This document discusses urinary tract infections (UTIs). It covers the types of UTIs including cystitis (bladder infection) and pyelonephritis (kidney infection). It discusses risk factors for UTIs like female anatomy, sexual activity, pregnancy. It also discusses symptoms, diagnosis through urinalysis and culture, typical causative organisms like E. coli, and first-line antibiotic treatments like nitrofurantoin and TMP-SMX. Adverse drug reactions to these antibiotics including nausea, rash, and pulmonary toxicity are also summarized.

1. URINARY TRACT INFECTION
By : Somayyeh nasiripour,Pharm.D
Clinical pharmacist
Assistant professor at Iums

2. • Infections of the bladder
cystitis
• Infections involving the parenchyma of the
kidneyspyelonephritis
• Encompasses a spectrum of clinical entities
ranging in severity from asymptomatic
infection to acute pyelonephritis with
sepsis
UTI

5. Incidence, Prevalence,
and Epidemiology

6. • 30 times higher in women than in men.
• because of anatomic and physiologic differences.
The female urethra is relatively short and allows
bacteria easy access to the bladder.
• Approximately 25% to 40% of all women will
experience at least one UTI during their lifetime.
• Urinary tract infections in males increased
frequency after age 50, when prostatic
obstruction, urethral instrumentation, and
surgery influence the infection rate & in infant

7. UNCOMPLICATED
• either cystitis or pyelonephritis, occurs in
women who have normal structure and
function of the genitourinary tract and who
have no other factors which would put them
at risk for more severe or complex infections
• Uncomplicated infections are nearly always
caused by a single pathogen.

8. complicated infections
• which are associated with conditions that increase the
risk for acquiring infection, the potential for serious
outcomes, or the risk for therapy failure
• Infections in men, children, and pregnant
• with structural and neurologic abnormalities of the
urinary tract, metabolic or hormonal abnormalities,
impaired host responses, instrumentation and
catheterization of the urinary tract, and those caused
by unusual pathogens (e.g., yeasts, Mycoplasma).
• often polymicrobial in etiology and often associated
with more antibiotic-resistant pathogens. with a longer
duration of therapy

9. COMMUNITY-ACQUIRED INFECTIONS
• Most UTI are caused by gram-negative aerobic
bacilli from the intestinal tract.
• Escherichia coli cause 75% to 95% of
communityacquired, uncomplicated UTIs
• Coagulase-negative staphylococci (i.e.,
Staphylococcus sa’prophyticus) account for
another 5% to 20% of UTIs in younger women.
• Other Enterobacteriaceae (Proteus mirabilis,
Klebsiella) and Enterococcus faecalis also are
common pathogens

10. hospital-acquired infections
• E. coli remains the most common pathogen in hospital-acquired or other
complicated UTI, but it is responsible for only 20% to 30% of these
infections
• Other gram-negative organisms such as Pseudomonas aeruginosa,
Klebsiella, Proteus,Enterobacter, and Acinetobacter cause significantly
more infections (up to 25%) than in community-acquired infections
• Enterococcus is also a common pathogen in hospital-acquired infections
and causes approximately 15% of infections
• Candida is a common pathogen in hospital-acquired infections and may
be involved in 20% to 30% of cases
• UTIs caused by Staphylococcus aureus are usually the result of
hematogenous spread, although this pathogen is also associated with
urinary catheterization

11. • The usual pathway for the spread of bacteria
to the urinary tract is the ascending route.
• Less common: hamatogen

12. defense mechanisms
• Urination washes bacteria out of the bladder and is
effective if urine flows freely and the bladder is
emptied completely
• Substances in the urine, including organic acids (which
contribute to a low pH) and urea (which contributes to
a high osmolality), are antibacterial.
• The bladder mucosa also has antibacterial properties
• immunoglobulin A and glycoproteins (e.g., Tamm-
Horsfall protein), are actively secreted into the urine
and act to prevent adherence of bacteria to
uroendothelial cells.

