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Case 10: Medical Microbiology (Urinary Tract Infections) - Coggle Diagram
Case 10: Medical Microbiology (Urinary Tract Infections)
Anatomy and Basic Terminology
Describe the Anatomy and Basic Terminology of Urinary Tract Infections
Upper Urinary Tract System
Upper Urinary Tract System includes the Kidneys, Renal Pelvis and Ureters
Lower Urinary Tract Systems
Lower Urinary Tract Systems includes the Bladder,and Urethra
In males, the Urethra is typically 13-20 cm in length but in females, the Urethra is only 3-5 cm in length
The disparity in Urethral Length is often thought to be a reason why Urinary Tract Infections are more common in females than in males
Cystitis
Cystitis is a clinical syndrome involving Frequency, Urgency, Dysuria and Suprapubic pain
Cystitis is related to the inflammation of the Bladder Mucosa and Urethra
Differential includes UTIs and STIs
Pyelonephritis is the Acute Infection of the kidney
Where the patient presents with fever, flank pain or tenderness, nausea and vomiting
Pyelonephritis often associated with Frequency, Urgency and Dysuria
Uncomplicated UTI
Uncomplicated UTI refers to a Urinary Tract Infection that occurs in an Adult, Non-pregnant, Pre-menopausal woman without any comorbidities and with a Structurally and Functionally normal Urinary Tract
Complicated UTI
Complicated UTI refers to a Urinary Tract Infection that occurs in individuals who have factors that predispose them to the infection (Calculi, Catheters, Obstruction, Immunosuppression, Retention, Comorbidities, Structural or Functional defects of the Urinary Tract), or are pregnant/menopausal women, men or children
Routes of Infection
Describe the Routes of Infection
There are two routes of Infection:
Ascending Route
Ascending Route is the most common route
In the Ascending Route, Bacteria from the GIT colonise the Peri-urethral/Urethral area before Ascending the Urethra to the Bladder
Once in the Bladder, the Bacteria multiply causing a Cystitis
Bacteria can then potentially ascend the Ureters to the Kidney to cause Pyelonephritis
Further spread of the Bacteria into the bloodstream can cause Bacteraemia
Hematogenous Route
Hematogenous Route is the less common route
In the Hematogenous Route, Blood-Borne organisms can cause infection of the Renal Parenchyma to cause a Urinary Tract Infection
You should suspect this with all Staphylococcus aureus cultured from the urine and have a low threshold to do a blood culture
This also includes Candida
Can also occur with Mycobacterium tuberculosis and salmonella typhi
Pathogenesis of Urinary Tract Infections
Describe the Pathogenesis of Urinary Tract Infections
The Pathogenesis of Urinary Tract Infections is as follows:
Cystitis of the Bladder begins with the Uropathogens (Bacteria) of the Gut contaminating the Peri-Urethral Area and colonizing the Urethra
The Uropathogens then ascend the Urethra into the Bladder
In the Bladder the Uropathogens (Bacteria) express Adhesins such as Fimbriae, Pili and other Outer membrane proteins in order to colonize and attach to Bladder Cells
Host inflammatory responses include Neutrophil Infiltration
Some Bacteria evade the immune system and evade the host cells, and multiply resulting in the formation of a Biofilm
The Bacteria produce Toxins, Enzymes and Proteins like Proteases that damage the host cells
Bacteria then ascend the Ureters to the Kidneys to cause Pyelonephritis
Kidney colonization occurs and Bacteria releases toxins, enzymes and proteins to damage Kidney Cells
Urinary Tract Infection can cause Bacteraemia which is a Blood stream infection if the Bacteria cross the Tubular Epithelial Barriers
NOTE:
Bladder can be compromised by the presence of a Catheter
The Catheter causes an immune response and Fibrinogen accumulates on the Catheter providing an ideal environment for the attachment of Uropathogens that express Fibrinogen-Binding Proteins
Biofilms also form on the catheters and can be a continuous source of Bacteria if not replaced or removed
Urinary Tract Infections most commonly occur in patients with a Urine Catheter within 3-4 days
Therefore, it is important to have a low threshold to remove Catheters from those who do not require them
Bacterial Virulence Factors
List the Bacterial Virulence Factors
Adhesins such as Fimbriae, Pili and Outer membrane Proteins
Capsules
Flagella
Bacterial Enzymes, Toxins and Proteins
