Recurrent UTI in Adults

2.0 Last reviewed: 17/11/2022 Review date: 30/11/2025

Guidelines for Recurrent Urinary Tract Infections in Adults:

Antibiotic Prophylaxis

Definition

The symptoms of a lower urinary tract infection include frequency, dysuria, urgency and
suprapubic pain. Recurrent lower urinary tract infection (rUTI) is defined as:

Two or more episodes of lower urinary tract infection in the last 6 months, or
Three or more lower urinary tract infection episodes in the last 12 months1.

It does not include bacteriuria in the absence of symptoms or catheterised patients, i.e.,
asymptomatic bacteriuria. Asymptomatic bacteriuria should not be screened for or treated unless
prior to urological surgery or in pregnancy (positive cultures in pregnancy should be confirmed
with a second culture confirming the same organism prior to treatment)2.

1. Consider whether referral is required for patients with recurrent UTIs:

Consider whether the patient requires a specialist referral for the following factors1,3.

Red Flags for Referral to Urology:

• All men
• Frank haematuria, even in the context of confirmed UTI
(refer to current ‘2 week wait’ guidelines for further information)
• Neurological disease e.g., spinal cord injury, spina bifida
• Pneumaturia or faecaluria
• Proteus on repeat urine cultures
• Suspected stone
• Obstructive symptoms, or structural/functional abnormality, causing >200ml residual
urine on bladder scan
In pregnancy:
• All recurrent UTIs in pregnancy should be discussed with the Obstetrics team.

Consider risk factors:

Sexual history and investigations for sexually transmitted infections should be performed if
appropriate. In peri- and post-menopausal women, atrophic vaginitis may cause urinary symptoms
and may increase the risk of bacteriuria. Due to low oestrogen levels in post-menopausal women
with recurrent UTIs, consider using intravaginal oestrogens4.

Part of the Antimicrobial Prescribing Guidelines for Primary Care.

Updated November 2022. Next review: November 2025. page 1
 Recurrent UTI in Adults
2.0 Last reviewed: 17/11/2022 Review date: 30/11/2025

Microbiological Confirmation:

Patients with rUTIs should have a mid-stream urine (MSU) sample sent for culture before
antibiotics are initiated to confirm infection and guide antibiotic therapy3. Patients should be
counselled on how to provide a specimen to minimise the chance of contamination.
http://patient.info/health/midstream-specimen-of-urine-msu
In symptomatic patients with pyuria and a negative culture who do not respond to antibiotics as
expected, consider whether an alternative diagnosis may be relevant. Sterile pyuria can occur in a
number of infective conditions, including sexually transmitted diseases (e.g., Chlamydia), infections
with organisms that are difficult to grow on standard culture, and renal tuberculosis, as well as
non-infectious causes.
It is important to note that a negative urine culture in symptomatic patients with pyuria does not
rule out infection5. Symptomatic patients with persistent sterile pyuria (persistent presence of
white blood cells in the urine that repeatedly do not grow any organisms on routine culture) and
symptoms strongly suggestive of urinary tract infection should be discussed with the duty
microbiologist.
Urine cultures sent in the absence of symptoms are unlikely to be helpful, may detect
asymptomatic bacteriuria and lead to inappropriate antibiotic use. Antibiotic treatment of
asymptomatic bacteriuria is more likely to be harmful than beneficial4.
'Clearance' cultures are not recommended if symptoms have resolved.

2. Management of Initial Presentation of Recurrent UTI in non-pregnant females-

see flow chart
The following conservative measures may be advised however, the evidence is poor quality or
inconclusive:

Conservative Measures:

• Drink plenty
• Avoid use of scented washes/wipes
• For sexually active women:
o Advise post-coital voiding
o Avoid use of contraceptive diaphragm and spermicide
• Perineal hygiene i.e., wiping front to back.
• Avoid using flannels. A clean unscented disposable wipe is preferable.
• Over-the-counter products – limited evidence but some women may find useful:
o D-mannose (1g twice daily. Available without prescription)
o Cranberry tablets (Follow individual product instructions. Available without prescription.
Contraindicated in patients on Warfarin)6

Part of the Antimicrobial Prescribing Guidelines for Primary Care.

Updated November 2022. Next review: November 2025. page 2
 Recurrent UTI in Adults
2.0 Last reviewed: 17/11/2022 Review date: 30/11/2025

Recurrent UTI Prophylaxis Prescribing Strategies

The relative risks and benefits of the following recurrent UTI prophylaxis prescribing strategies
should be discussed with the patient. These strategies should be in addition to the conservative
measures detailed above and are based on the patient's history and risk factors.

