Recurrent Urinary Tract Infection in Women ( ≥ 4 UTIs in 12 months ) - Management of Infection Guidance for Primary Care

Publication: 30/09/2010  --
Last review: 11/01/2013  
Next review: 31/01/2019  
Clinical Guideline
UNDER REVIEW 
ID: 2242 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2013  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Recurrent Urinary Tract Infections in female adult patients: Assessment, investigation and management

  1. Summary table of routine recommendations
  2. Background, Definitions, Pathophysiology and Assessment
  3. Special prophylaxis recommendations

1. Summary table of routine recommendations

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2. Background, Definitions, Pathophysiology and Assessment

Urinary Tract Infection (UTI) is one of the most common reasons for presentation to primary care affecting 50 to 60% of women in their lifetime [1]. Relapsing and recurrent infection is common with one study demonstrating 44% of patients have a further infection within a year [2]. One third of these patients suffered relapsing infection caused by the same organism. Women over 55 years of age were more at risk with 53% suffering recurrence versus only 36% of younger women.
Recurrent UTI can be a debilitating disease for the patient but can also be a warning sign for abnormalities of the renal tract.
This guideline assists the user in identifying those patients that require specialist investigation and consultation in managing their condition.

Definitions

Bacteriuria
Presence of bacteria in the urine revealed by quantitative culture or microscopy

Asymptomatic bacteriuria
Bacteriuria in a patient without any symptoms or signs of upper or lower UTI and confirmed by a second sample of urine

Urinary Tract Infection (UTI); Symptomatic Bacteriuria
Symptoms of infection of the lower (dysuria, frequency, suprapubic pain) or upper (loin pain, fever, back ache) urinary tract associated with a significant bacteriuria.

Lower UTI
A UTI involving the bladder only. Also referred to as cystitis.

Upper UTI
A UTI involving the renal tract proximal to the bladder (i.e. kidneys). Also referred to as pyelonephritis.

Uncomplicated (Simple) UTI
An uncomplicated UTI is one that occurs in a healthy non-pregnant adult female in the absence of structural or functional abnormalities of the urinary tract [3]

Relapsed UTI
A UTI caused by the same organism and occurring not more than 2 weeks after treatment of the original UTI [4].

Recurrent uncomplicated UTI
3 or more uncomplicated UTI’s in 12 months

Complicated UTI
A UTI in a child, adult male, pregnant woman, catheterized individual or a patient with underlying pathology of the renal tract (for example, neuropathic bladder, structural abnormality of the renal tract, immunosupressed, renal transplantation etc.)

Post-coital UTI
A UTI may be considered post-coital if the interval between sexual intercourse and the onset of symptoms is consistently between 24 and 48 hours [5].

Pathophysiology

It is estimated that 80% of UTI’s are caused by uropathogenic E.coli. Other causes are Enterococci, Klebsiella sp., Staphylococcus saprophyticus, Proteus sp. and Pseudomonas sp.
It is commonly accepted that UTI’s develop from the patients own bacterial faecal flora. The uropathogen colonises the vagina and distal urethra before invading the bladder. Uropathogenic E. coli have virulence factors that assist attachment to the hosts epithelium and enable evasion of the hosts defense mechanisms.
Asymptomatic bacteriuria is not thought to be harmful and its treatment in the immuno-competent adult population does not reduce morbidity or mortalitiy. Conversely its treatment is associated with adverse effects (increased spectrum of resistance, adverse drug reactions to antimicrobials) and is thought to have a protective role against invasion of uropathogenic strains of bacteria. As such it should not be treated [6, 7].
Other conditions, both infective and non-infective can present with symptoms similar to those of a UTI for example vaginal candidiasis, genital Chlamydia, genital gonorrhea. It is essential these are excluded in those patients at risk.

