Urinary Tract Infections (UTIs)

Urinary Tract Infections (UTIs) Overview

• UTIs are infections affecting the urinary system
• The urinary system consists of the kidneys, ureters, bladder, and urethra

Learning Objectives

• Describe the pathogenesis of acute UTIs
• Recognize the microbial causes of UTIs
• Describe the laboratory diagnosis process for UTIs
• Be able to devise management strategies for UTIs
• Recognize other clinical conditions linked to UTIs like asymptomatic bacteriuria, acute pyelonephritis, and renal tuberculosis (TB)

Patient Presentation

• A 32-year-old female presents with a 24-hour history of dysuria, urgency, and increased frequency to her general practitioner (GP)
• Physical examination reveals the patient is afebrile with normal findings
• Dipstick testing shows positive results for leukocytes and nitrites in the urine
• Microscopy and culture results reveal a white blood cell (WCC) count greater than 100/ml
• E. coli count is greater than 100 x 10^5, which is susceptible to nitrofurantoin, trimethoprim, and ciprofloxacin

UTI Pathogenesis

• The bladder is normally a sterile environment
• The anterior urethra becomes inhabited with normal skin or bowel flora
• UTI incidence increases with age and is more prevalent in women
• Children diagnosed with a UTI need follow-up because renal failure and hypertension may occur

Determinants of Infection

• Inoculum size: The amount of bacteria present
• Virulence: The ability for bacteria to attach to uroepithelial cells, potentially leading to upper UTIs, particularly with certain E. coli strains
• Host defense mechanisms: Innate immunity

Host Defense Mechanisms

• Complete bladder emptying
• Increasing fluid intake and voiding frequency
• Vesico-ureteral valve function
• Urethral length (greater in males than females)
• Protective vaginal flora: Lactobacilli. Oral contraceptive and spermicide use can reduce lactobacilli numbers, increasing aerobic Gram-negative bacterial colonization such as Escherichia coli

Urinary Tract Abnormalities

• Obstructions caused by stones, stenosis, or an enlarged prostate
• Vesico-ureteric reflux (VUR), results in retrograde urinary flow
• Incomplete bladder emptying, which provides a medium for bacterial growth
• Neuropathic bladder, caused by a neurological condition, such as diabetes mellitus
• Bladder outlet obstruction, caused by prostatic hypertrophy, urethral stricture, pelvic mass, or retroperitoneal mass
• The presence of foreign bodies: stones/calculi, stents, urinary catheters, or nephrostomy tubes

Gender Differences

• UTIs are one of the most common reasons for women to visit their GP
• Most women will experience at least one UTI in their lifetime
• UTIs are more common in women because of a shorter and wider urethra
• UTIs are less common in men but increase with age and prostatic disease
• UTIs in men usually indicate an underlying problem

Influence of Age on UTIs

• Prostatic enlargement/hypertrophy increases the risk of UTIs
• Loss of bactericidal activity of prostatic secretions may increase UTI risk
• Faecal incontinence increases the risk of UTIs
• Pelvic floor muscle weakness, with prolapse of the uterus, can lead to incomplete bladder emptying and UTIs

Host Defenses Against UTIs

• Regular urine flow
• Mucosal defense mechanisms
• Balanced pH
• Sphincter integrity

Routes of Infection

• Ascending infection: Colonization of the ano-genital region and migration of enteric bacteria (Enterobacterales, enterococci) to the bladder, with potential spread to the renal pelvis
• Haematogenous infection: Kidneys receive about 33% of cardiac output, bloodstream infection can cause seeding into the kidneys
• Direct infection: Fistula, such as vesico-colic

Symptoms of Acute UTI

• New symptoms indicating the likely site of infection
• Suprapubic pain: Indicates cystitis (inflamed bladder)
• Flank pain: Indicative of pyelonephritis (inflamed kidney)
• Dysuria: Pain when passing urine
• Increased frequency: Passing urine every 1-2 hours
• Urgency: A very strong urge to urinate immediately
• Nocturia: Passing urine during the night outside of usual habit
• The presence of a systemic illness is nonspecific for UTI, but when paired with localizing symptoms, may point to complicated infection
• Obstructive uropathy may contribute to acute kidney injury
• Fever
• Rigors
• Acute confusional state/delirium in elderly patients
• Nausea and anorexia

