Urinary Tract Infections (UTIs)and ProstatitisPharm.D Balsam Alhasan

DEFINITION

• Infections of the urinary tract represent a wide variety of

clinical syndromes, including urethritis, cystitis, prostatitis, and

pyelonephritis.

• A urinary tract infection (UTI) is defined as the presence of

microorganisms in the urine that cannot be accounted for by

contamination. The organisms have the potential to invade the

tissues of the urinary tract and adjacent structures.

DEFINITION

• Lower tract infections include cystitis (bladder), urethritis

(urethra), prostatitis (prostate gland), and epididymitis. Upper

tract infections (such as pyelonephritis) involve the kidney and

are referred to as pyelonephritis.

DEFINITION

• Uncomplicated UTIs are not associated with structural or neurologic

abnormalities that may interfere with the normal flow of urine or the

voiding mechanism. Complicated UTIs are 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.

DEFINITION

• Recurrent UTIs are characterized by multiple symptomatic

episodes with asymptomatic periods occurring between these

episodes. 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.

• Relapse represents the development of repeated infections

caused by the same initial organism.

PATHOPHYSIOLOGY

• The bacteria causing UTIs usually originate from bowel flora of

the host.

• UTIs can be acquired via three possible routes: the ascending,

hematogenous, or lymphatic pathways.

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.

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.

PATHOPHYSIOLOGY

• An important virulence factor of bacteria is their ability to adhere

to urinary epithelial cells by fimbriae, resulting in colonization of

the urinary tract, bladder infections, and pyelonephritis. Other

virulence factors include hemolysin, a cytotoxic protein produced

by bacteria that lyses a wide range of cells including erythrocytes,

polymorphonuclear leukocytes, and monocytes; and aerobactin,

which facilitates the binding and uptake of iron by Escherichia coli.

MICROBIOLOGY

• The most common cause of uncomplicated UTIs is E. coli,

accounting for more than 85% of community-acquired

infections, followed by Staphylococcus Saprophyticus

(coagulase-negative staphylococcus), accounting for 5% to

15%.

MICROBIOLOGY

• 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.

MICROBIOLOGY

• Candida spp. have become common causes of urinary

infection in the critically ill and chronically catheterized

patient.

• 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.

CLINICAL PRESENTATION

• The typical symptoms of lower and upper UTIs

are presented in Table 50-1.

CLINICAL PRESENTATION

• Symptoms alone are unreliable for the diagnosis of bacterial

UTIs. The key to the diagnosis of a UTI is the ability to

demonstrate significant numbers of microorganisms present in

an appropriate urine specimen to distinguish contamination

from infection.

CLINICAL PRESENTATION

• Elderly patients frequently do not experience specific urinary

symptoms, but they will present with altered mental status,

change in eating habits, or GI symptoms.

• A standard urinalysis should be obtained in the initial

assessment of a patient.

DIAGNOSIS:

• Microscopic examination of the urine should be performed by

preparation of a Gram stain of unspun or centrifuged urine.

The presence of at least one organism per oil-immersion field

in a properly collected uncentrifuged specimen correlates with

more than 100,000 bacteria/mL of urine.

• Criteria for defining significant bacteriuria are listed in Table

50-2.

DIAGNOSIS:

DIAGNOSIS:

• The presence of pyuria (more than 10 white blood cells/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.

DIAGNOSIS:

• The most reliable method of diagnosing UTIs is by quantitative

urine culture. Patients with infection usually have more than 105

bacteria/mL of urine, although as many as one-third of women

with symptomatic infection have less than 105 bacteria/mL.

• A method to detect upper UTI is the antibody-coated bacteria

test, an immunofluorescent method that detects bacteria

coated with immunoglobulin in freshly voided urine.

TREATMENT

DESIRED OUTCOME

• The goals of treatment for UTIs are to prevent or treat

systemic consequences of infection, eradicate the

invading organism, and prevent recurrence of infection.

GENERAL PRINCIPLES

• The management of a patient with a UTI includes initial

evaluation, selection of an antibacterial agent and duration of

therapy, and follow-up evaluation.

• The initial selection of an antimicrobial agent for the treatment

of UTI is primarily based on the severity of the presenting signs

and symptoms, the site of infection, and whether the infection

is determined to be complicated or uncomplicated.

PHARMACOLOGIC TREATMENT

• The ability to eradicate bacteria from the urinary tract is directly

related to the sensitivity of the organism and the achievable

concentration of the antimicrobial agent in the urine.

• The therapeutic management of UTIs is best accomplished by

first categorizing the type of infection: acute uncomplicated

cystitis, symptomatic abacteriuria, asymptomatic bacteriuria,

complicated UTIs, recurrent infections, or prostatitis.

