Urinary Tract Infections Flashcards
(67 cards)
1
Q
Normal Commensals of Urinary Tract
A
Urinary tract in a healthy man is sterile, except its distal portion of urethra:
1. Lactobacilli
2. Diphtheroids
3. Coagulase-negative staphylococci
4. Anaerobes
5. Potential pathogens like Enterobacteriaceae &Candidaspecies.
Invasion of some of these pathogens (e.g. E. coli) into bladder can result in UTI.
2
Q
Predisposing factors for UTI
A
- Gender
- Age
- 🤰
- Structural and functional abnormality
- Bacterial virulence
- Vesicoureteral reflux
- Genetic factors
3
Q
UTI and 🤰
A
Anatomical and hormonal changes in 🤰 favor the development of UTIs.
Most females develop asymptomatic bacteriuria during pregnancy.
In some cases, it can lead to serious infections in both mother and fetus
4
Q
Ascending route of UTI
A
It is the most common route; the enteric endogenous bacteria (E. coli, other gram-negative bacilli and enterococci) enter the urinary tract which is facilitated by sexual inter-course, or instrumentation (e.g. catheterization), etc.
5
Q
Steps in ascending route of UTI
A
1. Colonisation: Most imp Virulence factors (e.g. P fimbriae, mannose resistant fimbriae in E. coli) help in adhesion to urethral epithelium 2. Ascension: Cystitis (sometimes peristalsis 🅱️) 3. Further ascension: Vesicoureteral reflux ➡️ pyelonephritis 4. Acute tubular injury
6
Q
Descending route of UTI
A
• Invasion of renal parenchyma through hematogenous seedling of the pathogen, following bacteremia. • These pathogens are invasive • Associated with pyelonephritis eg., S. aureus, Salmonella, M. tuberculosis, and Leptospira
7
Q
Host defense to UTI
1. Urinary factors
A
- Acidic pH
- High urine osmolality
- Urinary inhibition of bacterial adherence
- Mechanical flushing by urine flow
8
Q
Host defense to UTI
2. Mucosal immunity
A
- Uroepithelial secretion of cytokines (induced by 🦠 LPS)
- IgA prevents attachment of pathogen
- Tamm-Horsfall protein (uromodulin):
glycoprotein secreted by epithelial cells of kidney, serves as anti-adherence factor by binding to type-I fimbriae of E. coli - In men, Zn in prostatic secretion is bactericidal & long urethra
9
Q
UTI
classification of clinical manifestations
A
1. Lower UTI: • asymptomatic bacteriuria • cystitis • urethritis • acute urethral syndrome 2. Upper UTI: • pyelonephritis • ureteritis • perinephric abscess • renal abscess • renal TB 3. Immunological sequela: PSGN
10
Q
Significance of asymptomatic bacteriuria
A
- 🤰 (as chances of complication in mother and fetus are more)
- People undergoing prostatic surgery or any urologic procedure where bleeding is anticipated.
For them routine screening and treatment for asymptomatic UTI is recommended
Not in other scenarios
11
Q
Cystitis (Infection of Bladder)
A
Characterized by localized symptoms such as:
1. Dysuria, frequency, urgency, & suprapubic tenderness
2. Urine becomes cloudy, with bad odor, and in some cases grossly bloody
3. There is no associated systemic manifestation.
12
Q
Acute Urethral Syndrome
A
This is another form of lower UTI seen in young sexually active females, characterized by:
1. Presence of classical symptoms of lower UTI as described for cystitis
2. Bacterial count is often low (100 to 10^5 CFU/mL)
3. Pyuria is present
Agents:
Mostly due to the usual agents of UTI, a few cases may be caused by gonococcus, Chlamydia, herpes simplex virus, etc.
13
Q
Upper UTI (Pyelonephritis)
A
Pyelonephritis refers to inflammation of kidney parenchyma, calyces and the renal pelvis
Associated with systemic manifestations such as 🤒 , flank pain, 🤮
Lower tract symptoms such as frequency, urgency and dysuria may also be present
14
Q
Specimen collection for UTI
A
Urine should be collected in a wide mouth screw capped sterile container by various methods:
1. Clean voided midstream urine: M/C
Collected after properly cleaning the urethral meatus or glans
2. Suprapubic aspiration of urine: ideal for patients in coma or infants
3. In catheterized patients:
collected from the catheter tube (after clamping distally and disinfecting) but not from the uro bag
15
Q
Transport of urine sample
A
Urine sample should be processed immediately.
