Basics of Urinary Tract Infection

1. URINARY TRACT INFECTION

2. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
URINARY TRACT INFECTION
2
▰ Disease caused by microbial invasion of the urinary tract that extends from
the renal cortex of the kidney to the urethral meatus.
▰ Leading cause of morbidity and healthcare expenditures in persons of all
ages

3. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Classification
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▰ UTIs - classified into two types—lower UTI and upper UTI - depending
upon the anatomical sites involved
▰ Depending upon the source of infection: healthcare-associated (e.g.
CAUTI) and community-acquired.

4. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Comparison between lower and upper
UTIs
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Lower UTI Upper UTI
Sites involved Urethra, and
bladder
Kidney and ureter
Symptoms Local
manifestations:
dysuria, urgency,
frequency
Local and systemic
manifestations
(fever, vomiting,
abdominal pain)
Route of
spread
Ascending route Both ascending
(common) and
descending route

5. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Epidemiology
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▰ Second most common infection after respiratory tract infections in the
community
▰ most common HAIs (hospital acquired infections) - 35% of total HAIs
▰ Prevalence: About 10% of humans develop UTI in some part of their life

6. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Predisposing Factors
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▰ Gender: Higher prevalence in females
 Short urethra
 Close proximity of urethral meatus to anus
▰ Age: Incidence increases with age
▰ During first year of life prevalence same in both females and males -
incidence in males until old age

7. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Predisposing Factors (Cont..)
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▰ Females: incidence keeps increasing after first year of life
 5–17 years - incidence of bacteriuria - 1–3%
 Adult life - incidence is around 10–20%
 Reinfection is common in females (20–40 years of age)
▰ Pregnancy: Anatomical and hormonal changes - asymptomatic bacteriuria
common

8. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Predisposing Factors (Cont..)
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▰ Structural and functional abnormality of urinary tract - obstruction to
the urine flow - urinary stasis - infection
 Structural obstruction: urethral stricture, renal and ureteric stones,
prostate enlargement, tumors, renal transplants, etc.
 Functional obstruction: neurogenic bladder due to spinal cord injury
or multiple sclerosis

9. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Predisposing Factors (Cont..)
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▰ Bacterial virulence: pili - adhesion to uroepithelium
▰ Vesico-ureteric reflux: allows urine from bladder up into ureters and
sometimes into the renal pelvis
▰ Genetic factors: Genetically determined receptors help in bacterial
attachment

10. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Etiology
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▰ Escherichia coli (uropathogenic E. coli)
 Commonest cause (70%) of all forms of UTIs - community acquired &
nosocomial UTI and upper & lower UTI
▰ Other endogenous flora - gram-negative bacilli (E.coli, Klebsiella, Proteus,
etc.) & Enterococci
▰ Hospital acquired UTIs - Enterobacteriaceae and Staphylococci,
Pseudomonas

11. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Common microorganisms causing
UTIs
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Bacterial agents Other agents
Gram-negative bacilli:
Enterobacteriaceae
 Escherichia coli: Most
common (70%)
 Klebsiella pneumoniae
 Enterobacter species
 Proteus species
 Serratia species
Non-fermenters
 Pseudomonas
aeruginosa
 Acinetobacter species
Fungus:
Candida albicans
Parasites:
••Schistosoma
haematobium
••Trichomonas vaginalis
••Dioctophyme renale
Gram-positive bacilli:
Mycobacterium
tuberculosis
Viruses:
 BK virus
 Adenovirus types– 11

12. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Common microorganisms causing UTIs
(Cont..)
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Bacterial agents
Gram-positive cocci:
 Enterococcus
species
 Staphylococcus
saprophyticus
 Staphylococcus
aureus
 Staphylococcus
epidermidis
 Streptococcus
agalactiae