UTI Causative Pathogens

• Gram-negative bacilli
  • Enterobacterales: E. coli, K. pneumoniae, P. mirabilis, Enterobacter spp., Citrobacter spp.
  • Pseudomonas aeruginosa
• Gram-positive cocci
  • Staphylococci: Staphylococcus saprophyticus
  • Streptococci: Group B streptococcus also called Streptococcus agalactiae
  • Enterococci: Enterococcus faecalis and Enterococcus faecium

Escherichia Coli (E. coli)

• A member of the Enterobacterales order
• The most common pathogen involved in UTIs
• Some serotypes (-01, 02, 04) are more successful uropathogens due to fimbriae and poor immunogenicity
• Other Enterobacterales members that may produce UTIs: Klebsiella pneumoniae, Proteus mirabilis (associated with stones/calculi produce enzyme urease that makes urine more alkaline), Enterobacter spp., Citrobacter spp.

Staphylococcus Saprophyticus

• A coagulase-negative staphylococcus
• Can be part of the normal flora
• Another common cause of UTI in the wider community
• Tends to affect young women
• Reaches the bladder through an ascending route

Enterococci

• Another common cause of UTI
• An opportunistic pathogen and not particularly virulent
• Complicated infection in critically ill or immunocompromised patients

Pseudomonas Aeruginosa

• An opportunistic pathogen that is not a common cause of UTI
• Causes infection in critically ill or immunocompromised patients or structural urinary tract abnormalities
• It is a gram-negative bacillus
• Has a polysaccharide capsule that allows it to adhere to epithelial cells
• Has a characteristic sweet odour
• Can produce pigment and grows rapidly on media under aerobic conditions

Healthcare-Associated UTIs

• UTIs are a common healthcare-associated infection (HAI)
• Causative pathogens include the Enterobacterales, Pseudomonas aeruginosa, and Enterococcus faecalis/faecium
• Predisposing factors include presence of urinary catheters
• UTIs can be from manipulation of the urinary tract, such as TRUS-guided prostate biopsy, stone fragmentation, stenting, and urinary diversion
• Urinary stasis is a predisposing factor
• Dehydration is a predisposing factor
• Debility due to underlying disease is a predisposing factor

Healthcare-Associated UTIs: The Worry

• Higher risk of antimicrobial resistance, which means fewer treatment options, poor outcomes, and rising costs
  • In Enterobacterales, it can include extended-spectrum beta-lactamases (ESBLs) and carbapenemases (CRE/CPE)
  • In Enterococci, it can include glycopeptide or vancomycin resistance (VRE)
  • Pseudomonas is already inherently antimicrobial-resistant
• Device association: Urinary catheters
• Complicated infection that starts as a UTI but can travel to the bloodstream causing BSI

How to Prevent Healthcare-Associated UTIs

• Standard precautions, including hand hygiene, every patient, every time
• Antibiotics used appropriately by use of current guidelines to reduce antimicrobial resistance
• Mind the devices: Avoid inserting a catheter unless it's absolutely necessary Review the ongoing need for the catheter daily Remove the catheter as soon as it's no longer required Insert the catheter using an aseptic technique Take care of the catheter while in situ and maintain a closed drainage system

Confirmation of UTI

• Presence of clinical symptoms
• Supporting evidence from one or more tests
• Finding bacteria in the urine does not mean that a patient has a UTI
• Asymptomatic bacteriuria is bacteria in urine without symptoms of UTI

Asymptomatic Bacteriuria

• This is more common as people age
• Can be found in up to 40% of older women
• Almost universal in patients with urinary catheters in situ, with catheters becoming colonized with perineal and bowel flora within a few days of insertion
• Asymptomatic bacteriuria should not be treated in the majority of situations
• Exceptions include pregnancy, and manipulation of the urinary tract

Diagnostic Tools for UTI

The following specimens are used for testing:

• Mid-stream urine (MSU)
• Catheter specimen urine (CSU) if the urinary catheter is in situ
• Urine from a nephrostomy or ileal conduit.
• Near patient test (at bedside or point-of-care) – urinalysis/urine dipstick
• Laboratory test – urine microscopy, urine culture and susceptibility testing
• Also take blood cultures if patient systemically unwell or sepsis. Need to rule out bloodstream infection

Obtaining an MSU

• Anogenital area cleaned and labia separated
• Void first 5mls
• Collect MIDSTREAM urine into sterile container
• Get to the lab ASAP - within 2 hours of collection
• If not refrigerate (24 – 48 hours)

Taking a Catheter Specimen of Urine (CSU)

• Urine collected from the sampling port and NOT from the drainage bag

Urine Dipstick/Urinalysis

• This is done by the GP, in the emergency department or at bedside
• Tests for Protein, Blood, Glucose, Ketones, Leucocytes, and Nitrites
• Dipstick is a good test to rule out UTI
• A negative result for nitrites and leucocytes means UTI is very unlikely
• A positive result for nitrites and leucocytes mean careful interpretation is needed

Microbiology Processing of Urine

• Urine microscopy (manual or automated) showing >10 WBC or pus cells in MSU
• Urine culture and colony count demonstrating a pure growth of a uropathogen >105 = 100,000 cfu/ml
• Antibiotic susceptibility testing

Microscopy

• Examination of the urine directly under the microscope or using sediMAX (automated urinalysis analyser)
• White blood cells (WBC) or pus cells: normal is less than 10.
• Red blood cells (RBC) indicate: calculi, glomerulonephritis, tumours or cystitis
• Epithelial cells: The presence may indicate specimen contamination
• Bacteria: Visible bacteria on microscopy = bacteriuria
• Casts

Culture & Colony Count

• Use a 1µL = 0.001 mL sterile loop to transfer urine onto an agar plate
• Then, let it incubate overnight
• The next day, examine the plate for bacterial growth
• Count each bacterial colony:-
  • 10 colonies in 0.001ml urine = 10,000 bacteria/mL = 104/mL

Interpretation of the Colony Count

• 105/mL is supportive of a UTI diagnosis, provided the patient has symptoms

• 104/mL needs caution: review microscopy, determine if patient is symptomatic, and assess if they were on antimicrobials before the specimen
• 103/mL indicates probable contamination
• Mixed growth indicates likely contamination, only repeat the test if clinically indicated

Identifying Bacteria on the Agar Plate

• Chromogenic agar is used for presumptive identification based on colour of bacterial growth
• Automated bacterial identification can be done through (MALDI-TOF)
• Bacteria can be determined by what antibiotics to test it against = susceptibility testing

UTI Treatment: Key Points

• It is important to not take a urine sample unless the patient has symptoms of a UTI
• It is vital to never diagnose a UTI based on a positive dipstick for nitrites
• One should treat the patient, not the laboratory result
• Be aware of the possibility of asymptomatic bacteriuria
• If a positive dipstick for nitrites is shown, and a positive culture result is given, if the patient has a catheter, be aware of the possibility of infection
• Antibiotics should be used on younger women with uncomplicated cystitis

UTI Treatment: Antibiotics

• Local antibiotic guidelines should be followed
• Choice depends on susceptibility profile – check the patients history for antimicrobials use
• Use a narrow spectrum if possible
• Use a cheap antibiotic (e.g. trimethoprim, nitrofurantoin
• Use an oral route, unless systemic or complicated infection
• Duration:
  • Females cystitis should be 3 days
  • Males or urinary catheter in situ should be 7 days
  • Complicated infection, pyelonephritis, UTI, and BSI should be 7 – 14 days

Pregnancy and UTIs

• UTIs are the most common complication of pregnancy
• An MSU is taken at the first antenatal visit
• ~4-6% of pregnant women have asymptomatic bacteriuria
• Asymptomatic bacteriuria in pregnancy is different
• Asymptomatic bacteriuria in pregnancy can progress to UTI and pyelonephritis
• Predisposing factors to UTI due to decreased bladder size
• Predisposing factors include urethral muscle tone due to hormonal effects
• Predisposing factors include urinary stasis due to pressure from uterus

