Acute cystitis in non-pregnant women

• Convey a positive approach and reassure the woman that cystitis is generally self-limiting.
• Relieve the symptoms with paracetamol or ibuprofen.
• If cystitis symptoms are moderate or severe, offer a 3-day course of:
• Trimethoprim 200 mg twice daily, or
• Nitrofurantoin 50 mg four times a day, or 100 mg (modified-release) twice daily.
• If cystitis symptoms are mild:
• Dipstick test the urine and if results are negative, discuss not treating the cystitis with an antibiotic.
• Have a lower threshold for offering an antibiotic if there are risk factors for persistent infection, recurrent infection, or treatment failure.
• If there are concerns about not taking an antibiotic, offer a delayed antibiotic prescription to be dispensed if the symptoms become worse, or last more than 48 hours.
• Urine culture is not routinely required.
• Urine culture is useful to confirm the diagnosis and to guide choice of antibiotic when there are risk factors for more severe illness or treatment has failed.
• If cystitis symptoms fail to respond to an antibiotic chosen according to the urine culture result, check compliance, repeat the urine culture, change to another antibiotic, and consider referring for specialist assessment.

Recurrent cystitis

• Review the diagnosis.
• Review the medical and surgical history to assess risk factors for recurrent cystitis such as stones, papillary necrosis, and vesicoureteric reflux — this may require imaging or urological referral.
• Relieve the symptoms with paracetamol or ibuprofen.
• Treat the infection with a 3-day course of trimethoprim or nitrofurantoin (as above) if the symptoms are severe.
• Advise on lifestyle measures for prevention, such as use of cranberry products. High strength (at least 200 mg) capsules may be more effective and better tolerated than cranberry drinks.
• For women with troublesome recurrent cystitis, consider:
• A prescription for a 'stand-by' antibiotic to be used for future episodes of cystitis.
• Trimethoprim 200 mg to be taken within 2 hours of intercourse (off-label use).
• A 6-month trial of low-dose continuous antibiotic treatment: trimethoprim 100 mg or nitrofurantoin (immediate-release) 50–100 mg, every night.

Asymptomatic bacteriuria in pregnancy

• Screen for asymptomatic bacteriuria on the first antenatal visit by sending urine for culture.
• If asymptomatic bacteriuria is found, send a second urine sample for culture.
• If the second urine culture confirms asymptomatic bacteriuria, treat for 7 days with an antibiotic to which the organism is sensitive. Do not use trimethoprim first-line if there is a suitable alternative.
• After treatment, send urine for culture to screen for asymptomatic bacteriuria at every antenatal visit until delivery.
• If a group B streptococcus is isolated, inform the antenatal care service, as prophylactic antibiotics may be indicated during labour and delivery.

Cystitis during pregnancy

• Culture the urine.
• Relieve the symptoms with paracetamol.
• Treat the infection with an appropriate antibiotic for 7 days (in order of preference: nitrofurantoin, trimethoprim [if the woman is not folate deficient or taking a folate antagonist], amoxicillin, cefalexin).
• Have a low threshold for admitting the woman if upper urinary tract infection (UTI) is suspected (fever, loin tenderness, and pain).
• After treatment, send urine for culture to screen for asymptomatic bacteriuria at every antenatal visit until delivery.
• If a group B streptococcus is isolated, inform the antenatal care service, as prophylactic antibiotics may be indicated during labour and delivery.

Lower UTI in women with an indwelling urinary catheter

• For women with an indwelling urinary catheter, considerable clinical judgement is required to diagnose UTI.
• Assess the severity of the infection and the presence of any comorbidities.
• Admit the woman to hospital if there are symptoms and signs of severe infection.
• If there is fever, and flank pain or tenderness, manage as for upper UTI — see the CKS topic on Pyelonephritis - acute.
• Check that the catheter is correctly positioned and not blocked.
• Send urine for culture before antibiotic treatment is started.
• If it is practical, withhold antibiotics until the result of urine culture is available to guide the choice of antibiotic. Otherwise, empirically prescribe trimethoprim or nitrofurantoin for 7 days.
• Relieve the symptoms with paracetamol or ibuprofen.
• Check the urine culture report. If necessary, change the antibiotic to one to which the organism is sensitive.
• To prevent UTI:
• Use an indwelling urinary catheter only after alternative methods of management have been considered, and regularly review the need for a catheter.
• Ensure high standards of hygiene with catheter care: obtain urine samples from a sampling port using an aseptic technique, and change catheters only when necessary.
• When changing catheters, only use antibiotic prophylaxis for people with a history of catheter-associated UTI following catheter change.

• Convey a positive approach and reassure the woman that cystitis is generally self-limiting:
• Without antibiotics, symptoms can be expected to resolve in 4–9 days.
• With antibiotics, symptoms can be expected to resolve in 3–8 days.
• On average, antibiotics shorten the duration of symptoms by about a day.
• Relieve symptoms with paracetamol or ibuprofen — do not recommend urine alkalinizing agents or cranberry products.
• If cystitis symptoms are moderate or severe:
• Offer an antibiotic.
• Do not dipstick test the urine, as the decision to offer an antibiotic is not influenced by urine dipstick test results. Even if the tests for nitrite, and leucocyte esterase, and blood are all negative, an antibiotic should still be offered.
• If the woman prefers not to take an antibiotic, offer a delayed antibiotic prescription to be dispensed if the symptoms become worse, or last more than 48 hours.
• If cystitis symptoms are mild:
• Dipstick test the urine to guide treatment decisions.
• Discuss not using an antibiotic, especially if the urine dipstick test is negative for nitrites and leucocyte esterase and blood.
• Have a lower threshold for offering an antibiotic if there are risk factors for persistent infection, recurrent infection, or treatment failure.
• If there are concerns about not taking an antibiotic, offer a delayed antibiotic prescription to be dispensed if the symptoms become worse, or last more than 48 hours.
• Advise the woman to seek medical attention if she develops a high fever or becomes systemically unwell.

These recommendations are in line with Scottish [SIGN, 2006], European [European Association of Urology, 2009], and American [ICSI, 2004; American College of Obstetricians and Gynecologists, 2008] guidelines. The recommendations also take into account the evidence from a Health Technology Assessment (HTA) commissioned by the National Institute for Health Research (NIHR) to assess the diagnosis of cystitis, its prognosis, and five different treatment strategies [Little et al, 2009].

