Urinary Tract Infections (UTIs)

• The lecture is on Urinary Tract Infections (UTIs)
• The lecture was given by Dr. Rachel Grainger, Clinical Lecturer, Dept. of Clinical Microbiology, RCSI
• The lecture took place on March 10th, 2025 for Year 2 UG Medicine students

Learning Outcomes

• Define the pathogenesis of acute UTIs
• Describe the microbial aetiology of UTIs
• Outline the laboratory diagnosis of UTI
• Describe the management of UTIs
• Discuss other clinical conditions; asymptomatic bacteriuria, acute pyelonephritis & renal TB

Case Scenario

• A 32 year old woman presents to her GP complaining of a 24 hour history of pain passing urine (dysuria), urgency & frequency
• She is afebrile and examination is normal
• Dipstick is positive for leucocytes & nitrites
• Urinary microscopy & culture results: WCC > 100/ml and E. coli > 100 x 105 susceptible to nitrofurantoin, trimethoprim & ciprofloxacin

UTI Pathogenesis

• Bladder is normally sterile
• Anterior urethra is colonized with skin or bowel flora
• UTI increases with age & is more common in women than men
• Children with UTI must be followed up, as renal failure & hypertension may ensue

Determinants of Infection

• Inoculum size refers to how many bacteria are present
• Virulence refers to the ability to attach to uroepithelial cells associated with increased risk of upper UTI, e.g. some E. coli strains
• Host defence mechanisms are part of innate immunity
• Complete bladder emptying is a host defence mechanism
• Increased fluid intake & voiding frequency are host defence mechanisms
• The vesico-ureteral valve is part of host defense
• The length of the urethra (male>female) is a determinant
• Vaginal flora: Lactobacilli are protective, but oral contraceptives & spermicides decrease lactobacillary numbers and increase colonization with aerobic GNB such as Escherichia coli

Urinary Tract Abnormalities

• Urinary tract obstructions anywhere; stones, stenosis, enlarged prostate increase infection
• Vesico-ureteric reflux (VUR) that causes retrograde urinary flow increases infection risk
• Incomplete bladder emptying provides a culture medium and increases infection risk
• Neuropathic bladder secondary to neurological condition, diabetes mellitus increases infection risk
• Bladder outlet obstruction, prostatic hypertrophy, urethral stricture, pelvic mass, retroperitoneal mass increases infection risk
• Foreign bodies, stones/calculi, stents, urinary catheters, nephrostomy tubes all increase infection risk

UTI Demographics

• UTIs are one of the most common reasons for women to attend GP
• At least one UTI can occur in a woman's lifetime
• Shorter and wider urethra is the main reason that women are more likely to get a UTI
• UTIs are less common in men, but increase with age & prostatic disease
• UTIs in men are usually an underlying problem

Influence of Age

• Prostatic enlargement/hypertrophy increases UTI risk with age
• Loss of bactericidal activity of prostatic secretions increases UTI risk with age
• Faecal incontinence increases UTI risk wit age
• Pelvic floor muscle weakness and prolapse of the uterus leading to incomplete emptying of the bladder increases UTI risk with age

Host Defences Against UTI

• Regular flow of urine protects against UTI
• Mucosal defense mechanisms protect against UTI
• pH protects integrity of sphincter

Routes of Infection

• Ascending route is the most common infection route
• Ascending is colonisation of ano-genital region with migration of enteric bacteria (Enterobacterales, enterococci) to bladder +/- renal pelvis
• There is colonisation from anogenital region with migration of enteric bacteria to bladder and renal pelvis
• Kidneys receive about 33% of cardiac output; bloodstream infection (BSI) may seed in the kidneys
• Hematogenous route is responsible for <10% of infections, BUT spread from urine to blood far more common
• Direct infection routes include fistula, e.g. vesico-colic

