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Infective Syndromes of
Urinary Tract
Learning objectives
3
At the end of the session, the students will be able to understand:
▰ Urinary Tract Infection (UTI) and etiological Agents of UTI
▰ Identification, pathogenesis, clinical manifestations, lab diagnosis and
treatment of bacterial, viral, parasitic and fungal infections causing UTI
Essentials of Medical Microbiology
URINARY TRACT
INFECTION
4
Essentials of Medical Microbiology
URINARY TRACT INFECTION
5
▰ 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
Essentials of Medical Microbiology
Classification
6
▰ 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.
Essentials of Medical Microbiology
Comparison between lower and upper UTIs
7
Essentials of Medical Microbiology
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
Occurrence More common Less common
Epidemiology
8
▰ 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
Essentials of Medical Microbiology
Predisposing Factors
9
▰ 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
Essentials of Medical Microbiology
Predisposing Factors (Cont..)
10
▰ 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
Essentials of Medical Microbiology
Predisposing Factors (Cont..)
11
▰ 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
Essentials of Medical Microbiology
Predisposing Factors (Cont..)
12
▰ 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
Essentials of Medical Microbiology
Etiology
13
▰ 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
Essentials of Medical Microbiology
Common microorganisms causing UTIs
14
Essentials of Medical Microbiology
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 and 21
Common microorganisms causing UTIs
(Cont..)
15
Essentials of Medical Microbiology
Bacterial agents
Gram-positive cocci:
 Enterococcus species
 Staphylococcus saprophyticus
 Staphylococcus aureus
 Staphylococcus epidermidis
 Streptococcus agalactiae
Pathogenesis
16
Essentials of Medical Microbiology
Ascending Route
17
▰ 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
Essentials of Medical Microbiology
Ascending Route (Cont..)
18
▰ 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
Essentials of Medical Microbiology
Descending Route
19
▰ Bacteremia - Hematogenous seedling of pathogen (5% of UTIs)
▰ Organisms commonly associated with descending infection —
Staphylococcus aureus, Salmonella,Mycobacterium tuberculosis, Leptospira
and Candida.
Essentials of Medical Microbiology
Host Defense Mechanisms
20
1. Factors related to urine
2. Activation of host’s mucosal immunity by the uropathogens
Essentials of Medical Microbiology
Host defense mechanisms against UTIs
21
Essentials of Medical Microbiology
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 ofkidney,servesasanti-
adherencefactor by binding to type-I fimbriae of E. coli
Mechanical flushing by urine flow In men: (1) Zinc in prostatic secretion is bactericidal, (2)
long urethra
Clinical Manifestations
22
▰ 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).
Essentials of Medical Microbiology
1. Asymptomatic Bacteriuria
23
▰ 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
Essentials of Medical Microbiology
1. Asymptomatic Bacteriuria (Cont..)
24
▰ 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
Essentials of Medical Microbiology
1. Asymptomatic Bacteriuria (Cont..)
25
▰ 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
Essentials of Medical Microbiology
2. Cystitis (Infection of Bladder)
26
▰ Dysuria, frequency, urgency, and suprapubic tenderness
▰ Urine becomes cloudy, with bad odor, and in some cases hematuria
▰ No associated systemic manifestation
Essentials of Medical Microbiology
3. Acute Urethral Syndrome
27
▰ 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
Essentials of Medical Microbiology
Upper UTI (Pyelonephritis)
28
▰ 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
Essentials of Medical Microbiology
Laboratory Diagnosis - Specimen Collection
29
▰ 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
Essentials of Medical Microbiology
Laboratory Diagnosis - Direct Examination
30
▰ Wet mount examination - pus cells
▰ Leukocyte esterase test
▰ Nitrate reduction test (Griess test)
▰ Gram-staining
Essentials of Medical Microbiology
Laboratory Diagnosis - Culture
31
▰ 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.
Essentials of Medical Microbiology
Culture identification features of common
organisms causing UTI
32
Essentials of Medical Microbiology
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 colonies
BA: swarming type of growth
Gram-negative pleomorphic
bacilli Motile
Catalase positive, oxidase negative
ICUT tests: I–/+ C+/– U+ TSI (alkaline
slant/acidic butt, gas+/–, H2S+, PPA test
positive)
Culture identification features of common
organisms causing UTI (Cont..)
33
Essentials of Medical Microbiology
Culture Culture smear and motility
testing
Biochemical reactions
Enterococcus MAC: magenta pink colonies
BA: translucent non-
hemolytic colonies
Gram-positivecocciinpair,
spectacle shaped
Non-motile
Catalase negative
Bile aesculin test positive
Staphylococcus aureus BA: golden yellow hemolytic
colonies
Gram-positive cocci in
clusters Non-motile
Catalase positive, coagulase positive
Staphylococcus
saprophyticus
BA: white non-hemolytic
colonies
Gram-positive cocci in
clusters Non-motile
Catalase positive, coagulase
negative, Resistant to novobiocin
Laboratory Diagnosis - Antibody Coated Bacteria
Test
34
▰ 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.
Essentials of Medical Microbiology
Treatment of Urinary tract infections
35
▰ 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
Essentials of Medical Microbiology
ETIOLOGICAL AGENTS
OF UTI
36
Essentials of Medical Microbiology
BACTERIAL UTI
37
Essentials of Medical Microbiology
Enterobacteriaceae Causing UTI
38
▰ Several members of the family Enterobacteriaceae can cause UTI; among
which uropathogenic E. coli is most important.
Essentials of Medical Microbiology
1. Uropathogenic E. coli
39
▰ 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
Essentials of Medical Microbiology
1. Uropathogenic E. coli (Cont..)
40
▰ 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.
Essentials of Medical Microbiology
2. Klebsiella pneumoniae UTI
41
▰ Klebsiella pneumoniae - found as commensal in human intestines.