A positive approach to prognosis

• A positive approach to diagnosis and prognosis has been found to be independently associated with shorter duration of symptoms in observational studies and in randomized controlled trials [Thomas, 1987; Little et al, 2001; Little et al, 2009].
• The average duration of symptoms (that are at least moderately severe) is reported in the NIHR HTA [Little et al, 2009] and summarized in the Prognosis section.

Use of an analgesic for symptomatic relief

• CKS found no trials of analgesics for the painful symptoms of cystitis. The recommendation to use paracetamol or ibuprofen to treat the painful symptoms of cystitis is based on their use in other painful infections and the experience of experts [SIGN, 2006].
• There is insufficient evidence to recommend the use of:
• Urine alkalinizing agents (such as potassium citrate or bicarbonate): CKS found no controlled trials of urine alkalinizing agents. One observational study found no relationship between symptoms of cystitis and urine pH [Brumfitt et al, 1990].
• Cranberry products: a Cochrane systematic review found no good evidence to support the use of cranberry juice or other cranberry products for treating acute UTIs [Jepson et al, 1998].

Treatment strategy (to consider the options of an antibiotic, no antibiotic, or delayed antibiotic prescription)

• The evidence that a course of antibiotics is effective is discussed in Choice of antibiotic.
• The strategy for antibiotic prescribing is supported by evidence from a series of studies in the UK [Little et al, 2009], and a randomized controlled trial in New Zealand [Richards et al, 2005].
• No clinically (or economically) important differences were found between five different treatment strategies in which antibiotics were offered: (i) immediately, (ii) delayed for 48 hours, (iii) according to a symptom rule, (iv) according to a dipstick test rule, or (v) according to the results of urine culture.
• Women who did not meet the criteria for immediate antibiotic treatment were offered a delayed antibiotic prescription to use if their symptoms did not settle after 48 hours. In each group where women were offered a delayed prescription, a high proportion chose to use it.
• Women who presented with more severe symptoms of dysuria, urgency, frequency, and nocturia recovered more slowly.
• Antibiotics shortened the duration of symptoms (that were at least moderately severe) by about 1–2 days.
• CKS therefore recommends offering an antibiotic when:
• Presenting symptoms are moderate or severe — because antibiotics are likely to shorten the duration of symptoms by 1–2 days.
• The woman has a strong preference for antibiotic treatment — because there is no evidence that treatment leads to poorer outcomes, although there is also no evidence of effectiveness in women with less severe symptoms.
• It may be a complicated infection — because there is a greater risk of adverse effects from infection.
• While CKS recommends using severity of symptoms as a key decision criterion, other guidelines (for example [SIGN, 2006]) recommend using number of symptoms.
• CKS recommends considering a delayed antibiotic prescription whenever an antibiotic is not prescribed, because this may give some women the confidence needed to try not using an antibiotic, to see if the symptoms resolve spontaneously.

• Follow local guidelines when available.
• If local guidelines are not available:
• For an uncomplicated infection, prescribe either:
• Trimethoprim 200 mg twice daily, for 3 days, or
• Nitrofurantoin 50 mg four times daily, or 100 mg (modified-release) twice daily, for 3 days.
• For a complicated infection, prescribe a 5–10-day course of trimethoprim or nitrofurantoin.

Antibiotic treatment

• For women with urinary tract infection (UTI), there is evidence from a meta-analysis that antibiotics are more effective than placebo in eradicating bacteriuria and relieving UTI symptoms [Falagas et al, 2009].

Duration of antibiotic treatment

• A 3-day course of empirical treatment is recommended because there is good evidence from Cochrane systematic reviews that this achieves symptomatic cure in people with uncomplicated UTI; it is more effective than single-dose treatment and as effective as 5–10-day courses. This is also in line with recommendations from the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2006] and international guidelines [American College of Obstetricians and Gynecologists, 2008; European Association of Urology, 2009].
• For people with a complicated UTI, a longer course is recommended because there is evidence from a Cochrane systematic review that a 5–10-day course produced a higher bacteriological cure rate (but more adverse effects) than a 3-day regimen. The Cochrane systematic review concluded that a 5–10-day course may be considered for women in whom eradication of bacteriuria is important.

Route of administration

• The oral route is recommended, even for severe cystitis. A Cochrane systematic review found no evidence that oral antibiotic treatment is less effective than intravenous antibiotics for treating severe UTIs [Pohl, 2007].

Antibiotic choice: trimethoprim and nitrofurantoin as first-line options

• Trimethoprim and nitrofurantoin (both narrow spectrum antibiotics) are generally recommended as appropriate first-line antibiotics in the UK [SIGN, 2006; BNF 57, 2009].
• Narrow spectrum antibiotics are preferred over broad spectrum antibiotics such as co-amoxiclav, quinolones, and cephalosporins. This is in line with guidance issued by the Health Protection Agency which recommends avoiding the use of broad spectrum antibiotics when narrow spectrum antibiotics remain effective [HPA, 2009]. There are concerns that broad spectrum antibiotics increase the risk of Clostridium difficile, meticillin-resistant Staphylococcus aureus (MRSA), and resistant UTIs. Issues of antibiotic resistance are discussed below.
• Despite their widespread use, there are few comparative trials comparing these two antibiotics. There is evidence from four trials which found trimethoprim and nitrofurantoin to be equally effective and generally well tolerated.
• The dosages recommended are based on those recommended by the manufacturers of these antibiotics and are in line with doses used in trials [Goldshield Pharmaceuticals, 2002a; Goldshield Pharmaceuticals, 2002b; Actavis, 2007].

Bacterial resistance

• There are concerns that resistance to trimethoprim and nitrofurantoin is increasing, yet few data on the resistance patterns have been published.
• Evidence from older studies indicated trimethoprim resistance to be around 20–30% (although higher levels have been reported for certain parts of the UK) with a lower incidence for nitrofurantoin (less than 20%). However, these data should be treated with caution, because:
• Most of these studies were performed in the 1990s and resistance patterns may have changed.
• There are considerable geographic variations in antibiotic resistance pattern.
• It is difficult to compare results from different studies because of differences in populations (for example hospital or community) and differences in laboratory standards.
• Rates of clinical resistance to trimethoprim may be less common than expected from rates of resistance in laboratory samples. Statistics from laboratories are likely to be biased by higher proportions of samples from women with resistant infections [McNulty et al, 2006].
• Consequently, CKS recommends that, where available, local antibiotic guidelines should be followed, taking into account local resistance patterns.

Nitrofurantoin formulations

• Both immediate and modified-release formulations of nitrofurantoin are recommended because CKS found no evidence to prefer one formulation over another. For further information, see Dosage.