Virulence factors allow bacteria to evade the host defence mechanisms and evade the host tissue to produce disease
Organisms, and strains within certain organisms, do not all harbour and express the same Virulence Factors
Eg: E.coli Not all E.coli are able to cause UTIs
Only E.coli that express the relevant virulence factors can cause UTIs, these strains of E.coli are called Uropathogenic E.coli (UPEC)
Describe the Bacterial Virulence Factors
Adhesins
Adhesins such as Fimbriae, Pili and Outer Membrane Proteins facilitate the colonization and adherence to the Peri-Urethral Areas and the Urinary Tract
Capsule
Capsule protect the Bacteria from phagocytosis
Flagella
Flagella allows for the mobility and ascension of the Bacteria up the Ureter against the flow of Urine
Bacterial Toxins, Enzymes, and Proteins
Haemolysins, Cytotoxins, Proteases cause damage to host cells
Aerobactin is an Iron-scavenging protein that is necessary for uptake
Iron is required by the bacteria to survive and these Proteins assist with the adequate uptake of Iron from the Urine
Urease production which is seen in Proteus spp, Urease breaks down Urea from Urine and causes an increase in Urine pH
As a result, the Urine becomes less Acidic and more Basic
This initiates the precipitation of anions and cations in the urine, forming crystals and stones within the Urinary Tract and on foreign bodies like Catheters, thus predisposing an individual to infection
Host Risk Factors the Predispose individuals to Urinary Tract Infections
Describe the Host Risk Factors the Predispose individuals to Urinary Tract Infections
Host Risk Factors that predispose individuals to Urinary Tract Infections:
Females
Females have a short Urethra which is in close proximity to the Gastrointestinal Tract
Presence or Increased numbers of pathogens
Poor Perineal hygiene and sexual intercourse leads to an increased number of pathogens at the Urethral Area
Obstruction in the Urinary Tract
Physical obstruction such as Pregnancy, Prostate Enlargement, Renal calculi, Vesico-ureteral reflux and Congenital Anatomical Abnormalities
Neurological Deficits causing functional obstruction such as Paraplegia, Spina bifida and multiple Sclerosis
Comorbidities such as Diabetes mellitus and Immunosuppression
Foreign bodies and Instrumentation such as Catheterization or Surgery
Natural Host Defence Mechanisms
List the types of Natural Host Defence Mechanisms against UTIs
There are two types of Natural Host Defence mechanisms against UTIs:
Physical Defence Mechanisms
Presence of Vesico-Ureteral Valves
Peristalsis of the Ureters
Urine Flow and Micturition
Chemical Defence Mechanisms
Urinary pH which is acidic due to high Urea content
Urinary Tract Epithelial cells secrete Bactericidal Peptides like Defensins and IgA
Inflammatory response to bacteria (Neutrophil Infiltration)
Epidemiology of Urinary Tract Infections
Outline the Epidemiology of the Urinary Tract Infections
UTIs are common bacterial infections
Majority of Urinary Tract Infections are Acute and Short-lived
Prevalence of Urinary Tract Infections vary with Age, Gender, and Host Risk Factors
But generally:
UTIs are more common in Women than in Men
Up to 50-60% of all women will have a Urinary Tract Infection during their lifetime and 10% will have a UTI each year
Women over the age of 65 are more at risk of UTIs than younger women
UTIs in men are uncommon and are usually related to a predisposing factor
UTIs occur in 1-3% of infants, and affect girls more than boys
Approximately, 30-50% of pre-school children with UTIs have Vesico-Ureteral Reflux which can lead to Renal Damage
Therefore, it is important to have a low threshold for imaging in the paediatric population
Organisms associated with Urinary Tract Infections
Outline the Organisms associated with Urinary Tract infections
Most Urinary Tract Infections are caused by organisms from the Gastrointestinal Flora and include Gram-Negative and Gram-Positive Bacteria as well as Candida which is a yeast
The most common causative agents of Urinary Tract Infections by far are the Enterobacterales, for both Uncomplicated and Complicated UTIs
Examples of Enterobacterales Uropathogens which cause Complicated and Uncomplicated UTI include:
Uropathogenic E.coli (UPEC) groups are the most common cause UTIs, accounting for 65-75% of all infections
Klebsiella pneumoniae
Proteus mirabilis
Enterobacter species
Non-Enterobacterales Uropathogens include:
Staphylococcus saprophyticus
Enterococcus faecalis