▰ Causes infections - urinary tract infections, meningitis (neonates), septicemia
and pyogenic infections - abscesses and wound infections
Essentials of Medical Microbiology
3. Enterobacter UTI
42
▰ Enterobacter species have become increasingly important nosocomial
pathogens.
▰ Opportunistic pathogens, implicated in infected wounds, UTI and pneumonia
Essentials of Medical Microbiology
4. Citrobacter Infections
43
▰ Mostly environmental contaminants isolated from water, soil, food and feces
of man and animals.
▰ C. freundii and C. koseri - important species causing human infections.
▰ Occasionally cause urinary tract, gallbladder and middle ear infections and
neonatal meningitis
Essentials of Medical Microbiology
5. Proteeae Infections
44
▰ Three genera: Proteus, Morganella and Providencia
▰ PPA positivity is the unique tribe character of Proteeae
▰ Part of commensals in human intestine.
▰ Can cause nosocomial outbreaks of UTI, wound infections, etc.
Essentials of Medical Microbiology
Proteus
45
▰ Proteus species show pleomorphism
▰ Named after Greek God ‘Proteus’ who was able to assume any shape
Essentials of Medical Microbiology
Proteus (Cont..)
46
Naming of H and O antigens:
▰ H antigen
 Ability of flagellated strains of Proteus to grow on agar as a thin film
resembling the film of breath on glass (German, ‘Hauch’ = ‘film of
breath’)
Essentials of Medical Microbiology
Proteus (Cont..)
47
Naming of H and O antigens (Cont..):
▰ O antigen
 Thin film is not observed when strains carrying only the somatic antigen
(nonflagellated strains) grow on media (German, ‘Ohne Hauch’ = ‘without film
of breath’)
Essentials of Medical Microbiology
Pathogenesis
48
▰ Proteus mirabilis & P. Vulgaris commonly encountered species
▰ Saprophytes: widely distributed in nature - decomposing animal matter,
sewage & soil
▰ Commensals: moist areas of the skin, intestine of humans and animals
Essentials of Medical Microbiology
Pathogenesis (Cont..)
49
▰ Infections produced: opportunistic pathogens - urinary, wound and soft tissue
infections and septicemia
 Nosocomial outbreaks
 Struvite stones in bladder: produce urease - breaks down urea to form
ammonia that damages the renal epithelium and makes the urine alkaline
- deposition of phosphate - renal calculi
Essentials of Medical Microbiology
Pathogenesis (Cont..)
50
▰ Proteus as the basis of Weil–Felix Reaction
 Somatic antigen of non-motile Proteus strains OX2, OX19 (from P.vulgaris)
and OXK (from P.mirabilis) cross react with antigen of Rickettsia species
 Proteus antigens - detect heterophile antibodies in sera of patients suffering
from rickettsial infections
Essentials of Medical Microbiology
Laboratory Diagnosis
51
▰ Pleomorphism: Proteus species are gram-negative coccobacilli occasionally
appear bacillary and infilamentous forms
▰ Odor: Putrid fishy or seminal odor in cultures
▰ Swarming: Ability to spread on the surface of solid media
▰ Swarming patterns: Continuous & Discontinuous swarming
Essentials of Medical Microbiology
Laboratory Diagnosis (Cont..)
52
Essentials of Medical Microbiology
Proteus on blood agar, showing swarming growth
Laboratory Diagnosis (Cont..)
53
▰ Catalase positive and oxidase negative
▰ ICUT tests: Indole test (positive for P. vulgaris and negative for P. mirabilis),
citrate test (variably positive), urease test (positive) and TSI (triple sugar iron
agar) test shows alkaline/acid, gas variably present, H2S present.
Essentials of Medical Microbiology
Morganella
54
▰ Only one species - M.morganii
▰ Commonly found in human and animal feces
▰ Infections: Urinary tract infection, pneumonia and wound infection – Mostly
nosocomial
Essentials of Medical Microbiology
Providencia
55
▰ Infections: nosocomial urinary tract, wounds and burns
▰ Five species: P. rettgeri, P. stuartii, P. alcalifaciens, P.rustigianii and P.
heimbachae
Essentials of Medical Microbiology
Treatment of Tribe Proteeae infections
56
▰ Often multidrug resistant & resistant to many disinfectants.
▰ Intrinsic resistance - ampicillin, first and second generation cephalosporins,
nitrofurantoin, tetracyclines, tigecycline and polymyxins (colistin and
polymyxin B).
▰ P. mirabilis is more susceptible to antibiotics than P. vulgaris.
Essentials of Medical Microbiology
Treatment of Tribe Proteeae infections
(Cont..)
57
▰ They produce various β-lactamases - extended spectrum β-lactamases
(ESBL) and AmpC β-lactamases - resistant to most of the β-lactam drugs.
▰ Drug of choice depends on the antimicrobial susceptibility testing.
▰ In general, aminoglycosides, fourth generation cephalosporins (cefepime),
and carbapenems are effective in treatment
Essentials of Medical Microbiology
Non-fermenters Causing UTI
58
▰ Non-fermenters such as Pseudomonas, Acinetobacter are important cause of
healthcare-associated UTI.
▰ They also cause skin and soft tissue infections and pneumonia
Essentials of Medical Microbiology
Enterococcal Infections
59
▰ Enterococci - most common gram-positive cocci to cause UTI.
▰ Initially grouped under group D Streptococcus, but later - reclassified as a
separate genus Enterococcus.
▰ Based on the molecular structure, they are now placed under a new family;
Enterococcaceae.
Essentials of Medical Microbiology
Virulence Factors
60
▰ Aggregation substances or pheromones - Clumping of adjacent cells to
facilitate plasmid exchange (transfers drug resistance)
▰ Extracellular surface protein (ESP) – Adhesion to bladder mucosa
▰ Common group D lipoteichoic acid antigen - Cytokine release such as tumor
necrosis factor α (TNFα)
Essentials of Medical Microbiology
Clinical Manifestations
61
▰ Urinary tract infections
▰ Chronic prostatitis
▰ Bacteremia and left-sided endocarditis
▰ Intra-abdominal, pelvic and soft tissue infections, surgical site infections
▰ Neonatal infections: Sepsis (mostly late-onset), bacteremia, meningitis, and
pneumonia.
