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Urinary tract infection
Urinary tract infection

Urinary tract infection

Urinary tract infections include infections of the urethra (urethritis), bladder (cystitis) and kidneys (pyelonephritis)

In this CCC, we will be discussing UTIs in men, women and children and it will be divided into:

  • Lower UTIs in men
  • Lower UTIs in women
  • UTIs in children
  • Pyelonephritis
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LOWER UTI IN MEN

Lower UTI is considered to be bladder infection (cystitis). They are far less common in men, simply due to the length of the male urethra (~20cm) compared to the female urethra (~5cm). For this reason in men, it is typically due to some risk factor precipitating it (complicated UTI).

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Let’s clarify some definitions:
  • Lower UTI - cystitis. Technically urethritis and prostatitis too but when referring to lower UTI, we will be meaning cystitis.
  • Upper UTI - pyelitis (proximal ureter infection) and pyelonephritis (kidneys and proximally part of ureters).
  • Uncomplicated UTI - infection caused by usual pathogen in an individual with a normal urinary tract and normal kidney function.
  • Complicated UTI - UTI with risk factors present, recurrent infection, refractory to treatment.
  • Recurrent infection - repeated UTI due to relapse or reinfection. Considered 3 or more UTIs within 12 months, or 2 or more confirmed UTIs within 6 months.
    • Relapsing UTI - recurrent UTI with the same strain. Usually occurs within a short period after treatment (<2 weeks).
    • Reinfection - recurrent UTI with different strain. Usually occurs more than 2 weeks after treatment.
  • Catheter associated UTI (CAUTI) - symptomatic infection in an individual catheterised within the past 48 hours.
  • Asymptomatic bacteriuria - presence of significant bacteria in urine but no signs or symptoms of infection.

🏘️ Epidemiology

UTI is the most common nosocomial infection (40%) and second most common community-acquired infection. 80% of these are secondary to an indwelling catheter.

They are most common in men >50 years old.

Men only account for 20% of all UTI occurrences.

🦠 Pathophysiology and causative agents

UTIs develop when microorganisms (most commonly bacteria) access the urinary tract via the urethra and ascend into the bladder.

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There they infiltrate and colonise the bladder. Neutrophils infiltrate leading to an immune response, however, the bacteria are able to evade it. They form a biofilm on the epithelia and also damage the epithelia with toxins and proteases.

⭐️ The bacteria tend to originate from the intestine and as such the most common causative agent is E. coli which makes up approximately 75% of all uncomplicated UTIs (and 65% of complicated UTIs). The strains of E. coli that cause UTIs can be termed uropathogenic E. coli (UPEC).

In men there are more frequently varied organisms such as:

  • Gram-positive bacteria
  1. Staphylococcus saprophyticus
  2. Enterococcus spp.
  3. Streptococcus agalactiae
  • Gram-negative bacteria
  1. Klebsiella pneumoniae
  2. Proteus spp.
  3. Providencia spp.
  4. Pseudomonas aeruginosa

Candida albicans is a rare cause but can be seen in complicated UTIs more frequently, such as those with indwelling catheters or who are Immunocompromised.

⚠️ Risk factors

Structural or functional abnormalities of the UTI impair urine flow and allow for more opportunity for the bacteria to colonise. Presence of these risk factors will result in the classification of complicated UTI:

  • Prostate disorders
  • Renal stones
  • Indwelling catheter or catheter use (catheter associated UTI/CAUTI)
  • CKD
  • Diabetes
  • Immunodeficiency
  • Transplantation

Other risk factors include: sex, hospitalisation, uncircumcised men, previous UTI.

😷 Presentation

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  • Dysuria - pain or discomfort passing urine.
  • Frequency
  • Urgency
  • Nocturia
  • Suprapubic pain
  • Odorous urine
  • Cloudy urine
  • Haematuria
  • Confusion - sometimes it is the only symptom in elderly or frail patients.
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Fever, loin pain, back pain, nausea and vomiting as well as renal angle tenderness are issues more associated with pyelonephritis.

🔍 Investigations

  • 🥇 Urine dipsticks are not used to diagnose UTI in men. They can be used to decide if a working diagnosis should be made for a UTI and further investigations may be done to confirm the presence of infection.

