Editing AUA & CUA Recurrent UTI (2019) (section)

== Recurrent UTI ==

=== Definitions ===
*'''<span style="color:#ff0000">Definition of Recurrent UTI: Either (2):</span>'''
*#'''<span style="color:#ff0000">≥2 episodes of acute bacterial cystitis within 6 months or</span>'''
*# '''<span style="color:#ff0000">≥3 episodes within 1 year</span>'''
*#* These episodes are considered to be separate infections with resolution of symptoms between episodes, and do not include those who require >1 course of antibiotics for symptomatic resolution, as can occur with inappropriate initial or empiric treatment
*#* '''<span style="color:#ff0000">For diagnosis of recurrent UTI, each symptomatic episode must be associated with a document positive urine culture'''
*Patients with a long history of culture-proven symptomatic episodes of cystitis that occur at a lower frequency than this definition will likely benefit from management strategy similar to that for patients with rUTI.

=== Diagnosis and Evaluation ===

==== UrologySchool.com Summary ====

* '''<span style="color:#ff0000">Mandatory (1):</span>''' 
*# '''<span style="color:#ff0000">History and Physical Exam</span>'''
* '''<span style="color:#ff0000">Optional (1):</span>''' 
*# '''<span style="color:#ff0000">PVR</span>'''
* '''Not recommended'''
** '''Cystoscopy'''
** '''Upper tract imaging'''

==== Mandatory ====

===== History and Physical Exam =====
* '''<span style="color:#ff0000">History'''
** '''Characterize current LUTS''' (dysuria, frequency, urgency, nocturia, incontinence, hematuria, pneumaturia, fecaluria)
***'''Characterize baseline symptoms between infections'''
**Back or flank pain; catheter usage; vaginal discharge or irritation
**'''UTI history''': frequency of UTI, antimicrobial usage, and documentation of positive cultures and the type of cultured microorganisms, responses to treatment for each episode, the symptoms the patient considers indicative of a UTI, the relationship of acute episode to infectious triggers (e.g. sexual intercourse for post-coital UTIs), relationship of infections to hormonal influences (e.g., menstruation, menopause, exogenous hormone use), results of any prior diagnostic investigations
**'''Bowel symptoms''' such as diarrhea, accidental bowel leakage, or constipation
** '''Menopausal status; contraceptive method; and use of spermicides or estrogen- or progesterone-containing products'''
** '''Risk factors for complicated UTI (see [[Urinary Tract Infections|Urinary Tract Infections Chapter Notes]])'''
** '''Medications''' (immunosuppressive meds, recent use of antibiotics for any medical condition), '''PMHx, PSHx''' (may suggest complicated UTI), '''allergies, travel history'''
* '''<span style="color:#ff0000">Physical Exam'''
** '''<span style="color:#ff0000">Abdominal and pelvic examination'''
***'''Prolapse, urethral tenderness, urethral diverticulum, Skene’s gland cyst, or other enlarged or infected vulvar or vaginal cysts'''
***'''Any other infectious and inflammatory conditions (vaginitis, vulvar dermatitis, and vaginal atrophy''' (genitourinary syndrome of menopause)
***'''Pelvic floor musculature''' for tone, tenderness, and trigger points
** '''Focused neurological exam''' 
***'''May also be considered''' to rule out occult neurologic defects

==== Optional ====
*'''<span style="color:#ff0000">Post-void Residual'''
** '''<span style="color:#ff0000">Indications</span>'''
***'''<span style="color:#ff0000">Can be considered for all patients'''
***'''<span style="color:#ff0000">Should be performed in any patient with suspicion of incomplete emptying, such as those with (4):</span>'''
***# '''<span style="color:#ff0000">Significant anterior vaginal wall prolapse</span>'''
***# '''<span style="color:#ff0000">Underlying neurologic disease</span>'''
***# '''<span style="color:#ff0000">Diabetes</span>'''
***# '''<span style="color:#ff0000">Subjective sensation of incomplete emptying</span>'''.

==== Not recommended (2): ====
*'''Cystoscopy and upper tract imaging'''
** '''Low yield of anatomical abnormalities with cystoscopy and upper tract imaging in patients with uncomplicated rUTI.'''
*** '''However, if a patient does not respond appropriately to treatment of uncomplicated UTI, particularly rapid recurrence with the same organism repeatedly, the patient should be considered to have a complicated UTI, thereby necessitating further investigations of the urinary tract'''
** '''In patients with gross hematuria in the presence of a positive urine culture and no risk factors for urothelial malignancy''' (e.g., age under 40, non-smoker, no environmental risk), '''cystoscopy is not necessary.'''
*** '''If any risk factors are present, cystoscopy should be performed.'''