• Table 50-3 lists the most common agents used in the

treatment of UTIs, along with comments concerning

their general use.

PHARMACOLOGIC TREATMENT

THERAPEUTIC OPTIONS

• Table 50-4 presents an overview of various

therapeutic options for outpatient therapy for

UTI.

TREATMENT REGIMENS

• Table 50-5 describes empiric treatment regimens

for selected clinical situations.

Acute Uncomplicated Cystitis

• These infections are predominantly caused by E. coli, and

antimicrobial therapy should be directed against this organism

initially. Other causes include S. saprophyticus and

occasionally K. pneumoniae and Proteus mirabilis.

Acute Uncomplicated Cystitis

• Because the causative organisms and their susceptibilities are

generally known, a cost-effective approach to management is

recommended that includes a urinalysis and initiation of

empiric therapy without a urine culture (Fig. 50-1).

Acute Uncomplicated Cystitis

• Short-course therapy (3-day therapy) with trimethoprim–

sulfamethoxazole or a fluoroquinolone (e.g., ciprofloxacin,

levofloxacin, or norfloxacin) is superior to single-dose therapy

for uncomplicated infection and should be the treatment of

choice. Amoxicillin or sulfonamides are not recommended

because of the high incidence of resistant E. coli. Follow-up

urine cultures are not necessary in patients who respond.

Symptomatic Abacteriuria

• Single-dose or short-course therapy with trimethoprim–sulfamethoxazole

has been used effectively, and prolonged courses of therapy are not

necessary for the majority of patients.

• If single-dose or short-course therapy is ineffective, a culture should be

obtained.

• If the patient reports recent sexual activity, therapy for Chlamydia

trachomatis should be considered (azithromycin 1 g as a single dose or

doxycycline 100 mg twice daily for 7 days).

Asymptomatic Bacteriuria

• The management of asymptomatic bacteriuria depends on the

age of the patient and, if female, whether she is pregnant. In

children, treatment should consist of conventional courses of

therapy, as described for symptomatic infections.

Asymptomatic Bacteriuria

• In the nonpregnant female, therapy is controversial; however,

it appears that treatment has little effect on the natural course

of infections.

• Most clinicians feel that asymptomatic bacteriuria in the

elderly is a benign disease and may not warrant treatment. The

presence of bacteriuria can be confirmed by culture if

treatment is considered.

Complicated Urinary Tract Infections

Acute Pyelonephritis

• The presentation of high-grade fever (greater than 38.3°C

[100.9°F]) and severe flank pain should be treated as acute

pyelonephritis, and aggressive management is warranted. Severely

ill patients with pyelonephritis should be hospitalized and IV drugs

administered initially. Milder cases may be managed with oral

antibiotics in an outpatient setting.

Acute Pyelonephritis

• At the time of presentation, a Gram stain of the urine should

be performed, along with urinalysis, culture, and sensitivities.

• In the mild to moderately symptomatic patient for whom oral

therapy is considered, an effective agent should be

administered for at least a 2-week period, although use of

highly active agents for 7 to 10 days may be sufficient.

Acute Pyelonephritis

• Oral antibiotics that have shown efficacy in this setting include

trimethoprim–sulfamethoxazole or fluoroquinolones. If a

Gram stain reveals gram-positive cocci, Streptococcus faecalis

should be considered and treatment directed against this

pathogen (ampicillin).

Acute Pyelonephritis

• In the seriously ill patient, the traditional initial therapy has included an

IV fluoroquinolone, an aminoglycoside with or without ampicillin, or an

extended-spectrum cephalosporin with or without an aminoglycoside.

• If the patient has been hospitalized in the last 6 months, has a urinary

catheter, or is in a nursing home, the possibility of P. aeruginosa and

enterococci infection, as well as multiply-resistant organisms, should be

considered.

Acute Pyelonephritis

• In this setting, ceftazidime, ticarcillin-clavulanic acid, piperacillin,

aztreonam, meropenem, or imipenem, in combination with an

aminoglycoside, is recommended. If the patient responds to initial

combination therapy, the aminoglycoside may be discontinued after 3

days.

• Follow-up urine cultures should be obtained 2 weeks after the

completion of therapy to ensure a satisfactory response and to detect

possible relapse.

Urinary Tract Infections in Males

• The conventional view is that therapy in males

requires prolonged treatment (Fig. 50-2).

Therapeutic Options:

• A urine culture should be obtained before treatment, because

the cause of infection in men is not as predictable as in women.

• If gram-negative bacteria are presumed, trimethoprim–

sulfamethoxazole or a fluoroquinolone is a preferred agent.

