Pharmacist Treatment Guidance: Uncomplicated Cystitis

From 01 October 2022, the Queensland Government Extended Practice Authority ‘Pharmacists’ (EPA) authorises a pharmacist who has successfully completed training in accordance with the EPA to sell a medicine listed in the EPA to an eligible patient, without the requirement for a prescription, for the treatment of a urinary tract infection.

The EPA follows conclusion of the Urinary Tract Infection Pharmacy Pilot – Queensland (UTIPP-Q). Eminent pharmacy academics from the Queensland University of Technology reported outcomes of UTIPP-Q identifying that pharmacists have appropriate skills, competencies, and training, and reinforced their value to the health care system and patients, in the safe and appropriate care in community pharmacy of uncomplicated urinary tract infection. [1]

Title of the guidance

Pharmacist Treatment Guidance: Uncomplicated Cystitis (Queensland v1.0)

Endorsed September 2023

Content

  1. Purpose
  2. Supporting resources and training
  3. Setting for service delivery
  4. Background
  5. Definitions and acronyms
  6. Criteria for treatment
  7. Empirical antimicrobial cystitis therapy
  8. Symptom management
  9. Counselling, documentation, and follow up
  10. Related CPD activities for College members
  11. Appendix 1 - Safety, quality, and risk management Standards and Resources
  12. Appendix 2 - Summary of Australian and international UTI guidelines
  13. Comments
  14. References

Purpose

The Pharmacist Treatment Guidance: Uncomplicated Cystitis (“the guidance”) has been developed by the Australasian College of Pharmacy to assist pharmacists in the empirical antimicrobial treatment of uncomplicated cystitis via a urinary tract infection community pharmacy service in Queensland. The guidance should be used in conjunction with the following supporting resources.

Supporting resources and training

Setting for service delivery

A urinary tract infection community pharmacy service must be carried out in a setting as defined by relevant legislation and pharmacy guidelines.
(NB The setting for delivery of this service in Queensland is also stipulated in the current version of the Queensland Government Extended Practice Authority - Pharmacists).

Background

Urinary tract infections (UTIs) are prevalent in the community and a common cause of hospitalisation. Acute uncomplicated cystitis is most commonly caused by Escherichia coli (70 to 95% of cases) and Staphylococcus saprophyticus (5 to 10% of cases). [2]

UTIs are more prevalent in women than in men. On average 1 in 2 women develop a UTI during their lifetime, compared to only 1 in 20 men. [3]

When managed appropriately, the majority of UTIs can be treated effectively without hospitalisation. In 2020, it was found that UTIs were the second most frequent potentially preventable cause of hospitalisation in Australia. [4] The rate of preventable hospitalisation due to UTI is particularly high in remote areas, socioeconomically disadvantaged areas, and in Aboriginal and Torres Strait Islander communities. [5]

Preventing hospitalisation involves educating patients on the symptoms of UTI and accessing treatment in a timely manner.

Definitions and acronyms

Adapted from [6]

UTI: Urinary tract infection
STI: Sexually transmitted illness
Cystitis: Infection of the lower urinary tract (bladder and urethra in females) 
Uncomplicated cystitis: Acute, sporadic, or recurrent lower UTI, limited to non-pregnant women with no known relevant anatomical and functional abnormalities within the urinary tract or comorbidities
Complicated cystitis: UTIs that increase the risk of a complicated course, virulent infection, recurrence, or antibiotic failure. Including in: 

  • Men 
  • Pregnant women 
  • Patients with relevant anatomical or functional abnormalities of the urinary tract 
  • Patients with indwelling urinary catheters 
  • Renal diseases 
  • Other concomitant immunocompromising diseases e.g. diabetes 

Pyelonephritis#: Infection of the kidney/s
Ureteritis#: Infection of the ureter/s
Recurrent UTIs: Recurrences of uncomplicated and/or complicated UTIs, with a frequency of at least three UTIs in the previous 12 months or two UTIs in the previous six months.

# For the purposes of the guidance, pyelonephritis and ureteritis are considered to be complicated UTIs

Criteria for treatment

Eligible patients are females, 18 to 65 years old, presenting with uncomplicated cystitis and no other relevant history. Table 1 provides a more detailed summary of the inclusion criteria for pharmacists to supply antimicrobials for uncomplicated cystitis and exclusion criteria for patients requiring referral for further assessment under the guidance.