Summary of Prescribing Strategy Options

Consider prescribing a vaginal oestrogen in peri- and post-menopausal women.
Standby Antibiotics A 'self-start' course of antibiotics if <1 episode per month

Post Coital Antibiotics For rUTIs that are triggered by sexual intercourse

Continuous Antibiotic Continuous low-dose antibiotic prophylaxis

Prophylaxis

Continuous Urinary Antiseptic Continuous prophylaxis with methenamine hippurate as a first-

Prophylaxis line alternative to continuous antibiotic prophylaxis

• Standby Antibiotics

o This option limits antibiotic exposure and risk of resistance emerging and may be the
more suitable option for patients with <1 UTI per month. A Patient Advice Sheet and
boric acid container for pre-antibiotic MSU should be provided to the patient. A urine
specimen should be obtained when the patient becomes symptomatic, but patients can
self-initiate antibiotics whilst awaiting the culture results.
o Prescribe a 'self-start' antibiotic according to previously known sensitivities and choose
the narrowest spectrum agent available7. Refer to Nottinghamshire APC Antibiotic
Guidelines for more information.
o Safety-net with advice to seek medical attention if they develop fever, loin pain, or
symptoms are not improving by 48 hours.

• Post Coital Antibiotics

o For rUTIs triggered by sexual intercourse, this strategy is as effective as continuous

antibiotic prophylaxis8 and reduces antibiotic exposure and the risk of resistance
emerging.

Part of the Antimicrobial Prescribing Guidelines for Primary Care.

Updated November 2022. Next review: November 2025. page 3
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• Continuous Antibiotic Prophylaxis

o Continuous antibiotic prophylaxis is strongly associated with the development of

antimicrobial resistance.
o A 6-month trial of a low-dose nightly antibiotic may be beneficial if rUTIs are occurring
≥1 per month and are not triggered by sexual intercourse.
o Patients should be counselled at an early stage that antibiotic prophylaxis is not usually a
lifelong treatment. Documenting and triggering a review date in the patient's record and
on the repeat prescription is recommended to avoid prolonged courses of antibiotics
without review.

• Continuous Urinary Antiseptic Prophylaxis (Methenamine hippurate)

o Methenamine hippurate is a urinary antiseptic agent that is converted to formaldehyde

in an acidic urine environment which is directly toxic to bacteria
o A randomised control trial in 2022 demonstrated methenamine hippurate was non-
inferior to prophylactic antibiotics for reducing the incidence of symptomatic UTIs over a
12-month period9
o Continuous methenamine prophylaxis avoids the risks of long-term prophylactic
antibiotic treatment, including the development of antibiotic resistance and adverse
effects such as C. difficile infection
o Methenamine may now be offered as a first-line alternative to continuous antibiotic
therapy for UTI prevention in women. It may be initiated in primary care in women
without urinary tract abnormalities or neuropathic bladder (Amber 3 classification).
o Methenamine should NOT be used for the treatment of UTIs
o There is some evidence that methenamine works in an acidic urine environment. In the
ALTAR study, the value of urinary acidification was not explored. Therefore, routine
dipstick testing is currently not advised in this guideline until further evidence is
available.

Choice of Agents for Prophylaxis6,10:

The choice of agent should be based on patient preference, consideration of the patient's co-
morbidities, renal function and any contra-indicating factors. If prescribing antibiotics, the choice
of antibiotic should be based on confirmed culture and sensitivity results (wherever possible). The
antibiotics licensed for the prophylaxis of UTIs are trimethoprim and nitrofurantoin.

The risk of adverse effects (see box below), as well as common side-effects such as rashes,
oral/vaginal thrush and gastrointestinal upset, should be discussed with the patient.

Part of the Antimicrobial Prescribing Guidelines for Primary Care.

Updated November 2022. Next review: November 2025. page 4
 Recurrent UTI in Adults
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First-line antibiotic options

Antibiotic Dose Cautions and Monitoring

Trimethoprim 200 mg one dose • Hyperkalaemia: caution when prescribing medications
post-coital such as spironolactone, ACE inhibitor or angiotensin
(off-label) inhibitors.
• Renal Impairment: Avoid if eGFR <15ml/min.
or 100 mg nightly Discuss with a renal physician if eGFR <30ml/min.
It may increase serum creatinine.
• Patients should be counselled on the risk of blood
disorders and advised to seek attention if fever, sore
throat, purpura, mouth ulcers, bruising or bleeding
occurs.
OR:
Nitrofurantoin 100 mg immediate • Avoid if renal function eGFR <45ml/min. Consider
release one dose checking renal function prior to commencing
post-coital continuous prophylaxis, especially in the elderly.
(off-label) • Avoid if G6PD deficiency.
• Use with caution in anaemia, diabetes, vitamin B or
Or 50 mg nightly folate deficiencies.
• Monitor full blood count, renal function, and liver
function tests every 3-6 months.
• Advise the patient on the risk of pulmonary and hepatic
fibrosis and the symptoms to report if they develop
during treatment. Reactions can develop acutely or
insidiously.
• Advise the patient on the risk of peripheral and optic
neuropathy and the symptoms to report if they develop
during treatment.

