American Urogynecologic Society Best-Practice Statement: Recurrent Urinary Tract Infection in Adult Women: [WITHDRAWN]

Female pelvic medicine and reconstructive surgery (FPMRS) specialists provide care for women with recurrent urinary tract infection (rUTI). In a study of more than 1100 urogynecologic patients, investigators reported a patient-reported rUTI prevalence of 19%.1 However, clinical care varies because of a lack of evidence and best practices. In addition, variable rUTI definitions exacerbate the gap in our understanding of this common clinical problem. In the context of evolving evidence and reviews on rUTI, this document summarizes current best practice for rUTI diagnosis and management in women. These best practices do not apply to women who are pregnant, are immunosuppressed, have surgically altered urinary tracts (not including typical surgery for stress urinary incontinence or pelvic organ prolapse), or regularly use urinary catheters except where specified. In addition, this document does not cover diagnosis or treatment of asymptomatic bacteriuria. Terminology and Definitions A commonly used definition describes urinary tract infection (UTI) as an infection of the lower and/or upper genitourinary tract which is diagnosed based on the presence of a pathogen in the urinary tract and associated symptoms.2 This definition assumes that the symptoms are caused by the detected uropathogens. However, neither the uropathogen detection method nor any specific symptoms are inherent in this UTI definition. Although the umbrella term UTI formally includes both upper and lower urinary tracts, the term UTI is often used interchangeably with cystitis (more accurately bacterial cystitis). There is limited evidence to support any “gold standard” UTI definition for epidemiologic or clinical research. There are multiple definitions for rUTI. This best-practice statement endorses a clinically useful, culture-based definition: at least 2 culture-proven episodes in 6 months, or at least 3 in 1 year.3 It is assumed that these episodes are separate events; however, there is no consensus as to diagnostic requirements to document resolution of any episode, such as a posttreatment culture. Diagnosis and care of rUTI patients does not require use of the various terms proposed to further subtype frequent UTI, although the presence of persistent organisms may alter the diagnostic and/or treatment approach (eg, earlier search for foreign body or urinary stone). Relapse indicates that the same uropathogen causes UTI symptoms within 2 weeks of completing appropriate antibiotic therapy. Recurrence specifically applies to situations in which there is evidence that the subsequent UTI occurred beyond the initial 2 weeks or with a different uropathogen.4 Epidemiology Estimates of UTI incidence vary based on the research definition of UTI being used and the likely overuse of UTI codes before a completed diagnostic evaluation. Commonly cited references suggest that more than 8 million ambulatory visits (84% women) in the United States in 2007 were due to UTI; 21% were emergency department visits.5,6 Using a woman's report of a physician diagnosis of UTI, the National Health and Nutrition Examination Survey data reported a 12.6% annual incidence of UTI in women 18 years or older.7 In a mixed-sex population of more than 30,000 patients whose UTI diagnosis had urine culture confirmation, Canadian investigators reported the annual UTI incidence in women aged 20 to 79 years as 3% to 5% and those aged 80 to 89 years as 12%. Two percent of these women had at least 6 UTIs in 2 years.8 After a single UTI, 30% to 44% of women will have a recurrent UTI; 50% will have a third episode if they have had 2 UTIs in 6 months.3 In a study of college women with a UTI, 19% experienced recurrence within 6 months.9 In a recent study, Suskind et al,10 using a database of health care claims, studied women aged 18 to 64 years who had an evaluation and management visit associated with an International Classification of Disease, Ninth Revision code for UTI and an antibiotic prescription within 14 days of that visit. They reported an overall rate of incident rUTI cases of 102 per 100,000 women per year, with the highest rates in women 18 to 34 years old and 55 to 66 years old. Pathophysiology Adjacent pelvic microbial niches serve as reservoirs for uropathogens that can lead to UTI/rUTI.11 Currently, the majority of evidence for uropathogens in the urine comes from standard urine culture techniques, which have been refined to detect Escherichia coli. Standard cultures also detect other common pathogens including Klebsiella species, Staphylococcus saprophyticus, Enterococcus faecalis, and Streptococcus agalactiae. Culture-independent techniques, such as polymerase chain reaction testing and sequencing, confirm that standard urine cultures do not detect all uropathogens or other resident microbes of the