==== Management ====

===== Conservative =====
*'''<span style="color:#ff0000">Options (2):</span>''' 
*#'''<span style="color:#ff0000">Education</span>'''
*#'''<span style="color:#ff0000">Behavior modification</span>'''

====== Education and Informed Decision Making ======
* '''Discuss the option of delaying antibiotics while awaiting culture results as there is minimal risk of progression to tissue invasion or pyelonephritis for uncomplicated patients with episodes of acute cystitis.'''
** '''Antibiotic treatment for acute cystitis results in mildly faster symptomatic improvement but only modestly decrease the risk of pyelonephritis'''.
** Patients with urosepsis or pyelonephritis often do not have UTI-related symptoms.

====== <span style="color:#ff0000">Behavior modification (2):</span> ======
# '''<span style="color:#ff0000">Changing mode of contraception (avoid barrier contraceptives and spermicidal products</span>''' (has deleterious effect on lactobacillus colonization and/or the vaginal microbiome))
# '''<span style="color:#ff0000">Increasing water intake in those consuming < 1.5L/day</span>'''
#* Unclear if there is a benefit in women that normally consume over this amount

====== '''Changes that DO NOT play a role in rUTI prevention''' ======
# '''Hygiene practices (e.g., front to back wiping)'''
# '''Pre- and post-coital voiding'''
# '''Avoidance of hot tubs'''
# '''Tampon use'''
# '''Douching'''

===== Intervention =====
*'''<span style="color:#ff0000">Options (3):</span>''' 
**'''<span style="color:#ff0000">Antibiotics</span>'''
**'''<span style="color:#ff0000">Non-antibiotic prophylaxis</span>'''
***'''<span style="color:#ff0000">Cranberry</span>'''
***'''<span style="color:#ff0000">Vaginal estrogen (if post-menopausal)</span>'''