Symptoms of acute UTI

• New localizing symptoms point to likely site of infection
• Suprapubic pain (cystitis – inflamed bladder) symptoms include
• Flank pain (pyelonephritis – inflamed kidney)
• Dysuria = pain when passing urine
• Frequency = passing urine every 1-2 hours
• Urgency = The urge to pass urine, must pass urine NOW!
• Nocturia = passing of urine during night which is out of usual habit
• Systemic symptoms are non-specific for UTI, but in conjunction with localizing symptoms may indicate complicated infection
• Systemic symptoms include: Fever, Rigors, Acute confusional state/ delerium in elderly, Nausea, anorexia
• Obstructive uropathy may contribute to acute kidney injury and associated symptoms

UTI Causative Pathogens

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

Escherichia Coli

• Member of the Enterobacterales order
• E. coli is the most common pathogen causing UTI = uropathogen
• Some serotypes of E. coli (-01, 02, 04) are more successful uropathogens – fimbriae, poor immunogenicity
• Other Enterobacterales members cause UTI less frequently than E. coli – Klebsiella pneumoniae, Proteus mirabilis (associated with stones/calculi – produce enzyme urease that makes urine more alkaline), Enterobacter spp. Citrobacter spp. etc.

Staphylococcus Saprophyticus

• A coagulase-negative staphylococcus, can be part of the normal flora
• Another common cause of UTI in the community
• Tends to affect young women
• Reaches bladder via 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

• Opportunistic pathogen and not a common cause of UTI
• Complicated infection in critically ill or immunocompromised patients or structural urinary tract abnormalities
• Gram-negative bacillus
• Has polysaccharide capsule that anchors to epithelial cells
• Has characteristic sweet odour
• Can produce pigment & grows rapidly on media under aerobic conditions

Healthcare-Associated UTI

• UTI is a common HAI
• Causative pathogens inlcude any member of the Enterobacterales, Pseudomonas aeruginosa and Enterococcus faecalis/faecium
• Predisposing factors: Presence of urinary catheters, manipulation of the urinary tract – TRUS-guided prostate biopsy, stone fragmentation, stenting, urinary diversion – nephrostomy, ileal conduit
• Predisposing factors include Urinary stasis, dehydration and Debility due to underlying disease

Healthcare-Associated UTI Concerns

• Increased risk of antimicrobial resistance = fewer treatment options, worse outcomes, increased costs
  • Enterobacterales: Extended-spectrum beta-lactamases (ESBLs) and Carbapenemases (CRE/CPE)
  • Enterococci: Glycopeptide or vancomycin resistance (VRE)
  • Pseudomonas: Already an inherently antimicrobial-resistant organism
• Device association – urinary catheters
• Complicated infection – Starts as UTI, but can spread to bloodstream (BSI)

Healthcare-Associated UTI Prevention

• Standard precautions including hand hygiene – every patient, every time
• Use antibiotics appropriately and follow the guidelines – reduce the risk of antimicrobial resistance
• Mind the devices:
  • Don't insert a catheter unless it's absolutely necessary
  • Review the ongoing need for the catheter daily
  • Remove the catheter as soon as it is 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

• Confirmation requires both: presence of clinical symptoms PLUS supporting evidence for UTI
• It's common to find bacteria in urine and the presence of bacteria in urine does not automatically mean the patient has a UTI
• Asymptomatic bacteriuria is bacteria in urine without symptoms of UTI

Asymptomatic Bacteriuria

• More common with ageing; May be found in up to 40% of older women
• Almost universal in patients with urinary catheters in situ, catheters become colonized with perineal and bowel flora within a few days of insertion
• Asymptomatic bacteriuria should not be treated in the majority of situations
  • Exceptions inlcude Pregnancy and Manipulation of the urinary tract

Diagnostic Tools for UTI

• A specimen of urine is needed for testing:
  • Mid-stream urine (MSU)
  • Catheter specimen urine (CSU) if urinary catheter 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 & 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)

Urine Dipstick/Urinalysis

• Urine dipstick/urinalysis is carried out by GP, in emergency department or at bedside
• Looks for protein, blood, glucose, ketones, leucocytes and nitrites
• Dipstick is a good test to rule out UTI
• Negative for nitrites and leucocytes = UTI very unlikely
• Positive for nitrites and leucocytes = Careful interpretation needed