urinary microbiota.11 Enhanced culture techniques complement culture-independent methods to advance our understanding of UTI and rUTI prevention, pathogenesis, treatment, and recovery but are not yet widely available for clinical use. Current evidence, based on standard cultures, indicates that E. coli causes most (70%–95%) community-acquired UTIs. Studies in older women suggest that E. coli accounts for more than half of UTIs, whereas other common organisms are Klebsiella pneumoniae, Proteus mirabilis, and E. faecalis. E. coli is also the most common cause of rUTI (66%). The uropathogens associated with rUTI are the same microbes associated with episodic (non-rUTI) UTI episodes. However, non–E. coli pathogens and resistant organisms are more likely to be associated with UTI episodes in women with rUTI.3,7,12 E. coli has multiple strains and virulence factors.13 Uropathogenic E. coli (UPEC) has been widely studied in murine models, and some findings have been verified in human studies.14,15 Uropathogenic E. coli have special features that facilitate urothelial attachment, allowing the microbe to take up residence within the bladder.14,15 Uropathogenic E. coli can form intracellular bacterial communities that act like a biofilm, allowing bacteria to persist in quiescent intracellular reservoirs, acting as a source of recurrent infection.16,17 Episodes of rUTIs are often associated with the same bacterial strain; this has important implications for treatment, highlighting the need for careful antimicrobial sensitivity testing and treatment selection. In addition to bacterial factors, host factors, including hormonal status, anatomy, functional, and behavioral variables, and genetic factors likely modulate UTI and rUTI susceptibility.3,14,18 For example, E. coli has an increased ability to adhere to the urothelium in women who are nonsecretors of certain blood group antigens.3,19 Individual factors, such as pre-UTI microbiota/microbiome health, degree of inflammation, and urothelial exfoliation from an infection, may affect response to UTI, recovery from UTI, and susceptibility to future UTI.13,14 Risk Factors Many commonly recommended behaviors have not been established as reducing risk for rUTI (wiping away from the urethra; voiding before and after intercourse; increasing frequency of voiding; wearing certain types of underwear; avoiding douching; or avoiding hot tubs, bubble bath, or tampons).3 Physicians should consider the contribution of gross fecal soilage, as in women with fecal incontinence. A personal history of UTI before age 15 years and maternal UTI history are rUTI risk factors.3,20 A case-control study of more than 400 women reported an increased risk of rUTIs in women having a first-degree female relatives with a history of at least 5 UTIs.21 Sexual risk factors, such as a new sexual partner, intercourse frequency, and spermicide use, are more common in premenopausal women.21 Women with pelvic floor disorders are at increased risk for rUTIs, especially postmenopausal women with urinary incontinence. Some investigators suggest an association between postvoid residual of at leasy 50 mL and rUTI.19 The association with prolapse is unclear.22 There is a risk of rUTI after surgery for stress urinary incontinence. The early postoperative period is associated with a transient increased rUTI risk (11%) after retropubic tension-free vaginal tape with or without concomitant prolapse repair.23 Beyond the first 6 postoperative weeks, investigators reported rUTI in 2.3% to 2.4% of participants in 2 randomized surgical trials (Stress Incontinence Surgical Treatment Efficacy trial and Trial of Mid-Urethral Slings).24 Between 2 and 12 months, women who had a midurethral sling had a postoperative rUTI rate of 2.3%.25 No cases of rUTI were reported during a recent 10-year follow-up of 71 women who had transobturator midurethral slings.26 DIAGNOSIS Women with frequent UTI may experience diagnostic delay if clinicians do not review the UTI history; clinicians should order pretreatment urine cultures to document rUTI (culture-proven UTI ≥2 in 6 months or ≥3 in 12 months).3 Although infrequent UTI can be assessed with less rigor and treated empirically, women with frequent UTI who are being formally assessed for rUTI should have detailed symptom assessment and pretreatment urine culture and sensitivity.4 Symptoms Dysuria is a key symptom of bacterial cystitis. Frequency, urgency, hematuria, and suprapubic pain are variably present. Symptoms of flank pain, fever and chills, and nausea and vomiting should prompt consideration of pyelonephritis. In young women, there is a 90% probability of a UTI when she reports dysuria and frequency in the absence of vaginal discharge or irritation.6 The accuracy of history and physical examination for UTI diagnosis in women suggests an increased UTI probability with dysuria (likelihood ratio [LR], 1.5; 95% confidence interval [CI], 