Table 1: Summary of inclusion and exclusion criteria for pharmacist treatment of uncomplicated cystitis

Criteria

Inclusion

Exclusion (requires referral)
Cystitis
  • Uncomplicated
  • Complicated
Sex (biological)*
  • Female
  • Male
Age
  • 18-65 years
  • 18 years
  • 65 years
Pregnancy status
  • Not pregnant
  • Pregnant
  • Postpartum (commonly 4-6 weeks after birth)
Symptoms

Presenting with 2 or more symptoms of cystitis:

  • Dysuria
  • Urinary frequency
  • Urinary urgency
  • Suprapubic pain 
  • Presenting with only 1 symptom of cystitis
  • Fever (>38◦C)
  • Chills
  • Nausea
  • Vomiting
  • Back/side pain
  • Vaginal itch and/or discharge (consider appropriateness of S3 Pharmacist Only thrush or bacterial vaginosis treatment or refer to a medical practitioner)
UTI history

 
  • Recurrent UTI
    • 2 or more UTIs in previous 6 months; OR
    • 3 or more UTIs in previous 12 months
  • Reoccurrence of UTI symptoms within 2 weeks of completing appropriate antimicrobial treatment
  • Any other prior non-responsiveness to UTI treatment
  • Multidrug resistant infection within the previous 3 months
Medicines

 
  • Antimicrobial use within the previous 3 months
  • Frequent antimicrobial use
  • Intrauterine device in situ
  • Immunosuppressant medicines
  • Medicines that increase the risk of UTI e.g. SGLT2 inhibitors
Other relevant medical history

 
  • Any STI risk
  • Immunocompromise
  • History of:
    • Urinary tract obstruction
    • Pyelonephritis
    • urinary tract abnormality
    • Urolithiasis
    • Urinary catheterisation (last 48 hours)
    • Nephrostomy tube
    • Ureteral stent
    • Renal disease or impairment
    • Spinal cord injury
    • Asplenia
  • Diabetes
  • Any overseas travel within the previous 3 months
  • Overseas travel within the previous 6 months in regions with high prevalence of antibiotic resistance#
  • Recent inpatient of a hospital (within previous 4 weeks) or other health care facility (within previous 3 months) or frequent or long-term care facility resident

*Anatomical characteristics
#E.g. from Southeast Asia and South Asia, particularly if they received medical care or treatment with antibiotics in that region.

Empirical antimicrobial cystitis therapy

Recommendation of empirical therapy for UTI is ideally guided by antimicrobial susceptibility testing of organisms recently isolated from a patient urine sample. Or, if antibiotic susceptibility is not available, likely susceptibility from local antibiogram data. [7] Choice of empirical therapy is also based on efficacy, convenience, cost, availability, and potential for harm (e.g. adverse effects and risk of development of antimicrobial resistance). [2]

Table 2 describes the empirical antimicrobial regimens used to treat patients included in the guidance (based on Australian and international guidelines – See Appendix 2, Table 4 for more information).

The potential benefits versus risks, including adverse effects and drug interactions, should be considered before recommending empirical antimicrobial treatment in each patient. Key contraindications and some precautions when treating cystitis with antimicrobials are included in Table 2.

Pharmacists should note this is not an exhaustive list and are advised to consider all relevant safe use of medicine precautions when recommending empirical UTI therapy. Precautions for use of antimicrobials may exclude some patients from the service.

All symptoms should respond within 48 hours of commencing antimicrobial therapy. [8]

Table 2: Empirical antimicrobial regimens used to treat patients with uncomplicated cystitis included in the guidance (refer to Table 1 for inclusion and exclusion criteria)

Antimicrobial

Dose

Contraindications and precautions [9,10]

First line - Trimethoprim

  • Excluding patients who have taken trimethoprim in the previous 3 months
  • Although ≈ 20% of E. coli urine isolates from adults in the community are resistant to trimethoprim, it continues to be recommended as empirical therapy for acute cystitis as the risk of adverse outcomes from treatment failure is low. [2]

