Antimicrobial Stewardship (AMS)

• Escherichia coli
• Other Enterobacteriaceae (Klebsiella sp., Proteus sp.)

Last reviewed December 2023

• Increasing E.coli resistance to fluoroquinolones. These agents are not recommended for empiric or first-line treatment of uncomplicated UTIs. 
• Local uropathogens' susceptibilities should be considered when choosing empiric treatment: 
  • Sulfamethoxazole/trimethoprim should not be used if resistance exceeds 20 %
  • Ciprofloxacin should not be used if local resistance exceeds 10%

Last reviewed December 2023

• Signs and symptoms: dysuria, urgency, frequency, suprapubic pain/tenderness
• No symptoms of upper urinary tract infection: fever, chills, flank pain, costovertebral angle tenderness
• No risk factors for complicated infection: 
  • Pregnancy
  • Immunosuppression
  • Diabetes (especially if long term complications) 
  • Indwelling catheter
  • Anatomical abnormality 
  • Voiding dysfunction
  • Obstruction
  • Recent urogenital procedure 
• A UTI in men is often, but not always, considered complicated. Investigation for anatomical abnormalities or prostatitis should be considered. 
• Urine culture is not generally recommended unless:
  • Antibiotic use or UTI in last 3-6 months
  • Suspected UTI in a male
  • Travel outside North America in last 6 months
  • Recent hospitalization 
  • History of a UTI caused by a multidrug resistant microorganism 
  • Complicated UTI 
  • Failure to respond to empiric therapy after 48hrs 
• The reliability of the urine dipstick as a diagnostic tool for UTI is low due to an inability to differentiate between an infection and asymptomatic bacteriuria, and is not recommended as a test for diagnosing UTI. 

Last reviewed December 2023

Post treatment urine cultures are not recommended if adequate response to therapy

Last reviewed December 2023

• First line: 
  • Nitrofurantoin macrocrystals 100 mg PO twice daily x 5 days*
• Second line:
  • Fosfomycin 3 g PO x 1 dose*
  • Sulfamethoxazole-trimethoprim (SMX-TMP) 1 DS tablet (160/800 mg) PO BID x 3 days*
• Alternative:
  • Cephalexin 500 mg PO QID x 5-7 days*

* Treatment duration of 7 days is recommended in males with uncomplicated cystitis. If using fosfomycin in men, use 3 g PO every 3 days x 2-3 doses.

If recurrent UTIs, multiple antibiotic courses, or unable to use any of the above, suggest urine culture to guide targeted therapy.

Last reviewed December 2023

• Amoxicillin-clavulanate is not recommended due to adequate response rates with more selective agents. Can consider if high risk of resistance such as frequent UTIs requiring antibiotics or an infection resistant to first- and second-line options.
• Ciprofloxacin is no longer recommended as first line treatment due to high risk of adverse effects including tendinopathy, aortic dissection, peripheral neuropathy, central nervous system effects and C. difficile infection.
• Moxifloxacin should not be used as it does not attain sufficient concentration in the urine.
• Sulfamethoxazole-trimethoprim (SMX-TMP) 
  • Associated with higher risk of renal injury, hyperkalemia, and sudden death if
    • Patients aged 65 years and older
    • Patients on medications that can increase potassium: angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), or K⁺ sparing diuretic (e.g., spironolactone)
  • Regular monitoring of kidney function and electrolytes are recommended for patients with risk factors for hyperkalemia or prolonged duration of therapy.
• Nitrofurantoin should not be used in patients with: 
  • CrCl less than than 30 ml/min
  • Infections outside lower urinary tract due to poor distribution into serum and tissue
• If Staphylococcus aureus is isolated in the urine, bacteremia may be present. The patient must be assessed for other sources of infection. 

Last reviewed December 2023

1. Toronto Central Local Health Integration Network. Guidelines for Empiric Treatment of Urinary Tract Infections in Adults. January 2015. Accessed online 09/2017. www.antimicrobialstewardship.com.

2. Gupta K, Hooton TM, Naber KG, Wullt B, et al. International Practice Guidelines for the Treatment of Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20.

3. Fralick M, Macdonald EM, Gomes T, Antoniou T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of reninangiotensin system: population based study. BMJ. 2014 Oct 30;349:g6196

4. Crellin E, Mansfield KE, Leyrat C, Nitsch D, et al. Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study.BMJ. 2018 Feb 9;360:k341.

Last reviewed December 2023

• Escherichia coli
• Other Enterobacterales (Klebsiella spp., Proteus spp.)

