internal medicine lecture by doctor dumaaro

1. URINARY TRACT INFECTION
By Dr. AddisuT. (MD, Internist)

2. Definition
• Urinary tract infection (UTI)
• A broad term that encompasses a variety of clinical entities including:
• Asymptomatic bacteriuria (ABU)
• Cystitis: symptomatic infection of the bladder
• Prostatitis: infection of the prostate
• Pyelonephritis: symptomatic infection of the kidneys
• May be asymptomatic (subclinical infection) or symptomatic (disease)
•The distinction between symptomatic UTI and
ABU has major clinical implications.

3. • ABU
• Occurs in the absence of symptoms attributable to the bacteria in the
urinary tract
• Usually does not require treatment

4. • UTI – implies symptomatic disease that warrants antimicrobial
therapy
• Uncomplicated UTI
• Acute cystitis or pyelonephritis in nonpregnant outpatient women
without anatomic abnormalities or instrumentation of the urinary
tract
• Complicated UTI
• A catch-all term that encompasses all other types of UTI
• Recurrent UTI
• Individual episodes can be uncomplicated and treated as such.

5. • Catheter-associated bacteriuria
• Bacteriuria and symptoms in a catheterized patient
• Can be either symptomatic (i.e., catheter-associated UTI, or CAUTI) or
asymptomatic

6. Epidemiology
• Incidence
• 280 cases of acute uncomplicated pyelonephritis per 100,000 women in
the community between ages 18 and 49
• Approximately 7% of patients require hospitalization.
• 20–30% of pregnant women with asymptomatic bacteriuria
subsequently develop pyelonephritis.
• As many as 50–80% of women in the general population acquire at least
1 UTI during their lifetime.
• Usually uncomplicated UTI

7. • Prevalence
• ABU
• ~5% among women between ages 20 and 40
• May be as high as 40–50% among elderly women and men

8. • Sex
• Between 1 year and ~50 years of age, UTI and recurrent UTI are
predominantly diseases of females.
• During the neonatal period, the incidence of UTI is slightly higher
among males than among females.
• Male infants more commonly have congenital urinary tract
anomalies.
• After 50 years of age, the incidence of UTI is almost as high among men
as among women.
• Obstruction from prostatic hypertrophy becomes common.

9. Risk Factors
• Acute cystitis
• Female sex
• Frequent sexual activity
• Recent use of spermicidal compounds with a diaphragm
• History of UTI
• Risk factors in healthy postmenopausal women
• Sexual activity
• Diabetes mellitus
• Incontinence

10. • Recurrent UTI
• In premenopausal women
• Frequent sexual intercourse
• Use of spermicide
• New sexual partner
• First UTI before 15 years of
age
• Maternal history of UTI
• In postmenopausal women
• Anatomic factors affecting
bladder emptying
• Cystoceles
• Urinary incontinence
• Residual urine

11. • UTI in men
• Functional or anatomic abnormality of the urinary tract
• Most commonly a result of urinary obstruction secondary to
prostatic hypertrophy
• Lack of circumcision

12. • General
• Pregnancy
• Anatomic and functional abnormalities
• Any condition that permits urinary stasis or obstruction
• Foreign bodies such as stones or urinary catheters
• Vesicoureteral reflux
• Ureteral obstruction secondary to prostatic hypertrophy
• Neurogenic bladder
• Urinary diversion surgery

13. • Risk Factors
Female
Uncircumcised male
Vesico-urethral reflux
Toilet training
Voiding dysfunction
Obstructive uropathy
Urethral instrumentation
Wiping from back to front
Pregnancy
Bubble bath
Tight underwear
Pinworm infestation
Constipation
Anatomic abnormalities
Neurogenic bladder
Sexual activities

14. Etiology
• Most UTIs result when bacteria gain access to the bladder via the
urethra.
• Upper tract disease occurs when bacteria ascend from the bladder.
• Much less often, bacteria gain access to the urinary tract through the
bloodstream.
• Hematogenous spread accounts for < 2% of documented UTIs.
• Usually results from bacteremia caused by relatively virulent
organisms, such as Salmonella and Staphylococcus aureus
• Isolation of either of these pathogens from a patient without a
catheter or other instrumentation warrants a search for a
bloodstream source.