If delay is expected for more than 1–2 hours:
1. stored in refrigerator
2. stored by adding boric acid for maximum 24 hours.
16
Q
Screening tests for UTI
A
- Wet mount examination: for pus cells
• >8 pus cells/mm3 ➡️ significant
2. Leukocyte esterase test:
• rapid and cheaper
• detects leukocyte esterases secreted by pus cells in urine - Nitrate reduction test (Griess test): Nitrate reducing bacteria like E. coli ➡️ ➕ result
17
Q
Gram staining of urine is not a reliable indicator of UTI because
A
- Bacterial count in urine is usually low
- Pus cells rapidly deteriorate in urine and may not be seen well.
Gram staining may be limited to pyelonephritis and invasive UTI cases and a count of ≥1 bacteria/oil immersion field is taken as significant
18
Q
Culture media for UTI
A
Urine sample should be inoculated onto CLED agar (cysteine lactose electrolyte deficient agar) or combination of MacConkey agar and blood agar.
CLED agar is preferred in laboratories with higher sample load
19
Q
Kass concept of significant bacteriuria
A
This is based on the fact that, though the normal urine is sterile it may get contaminated during voiding, with normal urethral flora.
However, the bacterial count in contaminated urine would be lower than that caused by an infection
20
Q
Low counts of bacteria in urine (<10,000) can be significant in the following conditions
A
- Patient on antibiotic or on diuretic treatment
- Infection with some gram-positive organisms such as S. aureus
- Pyelonephritis and acute urethral syndrome
- Sample taken by suprapubic aspiration
- In catheterized patients:
If the patient is symptomatic, then a count of ≥10^3 CFU/mL is considered significant
21
Q
Quantitative culture of urine specimens
A
This is done to count the number of colonies. Each colony on plate corresponds to one bacterium in urine sample.
Quantitation is done by:
1. Semi-quantitative method such as standardized loop technique
2. Quantitative method such as pour plate method
22
Q
Antibody Coated Bacteria Test for UTI
A
This test is done to differentiate upper and lower UTI.
1. In upper UTI (hematogenous), 🦠 coated with specific Ab are found in
urine, detected by immunofluorescence method using fluorescent labeled antihuman globulin
2. In lower UTI, 🦠 found in urine are never coated with specific antibodies.
23
Q
Virulence factors of UPEC
A
- Cytotoxins (CNF 1 cytotoxic necrotizing factor 1 and SAT Secretory autotransporter toxin)
- Hemolysins
- Fimbriae (e.g. P fimbriae)–specific for strains causing lower UTI
- Capsular K antigen–specific for strains causing upper UTI
24
Q
Bacterial infections of UTI
A
- Enterobacteriaceae
- Non-fermenters: Pseudomonas, Acinetobacter
- Enterococcus
- Staph aureus, saprophyticus, Streptococcus agalactiae
- Renal tuberculosis
- PSGN
- Perinephric and renal abscesses
25
Enterobacteriaceae causing UTI
1. E. coli
2. Klebsiella pneumoniae
3. Enterobacter
4. Citrobacter
5. Proteeae tribe:
• Proteus, Morganella and Providencia
• positive for phenylalanine deaminase
(PPA) test
26
Proteus antigens
1. H (flagellar) antigen:
flagellated strains of Proteus grows on agar as a thin film
2. O (sOmatic) antigen:
The thin film is not observed when strains carrying only the somatic antigen (non-flagellated strains) grow on media
27
Infections caused by proteus and Struvite stone formation
```
• Opportunistic pathogens; urinary, wound and soft tissue infections and septicemia
• Involved in nosocomial outbreaks
• Struvite stones in bladder:
Proteus produces urease enzyme, ➡️
breaks down urea to form ammonia ➡️
renal epithelial damage and alkaline urine ➡️
🔼 deposition of phosphate ➡️
formation of renal calculi
```
28
Lab diagnosis of proteus
1. Pleomorphism:
gram-negative coccobacilli occasionally appear bacillary or filamentous
2. Odor: characteristic putrid fishy or seminal odor in cultures
3. Swarming
4. Identification:
by automated identification systems or by conventional biochemical tests:
catalase ➕ and oxidase ➖, ICUT tests
29
Proteus and swarming
Proteus has an ability to swarm (or spread) on solid media such as blood agar.
It is a uniform film of growth, may
1. Extend on the whole plate (continuous swarming)
2. Present as concentric circles of growth surrounding the point of inoculum (discontinuous swarming)
30
Proteus identification using ICUT tests
1. Indole test (positive for P. vulgaris and negative for P. mirabilis)
2. Citrate test (variably ➕)
3. Urease test ➕
4. TSI test shows alkaline/acid, gas variably present, H2S present
31
Providencia
Providencia species are associated with nosocomial infections of the urinary tract, wounds and burns.