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Pathogenesis
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Ascending Route
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▰ Most common route
▰ Enteric endogenous bacteria (E. coli, other gram-negative bacilli,
enterococci)
▰ Facilitated by sexual intercourse, or instrumentation
▰ Colonization: Adhesion to urethral epithelium with help of P fimbriae,
mannose resistant fimbria in E. Coli, etc

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Ascending Route (Cont..)
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▰ Ascension: pathogen ascends through urethra upwards towards bladder
to cause cystitis
 Bacterial toxins may facilitate ascension by inhibiting peristalsis
▰ Further ascension through ureter - vesico-ureteric reflux - pyelonephritis
▰ Acute tubular injury: inflammatory cascade - tubular obstruction and
damage occurs - interstitial nephritis

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Descending Route
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▰ Bacteremia - Hematogenous seedling of pathogen (5% of UTIs)
▰ Organisms commonly associated with descending infection —
Staphylococcus aureus, Salmonella,Mycobacterium tuberculosis,
Leptospira and Candida.

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Host Defense Mechanisms
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1. Factors related to urine
2. Activation of host’s mucosal immunity by the uropathogens

18. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Host defense mechanisms against
UTIs
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Urinary factors Mucosal immunity
Acidic urine: inhibits
pathogens
Uroepithelial secretion of cytokines
(induced by bacterial LPS)
High urine osmolality:
inhibits pathogens
Mucosal IgA–prevent attachment of
pathogen to uroepithelium
Urinary inhibition of
bacterial adherence
Tamm-Horsfall protein (uromodulin)—a
glycoprotein secreted by epithelial cells of
kidney, serves as anti-adherence factor by
binding to type-I fimbriae of E. coli
Mechanical flushing by In men: (1) Zinc in prostatic secretion is

19. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Clinical Manifestations
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▰ Lower UTI: Asymptomatic bacteriuria, cystitis, urethritis, acute urethral
syndrome
▰ Upper UTI: Pyelonephritis, ureteritis, perinephric abscess, renal abscess,
renal tuberculosis
▰ Immunological sequela: Post-streptococcal glomerulonephritis (PSGN).

20. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
1. Asymptomatic Bacteriuria
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▰ Isolation of specified quantitative count of bacteria in an appropriately
collected urine specimen, obtained from a person without symptoms of
UTI
▰ Common in females and incidence increases with age

21. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
1. Asymptomatic Bacteriuria
(Cont..)
21
▰ Clinically significant in - pregnant women, people undergoing prostatic
surgery or any urologic procedure where bleeding is anticipated
▰ Routine screening & treatment for asymptomatic UTI is highly
recommended

22. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
1. Asymptomatic Bacteriuria
(Cont..)
22
▰ Clinically not significant - in non-pregnant, pre-menopausal women, old
age, catheterized patient, or patients with spinal injury
▰ Neither screening nor treatment of asymptomatic UTI is needed

23. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
2. Cystitis (Infection of Bladder)
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▰ Dysuria, frequency, urgency, and suprapubic tenderness
▰ Urine becomes cloudy, with bad odor, and in some cases hematuria
▰ No associated systemic manifestation

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3. Acute Urethral Syndrome
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▰ Seen in young sexually active females
▰ Classical symptoms of lower UTI as described for cystitis
▰ Bacterial count is often low (102 to 105 CFU/mL)
▰ Pyuria is present
▰ Agents: Mostly due to usual agents of UTI, few cases - caused by
gonococcus, Chlamydia, herpes simplex virus, etc

25. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Upper UTI (Pyelonephritis)
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▰ Inflammation of kidney parenchyma, calyces and the renal pelvis
▰ Associated with systemic manifestations - fever, flank pain, vomiting
▰ Lower tract symptoms such as frequency, urgency and dysuria

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Laboratory Diagnosis - Specimen
Collection
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▰ Specimen:
1. Clean catch midstream urine
2. Suprapubic aspiration from bladder
3. Catheterized patients—urine aspirated from the catheter tube after
clamping distally and disinfecting, but never collected from urine bag
▰ Transport : Processed immediately - expected delay - refrigerated or
stored by adding boric acid