      • Some things we may look for on a urine dipstick are:

    1. Nitrites - presence of nitrites has a positive predictive value of 96%. Nitrites are a byproduct of nitrate breakdown by gram-negative bacteria.
    2. Leukocytes - a small number are present normally, however, a significant number indicates infection or other inflammatory causes.
    3. RBCs - this identifies microscopic haematuria which is when there is blood identified on the dipstick but it is not evident on appearance of the sample. This differs from macroscopic/gross haematuria which is when the urine has a pink/red/brownish (tea-coloured) appearance.
    4. Urine dipstick positive for (nitrites OR leukocytes) AND RBCs → UTI is likely.
    5. Urine dipstick negative for nitrites and positive for leukocytes → UTI is equally likely to other diagnoses.
    6. Urine dipstick negative for nitrites, leukocytes and RBCs → UTI is less likely.
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If symptoms are suggestive of UTI, we can confirm the diagnosis with urine culture and sensitivity this can be collected by:

  1. 🏆 Mid-stream urine - a urine sample needs to be obtained prior to starting empirical antibiotics.
  2. 🏆 Catheter specimen of urine - if there is an indwelling catheter.

🧰 Management

This section will cover management of:

  1. Lower UTIs in men
  2. Recurrent UTI in men
  3. UTI in men with indwelling catheter
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Managing lower UTI in men:

Antibiotics

It is important to consider previous antibiotic use (for resistance).

  • 🥇 Empirical antibiotic treatment
    • Trimethoprim - 200mg BD for 7 days.
    • Nitrofurantoin - 100mg BD for 7 days. ⚠️ It can only be used if eGFR >45ml/min.
    • If prostatitis is suspected → ciprofloxacin is first-line.

If the patient is severely unwell (nausea and vomiting, confusion, tachypnoea, tachycardia, hypotension all indicative of urosepsis) → admit to hospital.

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Managing recurrent UTI in men:

This is if the patient has had 2+ episodes in the past 6 months or 3+ in the past 12 months.

It is important to advise patients on the importance of hydration, not delaying habitual and post-coital urination as these can increase the likelihood of UTI.

Antibiotic prophylaxis

  • 🥇 Trimethoprim - 100mg at night or 200mg single dose when exposed to a trigger.

OR

  • 🥇 Nitrofurantoin - 50-100mg at night or 100mg single dose when exposed to a trigger.
    • ⚠️ It can only be used if eGFR >45ml/min.

If these are not suitable, second-line antibiotics are:

  • 🥈 Amoxicillin - 250mg at night or 500mg single-dose when exposed to a trigger.

OR

  • 🥈 Cefalexin - 125mg at night or 500mg single-dose when exposed to a trigger.

Antibiotic prophylaxis should be reviewed every 6 months. Local policies may have rotational regimens.

If there is an acute UTI, a different antibiotic to the one for prophylaxis should be used.

⚠️ Long-term use of nitrofurantoin may precipitate restrictive lung disease.

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Managing UTI in men with indwelling catheter:
  1. Check the catheter - ensure it is not blocked and that it is correctly positioned.
  2. Change the catheter - if it has been in place for >7 days.
  3. Empirical antibiotics
    1. 🥇 Nitrofurantoin
    2. 🥇 Trimethoprim
    3. 🥇 Amoxicillin
    4. 🥈 Pivmecillanim (piv when there is a pipe in the penis)

      5. Antibiotic treatment should be reassessed once culture and sensitivity results are available. Narrow-spectrum should be used when possible (if possible).

🚧 DO NOT treat asymptomatic bacteriuria in catheterised patients.

⚠️ Antibiotics should not be given prophylactically for CAUTI with indwelling catheters.

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LOWER UTI IN WOMEN

Women account for 80% of UTI infections due to the shorter urethra as well as proximity of urethra to anus. They are more common in older women but almost 1/3rd of women have had an acute UTI by age 24.

⚠️ Risk factors

Pre-menopausal women

  • Sexual intercourse
  • History of UTI
  • Mother with history of UTI
  • Pregnancy
  • Contraceptive diaphragm
  • Catheterisation

Post-menopausal women

  • History of UTI
  • Urinary incontinence
  • Atrophic vaginitis
  • Cystocoele
  • Catheterisation

🔍 Investigations

🥇 In women <65 years old and no risk factors for complicated UTI → urine dipstick can be used.

  • Urine dipstick positive for (nitrites OR leukocytes) AND RBCs → UTI is likely.
    • NICE states that in these patients, a sample for cultures should be sent if previous antibiotics have failed or risk of resistance. However, they also say that if haematuria is present (visible or non-visible) we should send it for cultures regardless.
  • Urine dipstick negative for nitrites and positive for leukocytes → UTI is equally likely to other diagnoses.
    • Send cultures to confirm diagnosis.
  • Urine dipstick negative for nitrites, leukocytes and RBCs → UTI is less likely. No cultures needed, consider other diagnosis.

🏆 Cultures need to be sent for all women who are:

  • Pregnant
  • >65 years old
  • Persistent symptoms that are refractory to treatment
  • Have recurrent UTI
  • Have a catheter in-situ/recently catheterised.
  • Have risk factors for complicated UTI.
  • Have atypical symptoms.
  • Have visible or non-visible (on urine dipstick) haematuria.