Group B Streptococcus (GBS)
Pseudomonas aeruginosa
Staphylococcus aureus
Candida Species
Rare causes of UTIs include:
Mycobacterium tuberculosis
Schistosoma haematobium
Urethritis from Neisseria gonorrhoea or Chlamydia Trachomatis as well as Trichomonas vaginalis infection can also cause UTI symptoms
Viral infection is rare but can occur with Adenovirus
Diagnosis and Treatment of Urinary Tract Infections
Outline the process of Diagnosis and Treatment of Urinary Tract Infections
Clinical
History-Taking
Physical Examination
Differential Diagnosis
Information collected from the History-Taking and Physical Exam can be used to support the differential diagnosis which in this case includes UTIs, STIs and Other Intra-abdominal Pathology
Side-room/POC Test
Side-room/POC Test such as Urine Dipstix
For UTIs, you could look for signs and symptoms of Cystitis and Pyelonephritis and could follow this with an onsite Urine Dipstick
Special Tests
If necessary send off urine to the laboratory for:
Urine Microscopy-Culture and Sensitivity Testing (Urine-MCS)
Radiology
Other lab test: Full Blood Count (FBC) and Chemistry
Other micro: Blood Cultures
Other
Depending on the severity of the patients illness and your differential diagnosis other investigations like Full Blood Count, Renal Function or Imaging may also be necessary
When sending any test off to the laboratory it is important to ensure that:
Specimens are collected appropriately
Specimens are placed in the appropriate sample collection containers
And sent to the lab timeously or stored correctly until the sample can be sent to the lab
Once results are out, it is important to interpret the findings in the context of the patients clinical status and not in isolation.
Urine Dipstick Analysis
Describe the Urine Dipstick Analysis
Urine Dipstick Analysis is usually a side-room test using aseptically collected urine where there is a likelihood/possibility of a Urinary Tract Infection
Urine Dipsticks can pick up the presence of:
Nitrites: Nitrate-reducing Enterobacterales
Leucocyte esterase (LE) activity: White Blood Cells
Haematuria
Proteinuria
The presence of Nitrites and Leucocytes are usually what is focused on to determine the presence of an infection
Describe the Biochemical Features picked up by a Urine Dipstick
Nitrites: Nitrate-Reducing Enterobacterales
Nitrites are not normally found in urine, but they will appear if there are Bacteria present that convert Nitrates to Nitrites
The Test can be Negative even if there are lots of Bacteria in the Urine if the Urine has not remained in the Bladder for long enough
Ideally, you should wait for 4 hours from the last time you voided before doing your Urine Sample
Similarly, False Positives Results can occur with delays in specimen processing, where the delay has led to an overgrowth of Nitrate-Reducing Bacteria
Some Bacteria like Enterococci do not reduce Nitrates and the test results will be Falsely Negative in these situations too
Presence of Leucocytes are picked by detecting Leucocytes Esterase Activity
There needs to more more than 10 WBCs/mm3 in the urine for this test to be Positive
If there are too few WBCs in the urine the Test will be Negative
The test does not indicate why there are Leucocytes present
Therefore, a Positive Test Result can indicate the presence of a Urinary Tract Infection but can also be due to other causes like trauma from Catheterization or Stones
A Negative Nitrite Test and Leucocyte Test in the presence of clinical suspicion of a Urinary Tract Infection, should prompt a Urine Microscopic Examination for Pyuria and Culture
Proteinuria and Haematuria
Proteinuria and Haematuria can be seen with urinary Tract Infections, but can also be indicative of other disorders such as Calculi, Tumour, Vasculitis, Glomerulonephritis and Renal Tuberculosis
Urine Microscopy, Culture and Sensitivity (U-MCS) Testing
Outline the concept of Urine Microscopy, Culture and Sensitivity (U-MCS) Testing
Urine Microscopy, Culture and Sensitivity (U-MCS) Testing is a Laboratory test
U-Microscopy, Culture and Sensitivity Test is usually sent in with:
Complicated, Upper or Recurrent Urinary Tract Infections
Hospitalized patients with Urinary Tract Infections
Pregnant women with UTI symptoms or abnormal Dipsticks that were done as apart of Antenatal Care
Individuals undergoing Urological Surgery or Instrumentation pre-procedure
The Sample should be taken before starting Antimicrobial Therapy and the Sample should be Transported to the lab without delay, within 2 hours