Last reviewed April 2024

• Increasing E. coli resistance to fluoroquinolones and sulfamethoxazole/trimethoprim

Last reviewed April 2024

• Symptoms of upper tract infection or systemic infection
  • Flank pain, fever, chills, nausea, vomiting, and costovertebral angle tenderness with or without symptoms of cystitis
• Urine culture prior to starting antibiotics recommended for all patients
• 2 sets of blood cultures if fever or other systemic symptoms

Last reviewed April 2024

• Asymptomatic bacteriuria does NOT require antibiotic therapy, unless in pregnancy or prior to invasive urological procedure
• Consider imaging if
  • Persistent clinical symptoms/instability despite 48 to 72 hours of appropriate antimicrobial therapy
  • Suspected urinary tract obstruction (e.g., if renal function has declined below baseline or there is a precipitous decline in the urinary output)
  • Recurrent systemic infection
• Pregnancy: IWK Firstline App

Last reviewed April 2024

• Consider recent urine culture results and antimicrobial use prior to selecting empiric antibiotic
• Adjust following dosing recommendations for renal function when required
• Lower urinary symptoms at risk of more severe infection without fever/systemic symptoms:
  • Ensure close monitoring for progression to systemic infection. 
    • First line: Nitrofurantoin macrocrystals 100 mg PO BID 
    • Second line: 
      • Fosfomycin 3 g PO every 3 days x 3 doses 
      • Sulfamethoxazole-trimethoprim (SMX-TMP) 1 DS tablet (160/800 mg) PO BID  
    • Alternatives: 
      • Cephalexin 500 mg PO QID if first episode of UTI and no risk factors for resistance such as frequent antibiotic use or colonization/infection with resistant bacteria in last 6 months 
      • Amoxicillin-clavulanate 875/125 mg PO BID if recurrent UTI and risk factors for resistance

Duration: unknown but usually recommend 7 days of therapy

• Hemodynamically stable with suspected infection extending beyond the bladder (e.g., fever, chills, back pain, nausea, vomiting and fever or additional systemic symptoms)
  • IV or oral depending on circumstance
    • If systemically unwell: consider initial dose of ceftriaxone IV, and then start one of the following based on culture results and clinical response: 
      • Amoxicillin-clavulanate 875/125 mg PO BID (875/125 mg PO TID if bloodstream infection and CrCl greater than 30 mL/min)
      • Cefixime 400 mg PO daily (avoid if bloodstream infection)
      • Ciprofloxacin 500 mg PO BID 
      • Sulfamethoxazole-trimethoprim (SMX-TMP) 1 DS tablet (160/800 mg) PO BID  
  • Duration: 7 days if rapid response to therapy, 10-14 days if delayed response to treatment or functional/structural abnormality
    • Infections with abscess, stents, or stones require an individualized approach and referral to urology for source control considerations
    • Prostatitis – see separate guidance
  • Nitrofurantoin and oral fosfomycin should not be used because of low renal tissue and systemic concentration

• Hemodynamically unstable with suspected urinary source
  • Ceftriaxone 1g IV q24h +/- consider ampicillin if sepsis or previous infection with enterococci
  • High risk of resistant Gram-negative infection:
    • Colonization or recent infection with resistant Gram-negative microorganisms (e.g., Pseudomonas), or
    • Healthcare associated, or
    • Broad-spectrum antibiotic use in last 3 months
    • Consider one of the following regimens and narrow when sensitivities available:
      • Ceftazidime 1-2 g IV q8h
      • Piperacillin-tazobactam 3.375 g IV q6h (if confirmed or suspected Pseudomonas use 4.5g IV q6h)
      • Tobramycin: Use with caution due to toxicities, refer to aminoglycoside handbook chapter  
  • Duration: 7 days if rapid response to therapy, 10-14 days if delayed response to treatment or functional/structural abnormality
    • Infections with abscess, stents, or stones require an individualized approach and referral to urology for source control considerations
    • Prostatitis – see separate guidance
  • Nitrofurantoin and oral fosfomycin should not be used because of low renal tissue and systemic concentration

Last reviewed April 2024

• Sulfamethoxazole-trimethoprim (SMX-TMP)
  • Associated with higher risk of renal injury, hyperkalemia, and sudden death if aged 65 years and older or on medications that can increase potassium
  • Regular monitoring of kidney function and electrolytes are recommended for patients with risk factors for hyperkalemia or prolonged duration of therapy.
• Aminoglycosides: risk of ototoxicity and nephrotoxicity. Monitoring required.