🧰 Management

This section will cover management of:

  1. Lower UTI in women (not catheterised/pregnant and no visible haematuria)
  2. Lower UTI in women (with visible haematuria)
  3. Recurrent UTI in women (not catheterised/pregnant and no visible haematuria)
  4. UTI during pregnancy
  5. Asymptomatic bacteriuria in pregnancy
  6. CAUTI
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Managing lower UTI in women (not catheterised nor pregnant and no visible haematuria):

🥇 If symptoms are mild and there are no risk factors for complicated UTI → back-up/delayed antibiotic can be prescribed (in accordance with the options listed below). This means if symptoms do not resolve within 48 hours or begin to worsen they may begin antibiotics.

If symptoms and risk of complications warrant antibiotic use, we should treat them according to urine culture sensitivities (if available), if not we can use empirical antibiotics:

  • 🥇 Nitrofurantoin - 100mg BD for 3 days.

OR

  • 🥇 Trimethoprim - 200mg BD for 3 days.

Other options include (if no improvement and the first-line used for 48 hours or if first-line is unsuitable)

  • Nitrofurantoin - if trimethoprim was used as first-line.
  • Pivmecillinam - 400mg initial dose, then 200mg three times a day for a total of 3 days.
  • Fosfomycin - 3g single dose sachet.

If haematuria is present (visible or non-visible):

🥇 Cultures need to be sent before starting treatment. A test of cure is also necessary.

The management of the UTI is the same depending on the scenario (e.g. uncomplicated, recurrent, pregnant, CAUTI).

If haematuria is persistent after antibiotic use then consider causes (pyelonephritis, cancer, CKD) then we need to make appropriate referrals.

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Managing recurrent UTI in women:

Women should be advised on:

  1. Avoiding douching and occlusive underwear
  2. Wiping front to back after defecation
  1. Avoiding delay of urination, including post-coital urination.
  2. Drinking adequate fluids.

Postmenopausal women

  • Vaginal oestrogen

Antibiotic prophylaxis

First we should try single-dose antibiotic prophylaxis when exposed to a trigger:

  • 🥇 Trimethoprim - 100mg at night or 200mg single dose when exposed to a trigger.

OR

  • 🥇 Nitrofurantoin - 50-100mg at night or 100mg single dose when exposed to a trigger.
    • ⚠️ It can only be used if eGFR >45ml/min.

If these are not suitable, second-line antibiotics are:

  • 🥈 Amoxicillin - 250mg at night or 500mg single-dose when exposed to a trigger.

OR

  • 🥈 Cefalexin - 125mg at night or 500mg single-dose when exposed to a trigger.

If this doesn’t work then we can use nightly antibiotic prophylaxis (the same drugs are first and second-line).

⚠️ Long-term use of nitrofurantoin may precipitate restrictive lung disease.

💊
Managing UTI during pregnancy and asymptomatic bacteriuria:

Pregnancy

  • Antibiotics - should be offered immediately after urine cultures and sensitivities are taken.
    1. 🥇 Nitrofurantoin - remember that trimethoprim is contraindicated in the first-trimester of pregnancy. 100mg modified-release twice a day for 7 days.

      2. 🚨 However, nitrofurantoin should be avoided in the third trimester and also in patients with G6PD deficiency (due to the risk of neonatal haemolysis). Therefore if in the 3rd trimester of pregnancy (>28 weeks) amoxicillin is first-line.

      Second-line options include:

    2. 🥈 Amoxicillin - only if culture results are available and it is sensitive to amoxicillin. It is first-line in 3rd trimester, however. 500mg three times a day for 7 days.
    3. 🥈 Cefalexin - 500mg twice a day for 7 days.

For asymptomatic bacteriuria

  1. 🥇 Nitrofurantoin - remember that trimethoprim is contraindicated in the first-trimester of pregnancy. 100mg modified-release twice a day for 7 days.
  2. 🥇 Amoxicillin - only if culture results are available and it is sensitive to amoxicillin. 500mg three times a day for 7 days.
  3. 🥇 Cefalexin - 500mg twice a day for 7 days.

If GBS (strep. agalactiae) is identified → notify antenatal services as intrapartum antibiotics will be needed.

For pregnant women, a culture should be sent once treatment is completed to ensure that it has been cleared.

💊
Managing CAUTI in women:
  1. Check the catheter - ensure it is not blocked and that it is correctly positioned.
  2. Change the catheter - if it has been in place for >7 days.
  3. Empirical antibiotics
    1. 🥇 Nitrofurantion - 100mg modified-release twice a day for 7 days.
    2. 🥇 Trimethoprim - 200mg modified-release twice a day for 7 days.
    3. 🥇 Amoxicillin - 500mg three times a day for 7 days.
    4. 🥈 Pivmecillanim - 400mg initial dose, then 200mg three times a day for a total of 7 days.