Or remain Refrigerated to prevent overgrowth of organisms until it can be transported to the lab
Urine-Microscopy, Culture and Sensitivity (U-MCS) Sample Types
List the types of U-MCS Sample Types
Mid-Stream urine
Catheter Sample of urine (CSU)
Supra-Pubic Aspiration (SPA)
Urine Bag specimens
Cystoscopy/Nephrostomy Specimens
U-MCS Samples Types: Mid-Stream Urine
Describe the concept of the Mid-Stream Urine
Mid-Stream Urine is the most common type urine samples that can be sent to the lab
When talking the MSU for Females you would advise the to:
Clean the Peri-Urethral Area and Perineum with gauze pads soaked in soapy water using a Front to Back Motion
Then rinse the area with a gauze soaked in Sterile Saline or Water
Then hold the Labia apart and void, making sure that they discard the first 2-5 ml of Urine, and collect the rest in a Sterile Container with a tight fitting lid
When taking the MSU for Males you would advise them to:
Follow the same procedure as Females
Except, they ONLY clean the Urethral meatus before voiding and sample the collection
Making sure that they discard the first 2-5 ml of urine and then collecting the rest in a Sterile Container with a tight fitting lid
Remember if samples are not collected properly, organisms cultured may only represent contamination during sample collection rather than the true infection
This will complicate the diagnosis and treatment options
To avoid this please send well collected sample
NOTE: Remember to write on the form what type of Urine Specimen was collected
This will help to determine the significance of Positive culture by assisting with differentiating contamination from a True Infection when interpreting the Results
And also alert the lab about difficult-to-collect samples like Catheter Samples or Samples collected at Surgery
It is important for the lab to know this as difficult-to-collect specimens are processed differently in the lab
Some exceptions to the Mid-Stream Urine Collection route include sending initial voided urine samples when a patient is worried about Neisseria gonorrhoea or Chlamydia trachomatis for urethritis
And sending Terminal urine collected at midday for Schistosoma haematobium
Urine-MCS Samples Types: Catheter Specimen of Urine (CSU)
Outline the Collection of Catheter Specimen of urine
Catheter Specimen can be collected from Catheter Tubing and NOT the drainage bag in patients who already have a Catheter in place
Or a Catheter Specimen can be collected via an In-Out Urine Catheter placed specifically for the purpose of collecting urine and then being removed immediately afterwards
In-Out Urine catheter is usually done in Infants or in patients with Spinal Cord Injuries who perform Intermittent Catheterisation
Catheter Specimen of Urine has minimal contamination if they are collected aseptically and correctly
With In-Out Urine Catheter Samples, the first ml of Urine can be discarded, before Urine Collection
With the introduction of any catheter there is always the risk of introducing organisms from the Urethra to the Bladder to cause infection
Therefore, It is important that the Catheter Specimen of Urine is aseptically collected via the Catheter Tubing or via the In-Out Urine Catheter method
ALWAYS specify on the form that: This is a sample collected from the catheters as the lab processes these Catheter Collected samples differently from the Mid-Stream Urine Samples
Other Urine Specimens
Describe the Other Urine Specimens
Supra-Pubic Aspiration (SPA)
Supra-Pubic Aspiration is uncommon
Supra Pubic Aspiration is collected the insertion of a needle and syringe directly through the abdominal wall
Urine Bag Specimens
Urine Bag specimens are usually collected from Infants
Urine Bag Specimens are collected by placing a Plastic Back stuck to the Perineum of an Infant after the area has been washed
Urine bag specimens are not ideal for culture as contamination with Perineal and Gastrointestinal Flora is common
Cystoscopy/Nephrostomy Specimens
Cystoscopy/Nephrostomy Specimens are usually collected by Urologists in the theatre
These specimens are applicable to patients who have abnormal drainage system requiring some form of surgical intervention
Urine Microscopy: Epithelial cells and Leucocytes
Describe the Urine Microscopy: Epithelial cells and Leucocytes
When Urine samples arrive at the Lab they are examined using a Light Microscope for the presence of Epithelial Cells, White Blood Cells, and Red Blood Cells
