DR.IHSAN EDAN ALSAIMARY

1. Urinary Tract Disorders
Dr. Ihsan Edan Alsaimary
Department Of Microbiology
College Of Medicine – University Of Basrah
Iraq

2. Susceptibility factors and
defense mechanisms
1.Bacterial virulence factors:
 The"nonspecific"infections of the
genitourinary tract are a gruop of diseases
with similar manifestations that are caused
mainly by aerobic gram-negative rods
(eg.E.coli) and gram-positive cocci
(eg.staphylococci).E coli accounts for about
90%of urinary tract infections.

3. 2.Extrinsic factors:
 In women, there are two factors. One is introital
factors. Bacteria are known to adhere
selectively to various mucosal surfaces by
means of tiny hairlike projections(pili or
fimbriae).Some E.coli adhere readily to urinary
tract mucosal surface cells. Another is urethral
factors, including periurethral glands, and the
nature and turbulence of urinary flow.
 In men, the main route of infection is ascent from
urethral colonization. But chronic bacterial infectoin
of the prostate appears to be main cause of recurrent
urinary infection

4. 3.Intrinsic susceptibility
factors
Efficient voiding may serve as a defense
mechanism against bladder infection.
 Other factors may concern the ease with which
bacteria adhere to bladder surface
cells:surface mucin, surface
glycosaminoglycan, urinary antibody, and the
antimicrobial properties of urine (eg.high
osmolality and extremes of pH).
 Genetic factor may also prove important(DM,etc).

5. Pathogenesis of Urinary Tract
Infection.
 There are 4 major pathways for the entry of
bacteria into the genitourinary tract:
 1.Ascending infection from the urethra is the
most common cause of genitourinary tract
infections. The tendency for rectal bacteria to
colonize the perineum and vaginal vestibule,
the sexual intercourse and the childrenbearing
enhance the susceptibility of women to urinary
tract infection.

6.  2.Hematogenous spread
 This mode is uncommon.
 3.Lymphatogenous spread:
 The bacterial pathogens travel through the
rectal and colonic lymphatics to the prostate and
bladder and through the periuterine lymphatics
to the female genitourinary tract, but this is rare.
 4.Direct extension from another organ:
 Intraperitoneal abscess, fulminant pelvic
inflammatory disease, paravesical absccsses,
and genitourinary tract fistulas can infect the
urinary tract by means of direct extension.

7. Risk factors in complicated
urinary tract infection
 Indwelling catheters
 Urinary calculi
 Neurogenic bladder
 Prostatic enlargement
 Uterine prolapse
 Urologic instrumentation or surgery
 Renal transplantation
 Diabetes mellitus

8. Bacterial virulence factors in
urinary tract infection
 Escherichia coli strains expressing O-antigens O1,
O2, O4, O6, O7, O8, O75, O150, and O18ab cause
high proportion of infections
 Capsular K1, K5, and K12 antigens of E. coli
associated with clinical severity (antiphagocytic)
 P-fimbriae enhance mannose-resistant attachment
of E. coli to globoseries glycosphingolipid
receptors (gal-gal) of uroepithelial cells (P-
fimbriated E. coli dominant as cause of
pyelonephritis and urosepsis)
 Type 1 fimbriae enhance mannose-susceptible
adherence of E. coli to uroepithelial cells (virtually
all cystitis-producing E. coli strains express type 1
fimbriae)
 Motile bacteria ascend the ureter against urine flow

9. Bacterial virulence factors in
urinary tract infection
 Bacterial urease (Proteus, Corynebacterium
urealyticum) splits urinary urea with generation of
ammonium ion that alkalinizes urine with loss of
acid pH as natural defense barrier against
infection, stone formation with ureteral obstruction
and survivial of bacteria deep within stones
resisting eradication by antibiotic, and alkaline-
encrusted cystitis
 Gram-negative endotoxin decreases ureteral
peristalsis
 Hemolysin produced by many uropathogens
damages renal tubular epithelium and promotes
invasive infection
 Aerobactin (a siderophore) present at increased
frequency in uropathogenic strains of E. coli
promoting intracellular iron accumulation for