Asymptomatic Bacteriuria in Pregnancy

• If untreated, 20-30% will develop acute pyelonephritis (AP)
• It can cause a miscarriage or premature labour
• Pregnancy is one situation where antimicrobial treatment of asymptomatic bacteriuria is needed

UTIs in Children

• 1-2% occurrence
• Risk factors:
  • poor urine flow
  • history suggesting previous UTI or confirmed previous UTI
  • antenatally diagnosed renal abnormality
  • FHx of vesicoureteric reflux (VUR) or renal disease
  • constipation
  • dysfunctional voiding
  • enlarged bladder
  • abdominal mass
  • evidence of spinal lesion

UTI Presentation in Children

• Infants: fever, irritability, lethargy, foul-smelling urine, haematuria
• Pre-verbal children: fever, abdominal pain, lethargy, foul-smelling urine, haematuria
• Verbal children: frequency, dysuria, fever, cloudy urine, haematuria

Urine Collection in Children

• Clean catch urine
• MSU
• Suprapubic aspirate

UTI Follow-up in Children

• Depends on the child's age, how well they respond to treatment, and their history
• Ultrasound identifies structural abnormalities of the urinary tract
• Dimercaptosuccinic acid (DMSA) scan can determine if residual renal parenchymal defects post infection
• Micturating cystourethrogram (MCUG) is also performed to determine if vesicoureteric reflux
• Follow NICE Guideline: Urinary tract infection in under 16s: diagnosis and management

Diabetes Mellitus and UTIs

• Increased incidence of UTI due to:
  • Bladder dysfunction (neuropathy)
  • Structural abnormalities
  • Recurrent vaginitis
  • Vascular disease
  • Glucose in urine: sugary culture medium supports bacterial growth

Case Scenario: the Older Male

• A 72-year-old man presents to GP with temperature, dysuria and right flank pain, frequency and nocturia and has had symptoms for 3 months
• The urinalysis shows leucocytes

Important Points

• Older male

• His symptoms point to a UTIs dysuria, and flank pain

• He has systemic symptoms: fever

• A urinalysis shows leucocytes

• The doctor referred is the patient to ED

• His Sepsis criteria met

• His impression Urosepsis

• Commenced on IV cefuroxime and IV gentamicin as per local guidelines, MSU microscopy & culture, Cultures return WBC or pus cells and he has an E. coli infection. Blood cultures confirm this. He is susceptible to cefuroxime & gentamicin

Acute Pyelonephritis

• Acute inflammation of the kidney
• It can cause renal abscess/necrosis and be accompanied by BSI
• The causes and risk factors are similar to those of acute UTI
• Risk Factors include structural abnormality, pregnancy, and urinary tract instrumentation
• Clinical presentation shows pain in the flank, and at the renal angles, and a fever with systemic symptoms
• Diagnosis will be urine, and blood culture
• Treatment involves: local guidelines, IV antibiotics and drainage of pus/abscesses

Sterile Pyuria

• WBC or pus cells are noted in a patients urine
• Although, the urine culture is sterile
• Causes: Antimicrobial therapy, tumour, urinary stones or calculi, Chlamydia urethritis or other STI, TB, Brucellosis

Renal Tuberculosis (TB)

• Hematogenous spread to the kidney
• Symptoms: frequency, painless hematuria, malaise, fever and weight loss

Laboratory Diagnosis

• Early morning urine (EMU) specimens x3- Taken on three consecutive days
• In laboratory, mycobacterial culture for up to 8 weeks. Microscopy (staining for AFB/ ZN not done)

Ascending Route

• Most predominant way for an infection to occur
• E. coli is the most common cause of UTI
• _Staphylococcus saprophyticus; _young females
• Proteus mirabilis - renal calculi
• Klebsiella pneumoniae, Pseudomonas aeruginosa and enterococci are also commonly seen Healthcare Associated UTIs are a risk

Additional Notes

• Asymptomatic bacteriuria is always treated in pregnancy because 20-50% risk of pyelonephritis, with increased incidence of premature labour/miscarriage
• Children with UTI should be assessed for structural abnormality
• One should Also think of TB in sterile pyuria