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Recurrent UTI

Recurrent UTI is defined as 2 more episodes of UTI within 6 months, or 3 or more episodes within a year.

 

Unresolved UTI is failure to clear the organism – may be due to resistant organisms, poor antibiotic compliance, impaired renal function or excretion, or persistent nidus.

Persistent UTI is repeated culture of the same organism despite appropriate antibiotic therapy within 1 – 3 weeks (this should prompt investigation for an underlying cause or nidus).

May be due to nidus, stones, poor drainage, or most commonly in men prostatitis

 

Bacterial reinfection refers to repeat invasion of bacteria after eradication, often with different organisms

 

Assessment of recurrent UTI

History:

  • Clearly define symptomatology, and relation to urine testing
    • DDx – overactive bladder, bladder pain syndrome, gynaecological pain, genitourinary syndrome of menopause
  • Response to antibiotics
  • Previous medical history and medications
    • SGLT2 inhibitors, steroids, diverticulitis
  • Urological history, surgical history
    • Gynaecological mesh, childhood urological surgery
  • Sexual history (relation to symptoms, spermicide)

 

Examination:

  • Focussed urological examination
  • General examination including habitus, frailty, mobility
  • Abdominal / genital / pelvic exam
    • Palpable bladder, urethral diverticulum, prostatitis, post menopausal atrophy

Investigations:

  • Urine microscopy and culture
  • Ultrasound – for recurrent UTI
  • Bloods – renal function for antibiotic choices

 

  • ?CT – looking for specific diagnosis, e.g. stones, fistula
  • Urine cytology – if risk factors for urothelial cancer, haematuria
  • ?Cystoscopy – low pick up rate – if looking specifically for a cause e.g. fistula, foreign body

 

 

Management strategies for recurrent UTI

  1. Behavioural / conservative
  2. Find and treat underlying cause
  3. Non antibiotic strategies
  4. Antibiotic strategies

 

Behavioural / conservative

  • Increasing fluid intake does have a reasonable evidence base for reducing UTI frequency
  • Post coital micturition
  • Double voiding largely unsupported by evidence / apocryphal
  • Wiping front to back

 

Non antibiotic strategies

  1. Topical oestrogen
  • Lack of oestrogen causes changes in vaginal epithelium – loss of protective lactobacilli, increase in vaginal pH – predisposing to urine infection
  • Proven to reduce rates of UTIs in post-menopausal women (can take 12 weeks to get an effect)
  • Oral oestrogen not effective.
  • Topical/vaginal oestrogen has negligible systemic absorption.
  • No proven link to recurrence/development of breast cancer, but patients and oncologists often nervous
  • Additionally treats urinary frequency and urgency, and other symptoms associated with genitourinary syndrome of menopause
  • Dose – Ovestin cream (estriol) 15 g 1% – apply daily for 3 weeks, then twice a week indefinitely

 

  1. Pro-biotics
  • Lactobacillus has been shown to interfere with presences and colonisation of uropathogens.
  • Multiple systematic reviews have conflicting results – noting studies use different strains, doses and routes of administration
  • Certain strains of lactobacillus are likely to be more beneficial
  • Unclear whether oral or topical administration provides better effect

 

  1. Cranberry
  • Polyphenol type A proanthocyanidin (PAC) prevents the P fimbriae of E.coli adhering to urothelial cells
  • Systematic reviews have conflicting results – different formulations and doses – the effect is unclear
  • “Quality of evidence is low with contradictory findings”
  • Previously thought to interact with warfarin dosing – although no substantial proof of this.
  • Of note – cranberry juice has insignificant levels of PAC to make any feasible difference – if taking cranberry for effect, should really be taking tablets with highest level of PAC available

 

  1. Methenamine hippurate (Hiprex)
  • Standard dose is 1 g BD – should ideally be given with Vitamin C to acidify the urine.
  • Converted to ammonia and formaldehyde in an acidic environment – formaldehyde has bactericidal effect.
  • Systematic reviews conclude it “may be effective in preventing UTI”.
  • ALTAR study (2022) – multi-centre RCT – hiprex vs prophylactic ABx for 12 months – hiprex shown to be non-inferior
  • Contra-indicated in severe liver or renal dysfunction
  • Interacts with antacids, carbonic anhydrase inhibitors, sulfonamides

 

  1. D-mannose
  • Naturally occurring sugar, which binds to and blocks adhesins on type 1 pili on E.coli
  • Appears to be promising in reducing UTIs, with comparable efficacy to prophylactic antibiotics in some studies
  • “Based on limited evidence … can significantly reduce number of UTI episodes”

 

  1. Vaccine therapies
  • Variety of novel preparations which have been shown to be more effective than placebo in female patients with recurrent UTIs, with favourable safety profile
  • OM-89 (Uro-Vaxom) – oral vaccine – demonstrable efficacy in short term, tested to 6 months
  • MV-140 (UroMune) – sublingual – 4 heat inactivated bacteria (E.coli/Klebsiella/Enterococcus/Proteus) – available in NZ
  • Vaginal suppository with 10 heat-killed uropathogenic bacteria – shown to reduce UTI risk vs placebo

 

  1. Intravesical therapies
  • Intravesical instillations of hyaluronic acid and/or chondroitin sulfate, aiming to replenish the GAG layer
  • RCTs have suggested a reduction in number of UTIs/year, with longer time between UTIs and some improvement in urinary frequency and urgency
  • Available as iAluRil in Australia, expensive.
  • (Intravesical gentamicin also used in some centres with effect)

 

Prophylactic antibiotics

Proven efficacy vs placebo at reducing number of recurrent UTIs.

Different strategies exist:

 

  1. Post-coital

Trimethoprim 300 mg or nitrofurantoin 50 – 100 mg one-off post coital dose

Suitable for women with temporal UTI relationship to intercourse.

 

  1. Stop-start / self-directed

Women have a script or supply of antibiotics and can start taking immediately at onset of UTI symptoms.

Should be encouraged to send a urine culture prior to commencing to ensure not resistant organism.

 

  1. Low dose daily prophylaxis

Low dose once daily antibiotic – nitrofurantoin 50 mg nocte, cephalexin 250 mg daily, trimethoprim 150 mg daily

No consensus on duration – different studies have done 6 weeks, 3 months, 6 – 12 months

UTIs do tend to recur when patients stop antibiotics

Concerns regarding development of resistant organisms