Assessment (Patient questionnaire) and Basic Investigations

The purpose of the assessment is:

  1. to identify patients who require investigation and management by a specialist.
  2. to determine the patients risk factors for recurrence and target interventions accordingly (e.g. UTI’s related to sexual intercourse)

The assessment should include a full history (directed by the questionnaire) and physical examination including a pelvic examination [3].
A Mid Stream Urine specimen should be sent if the patient presents with symptoms suggestive of an acute UTI and should be repeated at the time of any relapse or recurrence to confirm the diagnosis of UTI, to differentiate relapse from recurrence and to assist in finding an explanation for the recurrence of symptoms [1, 3, 4]. A full Sexually Transmitted Infection (STI) screen should also be taken to eliminate STI as a cause of symptoms.
Basic investigations should be performed to exclude diabetes, urinary obstruction, renal tract calculi (especially in patients experiencing UTI’s caused by urea-splitting organisms such as Proteus sp. and multi-drug resistant organisms). Further imaging should be directed by the history and examination of the patient in consultation with a specialist [8]. Studies have demonstrated a low incidence (0-15%) of anatomical abnormalities on cystoscopy when undertaken on women complaining of recurrent UTI. As such cystoscopy should be limited to those women in whom an abnormality is suspected and not requested universally. If required it should be arranged through a specialist [3].

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3. Special prophylaxis recommendations

Management options

  • Non-antimicrobial strategies

Lifestyle Modification
There are a number of practices that may be suggested. Though no good evidence exists to support these practices, they are unlikely to be harmful:

  • Voiding before and after coitus
  • Alternative contraception for women currently using a cervical diaphragm with a spermicidal agent [9]
  • Increasing fluid intake

Cranberry products
A systematic review including 10 studies demonstrated a benefit in cranberry products (either juice or tablets) in reducing the incidence of UTI’s at 12 months especially in women suffering from recurrent UTI’s [10]. Indeed a study of older women (>45 years of age) compared cranberry extract to prophylactic antibiotics (continuous daily low-dose trimethoprim) [11].It found no statistically significant difference in the time to first recurrence but more adverse effects in the antibiotic group suggesting cranberry extract as a useful natural alternative to antibiotics without the risks of bacterial resistance, super-infection or antibiotic associated side effects.

Dose for prophylaxis: ill defined in the literature- tablet/capsule 200-400mg cranberry extract daily or 300mL of juice daily.
NB: Cranberry supplements/juices are not available on the NHS formulary

Oestrogen replacement (post-menopausal women only)
Decreased oestrogen is thought to contribute to vaginal prolapse, cystocoele, post-voidal residue and urinary incontinence. In addition the reduced oestrogens allows thinning of the vaginal epithelium and reduced glycogen resulting in a reduction in the numbers of Lactobacilli that prevent colonization with uropathogens. Studies have looked at recurrence rates of UTI’s with various means of oestrogen replacement:

  • Intra-vaginal Oestrogen significantly reduce the frequency of UTI’s applied as a cream or as an Oestrogen-releasing vaginal pessary [12, 13].
  • Oral oestrogen replacement does not significantly reduce the frequency of UTI’s [14-16]

Acupuncture
The effect of acupuncture on the recurrence rate of urinary tract symptoms in patients who suffer from recurrent UTI’s has been evaluated by two small studies. Acupuncture was comparing to sham acupuncture and no treatment [17] in one study and no treatment in another [18]. Both studies demonstrated a significant reduction in recurrences in the acupuncture groups. The mechanism is unclear but stress and anxiety may play a part in the exacerbation of chronic symptoms. Clearly more work is needed in this area to determine the role of acupuncture. Acupuncture is not available locally on the NHS however patients may wish to access services independently if they gain benefit from the therapy.

  • Antimicrobial strategies

The choice of strategy will depend on the individual patient (the trigger for symptoms, their motivation, compliance and strategies attempted previously). The counselling tool (appendix 1) can be used to inform the discussion with the patient.

Post-coital antibiotic therapy (post-coital UTI’s only)
Single dose post-coital antibiotic prophylaxis may be more favourable than continuous antibiotic prophylaxis and for the majority of women results in a reduced antibiotic consumption. A single post-coital dose of trimethoprim/sulphamethoxazole 40/200mg (co-trimoxazole 40/200mg) resulted in a reduction from 3.6 to 0.3 episodes per patient-year in a placebo-controlled trial [19]. Other studies have demonstrated similar effects with other agents [20, 21]. Agent choice may be tailored to the culture and susceptibilities from previous infections.