It consists of five species; P. rettgeri, P. stuartii, P. alcalifaciens, P. rustigianii and P. heimbachae
32
Treatment of Tribe Proteeae infections
Often multidrug resistant. Also resistant to many disinfectants.
1. Intrinsic resistance to ampicillin, 1st and 2nd gen cephalosporins, nitrofurantoin, tetracyclines, tigecycline and polymyxins (colistin and polymyxin B)
2. They produce various β-lactamases such as extended spectrum β-lactamases (ESBL) and AmpC β-lactamases.
• DoC depends on the AST.
In general, aminoglycosides, 4th gen cephalosporins (cefepime) and carbapenems are effective in treatment
33
Enterococcus
| basics
• M/C gram-positive cocci
to cause UTI.
• Initially grouped under group D Streptococcus, but later been reclassified as a separate genus and family
• Enterococci are part of normal flora of human intestine, biliary tract and to lesser extent vagina and male urethra.
• They are becoming increasingly
important agents of human disease especially in hospitals
34
Virulence factors of enterococci
1. Aggregation substances or pheromones:
clumping of adjacent cells to facilitate plasmid exchange
2. Extracellular surface protein (ESP):
adhesion to bladder mucosa
3. Common group D lipoteichoic acid antigen:
induces cytokine release such as TNF-α
35
Clinical manifestations of enterococcus (faecalis and faecium)
1. Healthcare-associated UTI (cystitis) M/C
2. Chronic prostatitis:
when urinary tract is manipulated surgically or endoscopically (poor antibiotics penetration ➡️ source of recurrent enterococcal bacteremia)
3. Bacteremia and left-sided endocarditis (drug abusers)
4. Intra-abdominal, pelvic and soft tissue infections, including SSTIs
5. Neonatal infections:
sepsis (late-onset), bacteremia, meningitis, and pneumonia
36
Basic difference between 2 main clinically important enterococcus species
1. E. faecalis is the most common species isolated from the clinical specimens, whereas E. faecium is more drug resistant
2. They can be differentiated by arabinose fermentation test
They can grow in presence of extreme conditions
37
Identification of enterococcus
1. Gram-positive oval cocci arranged in pairs at an angle to each other (spectacle-shaped appearance)
2. Blood agar: It produces non-hemolytic, translucent colonies (rarely produces α or β-hemolysis)
3. MacConkey agar:
Minute magenta pink colonies
4. Bile esculin hydrolysis test is positive
38
Treatment of less serious enterococcus infections
1. UTI: Oral therapy with ampicillin, nitrofurantoin or fosfomycin - DoC
2. Intra-abdominal and soft tissue infections:
Ampicillin, vancomycin or linezolid
39
Treatment of invasive infections caused by enterococcus
Combination therapy:
cell wall active agent (penicillin, ampicillin) and aminoglycoside (gentamicin)
• This synergistic effect is due to cell wall alterations produced by cell wall active agents, ➡️ 🔼 penetration of aminoglycoside into the bacteria
• combination therapy fails if it is found resistant to either drugs. Then, alternative drugs such as vancomycin, linezolid or daptomycin can be used
40
Intrinsic resistance of enterococcus
1. Aminoglycosides (monotherapy)
2. Clindamycin,
cephalosporins, cotrimoxazole
3. Vancomycin (for E. gallinarum
and E. casseliflavus)
4. Streptogramins (for E. faecalis)
41
Mechanism of Vancomycin Resistant Enterococci (VRE)
VRE is mediated by van gene, which alters target site present in the cell wall; i.e. D-alanyl-D-alanine side chain of peptidoglycan layer, is altered to D-alanyl-D-serine or D-alanyl-D-lactate. This altered side chains have less affinity for binding to vancomycin
Van gene has several genotypes; out of which van A and van B are common types; expressed by E. faecalis and more commonly by E. faecium
42
VRE carriers
| Screening, detection and management
VRE often colonizes the intestine
1. Screening for VRE:
for high risk patients such as from ICUs and transplantation units
2. Detection: Rectal swab is subjected to:
• Sodium azide agar with vancomycin
• PCR for detection of van gene
3. Management:
infection control measures such as hand hygiene and isolation precautions
Treatment (i.e. decolonization) is not recommended for them
43
Staphylococcus saprophyticus causes UTI in sexually active young women because
Due to expression of a 160 kDa hemagglutinin/adhesin protein that can adhere to uroepithelial cells.