Essentials of Medical Microbiology
Laboratory Diagnosis
62
▰ Gram-positive oval cocci arranged in pairs, arranged at an angle to each other
(spectacle-shaped appearance)
▰ Blood agar: Non-hemolytic, translucent colonies (rarely produces α or β-
hemolysis)
▰ MacConkey agar: Minute magenta pink colonies
Essentials of Medical Microbiology
Laboratory Diagnosis (Cont..)
63
Essentials of Medical Microbiology
A B C
A. Gram-positive oval cocci in pairs; B. translucent non-hemolytic colonies on
blood agar; C. Bile esculin hydrolysis test (left—negative, right—positive result,
black color due to esculin hydrolysis).
Laboratory Diagnosis (Cont..)
64
▰ Bile esculin hydrolysis test is positive
▰ Grow in presence of extreme conditions such as—6.5% NaCl, 40% bile, pH
9.6, 45oC and 10oC
▰ E. faecalis and E. faecium - differentiated by arabinose fermentation test
Essentials of Medical Microbiology
Treatment of Enterococcal infections
65
For less serious infections :
▰ UTI: Oral therapy with ampicillin, nitrofurantoin or fosfomycin
▰ Intra-abdominal and soft tissue infections: Ampicillin, vancomycin or linezolid
can be given.
Essentials of Medical Microbiology
Treatment of Enterococcal infections (Cont..)
66
For invasive infections:
▰ Endocarditis, bacteremia, and meningitis: Combination therapy with a cell
wall–active agent (e.g. penicillin or ampicillin) and an aminoglycoside (e.g.
gentamicin) is recommended
▰ Synergistic effect is due to cell wall alterations produced by cell wall–active
agents - facilitate penetration of aminoglycoside into the bacterial cell
Essentials of Medical Microbiology
Treatment of Enterococcal infections (Cont..)
67
For invasive infections (Cont..):
▰ This combination therapy fails if the isolate is found resistant to either
penicillin or high level aminoglycoside in vitro.
▰ In such case, alternative drugs - vancomycin, linezolid or daptomycin can be
considered.
Essentials of Medical Microbiology
Treatment of Enterococcal infections (Cont..)
68
▰ If resistant to vancomycin - linezolid, streptogramins (only active against E.
faecium) and daptomycin
Essentials of Medical Microbiology
Vancomycin Resistant Enterococci (VRE)
69
▰ In India, the VRE rate - 9.7% (overall); 2.5% for E. faecalis and 17.4% for E.
faecium (ICMR, 2019)
▰ Mechanism: Mediated by van gene - alters the target site for vancomycin
present in the cell wall - D-alanyl-D-alanine side chain of peptidoglycan layer -
altered to D-alanyl-D-serine or D-alanyl-D-lactate - less affinity for binding to
vancomycin
Essentials of Medical Microbiology
VRE Carriers
70
▰ Screening for VRE: High risk patients - ICUs and transplantation units
▰ Detection: Rectal swab collected and subjected to (i) Sodium azide agar with
vancomycin or (ii) PCR for detection of van gene.
▰ Management: Infection control measures - hand hygiene and isolation
precautions. Treatment (i.e. decolonization) - recommended for VRE carriers.
Essentials of Medical Microbiology
Other Gram-positive cocci Causing UTI
71
▰ Staphylococcus aureus
▰ Staphylococcus saprophyticus
▰ Streptococcus agalactiae
Essentials of Medical Microbiology
Other Bacterial Infections of Urinary Tract
72
▰ Renal Tuberculosis
▰ Post-streptococcal Glomerulonephritis (PSGN)
▰ Perinephric and Renal Abscesses
Essentials of Medical Microbiology
Differences between acute rheumatic fever and
poststreptococcal glomerulonephritis
73
Essentials of Medical Microbiology
Features Acute rheumatic fever (ARF) Post-streptococcal glomerulonephritis
(PSGN)
Prior history of infection
with
Pharyngitis strains Mainly pyoderma, or rarely pharyngitis
strains
Serotypes responsible Most of the strains of group A Streptococcus Only nephritogenic strains
Immune response Marked Moderate
Complement level Unaltered Low (due to deposition in glomeruli)
Genetic susceptibility Present Absent
Repeated attack Common Uncommon
Differences between acute rheumatic fever and
poststreptococcal glomerulonephritis (Cont..)
74
Essentials of Medical Microbiology
Features Acute rheumatic fever (ARF) Post-streptococcal glomerulonephritis
(PSGN)
Penicillin prophylaxis Indicated Not indicated
Course Progressive Spontaneous resolution
Prognosis Variable Good
Hypersensitivity reaction Type II Type III
VIRAL INFECTIONS OF
URINARY SYSTEM
75
Essentials of Medical Microbiology
BK Virus Infection
76
▰ BK virus causes nephropathy in kidney transplant recipients.
▰ Also cause hemorrhagic cystitis in hematopoietic stem cell transplant
recipients.
▰ Naming: Named after the initials of the patient in whom it was described first.
Polyomavirus, dsDNA
Essentials of Medical Microbiology
BK Virus Infection (Cont..)
77
Diagnosis: The diagnostic modalities include:
▰ Renal biopsy
▰ PCR
▰ Asymptomatic BK viruria (detection of BK virus DNA in urine)
Essentials of Medical Microbiology
BK Virus Infection (Cont..)
78
▰ Treatment: There is no specific treatment available.
▰ Cidofovir - treatment of refractory cases.
Essentials of Medical Microbiology
Adenovirus Cystitis
79
▰ Adenovirus serotypes 11 and 21 - acute hemorrhagic cystitis in children,
especially in boys.