13. • age,
• female sex,
• sexual activity,
• use of contraception,
• pregnancy, (incidence of bacteriuria in pregnant women is as high as 15%,
approximately twice similarly aged nonpregnant women.
• urinary tract instrumentation or catheterization,
• urinary tract obstruction,
• neurologic dysfunction,
• renal disease,
• previous antimicrobial use(within the previous 15–28 days)
• expression of A, B, and H blood group
• DM (because of glucose in urine, promotes bacterial growth & impairs
leukocyte function &neuropathy )
• Sexual intercourse
• contraceptive practices, particularly the use of spermicides then Oral
contraceptive
factors are associated with the development of
UTI

14. factors increased susceptibility
pregnant to infection
• hormonal changes
• anatomic changes,
• Progressive urinary stasis,
• glucose in the urine
• Estrogen promotes an acidic vaginal pH and
proliferation of normal flora such as Lactobacillus, both
factors which reduce pathogenic colonization of the
vagina.
• Reduction of estrogen production at the time of
menopause allows significant colonization of the
vaginal tract with E.coli and other enteric bacilli, thus
predisposing to subsequent infection

15. Clinical Presentation lower UTI
• Burning on urination (dysuria),
• frequent urination,
• Suprapubic pain,
• blood in the urine (hematuria),
• back pain.

16. upper tract infection
• also may present with:
• loin pain,
• costovertebral angle (CVA) tenderness,
• fever,
• chills,
• nausea, vomiting

17. • Fever, chills, flank pain, nausea and vomiting,
or CVA tenderness highly suggestive acute
pyelonephritis rather than cystitis
• Many elderly patients with UTI are
asymptomatic without pyuria.

18. Diagnosis

19. dipstick test
• nitrite test:a positive reading is useful,but false-
negative results do occur
• leukocyte esterase test:positive test correlateswell with
significant pyuria however, both false- and false+
findings can occur.
Nitrite and leukocyte esterase tests are useful in ruling
out the presence of infection if results of both tests are
negative, whereas positive results of both tests in
combination are highly suggestive of the presence of
infection.

21. gold-standard criterion for the diagnosis of UTI is the
urine culture with a positive urinanalysis
• The external urethral area must first be thoroughly cleaned and
rinsed, then the urine specimen collected from a “midstream”.
• Urine must be plated on culture media within 20 minutes of
collection
• Otherwise, urine should be promptly refrigerated until it can be
cultured
• Greater than 105 colonies of bacteria/mL cultured from a
midstream urine specimen confirms a UTI.
• two consecutive cultures of the same organism are virtually
diagnostic.
• in a symptomatic patient, greater than or equal to 102 bacteria/mL
is much more sensitive and avoids failure lower. Greater than 103
bacteria/mL is thus highly suggestive of UTI in men

22. Overview of Drug Therapy

23. • recommend 5-day course of nitrofurantoin,
(TMP-SMX) for 3 days, or a single dose of
fosfomycin as first-line antibiotics for
treatment of acute uncomplicated cystitis in
women

24. • recommend fluoroquinolones, cephalosporins,
aminoglycosides, TMP-SMX, extended-
spectrumpenicillins (i.e., piperacillin-tazobactam), or a
carbapenem for the treatment of acute pyelonephritis
in women.
• The choice of a specific agent for pyelonephritis
depends primarily on whether or not the patient is
hospitalized or treated as an outpatient, local
susceptibility patterns, and whether therapy is empiric
or based on known susceptibilities.
• The duration of therapy for acute pyelonephritis
rangesfrom5 to 14 days

30. • with uncomplicated, acute, lower UTI, it is
more cost-effective to order a urinalysis and, if
pyuria is present, a urine culture.
• empirically treated with a conventional 3-day
to 7-day course of antibiotic therapy.
• If V.Q. remains symptomatic 48 hours later, a
C&S test can then be ordered

