative bacteria require iron for
aerobic metabolism and multiplication.

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 PREDISPOSING FACTORS TO
INFECTION
• There are several known abnormalities of the urinary
tract system that interfere with its natural defense
mechanisms, the most important of which is
obstruction.
• Obstruction can inhibit the normal flow of urine
disrupting the natural flushing and voiding effect in
removing bacteria from the bladder and resulting in
incomplete emptying.
• Common conditions that result in residual urine
volumes include prostatic hypertrophy, urethral
strictures, calculi, tumors, bladder diverticula, and
drugs such as anticholinergic agents.
• Additional causes of incomplete bladder emptying
include neurologic malfunctions
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CLINICAL PRESENTATION OF URINARY TRACT INFECTIONS
IN ADULTS
Signs and symptoms:
Lower UTI: dysuria, urgency, frequency, nocturia, suprapubic heaviness

• Gross hematuria
Upper UTI: flank pain, fever, nausea, vomiting, malaise, costovertebral
angle tenderness
Laboratory tests:
• Bacteriuria
• Pyuria (white blood cell count >10/mm3)
• Nitrite-positive urine (with nitrite reducers)
• Leukocyte esterase-positive urine
• Antibody-coated
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 Diagnosis
The key to the diagnosis of a UTI
• Significant numbers of microorganisms present in an
appropriate urine specimen to distinguish
contamination from infection.
• The presence of pyuria (more than 10 white blood
ells/mm 3 ) in a symptomatic patient correlates with
significant bacteriuria.
• The nitrite test can be used to detect the presence of
nitrate-reducing bacteria in the urine, such as E. coli .
• The leukocyte esterase test is a rapid dipstick test to
detect pyuria.
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 Diagnosis. . .

The most reliable method of diagnosing UTIs is:

• Quantitative urine culture.
– Patients with infection usually have more than 10e5
bacteria/mL of urine, although as many as one-third of
women with symptomatic infection have less than 10e5
bacteria/mL
• A method to detect upper UTI is the antibody-
coated bacteria test, an immuno-fluorescent method
that detects bacteria coated with immunoglobulin in
freshly voided urine.

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 Urine Collection
Three acceptable collection methods…………
 Midstream clean-catch method….. preferred method for the routine
collection of urine for culture
 Clean urethral opening
 The 1st 20 to 30 mL of urine discarded
 Once collected…………refrigerated
 Catheterization…………...for unconscious patients….but…
 It also introduces organism…… in 1%-2% pts
 Suprapubic bladder aspiration
 inserting a needle directly into the bladder and aspirating the
urine.
 newborns, infants, paraplegics, seriously ill patients
 Bacteria count: quantitative count of greater than or equal to 105
CFU/mL (108 CFU/L) is considered indicative of a UTI.
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 Treatment of UTI
Desired Outcomes
• The goals of UTI treatments are
(a) to eradicate the invading organism(s),
(b) to prevent or to treat systemic consequences
of infection, and
(c) to prevent the recurrence of infection

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 Non-pharmacological
 Fluid hydration……rapid dilution; forced removal
 The antibacterial activity of the urine is……….
 Associated w/low pH and various organic acid
 Large volumes of cranberry juice …..
 prevent adhesion……contains tannins
 Lactobacillus probiotics: maintain urine normal PH(4-4.5)
decreas E. coli colonization
 Estrogen replacement (postmenopausal women)
 Topical estriol, vaginal cream …….reduces pH
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 Commonly Used Antimicrobial Agents in the
Treatment of Urinary Tract Infections
Oral therapy Comments
Sulfonamides These agents generally have been replaced by more agents due to
resistance.
Trimethoprim- This combination is highly effective against most aerobic enteric
sulfamethoxazole bacteria except Pseudomonas aeruginosa. High urinary tract tissue
levels and urine levels are achieved, which may be important in
complicated infection treatment. Also effective as prophylaxis for
recurrent infections.

Penicillins Ampicillin is the standard penicillin that has broad-spectrum activity.