Microbiology Processing of Urine

• Microscopy (manual or automated): >10 WBC or pus cells in MSU
• Culture & colony count: 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: normally <10
• Red blood cells (RBC): calculi or glomerulonephritis, tumours or cystitis
• Epithelial cells: presence may indicate specimen contamination
• Bacteria can be seen on microscopy and this shows bacteriuria
• Casts also

Culture & Colony Count

• Use a 1µL = 0.001 mL sterile loop to transfer urine onto an agar plate
• Incubate overnight
• Next day, examine the plate for bacterial growth and count each bacterial colony:
  • 10 colonies in 0.001ml urine = 10,000 bacteria/mL = 104/mL

Interpretation of the Colony Count

• 105/mL – supports UTI diagnosis, provided patient has symptoms of UTI

• 104/mL – interpret with caution – review microscopy, is the patient symptomatic, was the patient on antimicrobials before the specimen was taken?
• 103/mL - probable contamination
• Mixed growth – likely contamination, send repeat specimen only if clinically indicated

Bacteria Identification on Agar Plate

• Chromogenic agar provides presumptive identification based on colour of bacterial growth
• You can also use Automated bacterial identification (MALDI-TOF)

Treatment of UTI

• Don't take a urine sample unless the patient has symptoms of UTI
• NEVER diagnose UTI based on a positive dipstick for nitrites and leucocytes alone
• Treat the patient, not the laboratory result:
  • Beware of the possibility of asymptomatic bacteriuria
• Almost always get a positive dipstick for nitrites and leucocytes
• Culture result requires catheter specimen urine (CSU)
• For uncomplicated cystitis in younger women – delayed antimicrobial prescribing strategy may be considered - watch and wait, only take antibiotics if not settling or worsening within 48 – 72 hours
• Local antibiotic guidelines should be used
• Choice depends on susceptibility profile – ensure the patient has not had a history of antimicrobial resistant organisms in previous specimens
• The spectrum of the dose should be narrow, if possible
• Need to consider the cost, cheap if possible (e.g. trimethoprim, nitrofurantoin)
• Route: usually oral (PO), IV if systemic or complicated infection
• Duration: Females cystitis – 3 days, Males or urinary catheter in situ – 7 days, Complicated infection, pyelonephritis, UTI and BSI: 7 – 14 days

UTI and Pregnancy

• UTI is the commonest complication of pregnancy
• MSU routinely taken at first antenatal visit
• ~4-6% of pregnant women have asymptomatic bacteriuria
• Asymptomatic bacteriuria in pregnancy is different to other situations, because there is a significant risk it will progress to UTI and pyelonephritis
• Predisposing factors to UTI in pregnancy include: Decreased bladder size, Urethral muscle tone due to hormonal effects and Urinary stasis due to pressure from uterus
• If untreated, 20-30% will develop acute pyelonephritis (AP)
• Patients with untreated bacteriuria more likely to suffer miscarriage or premature labour
• Pregnancy is one situation where antimicrobial treatment of asymptomatic bacteriuria is warranted

UTI in Children

• Incidence 1-2%
  • 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
• Presentation
  • 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 requires : Clean catch urine, MSU and Suprapubic aspirate
• Follow-up depends on age of the child, how quickly they responded to treatment and if they have a history of recurrent UTI
• Ultrasound identifies structural abnormalities of urinary tract
• Dimercaptosuccinic acid (DMSA) scan determines if residual renal parenchymal defects post infection
• Micturating cystourethrogram (MCUG) determines if vesicoureteric reflux

Diabetes Mellitus

• Increased incidence of UTI due to: Bladder dysfunction (neuropathy)
• diabetes can also effect Structural abnormalities, cause Recurrent vaginitis and Vascular disease
• Glucose in urine is a sugary culture medium supporting bacterial growth