Last reviewed April 2024

1. Grant J, Le Saux N. Practice point: duration of antibiotic therapy for common infections. J Assoc Med Microbiol Infect Dis Can. Epub 2021 Apr 29. https:// jammi.utpjournals.press/doi/pdf/10.3138/jammi- 2021-04-29.

2. Wagenlehner FME, Bjerklund Johansen TE, Cai T, Koves B, Kranz J, Pilatz A, Tandogdu Z. Epidemiology, definition and treatment of complicated urinary tract infections. Nat Rev Urol. 2020 Oct;17(10):586-600.

Last reviewed April 2024

• Escherichia coli
• Other Enterobacterales (Klebsiella sp., Proteus sp.) 

Last reviewed April 2022

• Increasing E.coli resistance to fluoroquinolones and sulfamethoxazole/trimethoprim

Last reviewed April 2022

• Signs and symptoms: flank pain, fever, chills, nausea, vomiting and costovertebral angle tenderness with or without symptoms of cystitis 
• Urine culture prior to starting antibiotics recommended for all patients 
• Blood cultures may be considered in some clinical scenarios such as diagnostic uncertainty and sepsis, persistent fever or other systemic symptoms despite empiric therapy

Last reviewed April 2022

• Nitrofurantoin and fosfomycin should not be used for pyelonephritis because of low renal tissue concentration
• Pregnancy: IWK Firstline App

Last reviewed April 2022

• Outpatient, consider initial, single dose of ceftriaxone IV, and then start one of the following: 
  • Amoxicillin-clavulanate 875/125 mg PO BID x 10 days
  • Cefixime 400mg PO daily x 10 days
  • Ciprofloxacin 500 mg PO BID x 7 days
  • Sulfamethoxazole-trimethoprim (SMX-TMP) 1 DS tablet (160/800 mg) PO BID x 10 days
• Requiring admission or unable to take oral therapy:
  • Ceftriaxone 1 g IV q24h x 10 days
     
• High risk of resistant Gram-negative infection: 
  • Colonization or recent infection with resistant Gram-negative microorganisms (e.g., Pseudomonas), or 
  • Septic presentation and hospital acquired/frequent outpatient antibiotic use for urinary infections 
  • Consider following regimens and narrow when sensitivities available:
    • Ceftazidime 1-2 g IV q8h x 10 days
    • Piperacillin-tazobactam 3.375 g IV q6h (use 4.5 g IV q6h if confirmed or suspected Pseudomonas infection) x 10 days 
    • Tobramycin: Use with caution due to toxicities, refer to aminoglycoside handbook chapter  

Last updated June 2023

May require longer duration if patients are slow to respond to therapy or in complicated infections such as in the presence of abscess, stents, stones or other functional or structural abnormalities 

Last updated April 2022

• Complicated infections with abscess, stents, stones or other functional/structural abnormalities require an individualized approach and referral to urology for source control considerations.
• Sulfamethoxazole-trimethoprim
  • Associated with higher risk of renal injury, hyperkalemia, and sudden death if aged 65 years and older or on medications that can increase potassium
  • Regular monitoring of kidney function and electrolytes are recommended for patients with risk factors for hyperkalemia or prolonged duration of therapy.
• Aminoglycosides: risk of ototoxicity and nephrotoxicity. Regular monitoring required.

Last updated April 2022

1. Herness, Joel, Buttolph, Amelia, and Hammer, Noa C. Acute Pyelonephritis in Adults: Rapid Evidence Review. American Family Physician 102.3 (2020): 173-80.

2. NICE. Pyelonephritis (acute): antimicrobial prescribing guidelines. October 31, 2018. Available from https://www.nice.org.uk/guidance/ng111/resources/pyelonephritis-acute-antimicrobial-prescribing-pdf-66141593379781

3. Nicole, L. Urinary tract infection. Canadian Pharmacists Association. CPS. April 12, 2021. Available with subscription.

4. BMJ Best Practice. Acute pyelonephritis. June 10, 2021.

5. Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med. 2012 Mar 15;366(11):1028-37.

6. Grant J, Le Saux N. Practice point: duration of antibiotic therapy for common infections. J Assoc Med Microbiol Infect Dis Can. Epub 2021 Apr 29. https:// jammi.utpjournals.press/doi/pdf/10.3138/jammi-2021-04-29

Last reviewed April 2022