In the Clinic

Urinary Tract Infection

Background Screening and Prevention Diagnosis and Evaluation Treatment and Management Practice Improvement Tool Kit Patient Information CME Questions
Physician Writer Kalpana Gupta, MD, MPH Barbara Trautner, MD, PhD Affiliations: VA Boston Healthcare System and Boston University School of Medicine, Boston, Massachusetts; and Houston VA Health Services Research Center of Excellence at the Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, Texas. Section Editors Deborah Cotton, MD, MPH Darren Taichman, MD, PhD Sankey Williams, MD

page ITC3-2 page ITC3-3 page ITC3-5 page ITC3-8 page ITC3-13 page ITC3-14 page ITC3-15 page ITC3-16

The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including PIER (Physicians Information and Education Resource) and MKSAP (Medical Knowledge and SelfAssessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACPs Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from PIER and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://pier.acponline.org, http://www.acponline.org/products_services/ mksap/15/?pr31, and other resources referenced in each issue of In the Clinic. CME Objective: To review current evidence for the background, screening and prevention, diagnosis and evaluation, and treatment and management of urinary tract infection. The information contained herein should never be used as a substitute for clinical judgment. 2012 American College of Physicians

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

In theClinic

rinary tract infections (UTIs) are one of the most common infections in both outpatient and inpatient settings. The term urinary tract infection applies to a heterogeneous group of clinical syndromes. Clinical entities encompassed by UTI include asymptomatic bacteriuria, acute uncomplicated cystitis, recurrent cystitis, complicated UTI, catheter-associated asymptomatic bacteriuria, catheter-associated UTI (CAUTI), prostatitis, and pyelonephritis. Appropriate classification of the UTI syndrome is crucial for optimal diagnosis and management. The various categories of UTI are distinguished by the presence or absence of symptoms referable to the urinary tract; the patients sex and comorbid conditions; and genitourinary history, including the presence of stones or stents. Because acute cystitis is the most common manifestation of UTI and is most prevalent in women, most clinical research on UTI has been done in adult women. Clinicians must carefully consider whether recommendations derived from this evidence base are applicable to their patient populations.

Background
1. Hooton TM, Scholes D, Hughes JP, et al. A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med. 1996;335:46874. [PMID: 8672152] 2. Scholes D, Hooton TM, Roberts PL, Stapleton AE, Gupta K, Stamm WE. Risk factors for recurrent urinary tract infection in young women. J Infect Dis. 2000; 182:1177-82. [PMID: 10979915] 3. Hooton TM. Recurrent urinary tract infection in women. Int J Antimicrob Agents. 2001;17:259-68. [PMID: 11295405] 4. Hooton TM. Pathogenesis of urinary tract infections: an update. J Antimicrob Chemother. 2000;46 Suppl 1:1-7. [PMID: 11051617] 5. Scholes D, Hawn TR, Roberts PL, et al. Family history and risk of recurrent cystitis and pyelonephritis in women. J Urol. 2010;184:564-9. [PMID: 20639019] 6. Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM; Infectious Diseases Society of America. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40:643-54. [PMID: 15714408]

What patient populations are at greatest risk for UTI? In the absence of known abnormalities of the urinary tract, women are at higher risk for UTIs than are men. Premenopausal adult women are at especially high risk for acute cystitis; incidence is 0.5 to 0.7 per person-year among sexually active women (1). Other populations at risk for UTI include patients with voiding abnormalities related to diabetes, neurogenic bladder, spinal cord injury, pregnancy, prostatic hypertrophy, or urinary tract instrumentation. Bacteriuria, with or without accompanying symptoms, is generally considered unavoidable in patients requiring long-term indwelling catheters. What lifestyle factors or comorbid conditions are risk factors for UTI? The strongest risk factors for acute uncomplicated cystitis in premenopausal women include sexual intercourse, use of spermicides, pregnancy, and previous UTI. A history of maternal UTI and age at first UTI are also important risk factors in this group, suggesting a genetic component to susceptibility (2). Changes in vaginal microbial flora in perimenopausal women may increase risk for UTI.