• Urine microscopy and culture are not routinely required for women with uncomplicated cystitis.
• Send urine for microscopy and culture if any of the following apply:
• There are risk factors for a complicated urinary tract infection — for example the woman has recently had urological instrumentation, or is immunocompromised, or has been in hospital recently.
• Confirmation of the diagnosis or exclusion of other conditions is required.
• The woman has not responded to antibiotic treatment.
• The woman has recurrent episodes of cystitis and this has not been investigated.
• When underlying causes of recurrent cystitis and other conditions have been excluded, it is not necessary to routinely culture the urine for further episodes.

These recommendations are in line with Scottish Intercollegiate Guidelines Network guidelines [SIGN, 2006].

Urine culture

• Urine culture is mainly useful for identifying bacteria and their sensitivity to antibiotics [SIGN, 2006].
• Urine microscopy and culture are not routinely recommended for women with uncomplicated cystitis because the results are not available for immediate decision-making and, by the time they are available, most women's symptoms will be resolving. Three studies found that, if urine were to be routinely cultured for all women with acute cystitis, the average duration of symptoms would be reduced by between 0.04 and 0.32 days [SIGN, 2006]. Similar evidence is provided by a randomized controlled trial that compared different strategies for antibiotic treatment [Little et al, 2009]. An economic analysis estimated the cost of preventing 1 day of symptoms as £215, and the cost per QALY (quality adjusted life year gained) was £215,000 [SIGN, 2006].
• Urine culture is recommended for women with a complicated infection because the risks associated with treatment failure are increased [SIGN, 2006].

• Follow up is not routinely required for uncomplicated cystitis, but should be considered for women with a potentially complicated infection.
• If haematuria was found, follow up to re-test the urine and check that the infection and haematuria have resolved.

This recommendation is pragmatic as CKS found no published evidence on which to base recommendations [SIGN, 2006].

• Follow up is not routinely required for uncomplicated cystitis as most cases of uncomplicated urinary tract infection resolve in about 4–9 days without antibiotic treatment, and in about 3–8 days with antibiotic treatment — see Prognosis.

• If the woman fails to respond to two courses of antibiotics shown by urine culture results to be appropriate treatment, refer for specialist assessment.
• If urological cancer is suspected (for example haematuria persists after successful treatment of cystitis), refer urgently to a team specializing in the management of urological cancer.

Referral for failure to respond to appropriate antibiotics

• The recommendation to consider referring women who have failed to respond to an appropriate antibiotic (shown by urine culture) is pragmatic, as there is no direct evidence from clinical trials or recommendations in national guidelines.

Urgent referral for urological cancer

• The recommendation to refer women with suspected urological cancer is based on criteria in guidelines from the National Institute for Health and Clinical Excellence [NICE, 2005b].

• Continue symptomatic treatment with paracetamol or ibuprofen.
• Check compliance with antibiotic treatment.
• Send a urine sample for culture.
• If symptoms are troublesome, offer a different antibiotic (nitrofurantoin or trimethoprim) while waiting for the culture results — see Choice of antibiotic.
• If infection is confirmed on culture, treat with an antibiotic to which the organism is sensitive.
• If infection is not confirmed on culture, consider other possible causes for the symptoms — see Differential diagnosis.
• If cystitis symptoms fail to respond to two courses of antibiotic shown by culture to be appropriate treatment, refer for specialist assessment.

These recommendations are in line with guidance from the Scottish Intercollegiate Guidelines Network [SIGN, 2006].

• The recommendation to offer a different antibiotic if symptoms persist is supported by a study of the course of uncomplicated community-acquired urinary tract infection in women [McNulty et al, 2006]. The study found that, after 5 days of antibiotic treatment, symptoms had resolved in 70% of women infected with an organism sensitive to the antibiotic, and 24% of women with a resistant isolate. The study also found that 50% of those who reconsulted in the first week had a resistant isolate.

• Review the diagnosis.
• Culture the urine to confirm infection and exclude other causes.
• Refer urgently if urological cancer is suspected.
• Review the woman's medical and surgical history to assess risk factors for recurrent cystitis such as stones, papillary necrosis, and vesicoureteric reflux — this assessment may require imaging and urological referral.
• Relieve symptoms with paracetamol or ibuprofen.
• If symptoms are moderate or severe, offer an antibiotic immediately.
• If symptoms are mild, suggest delaying antibiotic treatment until culture results are available to guide choice of antibiotic.
• Advise on lifestyle measures such as high-strength cranberry capsules to reduce the risk of recurrent episodes.
• If troublesome cystitis recurs frequently:
• Consider offering a prescription for a 'stand-by' antibiotic to be used for future episodes.
• Consider preventive treatments.
• Refer or seek specialist advice if these measures are not successful.

Confirming urinary tract infection and excluding other causes

• The recommendation to confirm infection with urine culture, and exclude other causes, is pragmatic.
• The recommendation to refer urgently if cancer is suspected is based on guidelines from the National Institute for Health and Clinical Excellence [NICE, 2005b].

Treatments

• The basis for recommending symptomatic relief with paracetamol or ibuprofen is discussed in Managing suspected cystitis.
• The basis for offering empirical antibiotic treatment if symptoms are moderate or severe, or delaying treatment if symptoms are mild, is discussed in Managing suspected cystitis.
• The recommendation to consider 'stand-by' antibiotics is based on expert opinion [Harris et al, 2008].

Lifestyle measures and preventive treatment

• The basis for lifestyle measures and prophylactic treatments is discussed in the sections on Lifestyle measures and Preventive treatments.

Referral

• The basis for the recommendation to refer the woman if prophylactic measures are unsuccessful is pragmatic.

• Follow local guidelines when available. Otherwise:
• For empirical treatment, prescribe either:
• Trimethoprim 200 mg twice daily, for 3 days, or
• Nitrofurantoin 50 mg four times daily, or 100 mg (modified-release) twice daily, for 3 days.
• If the woman has been treated with trimethoprim recently (up to a year previously), consider prescribing nitrofurantoin instead of trimethoprim.

Choice of antibiotic

• The reasons for preferring trimethoprim and nitrofurantoin as first-line options for treating cystitis are discussed in Choice of antibiotic.