Or
Methenamine as an alternative to antibiotics

Antiseptic Dose Cautions and Monitoring

Methenamine 1 g twice a day • Check baseline LFTs, U&Es and eGFR.
• Not for the treatment of UTI.
• Avoid in patients with a history of febrile UTI or
previous urosepsis.
• Contra-indications: Gout, metabolic acidosis, severe
dehydration.
• Renal impairment: Avoid if eGFR <10ml/min.
• Hepatic impairment: Avoid.
• Pregnancy: Preferable to avoid as inadequate evidence
of safety.
• Uncommonly can cause epigastric discomfort and skin
reactions.

Part of the Antimicrobial Prescribing Guidelines for Primary Care.

Updated November 2022. Next review: November 2025. page 5
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2.0 Last reviewed: 17/11/2022 Review date: 30/11/2025

Second-line antibiotic options on urology or infection specialist advice only

If resistance to first-line antibiotics and methenamine, used as single agents, is not tolerated or
contra-indicated, other antibiotic agents may be considered after discussion with Urology and/or
an Infection Specialist if the patient is not under urology. Broader spectrum agents such as
cefalexin, ciprofloxacin and co-amoxiclav have a higher risk of C. difficile diarrhoea and selection
for resistance, so they should not be routinely used for prophylaxis and be reviewed with a trial of
stopping after 6 months. In addition, MHRA has issued an alert restricting the use of
Fluoroquinolone antibiotics, e.g. ciprofloxacin.

Second-line antibiotic options on urology or infection specialist advice only.

Trial of stopping after 6 months.
Antibiotic Dose Cautions and Monitoring
Cefalexin 500 mg one dose post- • Higher risk of selection for resistant infections
coital • Higher risk of C. difficile infection
or 125 mg nightly
Pivmecillinam 200 mg one dose post- • Unknown safety profile and potential carnitine
coital deficiency with prolonged use 10
or • Note the BNF pivmecillinam dosing for "chronic or
200 mg nightly recurrent bacteriuria" is not applicable for recurrent
symptomatic urinary tract infections.

3. Managing 'breakthrough' UTIs on a continuous prophylactic agent

Antibiotic prophylaxis

• The first breakthrough infection should be treated according to culture and sensitivity
results if available, with the original prophylaxis being held and then restarted once the
infection has resolved if the culture confirms susceptibility to the prophylactic agent
• If the culture shows resistance to the prophylactic agent, or multiple breakthrough UTIs
occur (≥2 UTIs in 6 months), prophylaxis has therefore proved ineffective and should be
stopped or changed to an alternative prophylactic agent (antibiotic or methenamine)
• Consider referral to Urology at this point if you have not already been referred

Methenamine prophylaxis

• The breakthrough infection should be treated according to culture and sensitivity results if
available
• Methenamine prophylaxis should be continued alongside the antibiotic course for the
breakthrough infection if there has been a good response
• If multiple breakthrough UTIs occur (≥2 UTIs in 6 months), methenamine should be stopped
or changed to an alternative prophylactic agent (antibiotic)
• Consider referral to Urology at this point if not already been investigated

Part of the Antimicrobial Prescribing Guidelines for Primary Care.

Updated November 2022. Next review: November 2025. page 6
 Recurrent UTI in Adults
2.0 Last reviewed: 17/11/2022 Review date: 30/11/2025

4. Managing a patient who has had a prolonged course of a continuous

prophylactic agent:
Antibiotic prophylaxis

Identifying patients for review:

• Patients should be reviewed after 6 months of prophylactic antibiotics with a view to

stopping
• 12 months is a suggested trigger for audit purposes for patients on long-term antibiotic
prophylaxis
• Patients who have urine cultures confirming resistance to the prophylactic agent they are
on should have their prophylaxis stopped (exposure to antibiotic without benefit) and a
clinical review to discuss ongoing management and/or the need for referral

Methenamine prophylaxis

Identifying patients for review:

• Patients should be reviewed after 6 months of prophylactic methenamine with a view to

stopping
• If the patient starts to suffer from recurrent UTIs again and methenamine was effective
previously, this can be restarted. Consider referral for investigation (if the patient has not
already been investigated)

Stopping continuous prophylaxis:

It is understandable for patients to be anxious about a return to frequent UTIs after stopping
continuous prophylaxis. However, a prolonged period of a prophylactic agent may allow bladder
epithelial healing, reducing the risk of future UTIs when antibiotics are then stopped.