Case Scenario for 72 year old man

• A 72 year-old man presents to GP with temperature 39°C, dysuria & right flank pain, frequency & nocturia x 3 months earlier
• Urinary dipstick showed leucocytes and blood
• He is an Older male with symptoms localizing to the Urinary tract like dysuria and flank pain
• He also had systemic symptoms like fever
• Urinalysis shows leucocytes
• He was Referred to ED where history and examination, sepsis screening tool, blood tests, MSU and blood cultures taken
• Sepsis criteria met – SEPSIS 6 = TAKE 3, GIVE 3
  • Clinical impression – Urosepsis
• Commenced on IV cefuroxime and IV gentamicin as per local guidelines
• MSU microscopy & culture results: >100 WBC or pus cells seen and Culture: E. coli
• Blood cultures: E. coli, Susceptible to cefuroxime & gentamicin

Acute Pyelonephritis

• Acute inflammation of kidney can lead to renal abscess / necrosis
• Causes and risk factors similar to those of acute UTI
• May be accompanied by BSI
• Risk Factors include Structural abnormality of urinary tract; congenital, obstruction like calculi, tumour and foreign body
• Additional risk factors include Pregnancy and some Urinary tract instrumentation
• Clinical Presentation: Pain in flank, renal angle but May not have symptoms of cystitis like dysuria and urgency
• Systemically unwell with Fever, Rigors, Nausea, vomiting and possible BSI
• Diagnosis with Urine culture and Blood cultures
  • positive in 30-40% of cases of pyelonephritis
  • longer treatment course may be required: 7 – 14 days
  • blood cultures should always be performed if sepsis criteria met or clinical concern
• Treatment with Follow local guidelines and IV antibiotics such as empiric cefuroxime + gentamicin and Drainage, if pus or abscess present

Sterile Pyuria

• Sterile Pyuria is WBC or pus cells (>10/mm³) in urine, but sterile urine culture
• Causes: Antimicrobial therapy - the commonest cause by far, Tumour and Urinary stones or calculi
• Additional Causes include Chlamydia urethritis and other STI, Less common infectious causes like Tuberculosis and Brucellosis

Renal Tuberculosis (TB)

• Renal TB presents with Haematogenous spread to kidney
• Symptoms: usually systemically unwell & less acute than conventional UTI
  • frequency, painless haematuria, malaise, fever and weight loss
• Diagnosis: Think about renal TB if sterile pyuria especially if persistent symptoms for weeks or months, Laboratory Diagnosis with Early morning urine (EMU) specimens x 3 Taken on three consecutive days
  • In laboratory, mycobacterial culture for up to 8 weeks. Microscopy (staining for AFB/ ZN not done)

Summary 1

• Ascending route of bacteria from anogenital area responsible for most UTI
• Pathogens:
  • E. coli is the commonest cause of UTI by far
  • Staphlococcus saprophyticus; young females
  • Proteus mirabilis - renal calculi
  • Klebsiella pneumoniae, Pseudomonas aeruginosa and enterococci are also commonly seen
• Healthcare-associated UTI:
  • Common type of HAI
  • Risk of antimicrobial-resistant pathogens
  • Associated with urinary catheters
  • Risk of BSI

Summary 2

• Asymptomatic bacteriuria is common, especially in older patients and in patients with catheters and does not require antibiotic treatment
• 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
• Think of TB in sterile pyuria

Additional Information

• A sample PSA MCQ presented includes a case of a 22 year old female attending her GP complaining of a 2 day history of urinary frequency and dysuria
• She is systemically well with a past medical history of two previous urinary tract infections and an allergy to penicillin
• Investigations showed a recent MSU cultured an organism which was sensitive to Amoxicillin and Nitrofurantoin but resistant to Trimethoprim
• The appropriate prescription is Nitrofurantoin as it is used to prescribe an uncomplicated UTI in a female, in addition the dose and frequency matches what the immediate release capsule is showing
• Amoxicillin is inappropriate due to the patient's allergies
• Trimethoprim is inappropriate due to the cultures resistance
• Piperacillin-tazobactam is inappropriate as IV antibiotics are not indicated for an uncomplicated UTI
• Optional Additional Reading: New Eng J Med 2012; 366: 1028-37 (Uncomplicated UTI with Case), Br Med J 2011; 343:d4780 doi: 10.1136/bmj.d4780 (Asymptomatic bacteriuria) and NICE guidelines on UTI in children https://www.nice.org.uk/Guidance/CG54