10. Host protective factors in
urinary tract infection
 Flushing mechanism of micturition a major
protective factor
 Low vaginal pH (3.5-4.5) (due to lactic acid
produced by action of Lactobacilli on glycogen of
sloughed vaginal epithelial cells) suppresses
colonization by uropathogens
 Normal acid pH of urine (4.6-6) anti-bacterial
 Urinary Tamm-Horsefall protein (secreted by
ascending loop of Henle) binds to mannose-
sensitive fimbriae and blocks E. coli attachment to
uroepithelial cells
 Chemotactic interleukin-8 released upon bacterial
attachment to uroepithelial cells with recruitment of
phagocytic neutrophils and eradication of
bacteriuria

11. Immune responses in urinary
tract infection
 Large numbers of submucosal IgA-
producing plasma cells in bacterial cystitis
 IgM and/or IgG antibodies produced against
O-antigen, K antigen, type 1 and P fimbriae,
and lipid A
 Protective role of antibodies unclear, may
limit damage within the kidney and prevent
persistent colonization and thus recurrence
of infection

12. Common Uropathogens
 Escherichia coli
 Other Enterobacteriaceae (Klebsiella, Enterobacter,
Proteus, Citrobacter)
 Pseudomonas aeruginosa
 Enterococcus
 Staphylococcus saprophyticus
 Staphylococcus aureus1
 Streptococcus agalactiae (group B)2
 Candida
1Associated with staphylococcemia
2Denotes vaginal colonization in pregnant women

13. Uncommon Uropathogens
 Corynebacterium urealyticum1
 Haemophilus influenzae and H. parainfluenzae2
 Blastomyces dermatitidis3
 Neisseria gonorrhaeae4
 Mycobacterium tuberculosis5
1Colistin nalidixic acid (CNA) agar
2Chocolate agar
3Brain heart infusion, inhibitory mold, or Sabourad
dextrose agar
4Enhanced recovery with chocolate agar
5Lowenstein-Jensen medium, Middlebrook broth or
agar

14. Commensal Microflora of
the Urethra
 Coagulase-negative staphylococci
(except S. saprophyticus)
 Viridans and non-hemolytic
streptococci
 Lactobacilli
 Diphtheroids (Corynebacterium
except C. urealyticum)
 Saprophytic Neisseria
 Anaerobic bacteria

15. Common Risk Factors for
Urinary Tract Infection:
Women
 Urinary tract obstruction (including calculi)
 Catheterization (straight, indwelling)
 Pregnancy
 Urologic instrumentation or surgery
 Neurogenic bladder
 Renal transplantation
 Sexual intercourse
 Estrogen deficiency (loss of vaginal
lactobacilli)

16. Common Risk Factors for
Urinary Tract Infection:
Men
 Urinary tract obstruction (including calculi)
 Catheterization (straight, indwelling)
 Prostatic enlargement
 Urologic instrumentation or surgery
 Neurogenic bladder
 Renal transplantation
 Insertive rectal intercourse
 Lack of circumcision (children and young
adults)

17. Signs and Symptoms of Lower
Urinary Tract Infection
 Inflammatory irritation of urethral and
bladder mucosa
 Frequent and painful urination of
small volumes of turbid urine
 Occasional suprapubic pain or
sensation of heaviness
 Fever generally absent

18. Signs and Symptoms of
Upper Urinary Tract Infection
 Fever and chills (systemic reaction)
 Flank pain
 Lower urinary tract signs and
symptoms (frequency, urgency, and
dysuria)

19. Urinary Tract Specimens
 First-voided morning urine optimal (generally
bacteria have been proliferating in bladder urine for
several hours)
 Midstream urine specimens (initially voided urine
contains urethral commensals)
 Indwelling catheters (freshly placed, urine
aspirated by needle inserted into catheter) (Foley
catheter tips not acceptable)
 Straight catheter specimens
 Suprapubic aspirates (infants or children, recovery
of anaerobes)1
 Cystoscopic collection of urine
1Contamination-free specimen

