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 abhere 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 bacterial replication

10. Host protective factors in urinary tract infection
Flushing mechanism of micturition a major protective factor
Low vaginal pH ( ) (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 mL and 0.01 mL plastic or wire loop
Sheep blood agar (SBA) utilized for quantitative urine culture
With 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 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 ( 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 sx or asx

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 % 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 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