Urinary Tract Infection (Cystitis) - acute, uncomplicated

Description
  • An acute infection of the bladder (acute cystitis).
  • Most commonly caused by Escherichia coli (80%), with the remaining 20 % caused by Staphylococcus species, proteus mirabilis, and enterococci.
  • Incidence of acute cystitis is high; among sexually active young women, incidence of 0.6 UTIs per person per year.
  • Risk factors include:
    • Sexual intercourse
    • New partner
    • Vaginal atrophy in postmenopausal women
    • Abnormalities of urinary tract (eg. catheter, neurogenic bladder)
    • Voiding dyfunction (incontinence)
    • Diaphragm or spermicide-coated condom use
    • Diabetes
    • Immunocompromised state (disease or drug-induced)
  • There are several classifications of UTIs that are important when making the decision to prescribe:
    • Uncomplicated UTI: an infection caused by the usual pathogens in a patient with a normal urinary tract and with normal kidney function. 
    • Complicated UTI:  infection in a patient with risk factors for a severe infection or sequalae.  All complicated UTIs must be referred.   Examples include:
      • Abnormal urinary tract due to an indwelling catheter, urinary obstruction or neurogenic bladder
      • Immunosuppression (due to medications or health conditions, including poorly controlled diabetes)
      • Impaired renal function
      • All UTIs in men are considered complicated
      • Symptoms persisting longer than two weeks
      • Renal impairment
      • 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 immunocompromised (these patients should be referred to their MD)
    • Recurrent UTI: defined as at least two culture positive episodes in 6 months or 3 culture positive episodes in one year
      • 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 a doctor or nurse practitioner.
      • 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.
    • Upper UTI or pyelonephritis:  an infection of the kidneys.  Requires referral.
Signs and Symptoms
  • Symptoms of uncomplicated UTI:
    • Primary symptoms - dysuria, urinary frequency, urinary urgency
    • May also present with suprapubic pain, mild hematuria, foul-smelling or cloudy urine
  • Symptoms may be subtle or atypical (such as confusion or agitation) in the very young or elderly (<16 or >65). These patients should be referred
  • Signs and symptoms NOT characteristic of UTIs: 
    • Systemic symptoms, such as fever, chills, nausea, or vomiting, flank pain (pain in the side or back below the ribs)
    • Vaginal discharge or irritation
  • Urine culture is not recommended except in the following circumstances:
    • Failure to respond to appropriate empiric therapy
    • Relapse (recurrence within 2 to 4 weeks) following therapy
    • Uncertainty about diagnosis
    • Pregnant patient
Differential Assessments

Women can accurately self-diagnose a recurrent UTI based on symptoms 85 to 95% of the time; presumptive diagnosis can be made based on presence of dysuria and urinary frequency and urgency and absence of vaginal symptoms (abnormal discharge, irritation). 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 uncomplicated UTI symptoms but will also have one or more of the following:
      • Fever (>38ºC)
      • Chills
      • Flank pain
      • Nausea and 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
    • Recommend OTC treatment for vaginitis 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)
    • Patients with typical UTI 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
    • Causes include chlamydia, gonorrhea, E. coli, etc.
    • 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
When to Refer
  • 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.
  • Pregnant patients
  • Atypical signs and symptoms e.g. fever, GI symptoms, flank pain
  • Severe pain / discomfort
  • Previous  UTI within last four weeks 
    • May be a relapse and patient  should be referred for a urine culture
  • 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
    • Spinal cord injury
    • Immunocompromised patient (HIV, lymphoma, leukemia, uncontrolled diabetes) or on immunosuppressive drugs (see below):

6-MP

Cytoxan

Chemotherapies (except tamoxifen and hydroxyurea)

Abatacept

Cyclosporin

Mycophenolate mofetil

Adalimumab

Etanercept

Rituximab

Alemtuzumab

Systemic corticosteroids(20mg/day or more of prednisone or equivalent) for 14 days or more

Sirolimus

Anti-thymocyte globulin

Infliximab

Tacrolimus

Azathioprine

Leflunomide

 

Basiliximab

Methotrexate

Cyclophosphamide

Mitoxantrone

  • Unable to use first or second line options due to allergies or previous intolerance (see treatment, below)
  • Consider referral if patient has had at least 2 culture-proven UTIs in past 6 months or 3 in past 12 months and patient is interested in prophylactic therapy (postcoital antibiotics, ongoing antibiotic treatment)
Treatment

Non-pharmacologic:
Prevention:

  • Spermicides are associated with increased risk of UTI - use alternative methods of contraception
  • Not proven to reduce UTIs but often recommended:
    • Early post-coital voiding
    • Keep fluid intake up

Pharmacologic:

  • An OTC analgesic such as acetaminophen or ibuprofen can be used to treat pain
  • Uncomplicated UTIs are self-limited conditions and in most cases will resolve without treatment, however antibiotic treatment reduces the duration of symptoms and decreases the risk of progression to pyelonephritis
  • When choosing empiric antibiotic therapy, local resistance patterns are important considerations
    • E. Coli is most common causative organism and has high rates of resistance in Saskatchewan
      • Approximately 20% of E.Coli infections are resistant to sulfamethoxazole-trimethoprim and trimethoprim
    • Amoxicillin and cephalexin should be used ONLY if culture and sensitivity show susceptibility

  • First Line:
    • Nitrofurantoin (Macrobid) 100mg PO BID x 5 days
      • Clinical efficacy - 93%
      • Resistance rates:
        • Saskatoon - 4%
        • Regina - 4%
        • Prince Albert - 2%
      • Common side effects: nausea and headache
  • 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 - 93%
      • Resistance rates:
        • Saskatoon - 23%
        • Regina - 22%
        • Prince Albert - 30%
      • Common side effects: rash, urticaria, nausea, vomiting

    • Trimethoprim 100mg PO BID (or 200mg PO once daily) x 3 days
      • Option if allergy to sulfonamides

    • Fosfomycin 3g dissolved in ½ cup of cold water OD x 1 day
      • Clinical efficacy - 91%
      • Very low resistance rates; however, suggest reserving use for resistant infections
      • Common side effects: diarrhea, nausea, and headache
General Advice / Monitoring

Advice:

  • Expect reduction in dysuria within a few hours of beginning effective antimicrobial therapy and resolution of all symptoms within 7 days
  • Nitrofurantoin may cause urine to turn 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 pharmacist or primary healthcare provider right away

Monitoring:

  • Follow up in three days:
    • Assess effectiveness:
      • All symptoms should be improved by 72 hours
      • Remind to finish full course of therapy if taking nitrofurantoin
      • Refer to MD 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 (>4 loose stools per day) or rash should be referred to MD for assessment and alternate options
Products

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 macro

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

 

Prescribing and Billing Details
  • Currently, no assessment fee will be covered by the Drug Plan.  Optionally, the pharmacist may charge the patient a fee of their choice.
  • May prescribe sufficient quantity to treat one UTI.
  • Only products with an official indication from Health Canada for urinary tract infections are considered for these guidelines.  Only the active ingredients in the "products" section are approved for pharmacist prescribing. 
Treatment Flowchart
Pharmacist Assessment Documents
References / Suggested Reading
  1. Imam T. Bacterial urinary tract infections. In Merck Manual online. Available at www.merckmanuals.com.
  2. Nicolle L. Urinary tract infection. Compendium of Therapeutic Choices, In RxTx online database. Available from www.e-therapeutics.ca. (By subscription). (Available in Saskatchewan through SHIRP (www.shirp.ca).
  3. Acute Urinary Tract Infections.  Dynamed.  Available at https://dynamed.ebscohost.com/ (by subscription).
  4. Bloom, A.  Acute uncomplicated cystitis and pyelonephritis in women.  In UpToDate online database.  Available at www.uptodate.com (by subscription).
  5. Brusch, J.  Acute Cystitis in Females.  Emedicine online database.  Available at http://emedicine.medscape.com/article/233101-overview  (free access, requires registration).
  6. SOGC Clinical Practice Guideline. Recurrent urinary tract infection. J Obstet Gynaecol Can 2010;32:1082–1090. Available at http://sogc.org/wp-content/uploads/2013/01/gui250CPG1011E_001.pdf.
  7. Regier L. Urinary Tract Infections (UTI): Treatment options. In: RxFiles online. Available at www.rxfiles.ca by subscription. (Available in Saskatchewan through SHIRP (www.shirp.ca).
  8. Michels T, Sands J. Dysuria: Evaluation and differential diagnosis in adults. Am Fam Physician 2015 Nov 1;92(9):778.
  9. Grigoryan L. Diagnosis and management of urinary tract infections in the outpatient setting: a review. JAMA  2014 Oct 22-29 ;312(16):1677-84.
  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.
  11. Thomas M. Hooton, M.D. Uncomplicated Urinary Tract Infection. N Engl J Med 2012; 366:1028-1037. DOI: 10.1056/NEJMcp1104429.
Written by medSask
Posted Nov 2017