Considering nitrofurantoin when trimethoprim has been used recently

• Nitrofurantoin may be preferable for empirical prescribing when the woman has recently used trimethoprim because there is evidence that uropathogens are more likely to be resistant to trimethoprim if it has been used recently (up to the past year). The evidence is not clear enough to recommend precise thresholds of exposure.
• Trimethoprim is not preferred when nitrofurantoin has previously been used because there is no evidence that previous treatment with nitrofurantoin increases the chance that future infections will be resistant organisms. Furthermore, laboratory studies find that nitrofurantoin-resistant Escherichia coli reproduce substantially less effectively than nitrofurantoin-sensitive E. coli (in other words, nitrofurantoin resistance imposes a high fitness cost on the organism) [Sandegren et al, 2008].

Advise women with recurrent cystitis that:

• Cranberry products reduce the recurrence rate of cystitis, and are available from shops (but not on the NHS).
• Cranberry products should not be taken if warfarin is being used.
• High strength capsules (containing at least 200 mg of cranberry extract) are recommended because:
• They may be more effective than cranberry drinks, which require a large volume to be drunk to provide the same amount of cranberry extract: 200 mg of cranberry extract is equivalent to about 5000 mg of fresh cranberries.
• Cranberry capsules may be more acceptable than cranberry juice, which some women find difficult to take regularly because of the bitter taste or the large amount of sugar added to mask the bitterness.
• If cystitis is related to sexual intercourse, options to be considered include:
• A different contraceptive method, if a diaphragm is being used.
• Voiding soon after intercourse.
• Using a lubricant if symptoms could be due to mild trauma rather than infection.

Cranberry extract for preventing cystitis

• There is good evidence that cranberry products effectively prevent cystitis. A Cochrane systematic review of randomized controlled trials found that cranberry products significantly reduced the incidence of urinary tract infections (UTIs) over 12 months, compared with placebo or control treatments. However, withdrawal rates in the trials were high, which may indicate that many women find taking cranberry products unacceptable in the long term. Also, the benefits of cranberry may be less in elderly women and women with a urinary catheter.
• The optimal dose and form of administration of cranberry products is not established. However, higher doses may be more effective than lower doses [SIGN, 2006].
• Cranberry products should be avoided by people taking warfarin, as they can potentiate its effects [CSM, 2003; CSM, 2004].

Recurrent cystitis related to sexual intercourse

• These recommendations are based on expert opinion [Harris et al, 2008].
• The Scottish Intercollegiate Guidelines Network (SIGN) guidelines explain that because 'there is no conclusive association between lifestyle factors, such as diet, hydration, clothing, toileting activity, and sexual activity, and susceptibility to bacterial UTI in adult, non-pregnant women, there is no evidence to support healthcare professionals giving routine advice about lifestyle factors' [SIGN, 2006].
• The incidence of UTI may be increased in women who use diaphragms — this may relate to the fit and size of the diaphragm putting pressure on the urethra. The incidence of UTI may also be increased in women who use spermicides, but the use of spermicides with condoms is no longer recommended. For further information, see the sections on Diaphragm and cap, and Male condom in the CKS topic on Contraception.

• Consider offering a prescription for a 'stand-by' antibiotic to be used for future episodes of cystitis before prescribing prophylactic drug treatment.
• When deciding to offer prophylactic drug treatment, consider the frequency, severity, and impact of recurrent cystitis, and whether referral for urological investigation would be appropriate.
• For recurrent cystitis associated with sexual intercourse:
• Offer trimethoprim 100 mg to be taken within 2 hours of intercourse (off-label use).
• For recurrent cystitis not associated with sexual intercourse:
• Offer a 6-month trial of low-dose continuous antibiotic treatment.
• Suitable antibiotics are:
• Trimethoprim 100 mg every night.
• Nitrofurantoin (immediate-release) 50 mg to 100 mg every night (modified-release nitrofurantoin is not licensed for prophylaxis).
• Treatments that are not recommended include:
• Methenamine hippurate.
• Oestrogen products (for post-menopausal women).

'Stand-by' antibiotics as an alternative to preventive antibiotics

• The recommendation to consider 'stand-by' antibiotics is based on expert opinion [Harris et al, 2008].

Post-coital antibiotics

• There is limited evidence from a Cochrane systematic review that post-coital antibiotics may be more effective than placebo and as effective as continuous antibiotic treatment in preventing urinary tract infection (UTI) associated with sexual intercourse.
• The recommendation to offer trimethoprim 100 mg is extrapolated from evidence provided by a small, double-blind, randomized controlled trial that co-trimoxazole 240 mg (containing trimethoprim 40 mg and sulfamethoxazole 200 mg) given within 2 hours of intercourse was more effective than a post-coital placebo [Stapleton et al, 1990]. Trimethoprim (a narrow spectrum antibiotic) has been found to be as effective as co-trimoxazole in treating UTI and produces fewer adverse effects [SIGN, 2006; BNF 57, 2009; European Association of Urology, 2009]. The European Association of Urology also recommend that it is reasonable to offer the doses of antibiotics used for nightly prophylaxis for post-coital use [European Association of Urology, 2009].
• Although another study supported the post-coital use of ciprofloxacin (a quinolone) [Melekos et al, 1997], broad spectrum antibiotics are less preferred. This is in line with guidance issued by the Health Protection Agency which recommended avoiding the use of broad spectrum antibiotics when narrow spectrum antibiotics remain effective [HPA, 2009]. There are concerns that broad spectrum antibiotics increase the risk of Clostridium difficile, meticillin-resistant Staphylococcus aureus (MRSA), and resistant UTIs.

Referral before starting continuous antibiotic prophylaxis

• Seeking specialist advice before starting continuous antibiotic prophylaxis is recommended pragmatically to decide whether the woman needs investigation to exclude an underlying cause.

Continuous antibiotic prophylaxis

• Effectiveness
• There is weak evidence from a Cochrane systematic review that continuous antibiotics reduce recurrence of urinary tract infections more than placebo but are associated with more adverse effects [Albert et al, 2004]. There are limited data showing that antibiotics do not continue to prevent bacteriuria after treatment is stopped.
• Continuous antibiotics have not been directly compared with cranberry products [SIGN, 2006].
• Choice of antibiotic
• There is insufficient direct evidence to prefer any particular antibiotic over another. Trimethoprim and nitrofurantoin are recommended options for prophylaxis of recurrent UTI because:
• Narrow spectrum antibiotics, such as trimethoprim and nitrofurantoin, are generally preferred over broad spectrum antibiotics due to concerns over increasing the risk of Clostridium difficile, MRSA, and resistant UTIs [HPA, 2009].
• Both trimethoprim and immediate-release nitrofurantoin are licensed for the prophylaxis of recurrent UTI [Goldshield Pharmaceuticals, 2002b; Goldshield Pharmaceuticals, 2002c; Actavis, 2007]. The modified-release formulation of nitrofurantoin is not licensed [Goldshield Pharmaceuticals, 2007].
• Dosage and duration of treatment
• The dosages are based on those recommended by manufacturers of these antibiotics and in line with the dosages used in trials investigating prophylaxis of recurrent UTIs [Goldshield Pharmaceuticals, 2002c; Goldshield Pharmaceuticals, 2002b; Albert et al, 2004; Actavis, 2007].
• A 6-month trial is recommended, as this reflects the duration of most trials on prophylactic antibiotics. Information on long-term follow up is lacking.
• Bacterial resistance
• There are concerns that resistance to trimethoprim and nitrofurantoin is increasing, but there is little current published evidence on resistance patterns for trimethoprim and nitrofurantoin (see the evidence section on Prevalence).
• Consequently, CKS recommends that local antibiotic guidelines should be followed, taking into account local resistance pattern.