1.2–2), frequency (LR, 1.8; 95% CI, 1.3–3), hematuria (LR, 2.0; 95% CI, 1.3–2.9), back pain (LR, 1.6; 95% CI, 1.2–2.1), and costovertebral angle tenderness (LR, 1.7; 95% CI, 1.1–2.5). The probability of UTI diagnosis is reduced with a history of vaginal discharge (LR, 0.3; 95% CI, 0.1–0.9) or vaginal irritation (LR, 0.2; 95% CI, 0.1–0.9).27 With aging, symptoms potentially associated with a UTI may be less clear. Acute dysuria remains a reliable symptom, new-onset frequency or urgency has been found to correlate with UTI, and new-onset urinary incontinence should prompt evaluation for UTI.28,29 Nontraditional symptoms, such as urinary odor or urinary appearance, may be triggers for urogynecologic patients to seek care for presumed UTI.2,3,30 Women with cognitive limitations may have difficulty reporting symptoms; family/caregivers may alert health care providers to changes in mentation or energy levels, which may indicate UTI, although this is a diagnostic challenge.2 Despite the common clinical observation, worsening of chronic incontinence or other urinary symptoms are not reliably associated with UTI.2,31 There is significant symptom overlap between UTI and many urogynecologic conditions, including urgency urinary incontinence, overactive bladder, and bladder pain syndrome. Currently, our understanding of appropriate symptom attribution in this patient population is lacking. Urine Dipstick The urine dipstick has value to rule out, rather than rule in, UTI in patients with lower pretest probably of UTI. Because women with rUTI do not have a low pretest probability of UTI, dipstick testing is not advised and pretreatment urine culture is necessary. Urinalysis Beyond the standard indications for testing (hematuria, proteinuria, etc), urinalysis in women with rUTI can confirm pyuria (at least 10 white blood cells per high-power field). The interpretation of pyuria for women with rUTI remains debatable because of a lack of relevant studies in urogynecologic populations. When the finding of pyuria would alter the treatment plan, the clinician should obtain a urinalysis. Urine Culture The criteria for UTI diagnosis by urine culture varies and has not been validated in any urogynecologic population. The standard urine culture along with microscopic urinalysis has been used as a criterion standard for confirming suspected UTI. A positive culture is typically characterized by bacteriuria of at least 105 colony-forming unit s (CFU)/mL,32 although according to the European Association of Urology guidelines, a count of 103 CFU/mL in symptomatic patients is sufficient for diagnosis.33 The Society of Obstetricians and Gynaecologists of Canada clinical practice guidelines state that even 102 CFU is sufficient in the setting of UTI symptoms.32 Clinicians should have a clear understanding of their clinical laboratory protocols as certain laboratories may report 104 or less as “no growth.” Best practices for posttreatment test of cure (test-treatment-test) urine culture vary and are based on expert opinion. Reliance on symptomatic resolution alone forgoes the ability to detect patterns of uropathogen persistence or recurrence.20 The Canadian Urological Association guidelines suggest repeating a urine culture 1 to 2 weeks after treatment to test for persistence.4 A repeat urine culture may allow for detection of patterns of uropathogen persistence or recurrence that may provide insight into the etiology or optimal treatment.20 A negative posttreatment urine culture provides evidence of effective treatment. In the absence of a negative posttreatment urine culture, it is possible that 2 or 3 UTI episodes are related to a single persistent uropathogen. However, clinicians face a dilemma when the posttreatment culture is positive and the patient's UTI symptoms have resolved. Some experts who believe that women with an active diagnosis of rUTI can also carry a diagnosis of asymptomatic bacteriuria recommend against posttreatment testing to reduce the risk of treating asymptomatic bacteriuria and lessen antibiotic exposure.2,3,34 Young women with asymptomatic bacteriuria participating in a randomized trial who were treated were (1) more likely to develop subsequent infections at a higher rate than those who were not treated and (2) more likely to develop antibiotic-resistant organisms.34,35 Physical Examination Although a physical examination may not be necessary before treatment for a woman with infrequent UTI, an examination should always occur as part of the rUTI evaluation to detect an underlying etiology, potential contributors (hypoestrogenism), and findings suggestive of upper tract involvement. In addition to an assessment of the patient's general status, focused examination should include palpation for costovertebral angle and suprapubic tenderness. The pelvic examination, including bimanual, can check for vulvar skin and/or architecture changes, urethral diverticulum, tenderness