15. • The hematogenous route is common in candiduria.
• Presence of Candida in the urine of a noninstrumented
immunocompetent patient implies:
• Genital contamination or
• Potentially widespread visceral dissemination

16. • Bacterial virulence factors markedly influence the likelihood that a
given strain, once introduced into the bladder, will cause UTI.
• In acute uncomplicated cystitis the etiologic agents are:
• Escherichia coli accounts for 75–90% of isolates.
• Staphylococcus saprophyticus accounts for 5–15% and is especially
common among younger women.
• Klebsiella, Proteus, Enterococcus, and Citrobacter species as well as
other organisms account for 5–10%.
• In uncomplicated pyelonephritis, the spectrum of causative
agents is similar, with E. coli predominating.

17. • In complicated UTI
• E. coli remains the predominant organism.
• Other aerobic gram-negative organisms also are frequently isolated.
• Klebsiella species
• Proteus species
• Citrobacter species
• Acinetobacter species
• Morganella species
• Pseudomonas aeruginosa
• Gram-positive bacteria (e.g., enterococci and S. aureus) and yeasts are
also important pathogens.

18. • Most Proteus infections arise from the urinary tract.
• P. mirabilis causes only 1–2% of UTIs in healthy women, and Proteus
species collectively cause only 5% of hospital-acquired UTIs.
• However, Proteus is responsible for 10–15% of cases of complicated
UTI, primarily those associated with catheterization.
• indeed, among UTI isolates from chronically catheterized patients, the
prevalence of Proteus is 20–45%.
• This high prevalence is due in part to bacterial production of urease,
which hydrolyzes urea to ammonia and results in alkalization of the
urine.

19. • Alkalization of urine, in turn, leads to precipitation of organic and
inorganic compounds, which contributes to formation of struvite and
carbonate-apatite crystals, formation of biofilms on catheters, and/or
development of frank calculi.
• Proteus becomes associated with the stones and biofilms; thereafter,
it usually can be eradicated only by removal of the stones or the
catheter.
• Over time, staghorn calculi may form within the renal pelvis and lead
to obstruction and renal failure.

20. • Thus, urine samples with unexplained alkalinity should be cultured for
Proteus, and identification of a Proteus species in urine should prompt
consideration of an evaluation for urolithiasis.
• Proteus is readily isolated and identified in the laboratory. Most
strains are lactose negative, produce H2S, and demonstrate
characteristic swarming motility on agar plates.
• P. mirabilis and P. penneri are indole negative, whereas P. vulgaris is
indole positive.
• The inability to produce ornithine decarboxylase differentiates P.
penneri from P. mirabilis.

21. • Pseudomonas aeruginosa, the major pathogen of the group, is a significant
cause of infections in hospitalized patients and in patients with cystic
fibrosis .
• Cytotoxic chemotherapy, mechanical ventilation, and broad-spectrum
antibiotic therapy probably paved the way for colonization and infection of
increasing numbers of hospitalized patients by this organism.
•Thus most conditions predisposing to P. aeruginosa
infections have involved host compromise and/ or
broad-spectrum antibiotic use.

22. Symptoms & Signs
Acute UTI (manifestations of all types)
• Symptoms
• Dysuria
• Frequency
• Urgency
• Gross hematuria (much less common than microscopic hematuria)
• Back pain

23. • In a women presenting with at least 1 symptom of UTI and without
complicating factors:
• The probability of acute cystitis or pyelonephritis is 50%.
• If vaginal discharge and complicating factors are absent and risk
factors for UTI are present:
• The probability of UTI is close to 90%.
• If there is a combination of dysuria and urinary frequency in the
absence of vaginal discharge:
• The probability of UTI increases to 96%.

24. ABU
• Diagnosis can be considered only when the patient does not have
local or systemic symptoms referable to the urinary tract.
• However, systemic manifestations may dominate the clinical picture and
even be the sole presenting features, particularly in elderly patients
with bacteriuria.
• Clinical presentation is usually that of incidentally found bacteriuria.

25. Cystitis
• The typical symptoms are:
• Dysuria, urinary frequency & urgency
• Nocturia, hesitancy, suprapubic discomfort, and gross hematuria are
often noted as well.
• Unilateral back or flank pain is generally an indication that the upper
urinary tract is involved.
• Fever is also an indication of invasive infection of either the kidney or
the prostate.
• Possibility of bacteremia must be considered with fever, hypotension,
and other manifestations of shock syndrome.