Treatments not recommended

• Methenamine hippurate
• Methenamine hippurate is not recommended for preventing UTI because there is only weak evidence from a Cochrane systematic review that treatment may be effective for up to 7 days [Lee et al, 2007].
• Oestrogen products (for postmenopausal women)
• Oestrogen products are not recommended for use as preventive treatment in primary care because there is evidence from a Cochrane systematic review that oral oestrogens are no more effective than placebo in reducing recurrent UTIs in postmenopausal women, and there is conflicting evidence from two small trials on intravaginal oestrogen [Perrotta et al, 2008].

• If prophylactic antibiotics are prescribed, follow up to review progress after 6 months, or sooner if clinically indicated.
• If haematuria was found, follow up to re-test the urine and check that the infection and haematuria have resolved.

CKS found no recommendations regarding follow up in national guidelines. The recommendation to follow up every 6 months is based on trials of prophylactic antibiotics, most of which followed their participants for 6 months.

• Refer urgently, to a team specializing in the management of urological cancer, if urological cancer is suspected (for example if haematuria persists after successful treatment of acute cystitis).
• Refer the woman if:
• Risk factors for recurrent cystitis (such as urinary tract abnormalities, stones, vesicoureteric reflux, papillary necrosis) are present or suspected.
• There is any known abnormality on ultrasound of kidneys, ureters, and bladder.
• The response to preventive treatments and lifestyle measures is ineffective.

These recommendations are in line with guidelines issued by the Scottish Intercollegiate Guidelines Network (SIGN) and are based on expert opinion [SIGN, 2006]. Given the evidence supporting the use of prophylactic antibiotics and cranberry products, SIGN recommends that these strategies should be explored before referring the woman for specialist investigation.

Urgent referral for urological cancer

• The recommendation to refer women with suspected urological cancer is based on criteria in guidelines from the National Institute for Health and Clinical Excellence (NICE) [NICE, 2005b].

Referral for assessment of risk factors for recurrent cystitis

• The recommendation to refer for specialist assessment of risk factors for recurrent cystitis is based on expert opinion [Harris et al, 2008].

Poor response to preventive measures

• The recommendation to seek specialist opinion when preventive measures have failed is pragmatic.

• Screen for asymptomatic bacteriuria on the first antenatal visit by sending urine for culture. If asymptomatic bacteriuria is found, send a second urine sample for culture.
• If the second urine culture confirms asymptomatic bacteriuria, treat for 7 days with an antibiotic to which the organism is sensitive.
• Preferred options when sensitivities are known are (in order of preference):
• Amoxicillin: 250 mg three times daily, for 7 days.
• Nitrofurantoin: 50 mg four times daily, or 100 mg (modified-release) twice daily, for 7 days.
• Trimethoprim: 200 mg twice daily, for 7 days (unless the woman is folate deficient or taking a folate antagonist).
• Cefalexin (500 mg twice daily, or 250 mg 6-hourly, for 7 days) may be used but is less preferred.
• After treatment, send urine for culture to screen for asymptomatic bacteriuria at every antenatal visit until delivery.
• If a group B streptococcus is isolated, inform the antenatal care service, as prophylactic antibiotics may be indicated during labour and delivery.

Screening for asymptomatic bacteriuria

• Guidelines from the National Institute for Health and Clinical Excellence (NICE) on antenatal care recommend that 'Women should be offered routine screening for asymptomatic bacteriuria by midstream urine culture early in pregnancy' [NICE, 2008a]. Guidelines from the Scottish Intercollegiate Guidelines Network (SIGN) are clearer: 'Women who do not have bacteriuria in the first trimester should not have repeat urine cultures' [SIGN, 2006].
• Culture of urine is recommended rather than dipstick (reagent strip) tests because there is good evidence that dipstick tests are insufficiently sensitive (in whatever combination) to be used for screening. Urine culture is regarded as the gold standard and is assumed to have (close to) 100% sensitivity for detecting bacteriuria.
• The recommendation that a positive culture be confirmed with a second culture before treating asymptomatic bacteriuria in pregnancy is based on expert opinion [Nicolle et al, 2005; SIGN, 2006].
• The recommendation to continue to screen for asymptomatic bacteriuria at each subsequent visit after completing antibiotic treatment is consistent with practice in multinational clinical trials, such as that conducted by the World Health Organization's Asymptomatic Bacteriuria Trial Group [Lumbiganon et al, 2009].

Treating asymptomatic bacteriuria

• Asymptomatic bacteriuria in pregnancy should be treated with an antibiotic because there is consistent evidence from a Cochrane systematic review that the risk of pyelonephritis is reduced: about seven women need to be treated to prevent one episode of pyelonephritis.
• There is inconsistent evidence that treatment may also reduce the incidence of low birthweight and prematurity.