20. Collection of Urine
Specimens
 Urine collected in sterile specimen
container must be processed within 2
hours, or refrigerated and processed
within 24 hours
 Urine collected in sterile specimen
container with borate preservative
should be processed within 24 hours
(no refrigeration required)

21. Inoculation of Urine
 Inoculation of urine for quantitative culture (colony
forming units→cfu’s) performed with a calibrated
0.001 mL and 0.01 mL plastic or wire loop
 Sheep blood agar (SBA) utilized for quantitative
urine culture
 With 0.001 ml loop, 1 colony on SBA equivalent to
1,000 cfu’s per mL of urine
 With 0.01 ml loop, 1 colony on SBA equivalent to
100 cfu’s per mL of urine
 MacConkey agar utilized as selective differential
agar for gram-negative bacteria, colistin nalidixic
acid agar as selective agar for gram-positive
bacteria, and chocolate agar for fastidious gram-
negative bacteria (Haemophilus)

22. Interpretation of Urine
Cultures: General Guidelines
 A single species of Enterobacteriaceae recovered
at >105 cfu’s/mL urine: with patients symptomatic
for urinary tract infection, 95% probability of true
bacteriuria
 A single species of Enterobacteriaceae recovered
at 104-105 cfu’s/mL urine: with patients
symptomatic for urinary tract infection, 33%
probability of true bacteriuira
 Gram-positive, fungal, and fastidious uropathogens
often present in lower numbers (104-105 cfu’s/mL
urine)
 Urethral commensals recovered at <104 cfu’s/mL
urine

23. Urinary Tract Infection
Lower
urethritis
cystitis
prostatitis
Upper
pyelonephritis
intrarenal and perinephric abscess

24. Also categorized into
 Non-catheter associated (commum.
acquired)
 Catheter associated (hosp. acquired)
 Any category may be sexual or asexual

25. Urinary Tract Infection
 Pathogenic microorganisms in urine, urethra,
bladder, kidney, prostate
 Usually growth > 105 organisms per milliliter
 From midstream “ clean catch” urine sample
 If sx or from catheter specimen can be
significant with 102 or 104 organisms per mL

26. Etiology
 Most common is Gram neg. bacteria
 E. coli = 80% of uncomp. acute UTI
 Proteus – assoc. with stones
 Klebsiella – assoc. with stones
 Enterobacter
 Serratia
 Pseudomonas

27. Etiology
 Gram pos. cocci
 Staphylococcus saprophyticus 10-15 %
acute sx UTI in young females
 Enterococci – occas. in acute uncomp.
cystitis
 Staphylococcus aureus – assoc. with renal
stones, instrumentation, increased susp. of
bacteremic kidney infection

28. Etiology
 Urethritis from chlamydia, gonorrhea,
HSV – acute sx female with sterile pyuria
 Ureaplasma urealyticum
 Candida or other fungal species –
commonly assoc. with cath. or DM
 Mycobacteria

29. Pathogenesis
 Usually ascent of bacteria from urethra to
bladder to kidney
 Vaginal introitus, distal urethra colonized
by normal flora
 Gram negative bacilli from bowel may
colonize at introitus, periurethra

30. ?
Predisposing conditions to
UTI
 Female
 Short urethra, proximity to anus, termination
beneath labia
 Sexual activity
 Pregnancy
 2-3% have UTI in preg, 20-30% with asx bacteriuria
 may lead to pyelo
 Increased risk of pyelo = decreased ureteral tone,
decreased ureteral peristalsis, temp. incomp of
vesicoureteral valves

