• Acute uncomplicated cystitis is a bacterial infection of the lower urinary tract e.g.bladder.
  • Most commonly caused by Escherichia coli (75-95%), with the remainder caused by Staphylococcus species, Proteus mirabilis, Klebsiella pneumoniae and enterococci.
  • Incidence of acute uncomplicated cystitis is high; among young women, incidence of 0.5 UTIs per person per year
  • Risk factors for urinary tract infections (UTI) include:
    • Sexual intercourse
    • New partner
    • Vaginal atrophy in postmenopausal women
    • Abnormalities of urinary tract (e.g. catheter, neurogenic bladder)
    • Voiding dysfunction (incontinence)
    • Spermicide use
    • Poorly controlled diabetes
    • Immunocompromised state (disease or drug-induced)
  • Cystitis refers to UTI in the lower part of the urinary tract e.g bladder, while pyelonephritis refers to UTI in the upper part of the urinary tract e.g. kidneys.
  • There are several classifications of UTIs that are important when making the decision to prescribe. Classification of a UTI as uncomplicated versus complicated varies based on different resources and expert opinions. For the purposes of this guideline, they will be defined as below.
    • Uncomplicated UTI: a urinary tract infection caused by the usual pathogens in a patient with a normal urinary tract, which hasn't extended beyond the bladder. 
    • Complicated UTI: a urinary tract infection in a patient with risk factors for a severe infection or sequelae. It may be cystitis that doesn't meet the criteria to be classified as uncomplicated, or pyelonephritis, or the patient has structural, functional or metabolic conditions that promote UTI. These patients have an increased risk of resistant pathogens & may require different treatment protocols. All complicated UTIs must be referred. Examples of complicating factors include:
      • Abnormal urinary tract due to an indwelling catheter, urinary obstruction or neurogenic bladder
      • Immunocompromised (due to disease state or drug-induced)
      • Poorly controlled diabetes
      • Impaired renal function (CrCl <60mL/min)
      • All UTIs in men are considered complicated
      • Symptoms persisting longer than two weeks
      • Spinal cord injury
    • Asymptomatic bacteriuria: when a urine culture shows significant presence of bacteria in the urine but with no presenting symptoms. It is not necessary to treat unless the patient is pregnant or will be undergoing an invasive genitourinary procedure (these patients should be referred to their primary healthcare provider). Treating patients unnecesarily leads to antibiotic resistance & increasedr risk of adverse effects. 
    • Recurrent UTI: defined as ≥2 episodes of acute uncomplicated cystitis in 6 months or ≥3 episodes in 12 months, with symptom resolution between episodes. 
      • Relapse: UTI recurs with the same strain of organism which caused the previous infection. Relapse is likely if infection recurs within a short period after treatment (two to four weeks). Patients with suspected relapses should be referred to their primary healthcare provider.
      • Reinfection: UTI recurs more than four weeks after treatment. The cause may be a different strain or the original organism. Pharmacists may consider prescribing to treat UTI reinfections that have occurred more than 1 month ago. 
  • Symptoms of acute uncomplicated cystitis:
    • Primary symptoms - dysuria, urinary urgency or frequency
    • May also present with suprapubic pain or mild hematuria 
    • Absence of vaginal discharge
    • Some patients may also have foul-smelling or cloudy urine. (note: foul-smelling or cloudy urine alone is not an indicator of bacterial infection)
  • Signs and symptoms NOT characteristic of acute uncomplicated cystitis:
    • Systemic symptoms, such as fever, chills, nausea or vomiting, flank or back pain (pain in the side or back below the ribs), or significant malaise
    • Vaginal discharge or pruritus
    • Dyspareunia (painful intercourse)
    • Significant hematuria
  • Symptoms may be subtle or atypical (such as confusion, agitation/irritability, poor feeding) in the very young or elderly. These patients should be referred.

  • Urine culture is not recommended except in the following circumstances:
    • Failure to respond to appropriate empiric therapy
    • Recurrence within 1 month of previous treatment
    • Pregnant patient
    • Complicated UTIs
    • Upper UTI or pyelonephritis
    • Uncertainty about diagnosis

Women can accurately self-diagnose a recurrent UTI based on symptoms 84% of the time; presumptive diagnosis can be made based on presence of dysuria, urinary frequency and urgency, and the absence of vaginal symptoms (abnormal discharge, pruritus). However, the following conditions may present with similar signs and symptoms and should be ruled out before proceeding with treatment:

  • Pyelonephritis
    • Infection of the kidneys with potentially serious sequelae
    • May present with typical acute uncomplicated cystitis symptoms but will also have one or more of the following:
      • Fever (>38ºC)
      • Chills
      • Flank or back pain
      • Nausea or vomiting
      • Must be referred for assessment and treatment