26. Prostatitis
• Acute bacterial prostatitis
• Dysuria
• Frequency
• Pain in the prostatic, pelvic, or perineal area
• Fever and chills usually present
• Symptoms of bladder outlet obstruction common
• Chronic bacterial prostatitis
• Presents more insidiously as recurrent episodes of cystitis
• Sometimes with associated pelvic and perineal pain

27. Pyelonephritis
• Fever is the main feature distinguishing cystitis and pyelonephritis.
• A high, spiking “picket-fence” pattern that resolves over 72 hours of
therapy
• Mild pyelonephritis
• Low-grade fever with or without lower-back or costovertebral-angle
pain
• Severe pyelonephritis can manifest as:
• High fever, rigors, nausea, vomiting, flank and/or loin pain
• Bacteremia develops in 20–30% of cases.

28. CA-UTI
• Signs and symptoms may be localized to the urinary tract
• Unexplained systemic manifestations, such as fever
• The typical signs and symptoms of UTI, including pain, urgency,
dysuria, fever, peripheral leukocytosis, and pyuria
• Have less predictive value for the diagnosis of infection in catheterized
patients
• Bacteriuria in a patient who is febrile and catheterized does not
necessarily predict CAUTI.

29. Laboratory Tests
• Urine dipstick
• Can confirm the diagnosis of uncomplicated cystitis in a patient with a
reasonably high pretest probability of this disease
• Either nitrite or leukocyte esterase positivity can be interpreted as a
positive result.
• If negative for both nitrite and leukocyte esterase, consider
• Other explanations for the patient’s symptoms
• Collection of urine for culture

30. • Nitrite test
• Only members of the family Enterobacteriaceae convert nitrate to
nitrite.
• Enough nitrite must accumulate in the urine to reach the threshold
of detection.
• Leukocyte esterase test
• Detects this enzyme in polymorphonuclear leukocytes (intact or
lysed) in urine

31. • Blood in urine may also suggest a diagnosis of UTI
• A negative dipstick test is not sufficiently sensitive to rule out
bacteriuria in pregnant women.
• Important to detect all episodes of bacteriuria
• Performance characteristics of the dipstick test differ.
• Highly specific in men
• Highly sensitive in noncatheterized nursing-home residents

32. • Urine microscopy
• Pyuria
• Seen in nearly all cases of cystitis
• Hematuria
• Seen in ~30% of cases of cystitis
• Bacteria in urine
• In general, bacterial counts are less accurate than are counts of red
and white blood cells.
• Patient’s symptoms and presentation should outweigh an
incongruent result on automated urinalysis.

33. • Urine culture
•Detection of bacteria in a urine culture is the
diagnostic "gold standard" for UTI.
• Culture results do not become available until 24 hours after the
patient’s presentation.
• Identifying specific organism(s) can require an additional 24 hours.
• A colony-count threshold of >102 bacteria/mL is more sensitive (95%)
and specific (85%) than a threshold of 105/mL for diagnosis of acute
cystitis in women.
• In men, the minimal level indicating infection is ~103/mL.

34. • A culture that yields mixed bacterial species is usually contaminated
except in
• Long-term catheterization
• Chronic urinary retention
• Presence of a fistula between the urinary tract and the GI or genital
tract
•The microbiologic criterion for diagnosis of
ABU is ≥105 bacterial cfu/mL.
• The accepted threshold for bacteriuria in CAUTI varies from ≥103 cfu/mL
to ≥105 cfu/mL.

35. Imaging
• No imaging studies are required for uncomplicated UTIs.
• Ultrasound, CT, or intravenous pyelography may be necessary if there
is suspicion of renal obstruction or stones.
• Voiding cystourethrography is used to detect vesicoureteral reflux,
predominantly in children.

36. Differential Diagnosis
• Sexually transmitted disease
• Particularly infection with Chlamydia trachomatis
• Particularly relevant for female patients under the age of 25
• Differential diagnosis to be considered when women present with
dysuria includes:
• Cervicitis (C. trachomatis, Neisseria gonorrhoeae)
• Vaginitis (Candida albicans, Trichomonas vaginalis)
• Herpetic urethritis
• Interstitial cystitis
• Noninfectious vaginal or vulvar irritation

37. • UTI in males
• Acute and chronic bacterial prostatitis must be distinguished from the
very common entity of chronic pelvic pain syndrome.

38. Treatment Approach
1) Uncomplicated cystitis in women
• The species and antimicrobial susceptibilities of the bacteria that
cause acute uncomplicated cystitis are highly predictable.
• Many episodes of uncomplicated cystitis can be managed over the
telephone.
• Most patients with other UTI syndromes require further diagnostic
evaluation.