Essentials of Medical Microbiology
PARASITIC INFECTIONS
OF URINARY SYSTEM
80
Essentials of Medical Microbiology
Urinary Schistosomiasis (S. haematobium)
81
▰ Schistosoma haematobium - causative agent of urinary schistosomiasis or
Bilharziasis
▰ Blood trematode (or fluke), resides in venous plexus of urinary bladder and
ureter
▰ Other two blood flukes Schistosoma mansoni and S. japonicum reside in
venous plexus of intestine and mesentery, produce intestinal disease
Essentials of Medical Microbiology
Life Cycle
82
Essentials of Medical Microbiology
Pathogenesis and Clinical Features
83
Acute Schistosomiasis
▰ The invasion of cercariae in the skin causes dermatitis at penetration site
followed by allergic pruritic papular lesion.
Essentials of Medical Microbiology
Pathogenesis and Clinical Features (Cont..)
84
Chronic Schistosomiasis
▰ Urogenital disease - cystitis glandularis
▰ Obstructive uropathies
▰ Bladder carcinoma - Squamous cell carcinoma
Essentials of Medical Microbiology
Laboratory Diagnosis
85
Urine Microscopy
▰ Diagnosis of S. haematobium
infection - detection of non-
operculated terminal spined eggs in
the urine or rarely in feces
Essentials of Medical Microbiology
A B
Laboratory Diagnosis (Cont..)
86
Histopathology:
▰ S. haematobium eggs - bladder mucosal biopsy or wet cervical biopsy
specimens (in females).
▰ Number of eggs present in crushed tissue correlates significantly with the
size of the genital lesions.
Essentials of Medical Microbiology
Laboratory Diagnosis (Cont..)
87
Antibody Detection:
▰ Useful for sero-epidemiology. Detect serum antibodies against S.
haematobium adult worm microsomal antigen (HAMA).
 HAMA-FAST-ELISA (Falcon assay screening test ELISA)
 HAMA-EITB (Enzyme-linked immunotransfer blot)
 IgE and IgG4 are elevated
Essentials of Medical Microbiology
Laboratory Diagnosis (Cont..)
88
Antigen Detection:
▰ Detection of circulating antigen - recent infection
▰ Circulating cathodic antigen (CCA) and circulating anodic antigen (CAA) -
detected in serum and urine by ELISA or dip stick assays
▰ CCA levels are much higher in urine than CAA.
Essentials of Medical Microbiology
Treatment of Urinary schistosomiasis
89
▰ Praziquantel - drug of choice; given 20 mg/kg/dose, two doses in single day.
▰ Metrifonate – alternatively - inhibits acetylcholine receptors on tegument
surface of adult male worm.
▰ Administered in multiple oral doses over weeks - not preferred in control
programs.
Essentials of Medical Microbiology
Prevention
90
▰ Proper disposal of human excreta and urine
▰ Eradication of snails by using molluscicides - metal salts (iron or aluminum
sulfate), metaldehyde, methiocarb and acetylcholine esterase inhibitors
▰ Treatment of infected persons.
Essentials of Medical Microbiology
Dioctophyme renale Infection
91
▰ Dioctophyme renale - “giant kidney worm” - nematode of lower animals
▰ Life cycle: Human infection - ingestion of fish infected with larva of D. renale.
▰ Larva penetrates - intestine - kidney - transform into adult worms. Adult
worms - larger in size - block the kidney and ureter.
▰ Adult worms lay eggs, that are passed in urine
Essentials of Medical Microbiology
Dioctophyme renale Infection (Cont..)
92
▰ Clinical features: Hematuria and renal colic,
extensive destruction of kidney parenchyma.
▰ Laboratory diagnosis: Eggs in urine - oval-
shaped, 60–80 μm size, contain an embryo
surrounded by characteristic thick
sculptured or pitted egg shell
Essentials of Medical Microbiology
A B
Trichomonas vaginalis Urethritis
93
▰ T. vaginalis is a sexually-transmitted parasite that primarily cause urethritis.
▰ The trophozoites may be detected in urine sediment.
Essentials of Medical Microbiology
FUNGAL INFECTIONS OF
URINARY SYSTEM
94
Essentials of Medical Microbiology
Candiduria
95
▰ Isolation of Candida species in urine - common finding - result from
contamination during collection, bladder colonization, or upper UTI (due to
hematogenous or ascending infection from bladder).
Essentials of Medical Microbiology
Candiduria (Cont..)
96
▰ Treatment of candiduria - considered in the following situations:
 Symptomatic cystitis or pyelonephritis, high-risk for disseminated disease
 Neutropenic or immunosuppressed patients
 Patients undergoing urologic manipulation
 If upper-pole or bladder-wall invasion or obstruction is associated
 Critically-ill patients (have higher risk for invasive candidiasis)
 Low birth weight infants
Essentials of Medical Microbiology
Candiduria (Cont..)
97
▰ Fluconazole (for 14 days) - drug of choice, as it reaches high levels in urine.
▰ Fluconazole resistance - oral flucytosine and/or parenteral amphotericin B can
be considered.
Essentials of Medical Microbiology
Questions:
98
▰ Q1. Which culture medium is preferred for processing of urine specimens:
a. TCBS agar
b. CLED agar
c. Chocolate agar
d. XLD agar
Essentials of Medical Microbiology
Questions:
99
▰ Q2. Which of the following is the most common etiological agent of UTI:
a. Escherichia coli
b. Klebsiella
c. Proteus
d. Enterobacter
Essentials of Medical Microbiology

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chapter 76 - Infective Syndromes of Urinary Tract.pptx

  • 2.