  • Vaginitis
    • May present with dysuria, but will also have one or more of the following symptoms:
      • Vaginal discharge or odor
      • Pruritus
      • Dyspareunia
    • Urinary frequency and urgency usually absent
    • Common causes: yeast infection, trichomoniasis or bacterial vaginosis
    • Recommend OTC treatment for yeast infection or if risk of sexually transmitted infection (STI), refer

  • Acute urethritis
    • Inflammation of the urethra accompanied by dysuria; no urinary frequency or urgency
    • Most common in sexually active women
    • Causes include chlamydia, gonorrhea, trichomoniasis, candidiasis and herpes simplex virus
    • History may indicate STI risk

  • Interstitial cystitis (painful bladder)
    • Patient presents with typical acute uncomplicated cystitis symptoms (dysuria, frequency and urgency), but no evidence of infection or other identifiable cause.
    • A diagnosis of exclusion
    • Chronic condition - history of persistent symptoms
  • Pelvic inflammatory disease
    • May present with dysuria
    • Most common symptoms include lower abdominal or pelvic pain, and fever
    • Vaginal discharge also present
    • Infection of upper female genital tract including endometrium, fallopian tubes, ovaries or pelvic peritoneum
    • Causes include chlamydia & gonorrhea
    • History may indicate STI risk

  • Nephrolithiasis
    • Kidney stones which present with significant flank pain
    • Hematuria may be present

  • Drug-induced cystitis
    • Cyclophosphamide, allopurinol, danazol, or tiaprofenic acid have been associated with symptoms of cystitis
  • Patients who have not had a previous diagnosis of a UTI
    • Ensures the patient knows the typical signs and symptoms of a UTI and rules out any urinary tract abnormalities. Increases accuracy of self-diagnosis.
  • Previous UTI within 1 month
    • May be a relapse and patient should be referred for a urine culture
  • Unable to use first, second or third line options due to allergies or previous intolerance (see treatment below)
  • Consider referral if patient has had recurrence- defined as ≥2 uncomplicated UTIs in 6 months or ≥3 uncomplicated UTIs in 12 months AND patient is interested in prophylactic therapy (postcoital antibiotics, ongoing antibiotic treatment) ** you may still prescribe for the current episode**
  • Patients under 16 years of age
  • Patients residing in Long Term Care
  • Pregnant patients
    • Treated even if asymptomatic
    • Often treated for longer durations & may require different antibiotics
  • A patient who is breastfeeding an infant < 1 month old 
  • Atypical signs and symptoms e.g. fever, nausea or vomitting, flank or back pain, significant malaise
  • Dyspareunia (painful intercourse)
  • Vaginal discharge or pruritus
    • Requires further investigation to ensure correct diagnosis
  • Patient is at risk of a complicated UTI, including:
    • Abnormal urinary tract due to an indwelling catheter, urinary obstruction or neurogenic bladder
    • Male patients
    • Symptoms have lasted longer than two weeks
    • Renal impairment (CrCl <60 mL/min)
    • Spinal cord injury
    • Poorly controlled diabetes
    • Immunocompromised due to disease state e.g. HIV, lymphoma, leukemia
    • Immunocompromised due to medication e.g. azathioprine, methotrexate, leflunomide, cyclosporine, monoclonal antibodies, TNF blockers, calcineurin inhibitors, systemic corticosteroids (>20mg/day of prednisone or equivalent for 14 days or more)
  • Patients with history of interstitial cystitis - patients may have typical UTI symptoms (dysuria, frequency and urgency), but no evidence of infection or other identifiable cause. Chronic/persistent presentation of symptoms.  
  • Patients taking a medication associated with cystitis e.g cyclophosphamide, allopurinol, danazol, or tiaprofenic acid
  • Unable to confirm diagnosis

Non-pharmacologic:

Prevention:

  • Spermicides are associated with increased risk of UTI - use alternative methods of contraception.
  • Remind patients to wipe from front to back.
  • Not proven to reduce UTIs but often recommended:
    • Early post-coital voiding
    • Ensure adequate fluid intake 

Pharmacologic:

  • An OTC analgesic such as acetaminophen or ibuprofen can be used to treat pain. **Note: NSAIDs should not be used as monotherapy**
  • Acute uncomplicated cystitis is a self-limiting condition, and in most cases will resolve without treatment, however, antibiotic treatment reduces the duration of symptoms and decreases the risk of progression to pyelonephritis. All symptomatic women should be offered antibiotic therapy. 
  • When choosing empiric antibiotic therapy, local resistance patterns are important considerations.
    • E. coli is the most common causative organism and has high rates of resistance in Saskatchewan.
      • Over 20% of E. coli infections are resistant to sulfamethoxazole-trimethoprim and trimethoprim in Saskatchewan. 
    • Amoxicillin and cephalexin should be used ONLY if culture and sensitivity show susceptibility.
    • Keep in mind that reported resistant rates in hospital antibiograms may not be representative of uncomplicated infection resistance patterns, as they are often influenced by complicated infections which tend to be more resistant.  
  • First Line:
    • Nitrofurantoin monohydrate macrocrystals (Macrobid) 100mg PO BID x 5 days
      • Drug of choice for empiric therapy 
      • Clinical efficacy: 84-95%
      • Retained excellent susceptibility
      • Resistance rates from 2018 health region antibiogram:
        • Saskatoon - 4%
        • Regina - 4%
        • Prince Albert - 1%
      • Common side effects: nausea, headache, rusty/brown discoloration of urine
      • Avoid in patients with CrCl ≤ 30mL/min
  • Second Line:
    • Sulfamethoxazole-trimethoprim 800mg/160mg PO BID x 3 days
      • Avoid if local resistance to sulfamethoxazole-trimethoprim is >20% or if used for UTI in the previous 3 months.
      • Clinical efficacy: 79-100%
      • Resistance rates from 2018 health region antibiogram:
        • Saskatoon - 23%
        • Regina - 23%
        • Prince Albert - 29%
      • Keep in mind, however, that resistance rates portrayed in hospital antibiograms may not be representative of the expected resistance patterns of uncomplicated infections, as these antibiograms are often heavily influenced by patients with complicated and nosocomial infections, which tend to be more resistant in nature.
      • Common side effects: rash, urticaria, nausea, vomiting
    • Trimethoprim 100mg PO BID (or 200mg PO once daily) x 3 days
      • Option if allergy to sulfonamides
  • Third Line:
    • Fosfomycin 3g sachet OD x 1 day
      • Dissolve sachet contents in ½ cup of cold water, stir and take immediately
      • Recommended to take on an empty stomach or at least 2-3 hours after a meal
      • Clinical efficacy:  up to 91%
      • Very low resistance rates; however, suggest reserving use for resistant infections
      • Reserve for patients unable to take 1st and 2nd line agents
      • Common side effects: diarrhea, nausea, and headache

Special populations

  • Pediatrics:
    • May prescribe for patients 16 years of age and older, assuming all other criteria is met.
    • Treatment is the same, except fosfomycin is not indicated for patients under 18 years old.
  • Breastfeeding:
    • The American Academy of Pediatrics considers nitrofurantoin and sulfamethoxazole-trimethoprim compatible with breastfeeding. 
    • If the infant is < 1month old referral to a primary healthcare provide is required. (There is a risk of hemolysis in the infant during the newborn period. Alternate antibiotics may be preferred, and would therefore, require referral).
    • There is very limited information with fosfomycin and breastfeeding. 

Advice:

  • Expect improvement in symptoms within 48-72 hours of beginning effective antimicrobial therapy and resolution of all symptoms within 7 days.
  • Ensure the patient is aware of possible side effects of the prescription. 
  • Nitrofurantoin may cause urine to turn rusty/brown - not a concern.
  • If on sulfamethoxazole-trimethoprim, patient should maintain adequate fluid to reduce chance of kidney stones developing (very rare occurrence).
  • If fever or chills develop or symptoms worsen, contact your primary care provider right away.

Monitoring:

  • Follow up in 3 days:
    • Assess effectiveness:
      • All symptoms should be improved by 72 hours.
      • Remind to finish full course of therapy if taking nitrofurantoin.
      • Refer to primary care provider if no or little improvement after 72 hours.
  • Assess safety:
    • Ask about side effects
      • Oral and vaginal candidiasis - recommend OTC treatment for vaginal symptoms, see treatment guidelines for thrush for oral symptoms.
      • Significant diarrhea (≥3 loose stools/24 hours) should be referred to primary care provider for assessment and alternate options.
      • Development of rash- medication should be stopped and patient should be referred to primary care provider for assessment and alternate options.

Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in RxTx - CPS from CPhA, RxTx (Internet), Lexi-Comp, AHFS, www.drugs.com or other reliable drug monograph references. For comprehensive drug comparisons, see RxFiles charts (www.rxfiles.ca). This information should be routinely consulted before prescribing.

Drug

Dosage

Nitrofurantoin monohydrate macrocrystals

100mg BID x 5 days

Sulfamethoxazole-trimethoprim

800mg/160mg BID x 3 days

Trimethoprim

100mg BID (or 200mg once daily) x 3 days

Fosfomycin

3g once daily x 1 dose

  • Fee pseudoDIN 00951103; maximum of 3 claims per year
  • May prescribe sufficient quantity to treat one episode of acute uncomplicated cystitis.
  • Only products with an official indication from Health Canada for acute uncomplicated UTIs are considered for these guidelines. Only the active ingredients in the "products" section are approved for pharmacist prescribing.
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  8. Michels T, Sands J. Dysuria: Evaluation and differential diagnosis in adults. Am Fam Physician 2015 Nov 1;92(9):778.
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  10. Gagyor I, Bleidorn J et cl. BMJ. Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial.  BMJ 2015 Dec 23;351:h6544. doi: 10.1136/bmj.h6544.
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Written by medSask
Posted Nov 2017, Updated October2018