39. • Effective therapeutic regimens are available for acute uncomplicated
cystitis in women.
• First-line agents include TMP-SMX and nitrofurantoin.
• TMP-SMX
• Can consider use of this drug in regions with resistance rates not
exceeding 20%
• Increased risk of resistant E. coli
• Recent use of TMP-SMX or another antimicrobial agent
• Recent travel to an area with high rates of TMP-SMX resistance

40. • Nitrofurantoin
• Resistance to nitrofurantoin remains low despite >60 years of use.
• Highly active against E. coli and most non–E. coli isolates
• Proteus, Pseudomonas, Serratia, Enterobacter, and yeasts are all
intrinsically resistant to this drug.
• A 5-day course of nitrofurantoin is as effective as a 3-day course of
TMP-SMX for treatment of women with acute cystitis.

41. • Second-line agents include fluoroquinolone and β-lactam
compounds.
• Most fluoroquinolones are highly effective for short-course therapy for
cystitis.
• The exception is moxifloxacin, which does not reach adequate urinary
levels.
• The fluoroquinolones commonly used for UTI include:
• Ofloxacin
• Ciprofloxacin
• Levofloxacin

42. 2) Complicated UTI in men and women
• The range of species and their susceptibility to antimicrobial agents
are varied.
• Therapy must be individualized and guided by urine culture results.
• Use prior urine-culture data, if available, to guide empirical therapy
while current culture results are awaited.

43. 3) UTI in pregnancy
• Ampicillin and cephalosporins
• Drugs of choice for treatment of asymptomatic or symptomatic UTI in
pregnancy
• Have been used extensively in pregnancy
• Nitrofurantoin, ampicillin, and cephalosporins are considered
relatively safe in early pregnancy.

44. 4) ABU
• Treatment decreases frequency of symptomatic infections or
complications in
• Pregnant women
• Persons undergoing urologic surgery
• Neutropenic patients
• Renal transplant recipients
• Treatment of ABU in pregnant women and patients undergoing
urologic procedures should be directed by urine culture results.

45. 5) UTI in men
• The goal in these patients is to eradicate prostatic infection as well as
bladder infection.
• The prostate is involved in the majority of cases of febrile UTI in men.
• With confirmed prostatitis, prolonged treatment is usually necessary to
eradicate the organism.

46. • In men with apparently uncomplicated UTI, a 7- to 14-day course of a
fluoroquinolone or TMP-SMX is recommended.
• If acute bacterial prostatitis is suspected
• Antimicrobial therapy should be initiated after urine and blood are
obtained for cultures.
• Tailor therapy to urine culture results, and continue for 2–4 weeks.
• For documented chronic bacterial prostatitis
• A 4- to 6-week course of antibiotics is often necessary.
• Recurrences are not uncommon.
• A 12-week course of treatment is often warranted.

47. 6) CAUTI
• The etiology of CAUTI is diverse.
• Urine culture results are essential to guide treatment.
• Fairly good evidence supports the practice of catheter change during
treatment for CAUTI.

48. 7) Candiduria
• In asymptomatic patients
• Removal of the urethral catheter results in resolution of candiduria in
more than one-third of cases.
• Treatment is recommended for patients who
• Have symptomatic cystitis or pyelonephritis
• Are at high risk for disseminated disease
• Those with neutropenia
• Those who are undergoing urologic manipulation
• Low-birth-weight infants

49. • Fluconazole (200–400 mg/d for 14 days)
• Reaches high levels in urine
• First-line regimen for Candida UTIs
• The newer azoles and echinocandins are not recommended.
• For Candida isolates with high levels of resistance to fluconazole
• Oral flucytosine and/or parenteral amphotericin B are options.
• Bladder irrigation with amphotericin B generally is not recommended.

50. Monitoring
• Recurrent infections
• Early recurrence (within 2 weeks) is usually regarded as relapse rather
than reinfection.
• May indicate the need to evaluate the patient for a sequestered
focus
• For uncomplicated UTIs that respond to therapy, no follow-up is
necessary.
• Complicated UTIs
• Follow-up cultures 2–4 weeks after cessation of therapy should be
performed to document cure.

51. • Pregnancy
• After treatment, a culture should be performed to ensure cure, and
cultures should be repeated monthly thereafter until delivery.
• Urologic evaluation should be performed in women with:
• Relapsing infection
• History of childhood infections
• Stones or painless hematuria
• Recurrent pyelonephritis

52. • Most men with UTI should be considered to have complicated
infection and should be evaluated urologically.
• Possible exceptions include young men who have cystitis associated
with sexual activity, who are uncircumcised, or who have AIDS.
• Men or women presenting with acute infection and symptoms or
signs suggestive of obstruction or stones should undergo prompt
urologic evaluation.