  • 3. Learning objectives 3 At the end of the session, the students will be able to understand: ▰ Urinary Tract Infection (UTI) and etiological Agents of UTI ▰ Identification, pathogenesis, clinical manifestations, lab diagnosis and treatment of bacterial, viral, parasitic and fungal infections causing UTI Essentials of Medical Microbiology
  • 5. URINARY TRACT INFECTION 5 ▰ 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 Essentials of Medical Microbiology
  • 6. Classification 6 ▰ 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. Essentials of Medical Microbiology
  • 7. Comparison between lower and upper UTIs 7 Essentials of Medical Microbiology 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 Occurrence More common Less common
  • 8. Epidemiology 8 ▰ 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 Essentials of Medical Microbiology
  • 9. Predisposing Factors 9 ▰ 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 Essentials of Medical Microbiology
  • 10. Predisposing Factors (Cont..) 10 ▰ 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 Essentials of Medical Microbiology
  • 11. Predisposing Factors (Cont..) 11 ▰ 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 Essentials of Medical Microbiology
  • 12. Predisposing Factors (Cont..) 12 ▰ 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 Essentials of Medical Microbiology
  • 13. Etiology 13 ▰ 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 Essentials of Medical Microbiology
  • 14. Common microorganisms causing UTIs 14 Essentials of Medical Microbiology 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 and 21
  • 15. Common microorganisms causing UTIs (Cont..) 15 Essentials of Medical Microbiology Bacterial agents Gram-positive cocci:  Enterococcus species  Staphylococcus saprophyticus  Staphylococcus aureus  Staphylococcus epidermidis  Streptococcus agalactiae
  • 17. Ascending Route 17 ▰ 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 Essentials of Medical Microbiology
  • 18. Ascending Route (Cont..) 18 ▰ 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 Essentials of Medical Microbiology
  • 19. Descending Route 19 ▰ Bacteremia - Hematogenous seedling of pathogen (5% of UTIs) ▰ Organisms commonly associated with descending infection — Staphylococcus aureus, Salmonella,Mycobacterium tuberculosis, Leptospira and Candida. Essentials of Medical Microbiology
  • 20. Host Defense Mechanisms 20 1. Factors related to urine 2. Activation of host’s mucosal immunity by the uropathogens Essentials of Medical Microbiology
  • 21. Host defense mechanisms against UTIs 21 Essentials of Medical Microbiology 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 ofkidney,servesasanti- adherencefactor by binding to type-I fimbriae of E. coli Mechanical flushing by urine flow In men: (1) Zinc in prostatic secretion is bactericidal, (2) long urethra
  • 22. Clinical Manifestations 22 ▰ 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). Essentials of Medical Microbiology
  • 23. 1. Asymptomatic Bacteriuria 23 ▰ 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 Essentials of Medical Microbiology
  • 24. 1. Asymptomatic Bacteriuria (Cont..) 24 ▰ 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 Essentials of Medical Microbiology
  • 25. 1. Asymptomatic Bacteriuria (Cont..) 25 ▰ 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 Essentials of Medical Microbiology
  • 26. 2. Cystitis (Infection of Bladder) 26 ▰ Dysuria, frequency, urgency, and suprapubic tenderness ▰ Urine becomes cloudy, with bad odor, and in some cases hematuria ▰ No associated systemic manifestation Essentials of Medical Microbiology
  • 27. 3. Acute Urethral Syndrome 27 ▰ 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 Essentials of Medical Microbiology
  • 28. Upper UTI (Pyelonephritis) 28 ▰ 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 Essentials of Medical Microbiology
  • 29. Laboratory Diagnosis - Specimen Collection 29 ▰ 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 Essentials of Medical Microbiology
  • 30. Laboratory Diagnosis - Direct Examination 30 ▰ Wet mount examination - pus cells ▰ Leukocyte esterase test ▰ Nitrate reduction test (Griess test) ▰ Gram-staining Essentials of Medical Microbiology
  • 31. Laboratory Diagnosis - Culture 31 ▰ 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. Essentials of Medical Microbiology
  • 32. Culture identification features of common organisms causing UTI 32 Essentials of Medical Microbiology 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 colonies BA: swarming type of growth Gram-negative pleomorphic bacilli Motile Catalase positive, oxidase negative ICUT tests: I–/+ C+/– U+ TSI (alkaline slant/acidic butt, gas+/–, H2S+, PPA test positive)
  • 33. Culture identification features of common organisms causing UTI (Cont..) 33 Essentials of Medical Microbiology Culture Culture smear and motility testing Biochemical reactions Enterococcus MAC: magenta pink colonies BA: translucent non- hemolytic colonies Gram-positivecocciinpair, spectacle shaped Non-motile Catalase negative Bile aesculin test positive Staphylococcus aureus BA: golden yellow hemolytic colonies Gram-positive cocci in clusters Non-motile Catalase positive, coagulase positive Staphylococcus saprophyticus BA: white non-hemolytic colonies Gram-positive cocci in clusters Non-motile Catalase positive, coagulase negative, Resistant to novobiocin
  • 34. Laboratory Diagnosis - Antibody Coated Bacteria Test 34 ▰ 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. Essentials of Medical Microbiology
  • 35. Treatment of Urinary tract infections 35 ▰ 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 Essentials of Medical Microbiology
  • 36. ETIOLOGICAL AGENTS OF UTI 36 Essentials of Medical Microbiology
  • 37. BACTERIAL UTI 37 Essentials of Medical Microbiology
  • 38. Enterobacteriaceae Causing UTI 38 ▰ Several members of the family Enterobacteriaceae can cause UTI; among which uropathogenic E. coli is most important. Essentials of Medical Microbiology
  • 39. 1. Uropathogenic E. coli 39 ▰ 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 Essentials of Medical Microbiology
  • 40. 1. Uropathogenic E. coli (Cont..) 40 ▰ 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. Essentials of Medical Microbiology
  • 41. 2. Klebsiella pneumoniae UTI 41 ▰ Klebsiella pneumoniae - found as commensal in human intestines. ▰ Causes infections - urinary tract infections, meningitis (neonates), septicemia and pyogenic infections - abscesses and wound infections Essentials of Medical Microbiology