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Laboratory Diagnosis - Direct Examination
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▰ Wet mount examination - pus cells
▰ Leukocyte esterase test
▰ Nitrate reduction test (Griess test)
▰ Gram-staining

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Laboratory Diagnosis - Culture
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▰ Culture media: CLED agar (cysteine lactose electrolyte deficient agar) or
combination of MacConkey agar and blood agar.
▰ Kass concept of significant bacteriuria: Based on the fact that, though the
normal urine is sterile - may get contaminated during voiding, with normal
urethral flora.

29. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Culture identification features of common
organisms causing UTI
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Culture Culture smear and
motility testing
Biochemical reactions
Escherichia coli MAC or CLED:
flat lactose
fermenting
colonies
BA: gray moist
colonies
Gram-
negative
bacilli
Motile
Catalase positive,
oxidase negative ICUT
tests: I+ C– U– TSI
(acidic slant/acidic butt,
gas+, H2S–)
Klebsiella
pneumoniae
MAC or CLED:
mucoid lactose
fermenting colonies
BA: gray mucoid
colonies
Gram-
negative
bacilli Non-
motile
Catalase positive, oxidase
negative
ICUT tests: I– C+ U+ TSI
(acidic slant/acidic butt,
gas+, H2S–)
Proteus
species
MAC or CLED:
lactose non-
fermenting
Gram-negative
pleomorphic bacilli
Motile
Catalase positive, oxidase
negative
ICUT tests: I–/+ C+/– U+

30. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Culture identification features of common
organisms causing UTI (Cont..)
30
Culture Culture smear and
motility testing
Biochemical reactions
Enterococcus MAC: magenta
pink colonies BA:
translucent non-
hemolytic colonies
Gram-positive
cocci in pair,
spectacle shaped
Non-motile
Catalase negative
Bile aesculin test positive
Staphylococcu
s aureus
BA: golden yellow
hemolytic colonies
Gram-positive
cocci in clusters
Non-motile
Catalase positive,
coagulase positive
Staphyloco
ccus
BA: white non-
hemolytic colonies
Gram-positive
cocci in clusters
Catalase positive,
coagulase negative,

31. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Laboratory Diagnosis - Antibody Coated Bacteria
Test
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▰ Done to differentiate upper and lower UTI.
▰ In upper UTI - route of spread is hematogenous - bacteria coated with
specific antibodies are found in urine.
▰ In lower UTI, bacteria found in urine are never coated with specific
antibodies.

32. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Treatment of Urinary tract infections
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▰ Based on antimicrobial susceptibility testing report
▰ Preferred Drugs: Quinolones (e.g. norfloxacin), nitrofurantoin,
cephalosporins, and aminoglycosides
▰ Hopsital acquired UTIs with MDR strains: Carbapenem (e.g.
meropenem), beta lactam-beta lactam inhibitor combinations (e.g.
piperacillintazobactam) or fosfomycin

33. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
Enterobacteriaceae Causing UTI
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▰ Several members of the family Enterobacteriaceae can cause UTI; among
which uropathogenic E. coli is most important.

34. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
1. Uropathogenic E. coli
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▰ Uropathogenic E. coli (UPEC) is the single most common pathogen of UTI.
▰ Accounting for 70–75% of all cases.
▰ UPEC serotypes O1, O2, O4, O6, O7 and O75 - responsible for most UTIs

35. Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
1. Uropathogenic E. coli (Cont..)
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▰ The virulence factors of UPEC include:
 Cytotoxins (CNF 1–cytotoxic necrotizing factor 1 and SAT: Secreted
autotransporter toxin)
 Hemolysins
 Fimbriae (e.g. P fimbriae)–specific for strains causing lower UTI
 Capsular K antigen–specific for strains causing upper UTI.

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