31. ?
Predisposing conditions
 Neurogenic bladder dysfunction or bladder
diverticulum (incomplete emptying)
 Age - Postmenopausal women with uterine or
bladder prolapse (incomplete emptying), lack
of estrogen, decreased normal flora,
concomitant medical conditions such as DM
 Vesicoureteral reflux
 Bacterial virulence
 Genetics
 Change in urine nutrients, DM, gout

32. Urethritis ?
 Acute dysuria, frequency
 Often need to suspect sexually
transmitted pathogens esp. if sx more
than 2 days, no hematuria, no suprapubic
pain, new sexual partner, cervicitis

33. Cystitis
 Sx: frequency, dysuria, urgency,
suprapubic pain
 Cloudy, malodorous urine (nonspec.)
 Leukocyte esterase positive = pyuria
 Nitrite positive (but not always)
 WBC (2-5 with sx) and bacteria on urine
microscopy

34. Pyelonephritis
 Fever
 chills, N/V, diarrhea, tachycardia, gen.
muscle tenderness
 CVAT or tenderness with deep
abdominal tenderness
 Possibly signs of Gram neg. sepsis

35. ?
Pyelonephritis
 Leukocytosis
 Pyuria with leukocyte casts, and bacteria
and hematuria on microscopy
 Complications: sepsis, papillary necrosis,
ureteral obstruction, abscess, decreased
renal function if scarring from chronic
infection, in pregnancy – may increase
incidence of preterm labor

36. Catheter-Associated ?
Urinary Tract Infections
 10-15% of hosp. patients with indwelling
catheter develop bacteriuria
 Risk of infection is 3-5% per day of
catheterization
 UTI after one-time bladder cath approx. 2%
 Gram neg. bacteremia most significant
complication of cath-induced UTI
 Greater antimicrobial resistance

37. Diagnosis of UTI
 History
 Physical exam
 Lab
 Urinalysis with micro = WBC, bacteria
 Urine culture
 Sensitivities of culture for tailored antibiotic therapy
 May dx acute uncomp. cystitis based on hx, PE, and
UA alone, no need for culture to treat

38. Diagnosis
 Urinalysis
 Leuk. Esterase pos. = pyuria
 Nitrite pos. from urea prod. bact. (but not
always)
 Micro – WBC (even 2-5 in patient with sx)
 Micro – Bacteria

39. Diagnosis
 Urine culture
 Once 105 colonies per mL considered
standard for dx but misses up to 50%
 Now, 102 to 104 accepted as significant if
patient symptomatic
 Needed in upper UTI, comp. UTI, and in
failed treatment or reinfection
 Sensitivities for better tailoring of tx

40. Treatment ?
 Uncomp. cystitis with less than 48 hours
of sx, non-pregnant, usu. 3 days tx
sufficient
 Bactrim DS, Septra DS
 Cipro or other FQ (avoid in preg.)
 Nitrofurantoin (7 days)
 Augmentin
 Bladder analgesis, Pyridium

41. Treatment
 Uncomp. cystitis in pregnant patient
 Requires longer tx of 7-14 days
 Cephalosporin, nitrofurantoin, augmentin,
sulfonamides (do not use near term, inc.
kernicterus)

42. Asymptomatic ?
Bacteriuria
 105 org/mL growth
 Empiric treatment of all asymptomatic
bacteriuria (ASB) in pregnancy. Screening
at first visit.
 ASB if untreated = inc. PTD and LBW, 20-
30% develop pyelo.
 Do TOC in 2 weeks and each trimester.
 Screen Sickle cell trait each trimester.
Twofold inc. risk of ASB

43. Asymptomatic Bacteriuria
 Treatment failures: repeat tx based on
sensitivities for 1 week, then prophylactic
therapy for remainder of pregnancy
 Prophylaxis: Nitrofurantoin, Ampicillin,
TMP/SMX

44. Treatment
Recurrent uncomp. UTI
 3 or more episodes in one year, 2 in 6 months
 Bactrim DS ( or septra DS) QD for 3-6 months
once infection eradicated, self-admin. Single
dose at symptom onset or one DS tab post-
coitus
 Measures for prevention: voiding after
intercourse, good hydration, frequent and
complete voiding