  • 42. 3. Enterobacter UTI 42 ▰ Enterobacter species have become increasingly important nosocomial pathogens. ▰ Opportunistic pathogens, implicated in infected wounds, UTI and pneumonia Essentials of Medical Microbiology
  • 43. 4. Citrobacter Infections 43 ▰ Mostly environmental contaminants isolated from water, soil, food and feces of man and animals. ▰ C. freundii and C. koseri - important species causing human infections. ▰ Occasionally cause urinary tract, gallbladder and middle ear infections and neonatal meningitis Essentials of Medical Microbiology
  • 44. 5. Proteeae Infections 44 ▰ Three genera: Proteus, Morganella and Providencia ▰ PPA positivity is the unique tribe character of Proteeae ▰ Part of commensals in human intestine. ▰ Can cause nosocomial outbreaks of UTI, wound infections, etc. Essentials of Medical Microbiology
  • 45. Proteus 45 ▰ Proteus species show pleomorphism ▰ Named after Greek God ‘Proteus’ who was able to assume any shape Essentials of Medical Microbiology
  • 46. Proteus (Cont..) 46 Naming of H and O antigens: ▰ H antigen  Ability of flagellated strains of Proteus to grow on agar as a thin film resembling the film of breath on glass (German, ‘Hauch’ = ‘film of breath’) Essentials of Medical Microbiology
  • 47. Proteus (Cont..) 47 Naming of H and O antigens (Cont..): ▰ O antigen  Thin film is not observed when strains carrying only the somatic antigen (nonflagellated strains) grow on media (German, ‘Ohne Hauch’ = ‘without film of breath’) Essentials of Medical Microbiology
  • 48. Pathogenesis 48 ▰ Proteus mirabilis & P. Vulgaris commonly encountered species ▰ Saprophytes: widely distributed in nature - decomposing animal matter, sewage & soil ▰ Commensals: moist areas of the skin, intestine of humans and animals Essentials of Medical Microbiology
  • 49. Pathogenesis (Cont..) 49 ▰ Infections produced: opportunistic pathogens - urinary, wound and soft tissue infections and septicemia  Nosocomial outbreaks  Struvite stones in bladder: produce urease - breaks down urea to form ammonia that damages the renal epithelium and makes the urine alkaline - deposition of phosphate - renal calculi Essentials of Medical Microbiology
  • 50. Pathogenesis (Cont..) 50 ▰ Proteus as the basis of Weil–Felix Reaction  Somatic antigen of non-motile Proteus strains OX2, OX19 (from P.vulgaris) and OXK (from P.mirabilis) cross react with antigen of Rickettsia species  Proteus antigens - detect heterophile antibodies in sera of patients suffering from rickettsial infections Essentials of Medical Microbiology
  • 51. Laboratory Diagnosis 51 ▰ Pleomorphism: Proteus species are gram-negative coccobacilli occasionally appear bacillary and infilamentous forms ▰ Odor: Putrid fishy or seminal odor in cultures ▰ Swarming: Ability to spread on the surface of solid media ▰ Swarming patterns: Continuous & Discontinuous swarming Essentials of Medical Microbiology
  • 52. Laboratory Diagnosis (Cont..) 52 Essentials of Medical Microbiology Proteus on blood agar, showing swarming growth
  • 53. Laboratory Diagnosis (Cont..) 53 ▰ Catalase positive and oxidase negative ▰ ICUT tests: Indole test (positive for P. vulgaris and negative for P. mirabilis), citrate test (variably positive), urease test (positive) and TSI (triple sugar iron agar) test shows alkaline/acid, gas variably present, H2S present. Essentials of Medical Microbiology
  • 54. Morganella 54 ▰ Only one species - M.morganii ▰ Commonly found in human and animal feces ▰ Infections: Urinary tract infection, pneumonia and wound infection – Mostly nosocomial Essentials of Medical Microbiology
  • 55. Providencia 55 ▰ Infections: nosocomial urinary tract, wounds and burns ▰ Five species: P. rettgeri, P. stuartii, P. alcalifaciens, P.rustigianii and P. heimbachae Essentials of Medical Microbiology
  • 56. Treatment of Tribe Proteeae infections 56 ▰ Often multidrug resistant & resistant to many disinfectants. ▰ Intrinsic resistance - ampicillin, first and second generation cephalosporins, nitrofurantoin, tetracyclines, tigecycline and polymyxins (colistin and polymyxin B). ▰ P. mirabilis is more susceptible to antibiotics than P. vulgaris. Essentials of Medical Microbiology
  • 57. Treatment of Tribe Proteeae infections (Cont..) 57 ▰ They produce various β-lactamases - extended spectrum β-lactamases (ESBL) and AmpC β-lactamases - resistant to most of the β-lactam drugs. ▰ Drug of choice depends on the antimicrobial susceptibility testing. ▰ In general, aminoglycosides, fourth generation cephalosporins (cefepime), and carbapenems are effective in treatment Essentials of Medical Microbiology
  • 58. Non-fermenters Causing UTI 58 ▰ Non-fermenters such as Pseudomonas, Acinetobacter are important cause of healthcare-associated UTI. ▰ They also cause skin and soft tissue infections and pneumonia Essentials of Medical Microbiology
  • 59. Enterococcal Infections 59 ▰ Enterococci - most common gram-positive cocci to cause UTI. ▰ Initially grouped under group D Streptococcus, but later - reclassified as a separate genus Enterococcus. ▰ Based on the molecular structure, they are now placed under a new family; Enterococcaceae. Essentials of Medical Microbiology
  • 60. Virulence Factors 60 ▰ Aggregation substances or pheromones - Clumping of adjacent cells to facilitate plasmid exchange (transfers drug resistance) ▰ Extracellular surface protein (ESP) – Adhesion to bladder mucosa ▰ Common group D lipoteichoic acid antigen - Cytokine release such as tumor necrosis factor α (TNFα) Essentials of Medical Microbiology
  • 61. Clinical Manifestations 61 ▰ Urinary tract infections ▰ Chronic prostatitis ▰ Bacteremia and left-sided endocarditis ▰ Intra-abdominal, pelvic and soft tissue infections, surgical site infections ▰ Neonatal infections: Sepsis (mostly late-onset), bacteremia, meningitis, and pneumonia. Essentials of Medical Microbiology
  • 62. Laboratory Diagnosis 62 ▰ Gram-positive oval cocci arranged in pairs, arranged at an angle to each other (spectacle-shaped appearance) ▰ Blood agar: Non-hemolytic, translucent colonies (rarely produces α or β- hemolysis) ▰ MacConkey agar: Minute magenta pink colonies Essentials of Medical Microbiology
  • 63. Laboratory Diagnosis (Cont..) 63 Essentials of Medical Microbiology A B C A. Gram-positive oval cocci in pairs; B. translucent non-hemolytic colonies on blood agar; C. Bile esculin hydrolysis test (left—negative, right—positive result, black color due to esculin hydrolysis).