31. TMP-SMX
• 1:5 (e.g., 80 mg trimethoprim and 400 mg sulfamethoxazole).
• effective for therapy of uncomplicated cystitis
• Gr + & gr - with the notable exceptions of P. aeruginosa,
Enterococcus, and anaerobes, are generally susceptible to TMP-
SMX.
• The efficacy of TMP-SMX largely depends on the sensitivity of the
organism to the trimethoprim component.
• trimethoprim and sulfamethoxazole are bacteriostatic, but in
combination they are bactericidal against most urinary pathogens
• initial agent of choice in the treatment of acute, uncomplicated
lower UTI in geographic areas where the incidence of TMP-SMX
resistance among E. coli is less than 20%
• GI intolerance to TMP-SMX is most commonly attributed to the
sulfamethoxazole componen

32. ADR
• Rash is one of the more common side effects
associated with sulfonamide use and occurs in
approximately 1% to 2%
• Various hypersensitivity skin and mucous membrane
reactions have been reported, including morbilliform,
scarlatinal, urticarial, erysipeloid, pemphigoid,
purpuric, and petechial rashes. Erythema nodosum,
exfoliative
• dermatitis, photosensitivity reactions, and the Stevens-
JohnsonnSkin eruptions
• usually appear after 1 week of treatment, although
more rapid onset may occur in a sensitized person

33. Nitrofurantoin
• empirical treatment of acute uncomplicated cystitis.
• completely absorbed after oral administration, but
barely reaches detectable levels in the plasma because
it is eliminated rapidly (half-life, 20 minutes) into the
urine and bile;
• high urine levels are 50 to 250 mg/L
• activity which includes
• E. coli, some strains of Pseudomonas, S. saprophyticus,
streptococci, and enterococci; on the other hand,
Proteus, Enterobacter, and Klebsiella are more likely to
be resistant

34. NITROFURANTOIN-INDUCED ADVERSE EFFECTS
• Nausea is a common complication
• Taking nitrofurantoin with food may reduce nausea. Food, also increase
the bioavailability of nitrofurantoin, but by Slowing of absorption is
particularly beneficial in decreasing the incidence of nausea and vomiting
• nitrofurantoin-induced acute, subacute, or chronic pulmonary reactions
• Discontinuation of nitrofurantoin results in complete symptomatic
recovery after several weeks
• Drug must be avoided in patients with history of nitrofurantoin-induced
pulmonary toxicity
• Peripheral neuropathy may also occur during nitrofurantoin therapy ,
characterized by symmetric dysesthesia and paresthesia in the distal
extremities,
• Neuropathy usually occurs within the first 60 days of chronic
nitrofurantoin treatment and is rarely seen during shorter courses of
therapy
• Renal failure is a risk factor for both neurotoxicity and pulmonarymtoxicity

35. PHENAZOPYRIDINE
• a urinary tract analgesic, occasionally is
prescribedmalone or along with an antibacterial agent
for the symptomatic relief of dysuria.
• Although phenazopyridine at a dose of 200 mg orally
TDS may relieve dysuria, it is ineffective in the actual
eradication of true UTI
• patients with severe dysuria or delayed response to
antibiotic therapy may benefit symptomatically from a
short trial (1–2 days) of phenazopyridine
• an azo dye and may discolor the urine to an orange-
red, orange-brown, or red color that can stain clothes
• about 50% of phenazopyridine is metabolized to
aniline, which can cause methemoglobinemia and
hemolytic anemia.

37. FQ
• as effective as TMP-SMX, nitrofurantoin, or β-lactams in treatment
of uncomplicated UTI,
• they are no longer recommended as first-line empirical therapy
because they are more expensive and provide no additional
treatment benefits & promotion of drug resistance.
• recommended as appropriate alternatives for patients with allergies
or other contraindications to the use of other first-line agents, or
for patients infected with organisms resistant to multiple
antibiotics, such as P. aeruginosa
• Fluoroquinolones appropriate initial therapy in geographic areas
with greater than 20% resistance of E. coli to TMP-SMX effective in
treating patients with structural or functional abnormalities of the
urinary tract and other complicated infections

38. • Fluoroquinolones are contraindicated in
children <18 years
• potential musculoskeletal toxicities in juvenile
populations.