45. Treatment of Pyelonephritis -
- Outpatient
 Uncomp. Nonpreg pyelo
 Primary – any FQ x 7 days, cipro
 Alt. -- Augmentin, TMP/SMX, or oral CSP
for 14 days

46. Treatment of
Pyelonephritis – Inpatient ?
 Treat IV until patient is afebrile 24-48 hours.
Then, complete 2 week course with PO meds
 Use FQ or amp/gent or ceftriaxone or
piperacillin
 If no improvement on IV, consider imaging
studies to look for abscess or obstruction
 All pregnant patients with pyelo get inpatient tx,
appropriate IV antibiotics immediately

47. Treatment of Complicated
UTI
 Catheter related
 Amp/gent or Zosyn or ticaricillin/clav or
imipenem or meropenem x 2-3 weeks
 Switch to PO FQ or TMP/SMX when
possible
 Rule out obstruction
 Watch out for enterococci and
pseudomonas

48. Nephrolithiasis ?
 Supersat. of urine by stone forming
constituents
 Crystals of foreign bodies act as nidi
 Freq. stone types: Calcium (most
common), struvite, oxalate, uric acid,
staghorn
 Risk factors: metabolic disturbances,
previous UTI, gout, genetic

49. Nephrolithiasis
 Incidence = 2-3%
 Morbidity
 Obstruction  pain
 Chronic obstruction, may be asx  loss of
renal function
 Hematuria (rarely dangerous by itself)
 Dangerous combo = obstruction + infection

50. Nephrolithiasis ?
 More prev. in Asians and whites
 Males > females, 3:1
 Struvite stones – from infection,
increased in females
 Ages 20-49
 Recurrent
 Uncommon after 50 y.o.

51. Nephrolithiasis
Patient History ?
 Often dramatic pain, poss. infection,
hematuria
 Even nonobst. May cause sx
 Bladder irritating sx
 Renal colic because of stone in ureter
 Severe, undulating cramps because of
ureter peristalsis, sever pain, N/V
 Pain may migrate

52. Nephrolithiasis
Patient History
 Duration, char, location of pain
 Hx of stones?
 UTI?
 Loss of renal function?
 FHx of stones
 Solitary/ transplanted kidney

53. Nephrolithiasis
Physical Exam
 Dramatic CVAT, may migrate as stone
moves
 Usu. Lacking peritoneal signs
 Calculus often in area of maximum
discomfort

54. Nephrolithiasis
Workup
 Urinalysis
 Evid. Of hematuria and infection
 24-hour urinalysis helpful in identifying
cause
 CMP, uric acid, CBC
 Calcium, oxalate, uric acid in the 24 hour
urine

55. Nephrolithiasis
Workup
 Plain abd film (KUB)
 Renal USG
 IVP
 Helical CT without contrast (stone
protocol)

56. Nephrolithiasis
Treatment
 If no obstruction or infection, stones < 5-6mm
may likely pass
 Restore fluid volume if dehyd.
 Analgesics – narcotics, nsaids
 Antiemetics
 Occasionally nifedipine (CCB) to relax ureteral
smooth muscle and prednisone used
 Urology consult

57. Nephrolithiasis
Treatment ?
 Surgical intervention (call urology)
 Extracorporeal shock-wave lithotrypsy (not in
pregnancy)
 Ureteral stent
 Percutaneous nephrostomy
 Ureteroscopy
 Indications = pain, infection, obstruction
 Contraindications = active untx infection,
uncorrected bleeding diathesis,
pregnancy (relative)

58. Nephrolithiasis
Prophylaxis ?
 Increase fluid intake (2 liters per day of
UOP)
 24 hour urine, eval calcium, oxalate, uric
acid to determine dietary prevention
 metabolic tests to determine cause (Ex:
hyperparathyroidism)
 Decrease salt intake