Choosing antibiotic treatment

• Where sensitivities are known, amoxicillin is preferred.
• The manufacturer of amoxicillin states that its use in pregnancy has been well documented in clinical studies. Unlike nitrofurantoin and trimethoprim, amoxicillin is licensed for the treatment of bacteriuria in pregnancy [ABPI Medicines Compendium, 2008].
• Penicillin and cephalosporins are generally the antibiotics of choice for use in pregnancy [Schaefer et al, 2007].
• Nitrofurantoin is an alternative if amoxicillin is not suitable.
• Nitrofurantoin has been used extensively since the 1950s, and its safety profile in human pregnancy has been well documented [Goldshield Pharmaceuticals, 2002b; Goldshield Pharmaceuticals, 2007].
• There is evidence from a Cochrane systematic review which supports the use of nitrofurantoin for treating asymptomatic bacteriuria in pregnancy [Smaill and Vazquez, 2007]. Nitrofurantoin was studied in five of the 14 studies identified (none on trimethoprim). Although significant heterogeneity was present, pooled results from five trials (two used nitrofurantoin) found antibiotics to be more effective than placebo in treating asymptomatic bacteriuria in pregnancy.
• The efficacy and safety profiles of nitrofurantoin are further supported in a recent large multicentre study undertaken by the World Health Organization (WHO) in which 778 pregnant women with asymptomatic bacteriuria were treated with nitrofurantoin [Lumbiganon et al, 2009]. A cure rate of 86% was achieved with a 7-day course.
• Trimethoprim, used carefully, has a good safety profile during pregnancy.
• Concerns have been expressed about the use of trimethoprim during pregnancy because it is a folic acid antagonist, and low levels of folic acid have been associated with serious birth defects.
• The evidence on the risks of trimethoprim during pregnancy has been critically assessed by the UK Teratology Information Service (UKTIS), formerly the National Teratology Information Service (NTIS) [NTIS, 2008]. A similar systematic review was conducted by the Centers for Disease Control (CDC) in the USA, to assess the safety of trimethoprim-sulfamethoxazole used for prophylaxis in HIV-infected pregnant women [Forna et al, 2006]. The NTIS and CDC concluded that the benefits outweighed the risks, which were small. Additionally the NTIS concluded that:
• Trimethoprim should not be used in pregnant women who are folate deficient, or who are taking a folate antagonist (unless they are taking a folate supplement).
• In women with normal folate status, who are well nourished, use of trimethoprim for a short period is unlikely to induce folate deficiency.
• For further information, see Pregnancy and breastfeeding with trimethoprim.
• Cefalexin is less preferred because:
• Although cefalexin can be used in pregnancy [Schaefer et al, 2007], the Health Protection Agency recommends avoiding the use of broad spectrum antibiotics (such as co-amoxiclav, cephalosporins, and quinolones) when narrow spectrum antibiotics remain effective [HPA, 2009]. There are concerns that broad spectrum antibiotics increase the risk of Clostridium difficile, meticillin-resistant Staphylococcus aureus (MRSA), and resistant UTIs.
• Duration of antibiotic treatment
• The use of a 7-day course is supported by evidence from a recent WHO study which found that a 1-day course of nitrofurantoin is less effective than a 7-day course for treating asymptomatic bacteriuria in pregnant women (n = 778) [Lumbiganon et al, 2009].
• Antibiotic dosages
• These are in line with dosages recommended by the manufacturers of these antibiotics.

Managing incidentally-found group B streptococcus infection

• The antenatal care service should be informed when a group B streptococcus (GBS), Streptococcus agalactiae, is isolated in urine. GBS bacteriuria, even if treated, may be associated with increased risk of neonatal GBS disease, and so antibiotic prophylaxis should be offered to the woman during delivery. This recommendation is based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2003].

• Convey a positive approach and reassure the woman that treatment with an antibiotic will prevent any harm to her baby, and will shorten the duration of symptoms.
• If the women has fever or loin tenderness, suspect upper urinary tract infection and admit or seek urgent specialist opinion.
• Offer paracetamol for symptomatic relief. Do not recommend urine alkalinizing agents or cranberry products.
• Send a urine sample for culture before starting antibiotic treatment.
• Prescribe an antibiotic empirically. If local guidelines are not available, suitable first-line antibiotics are (in order of preference):
• Nitrofurantoin 50 mg four times daily, or 100 mg (modified-release) twice daily, for 7 days.
• Trimethoprim 200 mg twice daily, for 7 days (if the woman is not folate deficient or taking a folate antagonist, and has not been treated with trimethoprim in the past year).
• Cefalexin 500 mg twice daily, or 250 mg 6-hourly, for 7 days.
• Follow up after 48 hours (or according to the clinical situation) to check response to treatment and the urine culture results.
• Amoxicillin 250 mg three times daily, for 7 days, is recommended only if the organism is reported to be susceptible on the culture results.

Sending urine for culture

• The recommendation to send urine for culture before starting treatment is pragmatic [SIGN, 2006]. The results can confirm the diagnosis and guide further treatment, especially if the uropathogen turns out to be resistant to the empirically chosen antibiotic.

Relieving symptoms with paracetamol

• The recommendation to relieve symptoms with paracetamol is pragmatic.
• Paracetamol is preferred over ibuprofen because it can be used all stages of pregnancy. For further information, see Choice in pregnancy or breastfeeding for analgesics and antipyretics.

Treating infection with an antibiotic

• Treatment with an antibiotic is recommended because there is good evidence from placebo-controlled trials in non-pregnant women with cystitis that antibiotics cure the infection, and experts suggest that urinary tract infection in pregnancy may increase the risk of fetal death, and, in the infant, increase the risks of developmental delay and cerebral palsy [Foxman, 2002; European Association of Urology, 2009].
• CKS did not recommend that women who have mild symptoms should be offered the option of waiting for the urine culture results before starting antibiotic treatment, although this option is recommended for women who are not pregnant. CKS made no recommendation because no evidence and no published expert opinion was found on this strategy.

Choosing antibiotics for empirical treatment

• The choice of antibiotic for empirical treatment should take into account local rates of resistance in uropathogens, and the safety, tolerability, and cost of antibiotic options [SIGN, 2006].
• For empirical treatment, nitrofurantoin is preferred over trimethoprim because:
• Nitrofurantoin has been used extensively since the 1950s and its safety profile in human pregnancy has been well documented [Goldshield Pharmaceuticals, 2002b; Goldshield Pharmaceuticals, 2007].
• Although the evidence on nitrofurantoin for treating symptomatic urinary tract infections (UTIs) in pregnant women is poor (only one small study was identified — none were found on trimethoprim), there is indirect evidence from a Cochrane systematic review and a large multicentre trial (undertaken by the World Health Organization [WHO], n = 778) supporting its efficacy and safety profiles for asymptomatic bacteriuria in pregnancy. For further information, see Screening for and managing asymptomatic bacteriuria in pregnancy.
• Although trimethoprim is commonly used to treat symptomatic UTIs, good evidence to support its use in pregnancy is lacking. In addition, a recent survey found that women's dietary intake of iron, vitamin D, calcium, and folate remain below recommended levels [Ruxton and Derbyshire, 2010].
• Cefalexin is less preferred because:
• Although the safety profile is well documented in pregnancy, the Health Protection Agency recommends avoiding the use of broad spectrum antibiotics (such as cephalosporins) when narrow spectrum antibiotics remain effective [HPA, 2009].
• There are concerns that broad spectrum antibiotics increase the risk of Clostridium difficile, meticillin-resistant Staphylococcus aureus (MRSA), and resistant UTIs.
• C. difficile infection can be life-threatening in pregnant women, and there are case-reports of both maternal deaths and stillborn infants [Rouphael et al, 2008].
• Amoxicillin is not recommended for empirical treatment because:
• There is evidence from several urine culture studies that resistance to amoxicillin is higher than for trimethoprim.