• The proportion of patients who will return to suffering recurrent UTIs after stopping
continuous prophylaxis may be around 50%8.
• This means a significant number of patients are able to stop continuous prophylaxis
without a return of symptoms and therefore avoid the risks of resistance emerging and
side-effects.
• One option is to provide ‘standby’ antibiotics when stopping continuous prophylaxis
which may give sufficient reassurance to patients for a trial off prophylaxis.
• Consider referring patients who relapse after stopping continuous prophylaxis, if not
already been investigated.
• Longer term prophylaxis with an antibiotic or methenamine may be helpful in those
patients whose UTIs are suppressed when on prophylaxis and recur when prophylaxis is
discontinued after 6 months.

Part of the Antimicrobial Prescribing Guidelines for Primary Care.

Updated November 2022. Next review: November 2025. page 7
 Summary of Management of Recurrent Lower UTIs (in non-pregnant females):
≥ 3 symptomatic lower UTIs / 12 months or
≥2 symptomatic lower UTIs / 6 months

Consider red flag indications for Urology referral (see page 1)

Advice on Conservative Measures (see page 2)

Consider risks and benefits with the patient of:

For Stand-by or Post-coital antibiotics:
1. Stand-by antibiotics
Review repeat prescriptions at 6 month to
2. Post-coital antibiotics (if associated with intercourse) assess benefit and if any resistant urine
3. Trial of continuous prevention (either antibiotics OR cultures
methenamine)

Continuous antibiotic prophylaxis Choice dependent on Continuous methenamine prophylaxis

Trial of 6 months of nightly antibiotics factors outlined on page 4 Trial of 6 months of methenamine (see page 3)
(see page 3)

No breakthrough Breakthrough UTI whilst on No breakthrough Breakthrough UTI whilst on

UTIs prophylaxis UTIs prophylaxis

After 6 months, stop prophylaxis If ≥2 breakthrough UTIs, After 6 months, stop prophylaxis If ≥2 breakthrough UTIs:
Around 50% will not return to or the urine cultures are Around 50% will not return to recurrent Methenamine
recurrent symptoms. resistant to the symptoms. prophylaxis has failed
prophylactic agent:
Consider offering stand-by antibiotics Consider offering stand-by antibiotics if and should be stopped
if patient concerned. Antibiotic prophylaxis has patient concerned. or changed
failed and should be Consider referral if not
stopped or changed already investigated
If recurrent UTIs return after Consider referral if not If recurrent UTIs return after stopping, 8
stopping, restart and consider referral already investigated restart methenamine and consider referral
Recurrent UTI in Adults
2.0 Last reviewed: 17/11/2022 Review date: 30/11/2025

References

1. Grabe, M., Bjerklund-Johansen, T. E., Botto, H., Çek, M., Naber, K. G., & Tenke, P. (2015).
Guidelines on urological infections. European Association of Urology.
2. Nicolle, L. E., Bradley, S., Colgan, R., Rice, J. C., Schaeffer, A., & Hooton, T. M. (2005).
Infectious Diseases Society of America guidelines for the diagnosis and treatment of
asymptomatic bacteriuria in adults. Clinical Infectious Diseases, 643-654.
3. NICE Clinical Knowledge Summaries: https://cks.nice.org.uk/urinary-tract-infection-lower-
women#!scenario:2 accessed June 2022.
4. Scottish Intercollegiate Guideline Network. A national clinical guideline 160. Management
of suspected bacterial urinary tract infection. Updated September 2020.
5. Public Health England. UK SMI B41i8.7. Updated January 2019.
6. Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane
Database of Systematic Reviews 2012, Issue 10. Art. No.: CD001321. DOI:
10.1002/14651858.CD001321.pub5
7. Public Health England. Diagnosis of UTI. Quick Reference Guide for Primary Care. Updated
May 2020.
8. Albert X, Huertas I, Pereiro I, Sanfélix J, Gosalbes V, Perrotta C. Antibiotics for preventing
recurrent urinary tract infection in non-pregnant women. Cochrane Database of Systematic
Reviews 2004, Issue 3. Art. No.: CD001209. DOI: 10.1002/14651858.CD001209.pub2
9. Harding C, Mossop H, Homer T, et al. Alternative to prophylactic antibiotics for the
treatment of recurrent urinary tract infections in women: multicentre, open label,
randomised, non-inferiority trial. BMJ. 2022;376:e068229. Published 2022 Mar 9.
DOI:10.1136/bmj-2021-0068229
10. Urinary tract infection (recurrent): antimicrobial prescribing NICE guideline [NG112] Published
date: October 2018: https://www.nice.org.uk/guidance/ng112 accessed online June 2022