Pharmacist Treatment Guidance: Uncomplicated Cystitis

Eminent pharmacy academics from the Queensland University of Technology reported outcomes of the Urinary Tract Infection Pharmacy Pilot - Queensland (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]

Following this Pilot, Queensland became the first state in Australia to authorise a pharmacist to supply medicine without a prescription for the treatment of urinary tract infection (in accordance with state- based legislation Extended Practice Authority).

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 jurisdictions that have authority. The guidance should be used in conjunction with the following supporting resources.

Supporting resources and training

Safety, quality, and risk management standards and resources (see Appendix 1).

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.

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 infection
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 should be used for guidance. [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 for 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 (potential for folate depletion with this antibiotic) 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 every 6 hours 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 Note: In Western Australia, registered pharmacists working in community pharmacy are NOT authorised to supply cefalexin for the treatment of uncomplicated urinary tract infection.	500mg every 12 hours for 5 days	Contraindications Previous hypersensitivity to cephalosporins or immediate or severe hypersensitivity to penicillins

*In Western Australia, the first line antibiotic treatment recommendation is nitrofurantoin and the second line recommendation is trimethoprim. This is due to local resistance patterns and antibiogram data.

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 some support for the use of D-mannose in treating cystitis symptoms [13] but 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 found 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.

Encourage a fluid intake of ≥ 1 litre/day of non-caffeinated fluids

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 Legislation may stipulate 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

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 every 6 hours for 5 days OR Cefalexin 500mg every 12 hours for 5 days
Acute cystitis in adults [2]	2019	Australia	e-Therapeutic Guidelines	Trimethoprim 300mg daily for 3 days OR Nitrofurantoin 100mg every 6 hours for 5 days OR Cefalexin 500mg every 12 hours 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 four times a day for 7 days OR Cefalexin 500mg twice a day 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 four times a day for 5 days or Pivmecillinam* 400mg three times a day for 3-5 days OR Cephalosporins 500 mg twice a day for 3 days OR Trimethoprim^ 200mg bd for 5 days OR Trimethoprim/sulfamethoxazole^ 160/800mg twice a day for 3 days
Urinary tract infection (lower): antimicrobial prescribing [20]	2018	United Kingdom	NICE Guideline	Nitrofurantoin 100mg twice a day for 3 days OR Trimethoprim 200mg twice a day 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 twice a day for 5 days OR Trimethoprim/sulfamethoxazole 160/800mg twice a day for 3 days OR Fosfomycin 3g as a single dose OR Pivmecillinam* 400mg three times a day 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

References

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