53. Complications
• Recurrent infections
• ~20–30% of women who have had 1 episode of UTI will have recurrent
episodes.
• Early recurrence (within 2 weeks) is usually regarded as relapse rather
than reinfection.
• May indicate need to evaluate the patient for a sequestered focus
• Pyelonephritis

54. • In pregnancy
• ABU during pregnancy is associated with:
• Preterm birth
• Perinatal mortality for the fetus
• Pyelonephritis for the mother
• Treatment of ABU in pregnant women has decreased the risk of
pyelonephritis by 75%.

55. • Obstructive uropathy
• May be seen in diabetics
• Associated with acute papillary necrosis
• Papillary necrosis
• May occur with acute pyelonephritis and can be further complicated by
obstruction, sickle cell disease, analgesic nephropathy, or combinations
of these conditions
• Rare cases of bilateral papillary necrosis
• A rapid rise in serum creatinine level may be the first indication.

56. • Emphysematous pyelonephritis
• Particularly severe form of kidney infection
• Associated with production of gas in renal and perinephric tissues
• Occurs almost exclusively in diabetic patients
• Xanthogranulomatous pyelonephritis
• Suppurative destruction of renal tissue caused by combination of:
• Chronic urinary obstruction (often by staghorn calculi)
• Chronic infection

57. • Intraparenchymal abscess formation
• Suspect when a patient has continued fever and/or bacteremia despite
antibacterial therapy.
• Urosepsis
• Bacteremia and seeding of other foci
• Death
• Renal insufficiency

58. • Bladder cancer
• Risk in spinal cord–injured patients with use of a long-term indwelling
bladder catheter
• Chronic bacteriuria resulting in chronic inflammation is one possible
explanation.

59. Prognosis
• Recurrent upper UTIs
• Approximately 20–30% of women who have had 1 episode of UTI will
have recurrent episodes.
• Early recurrence (within 2 weeks) is usually regarded as relapse rather
than reinfection.
• Evaluate the patient for a sequestered focus.
• It is not uncommon for multiple recurrences to follow an initial
infection, resulting in clustering of episodes.
• The likelihood of a recurrence decreases with increasing time since
the last infection.

60. • The fever of pyelonephritis typically exhibits a high, spiking picket-
fence pattern and resolves over 72 hours of therapy.
•Cystitis is a risk factor for recurrent cystitis and
pyelonephritis.
• ABU is common among elderly and catheterized patients.
• Does not in itself increase the risk of death

61. • In the absence of anatomic abnormalities, recurrent infection does
not lead to chronic pyelonephritis or to renal failure.
• Infection does not play a primary role in chronic interstitial nephritis.
• In the presence of underlying renal abnormalities (particularly
obstructing stones), infection as a secondary factor can accelerate
renal parenchymal damage.

62. Prevention
1) Prevention of recurrent UTI in women
• Preventive strategy is indicated if recurrent UTIs are interfering with a
patient’s lifestyle.
• The intervention threshold of ≥2 symptomatic episodes per year is
not absolute.
• Decisions about interventions should take the patient’s preferences
into account.

63. • Three prophylactic strategies are available:
• Continuous prophylaxis and postcoital prophylaxis
• Usually entail low doses of TMP-SMX, a fluoroquinolone,
or nitrofurantoin
• These regimens are all highly effective during the period of active
antibiotic intake.
• Typically, a prophylactic regimen is prescribed for 6 months and then
discontinued.
• At discontinuation, the rate of recurrent UTI often returns to
baseline.
• If bothersome infections recur, the prophylactic program can be
reinstituted for a longer period.

64. • Patient-initiated therapy
• Involves supplying the patient with materials for urine culture and
for self-medication with a course of antibiotics at the first symptoms
of infection
• Urine culture can be omitted when:
• An established and reliable patient–provider relationship
exists and
• Symptomatic episodes respond completely to short-course
therapy and are not followed by relapse

65. 2) Prevention of CAUTI
• The best strategy for prevention of CAUTI is to:
• Avoid insertion of unnecessary catheters
• Remove catheters once they are no longer necessary
• Intermittent catheterization may be preferable to long-term
indwelling urethral catheterization in certain populations (e.g., spinal
cord–injured persons) to prevent both infectious and anatomic
complications.