• Ampicillin Increasing Escherichia coli resistance has limited amoxicillin use in
acute cystitis. Drug of choice for enterococci sensitive to penicillin.
• Amoxicillin- Amoxicillin-clavulanate is preferred for resistance problems.
clavulanic acid
Cephalosporins There are no major advantages of these agents over other agents in
the treatment of UTIs, and they are more expensive. They may be
useful in cases of resistance to amoxicillin and trimethoprim–
3/25/2025 sulfamethoxazole. These agents are not active against enterococci.
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Tetracyclines These agents have been effective for initial episodes of urinary
tract infections; however, resistance develops rapidly, and
• Tetracycline their use is limited.
Doxycycline They are useful primarily for chlamydial infections.
Minocycline

Fluoroquinolone The newer quinolones have a greater spectrum of activity,

including P. aeruginosa. These agents are effective for
• Ciprofloxacin pyelonephritis and prostatitis.
Norfloxacin, Avoid in pregnancy and children.
Levofloxacin Moxifloxacin should not be used owing to inadequate urinary
concentrations.
Nitrofurantoin This agent is effective as both a therapeutic and prophylactic
agent in patients with recurrent UTIs. Main advantage is the
lack of resistance even after long courses of therapy. Adverse
effects may limit use (GI intolerance, neuropathies,
pulmonary reactions).
Azithromycin Single-dose therapy for chlamydial infections.
Fosfomycin
3/25/2025 Single-dose therapy for uncomplicated infections. 23
 Parenteral Therapy
Aminoglycosides Gentamicin and tobramycin are equally effective;
Gentamicin Tobramycin has better pseudomonal activity, which may
Tobramycin be important in serious systemic infections.
Amikacin generally is reserved for multiresistant bacteria.
Amikacin

Penicillins These agents generally are equally effective for susceptible

Ampicillin bacteria. The extended-spectrum penicillins are more
Ampicillin-sulbactam active against P. aeruginosa and enterococci and often are
preferred over cephalosporins. They are very useful in
Ticarcillin-clavulanate renally impaired patients or when an aminoglycoside is to be
Piperacillin-tazobactam avoided.
Cephalosporins Second- and third-generation cephalosporins have a broad
first-, second-, and spectrum of activity against gram-negative bacteria but are
third, fourth-generation not active against enterococci and have limited activity
against P. aeruginosa.
Ceftazidime and cefepime are active against P. aeruginosa.
They are useful for nosocomial infections and urosepsis due
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to susceptible pathogens. 24
 Parenteral Therapy (Cont’d)
Carbapenems/ These agents have broad spectrum of activity,
Monobactams including gram-positive, gram-negative, and anaerobic
Imipenem-cilastatin bacteria.
Meropenem Imipenem and meropenem are active against P.
Ertapenem aeruginosa and enterococci, but ertapenem is not.
All may be associated with candidal superinfections.
Aztreonam A monobactam that is only active against gram-negative
bacteria, including some strains of P. aeruginosa.
Generally useful for nosocomial infections when
aminoglycosides are to be avoided and in penicillin-
sensitive patients.
Fluoroquinolones These agents have broad-spectrum activity against both
Ciprofloxacin gram-negative and gram-positive bacteria. They provide
urine and high-tissue concentrations and are actively
Levofloxacin
3/25/2025 secreted in reduced renal function. 25
 Overview of Outpatient Antimicrobial Therapy
for Lower Tract Infections in Adults
Indications Antibiotic Dose Interval Duration
Lower tract Trimethoprim- 2 DS tablets Single dose 1 day
infections sulfamethoxazole
Uncomplicated 1 DS tablet Twice a day 3 days
Ciprofloxacin 250 mg Twice a day 3 days
Norfloxacin 400 mg Twice a day 3 days
Levofloxacin 250 mg Once a day 3 days
Amoxicillin 6 x 500 mg Single dose 1 day
500 mg Twice a day 3 days
Amoxicillin- 500 mg Every 8 hours 3 days
clavulanate
Trimethoprim 100 mg Twice a day 3 days
Nitrofurantoin 100 mg Every 6 hours 3 days
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Fosfomycin 3g Single dose 1 day26
 Indications Antibiotic Dose Interval Duration
Complicated Trimethoprim- 1 DS tablet Twice a day 7–10 days
sulfamethoxazole
Trimethoprim 100 mg Twice a day 7–10 days
Norfloxacin 400 mg Twice a day 7–10 days
Ciprofloxacin 250–500 mg Twice a day 7–10 days
Levofloxacin 250 mg Once a day 7–10 days
Amoxicillin- 625 mg Every 8 hrs 7–10 days
clavulanate
Recurrent Nitrofurantoin 50 mg Once a day 6 months
infections Trimethoprim 100 mg Once a day 6 months
Trimethoprim- 1/2 SS tablet Once a day 6 months
sulfamethoxazole
Acute urethral Trimethoprim- 1 DS tablet Twice a day 3 days
syndrome
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Indications Antibiotic Dose Interval Duration
Failure of Azithromycin 1g Single dose
trimethoprim-
Doxycycline 100 mg Twice a day 7 days
sulfamethoxazole