Duration of antibiotic treatment

• Evidence on different antibiotic regimens for treating symptomatic UTIs in pregnant women is lacking.
• Given the possible increased risk of fetal complications with a UTI, a 7-day course of antibiotics is preferred over shorter courses. This is extrapolated from indirect evidence which found a higher bacteriological cure with longer antibiotic regimens.
• For women with acute uncomplicated UTI who are not pregnant, a Cochrane systematic review found a 5–10-day course produced a higher bacteriological cure (but more adverse effects) than a 3-day course. The authors concluded that a 5–10 day regimen may be considered for women in whom eradication of bacteriuria is important.
• A recent large WHO study found a higher cure rate with a 7-day course of nitrofurantoin (86%) than a 1-day regimen (76%) in pregnant women with asymptomatic bacteriuria [Lumbiganon et al, 2009]. Adverse effects were not statistically different between the two groups.
• A 7-day course is supported by guidance issued by the European Association of Urology (no evidence provided) [European Association of Urology, 2009].

Following up to ensure eradication of infection

• Following up to ensure eradication of infection is based on expert opinion [SIGN, 2006].
• Subsequent screening for asymptomatic bacteriuria at antenatal visits is a pragmatic recommendation.

Managing incidentally-found group B streptococcus infection

• The antenatal care service should be informed when a group B streptococcus (GBS), Streptococcus agalactiae, is isolated from urine. GBS bacteriuria, even if treated, may be associated with increased risk of neonatal GBS disease, and so antibiotic prophylaxis should be offered to the mother during delivery. This recommendation is based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2003].

• Review culture results when available and, if necessary, change to an antibiotic that the organism is sensitive to.
• Send urine cultures to screen for asymptomatic bacteriuria 7 days after completion of treatment, and at every antenatal visit until delivery.
• If a group B streptococcus is isolated, inform the antenatal care service, as prophylactic antibiotics may be indicated during labour and delivery.

Following up to ensure eradication of infection

• Following up to ensure eradication of infection is a pragmatic recommendation [SIGN, 2006].
• Subsequent screening for asymptomatic bacteriuria at antenatal visits is a pragmatic recommendation.

Managing incidentally-found group B streptococcus infection

• The antenatal care service should be informed when a group B streptococcus (GBS), Streptococcus agalactiae, is isolated from urine. GBS bacteriuria, even if treated, may be associated with increased risk of neonatal GBS disease, and so antibiotic prophylaxis should be offered to the woman during delivery. This recommendation is based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2003].

• Admit, or seek urgent specialist opinion, if upper urinary tract infection is suspected (fever, loin tenderness, and pain).
• Seek specialist advice if symptoms fail to respond to antibiotic treatment guided by urine culture results, and if other causes have been excluded — see Differential diagnosis.

Admitting pregnant women with suspected pyelonephritis

• Experts recommend arranging admission for all pregnant women with acute pyelonephritis, for at least a short observation period, because of the risk of preterm labour and maternal renal complications [Ramakrishnan and Scheid, 2005].

Referring when treatment fails

• The recommendation to refer the woman when treatment fails is pragmatic. CKS found no relevant clinical trials or advice in national guidelines.

• Check compliance with antibiotic treatment.
• Continue symptomatic treatment with paracetamol.
• Send a urine sample for culture.
• If symptoms are troublesome, offer a different antibiotic (nitrofurantoin or trimethoprim) while waiting for the culture results — see Managing suspected acute cystitis during pregnancy.
• If infection is confirmed on culture, treat with an antibiotic to which the organism is sensitive.
• If infection is not confirmed on culture, consider other possible causes for the symptoms — see Differential diagnosis.
• If cystitis symptoms fail to respond to a second antibiotic shown by urine culture results to be appropriate treatment, seek specialist advice.

These recommendations are in line with guidance from the Scottish Intercollegiate Guidelines Network [SIGN, 2006].

• The recommendation to offer a different antibiotic if symptoms persist is supported by a recent study of the course of uncomplicated community-acquired urinary tract infection in women [McNulty et al, 2006]. The study found that, after 5 days of antibiotic treatment, symptoms had resolved in 70% of women infected with an organism sensitive to the antibiotic, and 24% of women with a resistant isolate. The study also found that 50% of those who reconsulted in the first week had a resistant isolate.

• Do not treat asymptomatic bacteriuria.
• Remember that considerable clinical judgement is required to diagnose urinary tract infection (UTI) in women with an indwelling urinary catheter.
• If symptoms are severe (for example, severe nausea and vomiting, confusion, tachypnoea, tachycardia, hypotension, reduced urine output), admit to hospital as intravenous antibiotics may be required.
• Check that the catheter is correctly positioned and not blocked.
• If the catheter has been in place for more than a week, consider changing it before starting antibiotic treatment.
• If there is fever, or loin pain, or both, manage as upper UTI, see the CKS topic on Pyelonephritis - acute.
• Otherwise, treat for lower UTI:
• Relieve symptoms with paracetamol or ibuprofen.
• Send urine for culture and microscopy before starting antibiotic treatment.
• Prescribe an antibiotic for 7 days, following local guidelines when available.
• If symptoms are mild, consider withholding antibiotics until the result of urine culture is available to guide choice of antibiotic.
• If symptoms are moderate or severe, empirically prescribe an antibiotic.
• Follow up after 48 hours (or according to the clinical situation) to check response to treatment and the result of urine culture.

Using clinical judgement to decide when to use antibiotics

• Careful clinical judgement is recommended when deciding to use an antibiotic in a person with an indwelling urinary catheter. This is because all people with a long-term indwelling urinary catheter will have bacteriuria at some stage; there is no good evidence that antibiotics are beneficial; and repeated treatment of asymptomatic bacteriuria increases the risk of colonization by drug-resistant bacteria [SIGN, 2006; European Association of Urology, 2009].