These parameters give you an indication of the quality of the sample collected as well as an indication of the presence of disease either from a Urinary Tract Infection or Something else
The presence of casts or parasites will also be commented on if present
Epithelial Cells
Epithelial Cells from the Distal Urethra or External genitalia are Squamous Cells
The presence of Squamous Epithelial Cells indicates a poorly collected specimen with contamination
These samples often results in a growth of a mixture of different organisms, that is commonly referred to as a Mixed Growth
This occurs as these cells often have bacteria attached them
These results can be difficult to interpret as you do not know if the growth of any of the organisms present are truly causing Infection or as a result of Contamination
Leucocytes (White Blood Cells)
The presence of leucocytes in the Urine sample indicates that an inflammatory process is occurring within the Urinary Tract
This occurs with infection, but can also be a result of other disease such as Neoplasm, Kidney stones or Catheter insertion, which all result in an inflammatory response
Sterile pyuria is when Leucocytes are present in the Urine Microscopy, BUT the culture is negative
This occurs when Antimicrobial Therapy is taken before a U-MCS sample collection
Or when there is an infection with an atypical organism that will not be detected by the Routine Urine Culture
Mycobacterium tuberculosis
Chlamydia
Ureaplasma
Or other disease described above and not related to the function
Urine Microscopy: Haematuria (Presence of blood in the urine)
Describe Urine Microscopy: Haematuria
Haematuria can either be grossly visibly with the naked eye or visible only on the Microscope
Haematuria can be caused by Urinary Tract Infections (Haemorrhagic Cystitis), but it is more commonly caused by other disorders like:
Stones
Neoplasms
Renal Disease such as Glomerulonephritis
Vasculitis
Infective endocarditis
Schistosomiasis
You can sometimes see Casts of White Blood Cells, or Red Blood Cells
These form and get shaped into cylindrical structured when passing through the Distal Convoluted Tubule and Collecting Ducts of the Nephrons
They can become dislodged and pass through the Urine
Trichomonas vaginalis
Yeast
Red Blood Cells
Ova of Schistosoma Haematobium
Urine Culture
Describe the formation and interpretation of Urine Culture
Urine Culture is formed as follows:
Urine is inoculated onto Culture Plates
The Urine is then incubated overnight in order to allow for the growth of organisms within the sample
These Culture Plates are then examined after 24-48 hours to detect any growth
Growth of organisms is Semi-Quantified into X Number of colony forming units (cfu) per ml
Pure Growth
Pure Growth means that there is only 1 Type of organism has grown on the Culture Plates during the examination of the Culture plates
This finding is usually followed up by the lab with Identification and Sensitivity testing
Mixed Growth
Mixed Growth means that more than 1 Type organism has grown on the Culture plates
This is usually not quantified or followed up further
Exceptions are made for Difficult-to-Collect Urine Samples like the Catheter Samples or Samples collected in Surgery/Theatre or Supra-Pubic Aspirations where any growth is followed up by Identification and Sensitivity testing
Sometimes, there is a predominant growth of a Uropathogens within a mixed growth
As a result this will be followed up with Identification and Sensitivity testing for the Uropathogens, but treating clinician will have determine if antibiotics are necessary based on clinical significance
Urine Culture
Outline the Interpretation of Urine Culture
The Growth of organisms is Semi-Quantified into the X Number of colony forming units (cfu) per ml
We Semi-Quantify the growth of Pure Uropathogens as follows:
Growth of Pure Uropathogens that is Greater than and Equal to 10^5 cfu/ml usually indicates Significant Bacteraemia
Growth of Pure Uropathogens that is Between 10^4-10^5 cfu/ml may indicate Significant Bacteraemia
Growth of Pure Uropathogens that is Less that 10^4 cfu/ml is usually not significant
ALWAYS correlate results to the patient:
For example, if a patient has a UTI clinically, has 2+ leucocytes and no epithelial cells on microscopy and growth of <10^4 cfu/ml of E. coli from a MSU – this growth is likely to be significant based on the clinical picture of the patient.