300mg daily (at night) for 3 nights

Contraindications

  • Previous serious adverse reaction to trimethoprim containing medicines
  • Megaloblastic anaemia due to folate deficiency
  • Other severe blood disorders
  • Renal impairment (CrCl < 15mL/min)
  • Porphyria
  • Pregnancy

Precautions

  • Hepatic impairment
  • Dose adjustment should be considered for creatinine clearance of 15-30mL/min
  • Hyperkalaemia – Trimethoprim causes retention of potassium. Concomitant renal impairment, potassium supplements, and other medicines that cause potassium retention may increase the risk of hyperkalaemia (average onset 4-5 days, therefore less likely with 3-day course)
  • May worsen folate deficiency and blood dyscrasias

Second line - Nitrofurantoin

  • When trimethoprim is contraindicated

100mg q6h for 5 days

Contraindications

  • Previous serious adverse reaction to nitrofurantoin
  • Renal impairment (CrCl < 60mL/min)
  • Glucose-6-phosphate dehydrogenase (G6PD), enolase, or glutathione peroxidase deficiency (may lead to haemolytic anaemia)
  • Anuria or oliguria
  • Avoid in breastfeeding if infant is < 4 weeks old or has G6PD deficiency

Precautions

  • Risk of polyneuropathy increases in renal failure (often accompanied by diabetes, electrolyte imbalance and vitamin B deficiency)
  • Medicines that alkalinise (e.g. antacids, urinary alkalinisers) reduce efficacy
  • Medicines that acidify (e.g. probenecid) may reduce excretion of nitrofurantoin leading to toxicity

Third line - Cefalexin

  • When both trimethoprim and nitrofurantoin are contraindicated
 500mg q12h for 5 days

Contraindications

  • Previous hypersensitivity to cephalosporins or immediate or severe hypersensitivity to penicillins

 

Symptom management

Symptoms of cystitis including pain and dysuria are commonly managed with non-prescription treatments and other self-care strategies. The evidence for their effectiveness is summarised in Table 3.

Table 3: Evidence for common symptomatic management of cystitis

Treatment

Proposed mechanism in cystitis

Evidence and comments

Urinary alkalinisers e.g. sodium bicarbonate

 Reduce discomfort of dysuria by reducing acidity of urine
  • Evidence for efficacy and safety of urinary alkalinisers for cystitis symptoms is lacking [2]
  • Consider patient preferences when recommending urinary alkalinisers
  • Avoid use with nitrofurantoin

Analgesics e.g. NSAIDs and paracetamol

 The symptoms of UTI are mostly due to the inflammatory effects of prostaglandins on the urinary mucosa
  • Where appropriate, patients should be offered analgesia to manage symptoms of acute cystitis [2]
Cranberry juice or tablets Inhibition of bacterial (mainly E. coli) adhesion to uroepithelial cells
  • Evidence is conflicting and clinical trials are often small and of variable design [11]
  • Outcomes of systematic reviews are contradictory [11]
  • Unlikely to be effective at preventing recurrent UTI [11]
  • eTG states cranberry products are not effective for UTI treatment [2]
Methenamine hippurate Methenamine salts are converted in acidic urine to the antibacterial formaldehyde
  • Methenamine hippurate may be effective for preventing UTI in patients without renal tract abnormalities, but there is a need for further large well‐conducted randomised controlled trials [12]
  • Contraindicated in renal impairment
  • eTG states methenamine hippurate is not effective for UTI treatment [2]
D-mannose Prevents bacterial adherence to uroepithelial cells
  • Evidence is conflicting
  • Systematic reviews find that there is some support for the use of D-mannose in treating cystitis symptoms [13] and that there is currently little to no evidence to support or refute the use of D-mannose to prevent or treat UTIs [14]
Probiotics Restoration of bowel and vaginal microbiota may decrease UTI risk
  • Clinical trials suggest probiotic supplements may reduce episodes of recurrent UTI [11]
  • However systematic reviews find the evidence to be limited and inconsistent [15,16]
Other self-care strategies and behavioural changes to reduce recurrent UTI episodes
  • Increased fluid intake
  • Avoid spermicide use
  • Post-coital bladder voiding
  • Wiping from front to back when toileting
  • Mostly clinically untested [17]
  • Increasing fluid intake above 1.5L per day is supported by clinical trial [17]
  • Evidence supporting behavioural changes such as post-coital voiding and hygiene practices is commonly anecdotal with the likelihood of strong bias [17]

 

Counselling, documentation, and follow up

Counselling

Antimicrobial dose and duration.