in pelvic floor muscles, urethra or bladder, vaginal discharge, and pelvic masses. In addition, detection of pelvic organ prolapse, presence of a foreign body such as a retained pessary, or eroded mesh or sutures will inform the treatment plan. These assessments should be performed with initial evaluation of a patient with rUTI and repeated as needed depending on status changes, including new signs, symptoms, or risk factors. Additional Testing Postvoid Residual A postvoid residual should be measured to ensure that there is no significant urinary retention. This can be done at the time of the physical examination. Imaging and Endoscopy There are currently no specific guidelines for imaging studies for women with rUTI. Indications for imaging in women with UTI include persistent symptoms (persistent fever after 72 hours of appropriate antibiotic therapy), rapid recurrence after appropriate treatment, suspected stone or obstruction, and women with diabetes who are at higher risk for complications such as abscess, emphysematous pyelonephritis, and so on.35,36 Cystourethroscopy should be considered if a woman is at risk for suspected foreign body within the bladder or urethra, although the utility of cystoscopy in evaluation of rUTI has not been well studied. One retrospective study reported that 3.8% of the 163 participants had specific findings on cystoscopy that imaging would not detect.37 Cystoscopy with cytology should be performed when there is clinical suspicion for premalignancy or malignancy. Assessment for urinary tract stones can be initiated with plain abdominal radiographs. When the clinical situation warrants more complete assessment of the upper tracts, renal ultrasound, or computed tomographic urography should be used. In general, a computed tomographic urogram, which is with and without intravenous contrast, is the imaging modality of choice in patients suspected of having pyelonephritis, and renal and perirenal abscess. This modality can also identify a possible source of infection such as renal or ureteric stones.38 Coding and Documentation Women who meet the criteria for rUTI should have this diagnosis added to their problem list to help alert other providers to the recurrent nature of the UTIs and to help ensure that best practices are followed for evaluation and treatment. In addition, methods to track UTIs (date, pathogen, antibiotic prescribed) can be developed in summary or flowsheets in the medical record. Accurate use of International Classification of Disease, 10th Revision, Clinical Modification (ICD-10-CM) is important for correct classification of patients for clinical diagnosis and population studies of rUTI. Table 1 describes many of the ICD-10 codes associated with lower UTI. The ICD-10 code of “positive urine culture” can be used instead of UTI or asymptomatic bacteriuria when a urine culture is positive but the clinical criteria are not met for a UTI: for example, if a patient is asymptomatic and a culture is inadvertently obtained before treatment completion or while the patient is on suppression but asymptomatic. We propose providers replace the active rUTI diagnosis with history of rUTI after 1 year of the affected woman no longer being treated for rUTI and not meeting the criteria for the diagnosis of rUTI.TABLE 1: ICD-10-CM UTI TerminologyTREATMENT Treatment options for rUTIs can be stratified by whether complicating features, such as abnormal genitourinary anatomy, immunosuppression, and chronic catheterization, are present. Most studies have focused on oral or parenteral antibiotic therapy, whereas data on intravesical and nonantibiotic treatments are limited. Antibiotic therapy is typically used to treat active infections and prevent future infections; the treatment regimen, route, and duration will vary based on the clinical situation and should be individualized for each patient. Various antibiotic treatment strategies have been described for symptomatic patients with recurrent infections. These can be divided into treatment of an acute episode (provider prescribed or self-treatment) or prophylaxis (to prevent further episodes). Whenever possible, rUTI patients should have a culture sent before treatment. Empiric therapy can be initiated before urine culture results if clinically indicated (such as history of UTI-related sepsis or pyelonephritis). Antibiotic choice should be tailored to the individual patient and pathogens, community and patient resistance patterns, costs, drug availability, patient allergies, and patient tolerance/ability to comply.39 Providers should be familiar with the antibiotic-resistant patterns in their communities which is generally available via antibiograms any clinical Empiric should be altered if necessary based on the urine culture Treatment of UTI in Women With UTI Treatment for acute UTI in women with rUTI have been from acute UTI treatment in women without rUTI. treatment