Other difficult-to-collect Urine specimens such as Catheter Samples, Samples collected in surgery, or Supra-Pubic Aspirations use different criteria where any number of organisms may be significant
Asymptomatic Bacteriuria
Describe Asymptomatic Bacteriuria
Asymptomatic Bacteriuria is when we have a Significant Quantitative Count of bacteria in urine from an individual without any signs and symptoms of a Urinary Tract Infection
If this occurs it does not usually warrant treatment and we do not recommend screening urine of Asymptomatic Patients
There are a few exceptions to this rule:
Pregnant Women, Asymptomatic Bacteriuria in pregnant women increases the risk of adverse pregnancy outcomes and Pyelonephritis
Screening of urine and Treatment is recommended
Patients who need to undergo an invasive surgery or procedure
This approach pre-surgery/procedure is to prevent infection post Surgery or Procedure
Young children are unable to complain of symptoms and present with non-specific signs when they have UTIs
Therefore, it is important to send the Urine of a Child as a part of the sepsis work up and the U-MCS results need to be correlated clinically and treated if appropriate
Management of Urinary Tract Infections
Describe the Management of Urinary Tract Infections
There are 2 types of management methods used for Urinary Tract Infections:
General Measures
General Measures include:
Adequate Hydration
Management of comorbidities
Consideration of Obstruction or Structural abnormalities
Timeous Removal or Replacement of Urine Catheters
Analgesia and Anti-pyrexials
Antibiotic Therapy
Empiric Treatment is chosen based on Local Susceptibility Data
Targeted or Directed Treatment is chosen based on the Patient's Urine Culture and Susceptibility Results
ALWAYS choose the narrowest Spectrum Antibiotics to prevent antimicrobial resistance
Antibiotic Choice and Duration depends of the Urinary Tract Infection:
Cystitis vs Pyelonephritis
Complicated UTI vs Uncomplicated UTI
Community-acquired vs Healthcare-associated Infection
Healthcare-associated Infection is usually treated with Broad-Spectrum antibiotics until the urine Culture and Susceptibility results of a Patient are received
Cystitis
Outline the Treatment used for Uncomplicated and Complicated Community-Acquired Cystitis
Uncomplicated Community-Acquired Cystitis:
Gentamicin
Gentamicin is administered as 5mg, Intramuscularly as a Single Dose
Gentamicin is not used for Pregnant women or Individuals with Kidney Disease
Nitrofurantoin
Nitrofurantoin is administered as 100mg, Per Os, 6 hourly 5-7 days
Nitrofurantoin can be used in pregnant women
Fosfomycin
Fosfomycin is administered as a 3g, Per Os as a Single Dose
Fosfomycin can also be used for Pregnant women
Complicated Community-Acquired Cystitis:
Adults: Ciprofloxacin for 7 days
Children: Amoxicillin clavulanic acid
Acute Pyelonephritis (Community-Acquired)
Describe the management of Acute Pyelonephritis Community-Acquired
There are 2 Types of management Methods for Acute Pyelonephritis (Community Acquired)
General Measures
Antibiotic Therapy
Usually start with Systemic Antibiotics administered Intravenously (IV)
Then switch to Oral Antibiotics when the patient can tolerate it and has clinically improved (Apyrexial) and is Stable
Duration is usually longer between 7 to 14 days
Empiric Therapy is based on Locale Susceptibility Data and the Penetration of antibiotics into the Upper Tract:
3rd Generation Cephalosporins like Ceftriaxone for 10-14 Days
Fluoroquinolones like Ciprofloxacin for 7-10 Days
Aminoglycosides like Gentamicin if the Renal Function of the patient permits for 10-14 days
Children: Ceftriaxone
Neonates: Cefotaxime
Prevention of Urinary Tract Infections
Outline the Prevention of Urinary Tract Infections
The Prevention of Urinary Tract Infections is called Urinary Catheter Care
Avoid unnecessary urinary catheters
This means to remove all catheters at the earliest possible time or to not insert unnecessary catheters to prevent UTIs
Insert urinary catheters using Aseptic technique
Maintain urinary catheter based on recommended guidelines
Drainage system should be closed and the Drainage should never be left on the floor
They need to be on the Catheter stands or hooked on the patients bed below the level of the badder
Review Urinary catheter necessity daily and remove promptly