  • 64. Laboratory Diagnosis (Cont..) 64 ▰ Bile esculin hydrolysis test is positive ▰ Grow in presence of extreme conditions such as—6.5% NaCl, 40% bile, pH 9.6, 45oC and 10oC ▰ E. faecalis and E. faecium - differentiated by arabinose fermentation test Essentials of Medical Microbiology
  • 65. Treatment of Enterococcal infections 65 For less serious infections : ▰ UTI: Oral therapy with ampicillin, nitrofurantoin or fosfomycin ▰ Intra-abdominal and soft tissue infections: Ampicillin, vancomycin or linezolid can be given. Essentials of Medical Microbiology
  • 66. Treatment of Enterococcal infections (Cont..) 66 For invasive infections: ▰ Endocarditis, bacteremia, and meningitis: Combination therapy with a cell wall–active agent (e.g. penicillin or ampicillin) and an aminoglycoside (e.g. gentamicin) is recommended ▰ Synergistic effect is due to cell wall alterations produced by cell wall–active agents - facilitate penetration of aminoglycoside into the bacterial cell Essentials of Medical Microbiology
  • 67. Treatment of Enterococcal infections (Cont..) 67 For invasive infections (Cont..): ▰ This combination therapy fails if the isolate is found resistant to either penicillin or high level aminoglycoside in vitro. ▰ In such case, alternative drugs - vancomycin, linezolid or daptomycin can be considered. Essentials of Medical Microbiology
  • 68. Treatment of Enterococcal infections (Cont..) 68 ▰ If resistant to vancomycin - linezolid, streptogramins (only active against E. faecium) and daptomycin Essentials of Medical Microbiology
  • 69. Vancomycin Resistant Enterococci (VRE) 69 ▰ In India, the VRE rate - 9.7% (overall); 2.5% for E. faecalis and 17.4% for E. faecium (ICMR, 2019) ▰ Mechanism: Mediated by van gene - alters the target site for vancomycin present in the cell wall - D-alanyl-D-alanine side chain of peptidoglycan layer - altered to D-alanyl-D-serine or D-alanyl-D-lactate - less affinity for binding to vancomycin Essentials of Medical Microbiology
  • 70. VRE Carriers 70 ▰ Screening for VRE: High risk patients - ICUs and transplantation units ▰ Detection: Rectal swab collected and subjected to (i) Sodium azide agar with vancomycin or (ii) PCR for detection of van gene. ▰ Management: Infection control measures - hand hygiene and isolation precautions. Treatment (i.e. decolonization) - recommended for VRE carriers. Essentials of Medical Microbiology
  • 71. Other Gram-positive cocci Causing UTI 71 ▰ Staphylococcus aureus ▰ Staphylococcus saprophyticus ▰ Streptococcus agalactiae Essentials of Medical Microbiology
  • 72. Other Bacterial Infections of Urinary Tract 72 ▰ Renal Tuberculosis ▰ Post-streptococcal Glomerulonephritis (PSGN) ▰ Perinephric and Renal Abscesses Essentials of Medical Microbiology
  • 73. Differences between acute rheumatic fever and poststreptococcal glomerulonephritis 73 Essentials of Medical Microbiology Features Acute rheumatic fever (ARF) Post-streptococcal glomerulonephritis (PSGN) Prior history of infection with Pharyngitis strains Mainly pyoderma, or rarely pharyngitis strains Serotypes responsible Most of the strains of group A Streptococcus Only nephritogenic strains Immune response Marked Moderate Complement level Unaltered Low (due to deposition in glomeruli) Genetic susceptibility Present Absent Repeated attack Common Uncommon
  • 74. Differences between acute rheumatic fever and poststreptococcal glomerulonephritis (Cont..) 74 Essentials of Medical Microbiology Features Acute rheumatic fever (ARF) Post-streptococcal glomerulonephritis (PSGN) Penicillin prophylaxis Indicated Not indicated Course Progressive Spontaneous resolution Prognosis Variable Good Hypersensitivity reaction Type II Type III
  • 75. VIRAL INFECTIONS OF URINARY SYSTEM 75 Essentials of Medical Microbiology
  • 76. BK Virus Infection 76 ▰ BK virus causes nephropathy in kidney transplant recipients. ▰ Also cause hemorrhagic cystitis in hematopoietic stem cell transplant recipients. ▰ Naming: Named after the initials of the patient in whom it was described first. Polyomavirus, dsDNA Essentials of Medical Microbiology
  • 77. BK Virus Infection (Cont..) 77 Diagnosis: The diagnostic modalities include: ▰ Renal biopsy ▰ PCR ▰ Asymptomatic BK viruria (detection of BK virus DNA in urine) Essentials of Medical Microbiology
  • 78. BK Virus Infection (Cont..) 78 ▰ Treatment: There is no specific treatment available. ▰ Cidofovir - treatment of refractory cases. Essentials of Medical Microbiology
  • 79. Adenovirus Cystitis 79 ▰ Adenovirus serotypes 11 and 21 - acute hemorrhagic cystitis in children, especially in boys. Essentials of Medical Microbiology
  • 80. PARASITIC INFECTIONS OF URINARY SYSTEM 80 Essentials of Medical Microbiology