Initial therapy is for 10 to 14 days. For recurrent infections in

males, cure rates are much higher with a 6-week regimen of

trimethoprim–sulfamethoxazole.

Recurrent Infections

• Recurrent episodes of UTI (reinfections and relapses) account

for a significant portion of all UTIs.

• These patients are most commonly women and can be divided

into two groups: those with fewer than two or three episodes

per year and those who develop more frequent infections.

Recurrent Infections

• In patients with infrequent infections (i.e., fewer than three

infections per year), each episode should be treated as a

separately occurring infection. Short-course therapy should be

used in symptomatic female patients with lower tract

infection.

Recurrent Infections

• In patients who have frequent symptomatic infections, long-

term prophylactic antimicrobial therapy may be instituted (see

Table 50-4). Therapy is generally given for 6 months, with

urine cultures followed periodically.

Recurrent Infections

• In women who experience symptomatic reinfections in

association with sexual activity, voiding after intercourse may

help prevent infection. Also, self-administered, single-dose

prophylactic therapy with trimethoprim– sulfamethoxazole

taken after intercourse has been found to significantly reduce

the incidence of recurrent infection in these patients.

Recurrent Infections

• Women who relapse after short-course therapy should receive

a 2-week course of therapy. In patients who relapse after 2

weeks, therapy should be continued for another 2 to 4 weeks.

If relapse occurs after 6 weeks of treatment, urologic

examination should be performed, and therapy for 6 months

or even longer may be considered.

SPECIAL CONDITIONS

Urinary Tract Infection in Pregnancy• In patients with significant bacteriuria, symptomatic or

asymptomatic, treatment is recommended in order to avoid

possible complications during the pregnancy. Therapy should

consist of an agent with a relatively low adverse-effect

potential (a sulfonamide, cephalexin, amoxicillin,

amoxicillin/clavulanate, nitrofurantoin) administered for 7

days.

Urinary Tract Infection in Pregnancy• Tetracyclines should be avoided because of teratogenic

effects, and sulfonamides should not be administered during

the third trimester because of the possible development of

kernicterus and hyperbilirubinemia. Also, the fluoroquinolones

should not be given because of their potential to inhibit

cartilage and bone development in the newborn.

Catheterized Patients

• When bacteriuria occurs in the asymptomatic, short-term

catheterized patient (less than 30 days), the use of systemic

antibiotic therapy should be withheld and the catheter

removed as soon as possible. If the patient becomes

symptomatic, the catheter should again be removed, and

treatment as described for complicated infections should be

started.

Catheterized Patients

• The use of prophylactic systemic antibiotics in patients with

short-term catheterization reduces the incidence of infection

over the first 4 to 7 days.

• In long-term catheterized patients, however, antibiotics only

postpone the development of bacteriuria and lead to

emergence of resistant organisms.

PROSTATITIS

DIFINITION:

• Prostatitis is an inflammation of the prostate gland and

surrounding tissue as a result of infection. It can be either

acute or chronic. The acute form is characterized by a severe

illness characterized by a sudden onset of fever and urinary

and constitutional symptoms.

DIFINITION:

• Chronic bacterial prostatitis (CBP) represents a recurring

infection with the same organism (relapse).

• Pathogenic bacteria and significant inflammatory cells must be

present in prostatic secretions and urine to make the diagnosis

of bacterial prostatitis.

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.

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.

• CBP is most commonly caused by E. coli, with other gram-

negative organisms isolated much less often.

CLINICAL PRESENTATION AND DIAGNOSIS• The clinical presentation of bacterial prostatitis is presented in

Table 50-6.

• Digital palpation of the prostate via the rectum may reveal a swollen,

tender, warm, tense, or indurated prostate. Massage of the prostate will

express a purulent discharge, which will readily grow the pathogenic

organism. However, prostatic massage is contraindicated in acute

bacterial prostatitis because of a risk of inducing bacteremia and

associated pain.

• CBP is characterized by recurrent UTIs with the same pathogen.

• Urinary tract localization studies are critical to the diagnosis of CBP.

CLINICAL PRESENTATION AND DIAGNOSIS

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.

• The total course of therapy should be 4 weeks, which may be prolonged

to 6 to 12 weeks with chronic prostatitis.

TREATMENT

• 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.

TREATMENT

• The choice of antibiotics in CBP should include those agents that are

capable of crossing the prostatic epithelium into the prostatic fluid in

therapeutic concentrations and that also possess the spectrum of

activity to be effective.

• Currently, the fluoroquinolones (given for 4 to 6 weeks) appear to

provide the best therapeutic option in the management of CBP.

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