It can be differentiated from other
staphylococci in being resistant to novobiocin disk
44
Renal Tuberculosis
• 10–15% of all
extrapulmonary TB
• involve any portion of
the genitourinary tract.
• Symptoms:
Urinary frequency, dysuria, nocturia, hematuria, and flank or abdominal pain
• Up to 75% of patients have chest
X-ray suggesting previous or concomitant pulmonary TB
• Genitourinary TB responds well to antitubercular therapy
45
Renal Tuberculosis
| diagnosis
1. Urinalysis: mostly pyuria and hematuria
• Sterile pyuria: pus cells in urine but negative routine bacterial urine culture ➡️ TB
• 3 consecutive early morning urine specimens usually yield a definitive diagnosis
2. Following centrifugation, it is sent for culture in MGIT or LJ medium
3. Radiology: Abdominal CT or MRI scan may show deformities, obstructions, calcifications and ureteral strictures.
(Severe ureteral strictures may lead to hydronephrosis and renal damage)
46
Post-streptococcal Glomerulonephritis (PSGN)
| pathology
* Non-suppurative sequela of group A streptococcal infection
* Lodging of antigen antibody complexes on the glomerular basement membrane (humps), followed by complement activation.
* Streptococcal pyogenic exotoxin-B (SPE-B) may be the main nephritogenic antigen involved
* PSGN usually occurs in children (2–14 years) and has a good prognosis
47
Post-streptococcal Glomerulonephritis (PSGN)
| clinical presentation
```
Urine retention and renal insufficiency occurs that leads to:
• edema
• hypertension
• hematuria
• pyuria
• proteinuria
• oliguria
```
48
Post-streptococcal Glomerulonephritis (PSGN)
| Serotypes involved
PSGN typically occurs following either
1. Streptococcal pyoderma (usually by M serotypes–47, 49, 55, 57, 60)
2. Rarely following pharyngitis (caused by M serotypes 1-4, 12, 25)
📝: PSGN due to impetigo develops 2–6 weeks after skin infection; whereas it develops 1–3 weeks after streptococcal pharyngitis
50
Perinephric and Renal Abscesses
• 2° to a UTI (not hematogenous)
• Infection ascends from bladder (cystitis) to kidney (pyelonephritis) to involve renal parenchyma (medulla to cortex) to produce abscess
• Abscess may rupture into the perinephric space
• Pre-existing renal stones obstructing urinary flow is the major risk factor
• Common etiologies: uropathogenic organisms such as E. coli, Proteus species and Klebsiella species
Treatment involves drainage of pus and antibiotic therapy
51
Viral infections of urinary system
1. BK virus:
• nephropathy in kidney transplant recipients
• hemorrhagic cystitis in hematopoietic
stem cell transplant recipients.
• in other individuals, asymptomatic
2. Adenovirus Cystitis
• serotypes 11 and 21 cause acute hemorrhagic cystitis in children, especially in 👦 .
3. Urinary retention may be seen in HSV infection secondary to ANS dysfunction
52
Life cycle of schistosoma haematobium in humans in brief
3 morphological forms: adult worms, eggs and
larvae.
1. Host: Man - definitive host and
freshwater snails - intermediate host
2. Transmission:
penetration of skin by the infective form (cercaria larvae) in contaminated water
3. Development in man: from skin,
• via dermal veins to systemic circulation
• portal system (adult worms developed)
• vesical and ureteric venous plexuses
• 3 months of pre-latent period
• fertilization to produce eggs that are excreted in urine
53
Clinical features of schistosomiasis
```
1. Acute schistosomiasis
Skin invasion of cercariae causes dermatitis at penetration site followed by allergic pruritic papular lesion.
2. Chronic schistosomiasis:
• urogenital disease
• obstructive uropathies
• bladder carcinoma
• Involvement of other sites:
• important risk factor for potential activation and transmission of HIV
```
54
Urogenital disease by chronic schistosomiasis
* May be asymptomatic.
* Symptoms develop after 3–6 months
* Main mechanism: deposition of eggs in various tissues (not adults)
* They have terminal spines which damage bladder mucosa that leads to dysuria and hematuria
* Soluble antigens released from the eggs provoke delayed type of hypersensitivity reaction ➡️ egg granuloma, which undergoes fibrotic changes
* In heavy infection, male genital organs are frequently affected.