39. Intraction
• Products containing multivalent cations (Mg2+, Ca2+, Zn2+,
Al2+, Fe2+) significantly decreased fluoroquinolone
absorption (20%–70% decrease [AUC]), may result in
therapeutic failures.
• Although this interaction can be avoided by taking the
antacids or other products at least 2 hours before or 4 to 6
hours after the fluoroquinolone dose, this practice is
complicated and inconvenient for the patient.
• theophylline levels should be monitored closely in patients
receiving these quinolones and theophylline together.
• Levofloxacin does not significantly alter methylxanthine
metabolism.
• quinolones (e.g., ciprofloxacin) and warfarin

41. RECURRENT URINARY TRACT
INFECTIONS

42. • Recurrent infections develop in approximately 20% to 30%
of women with acute cystitis
• Repeat C&S data should help determine whether this
infection represents a relapse or a reinfection
• Relapse refers to a recurrence of bacteriuria caused by the
same microorganism that was present before initial
therapy.
• Most relapses occur within 1 to 2weeks after the
completion of therapy and are caused by persistence of the
organism in the urinary tract.
• Relapses often are associated with an inadequately treated
upper UTI, structural abnormalities of the urinary tract, or
chronic bacterial prostatitis

43. Antibiotic Selection for Treatmentnof Relapse
• use of a different agent
• Relaplse acuure less than 2 W: The duration of
therapy 14 days
• relapse after a second 2 W: The duration of
therapy 6 weeks & some experts recommend
longer courses of 6 months to 1 year
• prolonged courses should be reserved for
children, adults who have continuous symptoms,
or adults who are at high risk for experiencing
progressive renal damage

44. Reinfection

45. • recurrence of bacteriuria with a different
organism than was present before therapy
• can occur at any time during or after the
completion of treatment,
• Most appear several weeks to several months
later.
• Approximately 80% of recurrences are caused
by reinfection

46. Chronic Prophylaxis
• chronic antimicrobial prophylaxis should be considered in
any adult patient with two or more episodes of UTI per
year
• prophylaxis should be continued for 6 months in patients
with fewer than three UTIs per year
• at least 12 months in adult patients with three or more
UTIs per year.
• Before chronic antimicrobial suppressive therapy is
initiated, active infections must be completely eradicated
with a full course of appropriate antibiotic therapy
• Patients with urologic abnormalities respond poorly to
prophylactic therapy

48. Urinary Tract Infection and
Sexual Intercourse

49. • Studies strongly support an association between sexual intercourse
and UTI
• risk of UTI was doubled in women having intercourse more than
four times per month compared with those women who did not
• Because UTI are uncommon in men, transmission of an infection
from the man is unlikely.
• Occasionally, bacteria harbored under the foreskin of an
uncircumcised man may be transmitted to his partner through
intercourse
• Postcoital antibiotic prophylaxis is usefulwhen recurrent UTI results
from sexual intercourse
• TMP-SMX or nitrofurantoin is the most commonly recommended
agent
• other agents such as fluoroquinolones and cephalexin may be used

50. Urinary Tract Infection and
Pregnancy

51. • UTI during pregnancy has been suggested to be associated with
increased rates of preterm labor,
• premature delivery, and lower birth-weight infants
• Nitrofurantoin is often recommended during pregnancy because
teratogenic effects have not been observed clinically
• The penicillins, cephalosporins, and aminoglycosides are safe for
use during pregnancy, although caution with the aminoglycosides is
warranted because of possible eighth nerve toxicity in the fetus.
• recommended that pregnant patients receive either a 3-day
regimen or a 7-day to 10-day regimen rather than singledose
therapy
• Irrespective of the duration of therapy, appropriate followup of
patients is crucial

52. SYMPTOMATIC ABACTERIURIA

54. • Most cases of UTI with low bacterial counts are
associated with bacteriuria or C. trachomatis and
also demonstrate pyuria (>8 WBC/LPF)
• doxycycline 100 mg twice a day (BID) in patients
with UTI and low bacterial counts
• Azithromycin as a single dose also has a major
role in treating chlamydial infections
• Prolonged therapy of 2 to 4 weeks in duration
and treatment
• of sexual partnersmay be required to prevent
reinfection through Intercourse