      5. Antibiotic treatment should be reassessed once culture and sensitivity results are available. Narrow-spectrum should be used when possible (if possible).

Trimethoprim is contraindicated with methotrexate as both alter folate metabolism (think triMETHoprim and METHotrexate). Trimethoprim is also associated with an isolated rise in creatinine as seen on U&E sampling.

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UTI IN CHILDREN

1 in 10 girls and 1 in 30 boys will have had a UTI by the age of 16.

⚠️ Risk factors

  • <1 years old
  • Female sex
  • Caucasian ethnicity
  • Vesicoureteral reflux - reflux of urine from the bladder into the ureter. Increases the risk of renal scarring.
  • Previous UTI
  • Sexual activity
  • No breastfeeding history
  • Immunosuppression

😷 Presentation

Presentation may differ depending on the child’s age

<3 months old

  • Fever - suggestive of acute pyelonephritis.
  • Vomiting
  • Lethargy
  • Irritability
  • Poor feeding
  • Failure to thrive

>3 months old

  • Fever
  • Frequency
  • Dysuria
  • Abdominal pain
  • Loin tenderness
  • Vomiting
  • Poor feeding
  • Changes to continence

🔍 Investigations

If there is a fever + bacteriuria → diagnose acute pyelonephritis/upper UTI.

  • If UTI is suspected in child <3 months → microscopy and culture.
  • If UTI is suspected in child >3 months → urine dipstick.

🧰 Management

💊
Managing UTI in children <3 months:
  • Refer to paediatrics for parenteral antibiotics and send for microscopy and culture.
💊
Managing pyelonephritis/upper UTI in children >3 months:

Oral antibiotics

  • 🥇 Cefalexin

OR

  • 🥇 Co- amoxiclav
💊
Managing cystitis/lower UTI in children >3 months:

Oral antibiotics

  • 🥇 Trimethoprim

OR

  • 🥇 Nitrofurantoin

Second-line options are:

  • 🥈 Nitrofurantoin - if not used first-line
  • 🥈 Amoxicillin - only if culture results are available and it is sensitive to amoxicillin.
  • 🥈 Cefalexin
💊
Managing recurrent UTI in children:

Antibiotic prophylaxis

  • 🥇 Trimethoprim

OR

  • 🥇 Nitrofurantoin

Second-line options are:

  • 🥈 Amoxicillin
  • 🥈 Cefalexin

Prophylactic antibiotics should be reviewed every 6 months.

Children should also have:

  1. Ultrasound KUB:
  • During the acute infection if: atypical UTI (sepsis, bladder mass, raised creatinine, refractory to treatment within 48 hours, non E. coli organisms) or <6 months old with recurrent UTI.
  • Within 6 weeks if: >6 months old with recurrent UTI or <6 months old with first UTI.
    • If it is abnormal → micturating cystourethrogram (MCUG).
  1. Dimercaptosuccinic acid scintigraphy (DMSA) scan - looks for renal parenchyma defects. Needs to be done within 4-6 months of acute infection.
  • All children with recurrent UTI
  • All children <3 years old with atypical UTI
  1. Micturating cystourethrogram
  • Children <6 months with atypical UTI or recurrent UTI to assess for vesicoureteric reflux (VUR)
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PYELONEPHRITIS

Pyelonephritis is the infection of the kidneys (and proximal ureters). The pathophysiology and causative agents are all the same. In pyelonephritis, however, the bacteria ascend the ureters and infect the kidneys. It may also occur due to bloodstream spread of the infection, for example with sepsis.

😷 Presentation

The features for pyelonephritis are indistinguishable from lower UTI, but there is a triad of symptoms that occur in pyelonephritis and is absent in lower UTI:

  1. Fever
  2. Flank/loin pain
  3. Nausea and vomiting

🔍 Investigations

🏆 All patient should have mid-stream urine sample or catheter specimen of urine for cultures (prior to empirical treatment).

🧰 Management

💊
Managing acute pyelonephritis:

First-line antibiotics include a choice of either:

  • 🥇 Cefalexin - 500mg twice or three times a day for 7-10 days.
  • 🥇 Co-amoxiclav - 500/125 mg three times a day for 7-10 days.
  • 🥇 Trimethoprim - 200mg twice a day for 14 days.
  • 🥇 Ciprofloxacin - 500 mg twice a day for 7 days.

Pregnant women

  • Cefalexin - 500mg twice or three times a day for 7-10 days.

If patients have signs of sepsis → admit to hospital.

🚨 Complications

  • Sepsis
  • Renal parenchyma scarring
  • Recurrent UTI
  • Renal abscess
  • Preterm labour in pregnant women
  • Emphysematous pyelonephritis - a necrotising infection of the renal parenchyma with gas formation in or around the kidneys.