* Deposition of the eggs in scrotal lymphatics may cause elephantiasis in scrotum and penis
55
Obstructive uropathies of chronic schistosomiasis
Fibrosis may cause obstruction of the lower end of the ureters that result in hydroureter and hydronephrosis, which may be seen in 25–50% of infected children
56
Bladder carcinoma chronic schistosomiasis
Metaplastic changes in urinary mucosa may lead to carcinoma of bladder
Squamous cell carcinoma M/C
Seen with high to moderate worm burden; whereas transitional cell carcinoma may occur in areas with lighter worm load
57
Predisposing factors for Bladder carcinoma by chronic schistosomiasis
1. Intake of diet containing nitroso-compounds, commonly found in Egyptian food (cheese, fava beans, raw salted fish)
2. Secondary bacterial infections, causing cystitis
3. Genetic factors such as activation of H-ras, inactivation of p53 and retinoblastoma genes
58
Chronic acidosis affecting other sites
Eggs may be carried by venous blood to various parts of the body like spinal cord, liver, lungs or intestine and produce similar granulomas
59
Lab diagnosis of schistosomiasis
1. Urine microscopy:
Non-operculated terminal spined eggs in the urine or rarely in feces
2. Histopathology bladder mucosal biopsy or wet cervical biopsy specimens
3. Antibody detection: epidemiology
HAMA-FAST-ELISA (Falcon Assay Screening Test)
HAMA-EITB (Enzyme-linked immunotransfer blot)
4. Antigen Detection
circulating antigen indicates recent infection
60
Uterine microscopy for schistosomiasis
Non-operculated terminal spined eggs in the urine or rarely in feces
Terminal hematuria portion of urine is collected between 12 noon to 3 pm, and concentrated
Presence of elliptical shaped egg of size 112–170 × 40–70 μm, with a sharp terminal spine. (S. mansoni egg has a lateral spine)
61
Histopathology for schistosomiasis
S. haematobium eggs can be demonstrated in bladder mucosal biopsy or wet cervical biopsy specimens.
The number of eggs present in crushed tissue correlates significantly with the size of the genital lesions
62
Antigen detection for schistosomiasis
• Detection of circulating antigen indicates recent infection and can be used for monitoring the treatment response.
• They are also useful when urine microscopy fails to detect eggs (chronic and ectopic cases).
• Circulating cathodic antigen (CCA) and circulating anodic antigen (CAA) can be detected in serum and urine
by ELISA or dip stick assays
• CCA levels are much higher in urine than CAA
63
Urinary schistosomiasis treatment
1. Praziquantel is the drug of choice; given 20 mg/kg/dose, two doses in single day.
2. Metrifonate can be give alternatively.
It inhibits acetylcholine receptors on tegument surface of adult male worm. It is administered in multiple oral doses over weeks; hence not
preferred in control programs
64
Prevention of urinary schistosomiasis
1. Proper disposal of human excreta and urine
2. Eradication of snails by using molluscicides such as metal salts (iron or aluminum sulfate), metaldehyde, methiocarb and acetylcholine esterase inhibitors
3. Treatment of infected persons
65
Dioctophyme renale Infection or giant kidney
worm infection
life cycle
1. Ingestion of fish infected with larva
2. Penetrates intestine
3. Reaches kidney (right kidney affected commonly) and transform into adult worms.
4. Adult worms are larger and can block the kidney and ureter.
5. Lay eggs, that are passed in urine
66
Dioctophyme renale Infection or giant kidney
worm infection
clinical features, diagnosis and prevention
Clinical features:
• hematuria and renal colic.
• Extensive destruction of kidney parenchyma may occur
Diagnosis: eggs in urine.
• oval-shaped, 60–80 µm size
• contain an embryo surrounded by thick sculptured or pitted egg shell
Prevention:
Proper cooking of fish prior to consumption.
67
Candiduria
Candida species in urine is common due to:
1. Contamination during
collection
2. Bladder colonization
3. Upper UTI (due to ascending infection from bladder).
• Rx in asymptomatic patients is not recommended, with exceptions
• Fluconazole (for 14 days) DoC (high levels in urine).
• In case of fluconazole resistance, oral flucytosine and/or parenteral amphotericin B can be considered.
68
Treatment of candiduria in asymptomatic patients is
not recommended, but can be considered in the following
situations:
1. Symptomatic cystitis or pyelonephritis & patients at high-risk for disseminated disease
2. Neutropenic or immunosuppressed patients
3. Patients undergoing urologic manipulation
4. If upper-pole or bladder-wall invasion or obstruction is associated
5. Critically-ill patients (have higher risk for invasive candidiasis)
6. LBW infants