  • 81. Urinary Schistosomiasis (S. haematobium) 81 ▰ Schistosoma haematobium - causative agent of urinary schistosomiasis or Bilharziasis ▰ Blood trematode (or fluke), resides in venous plexus of urinary bladder and ureter ▰ Other two blood flukes Schistosoma mansoni and S. japonicum reside in venous plexus of intestine and mesentery, produce intestinal disease Essentials of Medical Microbiology
  • 82. Life Cycle 82 Essentials of Medical Microbiology
  • 83. Pathogenesis and Clinical Features 83 Acute Schistosomiasis ▰ The invasion of cercariae in the skin causes dermatitis at penetration site followed by allergic pruritic papular lesion. Essentials of Medical Microbiology
  • 84. Pathogenesis and Clinical Features (Cont..) 84 Chronic Schistosomiasis ▰ Urogenital disease - cystitis glandularis ▰ Obstructive uropathies ▰ Bladder carcinoma - Squamous cell carcinoma Essentials of Medical Microbiology
  • 85. Laboratory Diagnosis 85 Urine Microscopy ▰ Diagnosis of S. haematobium infection - detection of non- operculated terminal spined eggs in the urine or rarely in feces Essentials of Medical Microbiology A B
  • 86. Laboratory Diagnosis (Cont..) 86 Histopathology: ▰ S. haematobium eggs - bladder mucosal biopsy or wet cervical biopsy specimens (in females). ▰ Number of eggs present in crushed tissue correlates significantly with the size of the genital lesions. Essentials of Medical Microbiology
  • 87. Laboratory Diagnosis (Cont..) 87 Antibody Detection: ▰ Useful for sero-epidemiology. Detect serum antibodies against S. haematobium adult worm microsomal antigen (HAMA).  HAMA-FAST-ELISA (Falcon assay screening test ELISA)  HAMA-EITB (Enzyme-linked immunotransfer blot)  IgE and IgG4 are elevated Essentials of Medical Microbiology
  • 88. Laboratory Diagnosis (Cont..) 88 Antigen Detection: ▰ Detection of circulating antigen - recent infection ▰ Circulating cathodic antigen (CCA) and circulating anodic antigen (CAA) - detected in serum and urine by ELISA or dip stick assays ▰ CCA levels are much higher in urine than CAA. Essentials of Medical Microbiology
  • 89. Treatment of Urinary schistosomiasis 89 ▰ Praziquantel - drug of choice; given 20 mg/kg/dose, two doses in single day. ▰ Metrifonate – alternatively - inhibits acetylcholine receptors on tegument surface of adult male worm. ▰ Administered in multiple oral doses over weeks - not preferred in control programs. Essentials of Medical Microbiology
  • 90. Prevention 90 ▰ Proper disposal of human excreta and urine ▰ Eradication of snails by using molluscicides - metal salts (iron or aluminum sulfate), metaldehyde, methiocarb and acetylcholine esterase inhibitors ▰ Treatment of infected persons. Essentials of Medical Microbiology
  • 91. Dioctophyme renale Infection 91 ▰ Dioctophyme renale - “giant kidney worm” - nematode of lower animals ▰ Life cycle: Human infection - ingestion of fish infected with larva of D. renale. ▰ Larva penetrates - intestine - kidney - transform into adult worms. Adult worms - larger in size - block the kidney and ureter. ▰ Adult worms lay eggs, that are passed in urine Essentials of Medical Microbiology
  • 92. Dioctophyme renale Infection (Cont..) 92 ▰ Clinical features: Hematuria and renal colic, extensive destruction of kidney parenchyma. ▰ Laboratory diagnosis: Eggs in urine - oval- shaped, 60–80 μm size, contain an embryo surrounded by characteristic thick sculptured or pitted egg shell Essentials of Medical Microbiology A B
  • 93. Trichomonas vaginalis Urethritis 93 ▰ T. vaginalis is a sexually-transmitted parasite that primarily cause urethritis. ▰ The trophozoites may be detected in urine sediment. Essentials of Medical Microbiology
  • 94. FUNGAL INFECTIONS OF URINARY SYSTEM 94 Essentials of Medical Microbiology
  • 95. Candiduria 95 ▰ Isolation of Candida species in urine - common finding - result from contamination during collection, bladder colonization, or upper UTI (due to hematogenous or ascending infection from bladder). Essentials of Medical Microbiology
  • 96. Candiduria (Cont..) 96 ▰ Treatment of candiduria - considered in the following situations:  Symptomatic cystitis or pyelonephritis, high-risk for disseminated disease  Neutropenic or immunosuppressed patients  Patients undergoing urologic manipulation  If upper-pole or bladder-wall invasion or obstruction is associated  Critically-ill patients (have higher risk for invasive candidiasis)  Low birth weight infants Essentials of Medical Microbiology
  • 97. Candiduria (Cont..) 97 ▰ Fluconazole (for 14 days) - drug of choice, as it reaches high levels in urine. ▰ Fluconazole resistance - oral flucytosine and/or parenteral amphotericin B can be considered. Essentials of Medical Microbiology
  • 98. Questions: 98 ▰ Q1. Which culture medium is preferred for processing of urine specimens: a. TCBS agar b. CLED agar c. Chocolate agar d. XLD agar Essentials of Medical Microbiology
  • 99. Questions: 99 ▰ Q2. Which of the following is the most common etiological agent of UTI: a. Escherichia coli b. Klebsiella c. Proteus d. Enterobacter Essentials of Medical Microbiology