Admitting to hospital

• The recommendation to admit to hospital if systemic symptoms and signs are present is based on expert opinion [SIGN, 2006].

Reviewing catheter care

• The recommendation to review the care of the catheter is based on expert opinion [NICE, 2003; European Association of Urology, 2009].
• The recommendation to consider changing the catheter before starting antibiotic treatment for urinary tract infection is based on evidence from one small trial and expert opinion [SIGN, 2006; European Association of Urology, 2009].

Using urine culture to guide the choice of antibiotic

• The recommendation to use urine culture to guide treatment and, if practical, to withhold treatment until culture results are available, is based on expert opinion and is intended to reduce the risks of complications and treatment failure, which are generally increased in people with an indwelling urinary catheter [SIGN, 2006].
• The recommendation to change to a more appropriate antibiotic if the antibiotic was started empirically and a resistant organism is isolated on urine culture is based on expert opinion; it is intended to reduce the risks of complications and treatment failure [SIGN, 2006; European Association of Urology, 2009].

Treating for 7 days

• Antibiotic treatment for 7 days is recommended because the evidence is too weak to recommend shorter courses as equally effective.

Relieving symptoms

• CKS found no trials of analgesics for the symptoms of cystitis. The recommendation to use paracetamol or ibuprofen to treat the symptoms of cystitis is based on their use in other painful infections and the experience of experts [SIGN, 2006].

• Follow local guidelines when available. Otherwise:
• For empirical treatment, prescribe either:
• Trimethoprim 200 mg twice daily, for 7 days, or
• Nitrofurantoin 50 mg four times daily, or 100 mg (modified-release) twice daily, for 7 days.
• If the woman has a history of recurrent infections, or has recently (within the past year) taken trimethoprim, do not use trimethoprim for empirical treatment.

Choosing an antibiotic

• As there is no direct evidence from clinical trials of different antibiotics in women with an indwelling urinary catheter, the recommendation to prescribe trimethoprim or nitrofurantoin for empirical treatment of cystitis is based on the recommendations in Managing suspected cystitis.

Treating for 7 days

• Antibiotic treatment for 7 days is recommended because there is only weak evidence from one small trial that shorter courses are equally effective for urinary tract infection in people with an indwelling urinary catheter.

• Ensure an indwelling urinary catheter is appropriate
• Use an indwelling catheter only after alternative methods of management have been considered.
• Regularly review the clinical need for catheterization and remove the catheter as soon as possible.
• Use intermittent catheterization in preference to an indwelling catheter if this is clinically appropriate and is a practical option for the person.
• Prevent the introduction of infection
• Healthcare personnel should be trained and assessed in their competence to perform urethral catheterization using aseptic procedures.
• Urine samples should be obtained from a sampling port using an aseptic technique.
• Catheters should be changed only when clinically necessary (for example, to prevent blockage), or according to the manufacturer's recommendations.
• When changing catheters, antibiotic prophylaxis should only be used for people with a history of catheter-associated urinary tract infection following catheter change.
• Do not use:
• Bladder instillations or washouts.
• Prophylactic antibiotics when changing catheters in women with a heart valve lesion, septal defect, patent ductus, or prosthetic valve.
• Topical antiseptics or antibiotics applied to the catheter, urethra, or meatus; daily washing of the meatus with soap and water is sufficient.

These recommendations are based on guidelines from the National Institute for Health and Clinical Excellence (NICE) [NICE, 2003].

Minimizing the use of indwelling urinary catheters

• The recommendations on training and practical ways to minimize the use of indwelling urinary catheters reflect guidelines from NICE [NICE, 2003].
• NICE based their recommendation to use intermittent catheterization rather than an indwelling urinary catheter on a systematic review which included 22 studies and 10 further studies.

Not using bladder instillations or washouts

• Bladder instillations and washouts are discouraged because the NICE systematic review found good evidence that they do not prevent urinary tract infections, and there is concern that they may have local toxic effects [NICE, 2003].

Not using prophylactic antibiotics or antiseptics

• The recommendation not to use prophylactic antibiotics when changing catheters is based on findings from two studies in the NICE systematic review that not using antibiotic prophylaxis did not increase the risk of urinary tract infection [NICE, 2003].
• The recommendation not to use prophylactic antibiotics when changing catheters in women with a heart valve lesion, septal defect, patent ductus, or prosthetic valve is based on the NICE clinical guideline on prophylaxis for infective endocarditis, which found this not to be cost-effective [NICE, 2008b]. 
• The recommendation not to use topical antiseptics or antibiotics applied to the catheter, urethra, or meatus is based in findings from six clinical studies that compared meatal cleansing with a variety of antiseptic/antimicrobial agents or soap and water; use of antiseptics and antimicrobial agents did not reduce the rate of bacteriuria [NICE, 2003].

• Review after 48 hours, or according to the clinical situation, to ensure the woman is responding to treatment, and to check the results of the urine culture.
• If urine culture shows that the organism is resistant to the current antibiotic, and:
• If symptoms have not resolved, change to an antibiotic that the organism is sensitive to.
• If symptoms have resolved, consider continuing with the current antibiotic.
• If symptoms recur, start treat with an antibiotic shown in the culture to cover the infecting organism.
• If the woman fails to respond to two courses of antibiotic shown by urine culture to be appropriate treatment, and compliance has been checked, consider referring for assessment and investigation.

These recommendations are pragmatic. CKS found no published expert opinion.

• When the uropathogen is resistant to the empirically chosen antibiotic and the woman has responded, the recommendation to consider continuing treatment until the end of the antibiotic course is based on comments of expert reviewers of previous versions of CKS topics on urinary tract infection. If symptoms have resolved, there is likely to be little added benefit from changing the antibiotic, because, either the woman is getting better of their own accord, or the laboratory assessment of resistance does not reflect the true susceptibility of the uropathogen.

• Consider referring for assessment and investigation if the woman fails to respond to two courses of antibiotic shown by urine culture to be appropriate treatment, and compliance has been verified.
• If urological cancer is suspected (for example if haematuria persists after successful treatment of cystitis), refer urgently to a team specializing in the management of urological cancer.

Referral for failure to respond to appropriate antibiotics

• The recommendation to consider referring women who have failed to respond to an appropriate antibiotic (shown by urine culture) is pragmatic, as CKS found no direct evidence from clinical trials or recommendations in national guidelines.

Urgent referral for urological cancer

• The recommendation to refer women with suspected urological cancer is based on criteria in guidelines from the National Institute for Health and Clinical Excellence (NICE) [NICE, 2005b].