Acute Self-treatment
For women who have infrequent episodes of recurrence (2 or less per year) [1] or who are unwilling to take daily antimicrobial prophylaxis acute self-treatment with delayed prescription may be a favourable option. The patient must be motivated, compliant and have a good relationship with their medical practitioner. Studies have demonstrated a cross concordance of 86-92% between patient self diagnosis (on the basis of symptoms) and culture [4]. Delayed prescriptions are usually issued for 3 days and the choice of agent should be based on the patients previous urine culture susceptibilities and local resistance patterns. The patient should be given a microbiology specimen request form and urine receptacle and instructed to submit a sample at the onset of symptoms and prior to commencing antibiotics to guide subsequent therapy if symptoms persist. The patient should be instructed to contact her medical practitioner 1. immediately if she has symptoms or signs of an upper or complicated UTI or 2. if her symptoms persists beyond 48 hours. This strategy can empower the patient and help reduce the amount of antibiotics consumed by the patient.

Continuous Prophylaxis with Methenamine
Methenamine is a drug licenced for prophylaxis against recurrent urinary tract infection in patients without renal tract abnormalities with evidence to support its efficacy for this indication [22]. The compound degrades to produce formaldehyde in the renal tract at an acidic pH. Unlike antibiotics, formaldehyde (an antiseptic) has a comprehensive spectrum of activity against all bacteria and its efficacy is not threatened by antibiotic resistance.
The most commonly encountered side effect is nausea and GI upset although rarely hypersensitivity reactions have been described. The drug has been associated with chemical cystitis and hemorrhagic cystitis in overdose or accumulation in impaired renal function and as such is contra-indicated in patients with an eGFR of <10mL/min.
Dose for prophylaxis: 1g 12-hourly.

Continuous Prophylaxis with Antibiotics
Numerous studies have demonstrated the efficacy of continuous antimicrobial prophylaxis (summarized in a Cochrane review [23]) with a NNT of 1.8. The long term consequences of the strategy, in terms of antimicrobial resistance, were not quantified. The number of proposed regimens almost equals the number of studies on the subject. No regimen has been shown to be superior and the regimen should be based on local resistance patterns and culture and sensitivity results from the patients previous infections taking into account the patients intolerances and allergies. There is minimal evidence to support rotation of agents either from the therapeutic or resistance prevention perspectives. Many studies report a significant side effect rate as may be expected, with gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea etc.), vulvo-vaginal candidiasis and skin rashes being the most commonly reported adverse reactions. The benefits of continuous antibiotic prophylaxis only continue for the period of treatment with many studies reporting a return of symptoms following cessation. Most authorities advocate a 6 month trial of therapy based on the extent of the extent of follow-up by most studies and the fact that UTI’s may cluster in some women. The regimen should be reviewed after this period or sooner if the patient suffers break-through infections. Break though infections, as with all recurrences, should be cultured to ascertain the reason for relapse.

Referral to a Specialist

For women with recurrent uncomplicated UTI’s, a referral is usually indicated when:

  • the diagnosis of UTI is uncertain (unable to confirm by MSU)
  • risk factors for complicated UTI exist
  • the potential for a surgically correctable cause of recurrence exists [3]

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Appendix 1- Counselling tool: Pros and Cons of antimicrobial strategies

 

Advantages

Disadvantages

Post-coital
Antibiotics

  • Usually results in consumption of less antibiotics than continuous prophylaxis
  • Only effective for patients who suffer from UTI’s related to sex
  • Risk of developing antibiotic resistance which makes treatment of subsequent infections much more difficult
  • Can cause side effects such as antibiotic associated diarrhoea (inc. C. difficile infection) and thrush (which could exacerbate symptoms)

Acute
Self-treatment

  • Empowers the patient resulting in greater satisfaction
  • Reduces consultations
  • Patient must be motivated and compliant
  • Patient must be able to recognise symptoms of UTI
  • Patient will still experience some symptoms
  • Patient must submit a specimen when symptoms start

Continuous methenamine prophylaxis

  • Proven to be effective
  • Broad spectrum of activity hence covers all bacteria likely to cause UTI’s
  • Not prone to development of resistance
  • Can be used as single agent rather than rotating
  • Should not be used in severely impaired renal function or anatomically abnormal renal tract
  • Can cause GI upset

Continuous antibiotic prophylaxis

  • Proven to be effective
  • Risk of developing antibiotic resistance which makes treatment of subsequent infections much more difficult
  • Can cause side effects such as antibiotic associated diarrhoea (inc. C. difficile infection) and thrush (which could exacerbate symptoms)

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Appendix 2 - Summary Flowchart

Provenance

Record: 2242
Objective:
  • to provide a simple, empirical approach to the treatment of common infections
  • to promote the safe, effective and economic use of antibiotics
  • to minimise the emergence of bacterial resistance and reduce the incidence of Healthcare Associated Infections in the community
Clinical condition:

Recurrent Urinary Tract Infection in Women (≥ UTIs in 12 months)

Target patient group: Women (≥ 4 UTIs in 12 months)
Target professional group(s): Primary Care Doctors
Pharmacists
Adapted from:

Evidence base

References

  1. Epp, A., et al., Recurrent urinary tract infection. J Obstet Gynaecol Can. 32(11): p. 1082-101.
  2. Ikaheimo, R., et al., Recurrence of urinary tract infection in a primary care setting: analysis of a 1-year follow-up of 179 women. Clin Infect Dis, 1996. 22(1): p. 91-9.
  3. Dason, S., J.T. Dason, and A. Kapoor, Guidelines for the diagnosis and management of recurrent urinary tract infection in women. Can Urol Assoc J. 5(5): p. 316-22.
  4. Hooton, T.M., Recurrent urinary tract infection in women. Int J Antimicrob Agents, 2001. 17(4): p. 259-68.
  5. Engel, J.D. and A.J. Schaeffer, Evaluation of and antimicrobial therapy for recurrent urinary tract infections in women. Urol Clin North Am, 1998. 25(4): p. 685-701, x.
  6. Nicolle, L.E., W.J. Mayhew, and L. Bryan, Prospective randomized comparison of therapy and no therapy for asymptomatic bacteriuria in institutionalized elderly women. Am J Med, 1987. 83(1): p. 27-33.
  7. Nicolle, L.E., Asymptomatic bacteriuria in institutionalized elderly people: evidence and practice. CMAJ, 2000. 163(3): p. 285-6.
  8. Segal, A.J., et al., Recurrent lower urinary tract infections in women. American College of Radiology. ACR Appropriateness Criteria. Radiology, 2000. 215 Suppl: p. 671-6.
  9. Hooton, T.M., et al., A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med, 1996. 335(7): p. 468-74.
  10. Jepson, R.G. and J.C. Craig, Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev, 2008(1): p. CD001321.
  11. McMurdo, M.E., et al., Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women. J Antimicrob Chemother, 2009. 63(2): p. 389-95.
  12. Eriksen, B., A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol, 1999. 180(5): p. 1072-9.
  13. Raz, R., et al., Effectiveness of estriol-containing vaginal pessaries and nitrofurantoin macrocrystal therapy in the prevention of recurrent urinary tract infection in postmenopausal women. Clin Infect Dis, 2003. 36(11): p. 1362-8.
  14. Brown, J.S., et al., Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors. Obstet Gynecol, 2001. 98(6): p. 1045-52.
  15. Cardozo, L., C. Benness, and D. Abbott, Low dose oestrogen prophylaxis for recurrent urinary tract infections in elderly women. Br J Obstet Gynaecol, 1998. 105(4): p. 403-7.
  16. Ouslander, J.G., et al., Effects of oral estrogen and progestin on the lower urinary tract among female nursing home residents. J Am Geriatr Soc, 2001. 49(6): p. 803-7.
  17. Aune, A., et al., Acupuncture in the prophylaxis of recurrent lower urinary tract infection in adult women. Scand J Prim Health Care, 1998. 16(1): p. 37-9.
  18. Alraek, T., et al., Acupuncture treatment in the prevention of uncomplicated recurrent lower urinary tract infections in adult women. Am J Public Health, 2002. 92(10): p. 1609-11.
  19. Stapleton, A., et al., Postcoital antimicrobial prophylaxis for recurrent urinary tract infection. A randomized, double-blind, placebo-controlled trial. JAMA, 1990. 264(6): p. 703-6.
  20. Nicolle, L.E., et al., Prospective, randomized, placebo-controlled trial of norfloxacin for the prophylaxis of recurrent urinary tract infection in women. Antimicrob Agents Chemother, 1989. 33(7): p. 1032-5.
  21. Melekos, M.D., et al., Post-intercourse versus daily ciprofloxacin prophylaxis for recurrent urinary tract infections in premenopausal women. J Urol, 1997. 157(3): p. 935-9.
  22. Lee, B.B., et al., Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev, 2007(4): p. CD003265.
  23. 23. Albert, X., et al., Antibiotics for preventing recurrent urinary tract infection in non-pregnant women. Cochrane Database Syst Rev, 2004(3): p. CD001209.

Approved By

Improving Antimicrobial Prescribing Group

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