====== Antibiotics ======
* '''<span style="color:#ff0000">Acute cystitis episodes in patients with recurrent UTI'''
** '''<span style="color:#ff0000">Obtain urinalysis, urine culture and sensitivity with each symptomatic acute cystitis episode prior to initiating treatment in patients with rUTIs'''
*** Continued documentation of cultures during symptomatic periods prior to starting antibiotics helps to provide a baseline against which interventions can be evaluated, to determine the appropriate pathway within the treatment algorithm, and to allow for the tailoring of therapy based on bacterial sensitivities.
*** '''In select patients with rUTIs with symptoms of recurrence, presumptive treatment with antibiotics can be initiated prior to finalization of the culture''' based on prior speciation, susceptibilities, and local antibiogram
** '''Use first-line therapy (See [https://www.auanet.org/guidelines-and-quality/guidelines/recurrent-uti Table 3] (statement 9, no direct link) from Original Guideline) dependent on the local antibiogram for treatment of symptomatic UTIs in women'''
*** <span style="color:#ff0000">'''Options (3):'''</span>
****<span style="color:#ff0000">'''Fosfomycin 3g PO x 1'''</span>
****<span style="color:#ff0000">'''TMP-SMX one tab DS PO BID x 3 days'''</span>
****<span style="color:#ff0000">'''Nitrofurantoin 100mg PO BID x 5 days'''</span>
***A systematic review found no differences between fluoroquinolones, β-lactams (e.g., penicillins and its derivatives, cephalosporins), nitrofurantoin or TMP-SMX in the efficacy or risk of discontinuation due to adverse events
*** TMP-SMX is not recommended for empiric use in areas where local resistance rates > 20%]
***'''Table 3 from guideline suggests that nitrofurantoin does not cover enterococcus but CW11 Table 12-5/CW12 Table 55-6 suggests that it does'''
** '''Clinicians should treat rUTI patients experiencing acute cystitis episodes with as short a duration of antibiotics as reasonable, generally < 7 days'''
*** '''In patients with rUTIs experiencing acute cystitis episodes associated with urine cultures resistant to oral antibiotics''', clinicians may treat with culture-directed parenteral antibiotics for as short a course as reasonable, generally no longer than 7 days. '''Many such infections will be caused by organisms producing ESBLs.'''
**** '''Generally, such organisms are susceptible only to carbapenems. However, clinicians should order fosfomycin susceptibility testing, as many MDR uropathogens, including ESBL-producing bacteria, retain susceptibility to Fosfomycin thereby providing an oral option'''.
** '''Do not perform a post-treatment test of cure (urinalysis or urine culture) in asymptomatic patients'''
*** Extrapolating from the asymptomatic bacteruria literature, repeat urine culture after successful UTI treatment may lead to overtreatment
*** '''Omit surveillance urine testing, including urine culture, in asymptomatic patients with rUTIs.'''
**** While pregnant women and patients undergoing invasive urologic procedures do benefit from treatment, substantial evidence supports that other populations, including women with diabetes mellitus and long-term care facility residents, do not require or benefit from additional evaluation or antibiotic treatment
** '''Repeat urine cultures to guide further management when UTI symptoms persist following antibiotic therapy'''
*** '''After initiating antibiotic therapy for UTI, clinical cure (i.e. UTI symptom resolution) is expected within 3-7 days.''' Although there is no evidence, it is reasonable to '''repeat a urine culture if symptoms persist > 7 days'''
* '''<span style="color:#ff0000">Antibiotics to reduce UTI episodes in patients with rUTI (self-start vs. prophylaxis)</span>'''
*# '''<span style="color:#ff0000">Self-start antibiotics: patient-initiated treatment for acute episodes while awaiting urine cultures.'''</span>
*#* '''For reliable patients, consider shared decision-making with regards to deferring therapy prior to obtaining results from the urine culture.'''
*#* Despite the original concept behind self-start therapy that allowed for women to treat their UTI without obtaining a culture. given more recent goals to reduce overuse of antibiotics and the development of antibacterial resistance, '''obtaining culture data for symptomatic recurrences is recommended''', when feasible.
*# '''<span style="color:#ff0000">Antibiotic prophylaxis (continuous vs. post-coital)</span>'''
*## '''Continuous:''' After discussion of the risks and benefits, clinicians may prescribe continuous antibiotic prophylaxis to decrease the risk of future UTIs in women of all ages previously diagnosed with UTIs.
*##* '''Antibiotic prophylaxis reduces the number of clinical recurrences but increases risk of adverse events. Once the antibiotics are stopped, UTIs recur at the baseline rate.'''
*##* '''The dosing options for continuous prophylaxis include the following:'''
*##** Nitrofurantoin monohydrate/macrocrystals 50mg daily
*##** '''Nitrofurantoin''' monohydrate/macrocrystals '''100mg daily'''
*##** Cephalexin 125mg once daily
*##** '''Cephalexin 250mg once daily'''
*##** TMP 100mg once daily
*##** '''TMP-SMX''' '''40mg/200mg once daily'''
*##** TMP-SMX 40mg/200mg thrice weekly
*##** '''Fosfomycin 3g every 10 days'''
*##* '''Potential adverse effects of gastrointestinal disturbances and skin rash are commonly associated with antibiotics, including TMP, TMP-SMX, cephalexin, and Fosfomycin'''
*##* '''<span style="color:#ff0000">Potentially serious risks with nitrofurantoin include pulmonary and hepatic toxicity.</span>'''
*##** The rate of possible serious pulmonary or hepatic adverse events has been reported to be 0.001% and 0.0003%, respectively.
*##* '''<span style="color:#ff0000">The use of fluoroquinolones (e.g. ciprofloxacin) for prophylactic antibiotic use is not recommended in current clinical practice.</span>'''
*##** '''<span style="color:#ff0000">Fluoroquinolone agents have potentially adverse side effects including QTc prolongation, tendon rupture, and increased risk of aortic rupture</span>'''
*##* '''The duration of prophylaxis can vary from 3-12 months''', with periodic assessment
*## '''Post-coital'''
*##* '''In women with UTIs temporally related to sexual activity, a single dose of antibiotic prophylaxis taken before or after sexual intercourse is effective and safe'''
*##** Options:
*##*** TMP-SMX 40mg/200mg
*##*** TMP-SMX 80mg/400mg
*##*** Nitrofurantoin 50-100mg
*##*** Cephalexin 250mg

====== <span style="color:#ff0000">Non-antibiotic prophylaxis (2):</span> ======
# '''<span style="color:#ff0000">Cranberry prophylaxis</span>'''
#* MOA: thought to be related to proanthocyanidins present in cranberries and their ability to prevent the adhesion of bacteria to the urothelium
#* '''<span style="color:#ff0000">Indications</span>'''
#**'''<span style="color:#ff0000">Can be offered for women with rUTIs</span>'''
#*Oral juice and tablet formulations are available
# '''<span style="color:#ff0000">Vaginal estrogen</span>'''
#* '''<span style="color:#ff0000">Indications</span>'''
#**'''<span style="color:#ff0000">Recommended in peri-and post-menopausal women with rUTIs,</span>''' if there is no contraindication to estrogen.
#*** '''Oral or other formulations of systemic estrogen therapy have not been shown to reduce UTI and are associated with different risks and benefits.'''
#*** Given low systemic absorption, risks generally associated with systemic estrogen (cardiovascular disease, thrombosis, breast cancer) are minimal with vaginal estrogen.
#* '''Patients with rUTI and are already on systemic estrogen therapy should still be placed on vaginal estrogen. There is no substantially increased risk of adverse events.'''
#* '''Vaginal estrogen therapy has not been shown to increase risk of cancer recurrence in women undergoing treatment for or with a personal history of breast cancer'''. Therefore, vaginal estrogen therapy should be considered in prevention of UTI women with a personal history of breast cancer in coordination with the patient’s oncologist.
* '''Lactobacillus is not recommended''' as a prophylactic agent for rUTI given the lack of data