and antibiotic therapy are the 2 treatment with evidence of in bacterial With treatment, a drug is used for symptomatic or patients are followed up without any form of treatment. Antibiotic therapy is initiated if symptoms or do not in a clinically time treatment has not been studied in women older than years or with rUTI. trials in women than years have resolution rates of to without antibiotic However, study a higher rate of in the group at to are treatment of bacterial cystitis in women with In women with rUTI, acute treatment can be initiated by a clinician or patient at the time of symptom Most studies of acute UTI treatment were not performed in women with rUTI or other pelvic floor for of for a UTI, the clinician should review drug and may have reported drug and/or to recommended UTI patients can be further to whether they have drug reaction a reaction Clinicians should not an antibiotic in patients with such as for of the may be considered for patients with microbial resistance is associated with a in the rate and this the and of that are such as as UTI with rate are more likely to experience treatment due to reduced renal is because of urine in patients with a of less than should be familiar with antibiotic of and specific for renal if Although more than of at least years old have an rate of less than changes in microbial or based on age alone are not has been based on renal although guidelines support use in but The Society has to the for using from to based on 2 retrospective studies the optimal antibiotic choice in older women and women with rUTI. In the Society of guidelines for premenopausal women, 3 for UTI treatment are and are from these guidelines for use in rUTI, older women, and women with urogynecologic Antibiotic for Acute UTI Treatment in Women With is and active in the lower urinary It is effective against E. coli and many with low of However, it is against other uropathogens including some Proteus and some strains of and The duration of treatment is typically to 10 A recent of studies of women from 12 to years old with variable criteria that are as although this is not to women with rUTI. The clinical practice guidelines for the treatment of acute cystitis in a of is a antibiotic that bacteria including Staphylococcus and most When there is than E. coli resistance to an treatment should be duration of treatment has from 3 to 14 with the being found to have to to duration of therapy the form of is in a single which is in the urine in urine that persist for to has against both and including and has low of it a drug of choice in infections with In addition, is an important for treatment of E. coli UTI. When are not available or be prescribed because of patient or or bacterial and can be used. (such as and have in against most uropathogens except trial evidence suggests that the of or is at have a lower cure rate than and like can also be used if are for any Although (eg, and are they are not because of increasing higher and as described in a and there is clear evidence of sensitivity to certain including and these should be used because of to be due in part to the lack of in the of The for the duration of acute bacterial cystitis treatment in women with rUTI is not evidence based and is from women without some experts use longer duration therapy in rUTI women. Although it not specifically women with rUTI, in a review and of 15 randomized trials of women antibiotic duration for treatment of acute UTI, the found that the standard duration for therapy with to 14 sufficient The review also reported that therapy associated with a higher rate of persistent UTI with therapy ratio CI, the 15 studies in this 2 studied This document the practice of using standard duration therapy and treatment as clinically necessary. The of of and has and cure and is widely for UTI treatment in the absence of complicating These are as effective for symptomatic as longer to and have costs, and lower rates of The of 5 days of is to 3 days of days of has than a of to With can be associated with physician for urine culture before after treatment, to help diagnostic For women who are or to a urine episodes of without culture are with is associated with a higher rate of infection UTI per year UTI per is an for women (1) with the ability to reliably UTI symptoms and (2) who are not for or who do not to take For clinicians the appropriate and duration of an antibiotic that will cover the most likely uropathogen based on the patient's history so that she can treatment based on Women who use the should be of their clinician if symptoms or to within Table 3 the recommended Antibiotic with are recommended to patient and and are not for because of risk of and We recommend use of other UTI With Factors Women with rUTI who have complicating factors, such as abnormal genitourinary anatomy, immunosuppression, and chronic

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