Acute pyelonephritis Trimethoprim- 1 DS tablet Twice a day 14 days

sulfamethoxazole

Ciprofloxacin 500 mg Twice a day 14 days

Levofloxacin 250 mg Once a day 14 days
Amoxicillin- 625 mg Every 8 hours 14 days
clavulanate

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 Complicated UTI
Acute Pyelonephritis
 Two of the hallmark symptoms…..
 High-grade fever (>38.3°C [100.9°F]) &
 Severe flank pain

 Hospitalization for IV therapy if:

 Severely ill
 Symptoms of nausea, vomiting, and dehydration
 Mild to moderate cases can be treated with oral
antibiotic at an outpatient setting

 Diagnosis:
 Gram stain, urinalysis, culture, and sensitivity tests 29
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 Acute Pyelonephritis. . .

 For mild to moderate symptomatic patients for whom

oral agents are indicated………
 Trimethoprim-sulfamethoxazole (DS BID)
 Or fluoroquinolones for 2 weeks
 Role of ampicillin. . . . Used when. . .
 Gram-positive cocci, Streptococcus faecalis

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 Acute Pyelonephritis. . .
 In the seriously ill patient:
 IV fluoroquinolone, an aminoglycoside with or
without ampicillin
 Extended-spectrum cephalosporins with or
without an aminoglycoside.
 Others:
 aztreonam, the Beta-lactamase inhibitor
combinations

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 PROSTATITIS

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 Definition

• Prostatitis is an inflammation of the prostate gland

and surrounding tissue as a result of infection.
It can be either acute or chronic:
• Acute form is characterized by a severe illness
characterized by a sudden onset of fever and urinary
and constitutional symptoms.
• Chronic bacterial prostatitis (CBP) represents a
recurring infection with the same organism (relapse).

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 PATHOGENESIS AND ETIOLOGY

• The exact mechanism of bacterial infection of the

prostate is not well understood.
• The possible routes of infection include
• Ascending infection of the urethra,
• Reflux of infected urine into prostatic ducts,
• Invasion by rectal bacteria through direct extension
or lymphatic spread, and
• By hematogenous spread.

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 PATHOGENESIS AND ETIOLOGY. . .

• Gram-negative enteric organisms are the most

frequent pathogens in acute bacterial prostatitis.
• E. coli is the predominant organism, occurring in 75% of
cases.

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 CLINICAL PRESENTATION AND
DIAGNOSIS
Signs and symptoms
• Acute bacterial prostatitis: High fever, chills, malaise,
myalgia, localized pain (perineal, rectal,
sacrococcygeal), frequency, urgency, dysuria,
nocturia, and retention
• Chronic bacterial prostatitis: Voiding difficulties
(frequency, urgency, dysuria), low back pain, and
perineal and suprapubic discomfort

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 CLINICAL PRESENTATION AND DIAGNOSIS

Physical examination
• Acute bacterial prostatitis: Swollen, tender, tense, or
indurated gland
• Chronic bacterial prostatitis: indurated (enlarged)
prostate in most patients
Laboratory tests
• Bacteriuria
• Bacteria in expressed prostatic secretions

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 TREATMENT
• The majority of patients can be managed with oral
antimicrobial agents,
– such as trimethoprim–sulfamethoxazole or the
fluoroquinolones (ciprofloxacin, levofloxacin).

When IV treatment is necessary,

• IV to oral sequential therapy with trimethoprim–
sulfamethoxazole or a fluoroquinolone, such as
ciprofloxacin or ofloxacin, would be appropriate.

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 Treatment. . .
• The total course of therapy should be 4 weeks,
which may be prolonged to 6 to 12 weeks with
chronic prostatitis.
• Parenteral therapy should be maintained until the
patient is afebrile and less symptomatic.
• The conversion to an oral antibiotic can be
considered if the patient has been afebrile for 48
hours or after 3 to 5 days of IV therapy.

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Evidence-Based Empirical Treatment of
UTIs and Prostatitis

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 Evidence-Based Empirical Treatment
of UTIs and Prostatitis …

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 The End


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