Common adverse effects of the selected antimicrobial.

Seek medical advice if:

  • Symptoms persist 48-72 hours after starting therapy 
  • Symptoms return within 2 weeks of completing therapy
  • Other/different symptoms present.

Offer analgesia to women with symptoms of acute cystitis.

Advise on safety of use during breastfeeding including potential for thrush, upset stomach, rash etc in the infant.

Advise on safe and effective self-care strategies to manage symptoms and reduce the risk of UTI recurrence.

Provide a Consumer Medicines Information leaflet. Consider providing a UTI fact sheet e.g. Urinary tract infections fact sheet from Kidney Health Australia.

Documentation

Keep a clinical record in accordance with relevant legislation and professional responsibilities. (NB The current version of the Queensland Government Extended Practice Authority - Pharmacists stipulates what this record must include).

Make a copy of the record of the service available to the patient.

Follow up

Follow up with the patient when clinically appropriate.

Related CPD activities for College members

Is it UTI or STI? Identifying the difference - Webinar (ACP Feb 2021)

Clinical review - Urinary Tract Infections in Adults: An Overview (ACP June 2022)

Coming soon
  • Urinary tract infection refresher
  • Pyelonephritis
  • Non-viral STIs
  • Non-infective genital conditions
  • HIV treatment and prevention
  • Pelvic inflammatory disease

Appendix 1

Safety, quality, and risk management Standards and Resources

Antimicrobial Stewardship Clinical Care Standard
Antimicrobial Stewardship in Australian Healthcare
Quality Care 2020 Pharmacy Services Guide
Clinical Governance Principles for Pharmacy Services (2018)
Pharmacist Professional Practice Standards (V5)
National Competency Standards Framework for Pharmacists (2016)
Code of Conduct for Pharmacists
Code of Ethics for Pharmacists
Guidelines for Advertising a Regulated Health Service

Appendix 2

Summary of Australian and international UTI guidelines
Table 4: Summary of empirical antimicrobial treatment regimens for uncomplicated cystitis from Australian and international guidelines

Guideline

Year

Region

Organisation

Antimicrobial
Treatment guideline for pharmacists Cystitis [18] 2022 Australia Pharmaceutical Society of Australia
  • Trimethoprim 300mg daily (night) for 3 nights OR
  • Nitrofurantoin 100mg q6h for 5 days OR
  • Cefalexin 500mg q12h for 5 days
Acute cystitis in adults [2] 2019 Australia Therapeutic Guidelines
  • Trimethoprim 300mg daily for 3 days OR
  • Nitrofurantoin 100mg q6h for 5 days OR
  • Cefalexin 500mg q12h for 5 days (if both above are not appropriate)
Urinary tract infections (adult): empirical treatment guideline [19] 2022 South Australia SA Health Department
  • Trimethoprim 300mg daily (night) for 3 days OR
  • Nitrofurantoin 100mg qid for 7 days OR
  • Cefalexin 500mg bd for 7 days
EAU guidelines on urological infections [6] 2022 Europe European Association of Urology
  • Fosfomycin 3g as a single dose OR
  • Nitrofurantoin 50-100mg qid for 5 days or
  • Pivmecillinam* 400mg tds for 3-5 days OR
  • Cephalosporins 500 mg bd for 3 days OR
  • Trimethoprim^ 200mg bd for 5 days OR
  • Trimethoprim/sulfamethoxazole^ 160/800mg bd for 3 days
Urinary tract infection (lower): antimicrobial prescribing [20] 2018 United Kingdom NICE Guideline
  • Nitrofurantoin 100mg bd for 3 days OR
  • Trimethoprim 200mg bd for 3 days (if low risk of resistance)
International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women [21] 2011 United States of America Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases
  • Nitrofurantoin 100mg bd for 5 days OR
  • Trimethoprim/sulfamethoxazole 160/800mg bd for 3 days OR
  • Fosfomycin 3g as a single dose OR
  • Pivmecillinam* 400mg tds for 3-5 days
  • Fluoroquinolones and other β-lactams should be used with caution in uncomplicated cystitis

*Not registered on the Australian Register of Therapeutic Goods [Accessed 12/09/2022]
^When resistance pattern for Escherichia coli is less than 20%

Comments

Comment on the guidance by emailing accreditation@acp.edu.au

© Copyright Australasian College of Pharmacy 2023

References

  1. Nissen, Lisa, Lau, Esther, & Spinks, Jean (2022) The management of urinary tract infections by community pharmacists: A state-wide trial: Urinary Tract Infection Pharmacy Pilot- Queensland (Outcome Report). Queensland University of Technology, Brisbane, Qld.
  2. eTG complete. (2019). Acute cystitis in adults. Therapeutic Guidelines Ltd. Melbourne. Published April 2019 [Accessed 09/09/2022]
  3. Kidney Health Australia. Urinary tract infections Fact sheet. [Last Review December 2018, Accessed September 2022].
  4. Australian Institute of Health and Welfare. (2020). Disparities in potentially preventable hospitalisations across Australia: Exploring the data.
  5. Australian Commission on safety and quality in Healthcare. (2021). The Fourth Australian Atlas of Healthcare Variation. 2.4 Kidney and urinary tract infections.
  6. Bonkat et al. European Association of Urology. (2022). EUA Guidelines Urological infections.
  7. Sullivan and Nicolaides. Community antibiogram report (Jan-Dec 2020).
  8. Hooton TM and Gupta K. UptoDate. (2021). Acute simple cystitis in women. Updated 15 March 2021. Available at: uptodate.com
  9. Rossi S, ed. Australian medicines handbook. Australian Medicines Handbook Pty Ltd. Adelaide. July 2022. [Accessed 13/09/2022].
  10. eMIMS. MIMS Australia. Sydney. 2022. [Accessed 13/09/2022]
  11. Wawrysiuk S, Naber K, Rechberger T, Miotla P. Prevention and treatment of uncomplicated lower urinary tract infections in the era of increasing antimicrobial resistance-non-antibiotic approaches: a systemic review. Arch Gynecol Obstet. 2019 Oct;300(4):821-828.
  12. Lee BS, Bhuta T, Simpson JM, Craig JC. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD003265.
  13. Parazzini F, Ricci E, Fedele F, Chiaffarino F, Esposito G, Cipriani S. Systematic review of the effect of D-mannose with or without other drugs in the treatment of symptoms of urinary tract infections/cystitis (Review). Biomed Rep. 2022 Jun 15;17(2):69.
  14. Cooper TE, Teng C, Howell M, Teixeira-Pinto A, Jaure A, Wong G. D-mannose for preventing and treating urinary tract infections. Cochrane Database Syst Rev. 2022 Aug 30;8(8):CD013608.
  15. Abdullatif VA, Sur RL, Eshaghian E, Gaura KA, Goldman B, Panchatsharam PK, Williams NJ, Abbott JE. Efficacy of Probiotics as Prophylaxis for Urinary Tract Infections in Premenopausal Women: A Systematic Review and Meta-Analysis. Cureus. 2021 Oct 17;13(10):e18843.
  16. New FJ, Theivendrampillai S, Juliebø-Jones P, Somani B. Role of Probiotics for Recurrent UTIs in the Twenty-First Century: a Systematic Review of Literature. Curr Urol Rep. 2022 Feb;23(2):19-28. doi: 10.1007/s11934-022-01085-x. Epub 2022 Feb 14. Erratum in: Curr Urol Rep. 2022 Jul 13;: PMID: 35156175.
  17. Gupta K. UptoDate. (2022). Recurrent simple cystitis in women. Updated 29 April 2022. Available at: uptodate.com
  18. Guidance for provision of antibiotics for acute uncomplicated cystitis in females (2020). Pharmaceutical Society of Australia Ltd. Endorsed April 2020, amended August 2022.
  19. SA Health. Government of South Australia. Urinary tract infections (adult): Empirical treatment clinical guideline. V2.1. Approved 25/08/2022. [Accessed 08/09/2022]
  20. National Institute for Health and Care Excellence. (2018). Urinary tract infection (lower): antimicrobial prescribing. NICE Guideline [NG109]. Published 31 October 2018. [Accessed 09/09/2022].
  21. Gupta K, et al. Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute 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.