In contrast to the predominant role of behavioral risk factors in premenopausal women, mechanical and physiologic factors that affect bladder emptying become important in postmenopausal women (3). Diabetes may increase the risk for certain urinary tract disorders, including asymptomatic bacteriuria, perirenal abscess, and emphysematous pyelonephritis (4). In men, risk for UTI is primarily related to the prostatic hypertrophy that occurs with advancing age. Temporary instrumentation of the urinary tract is the major medical intervention that increases the risk for UTI in hospitalized patients. Other comorbid conditions that increase risk in both sexes include stones or foreign bodies, such as ureteral stents, in the urinary system, and diseases associated with a neurogenic bladder.
A recent casecontrol study of 1261 female outpatients 18 to 49 years of age investigated the role of family history of UTI as a risk factor for recurrent UTI or pyelonephritis. A history of any UTI in the mother conferred an increased risk for both recurrent UTI (odds ratio [OR], 2.5; 95% CI, 1.93.4) and pyelonephritis (OR, 3.3; CI, 2.44.5). Having a sister or daughter with UTI also increased the risk for recurrent UTI, with ORs ranging from 2.6 to 4.1 (5).

2012 American College of Physicians

ITC3-2

In the Clinic

Annals of Internal Medicine

6 March 2012

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

Is there a role for screening for UTI or asymptomatic bacteriuria? In men and nonpregnant women, screening for asymptomatic bacteriuria is generally not recommended because treatment does not improve clinical outcomes (6). Asymptomatic bacteriuria does not lead to hypertension, chronic kidney disease, or decreased survival (7). Women with asymptomatic bacteriuria are at increased risk for symptomatic UTI, but treatment of asymptomatic bacteriuria does not decrease the frequency of symptomatic infection (8). Asymptomatic bacteriuria is a marker for poor overall health status in diabetic patients, noncatheterized women living in retirement homes, and catheterized inpatients, but asymptomatic bacteriuria itself is not an independent risk factor for mortality.
Abrutyn and coworkers prospectively followed 1491 female residents of retirement communities. Clean-catch urine cultures were obtained at enrollment and every 6 months. Women who had asymptomatic bacteriuria were older and sicker than those who had never had asymptomatic bacteriuria, but no relationship was found with mortality after adjusting for covariates, such as age at study entry. (7).

recommended. Dipstick urinalysis is not considered sensitive enough to be a stand-alone test in pregnant women.

Screening and Prevention

Screening for and treating asymptomatic bacteriuria is also recommended in men who are about to have transurethral resection of the prostate (TURP) or other urinary tract instrumentation resulting in mucosal bleeding. Studies have shown that TURP in bacteriuric men can precipitate bacteremia, with associated sepsis syndrome, and that antimicrobial treatment of the bacteriuria can prevent these complications. The level of risk associated with specific invasive urologic procedures other than TURP in patients with preexisting bacteriuria is not well-defined. However, the Infectious Diseases Society of America (IDSA) recommends that procedures anticipated to cause mucosal bleeding warrant preprocedure screening by urine culture and treatment of asymptomatic bacteriuria before the procedure (6). Simple catheter placement does not warrant screening. Evidence is inadequate to support definitive guidelines for the management of asymptomatic bacteriuria in renal transplant recipients and neutropenic patients. Patients with renal transplants who have asymptomatic bacteriuria are at higher risk for pyelonephritis, but whether pyelonephritis affects graft function is controversial (11, 12). The relationship of asymptomatic bacteriuria to UTI and sepsis in patients with neutropenia is not well-studied. Bacteriuria diagnosed in neutropenic patients as part of a fever workup by definition is not asymptomatic. How can UTI be prevented? Screening urine cultures should be obtained only in pregnant women and patients about to have an invasive urologic procedure. Infection should be treated with directed antimicrobial therapy based on culture results.

Asymptomatic bacteriuria during pregnancy (4%7% of pregnant women) is associated with a high rate of progression to symptomatic UTI, including pyelonephritis (20%40% of pregnant women with untreated asymptomatic bacteriuria) (9). Asymptomatic bacteriuria of pregnancy also is associated with low birthweight and preterm labor, although a causative relationship has not been established.
A meta-analysis of 14 studies involving 2302 pregnant women found that antibiotic treatment was effective at eradicating asymptomatic bacteriuria and at preventing pyelonephritis (10). The number needed to treat to prevent 1 episode of pyelonephritis was 7 (CI, 68). Thus, 1-time screening for asymptomatic bacteriuria by urine culture early in pregnancy is

7. Abrutyn E, Mossey J, Berlin JA, et al. Does asymptomatic bacteriuria predict mortality and does antimicrobial treatment reduce mortality in elderly ambulatory women? Ann Intern Med. 1994;120:82733. [PMID: 7818631] 8. Hooton TM, Scholes D, Stapleton AE, et al. A prospective study of asymptomatic bacteriuria in sexually active young women. N Engl J Med. 2000; 343:992-7. [PMID: 11018165] 9. Patterson TF, Andriole VT. Detection, significance, and therapy of bacteriuria in pregnancy. Update in the managed health care era. Infect Dis Clin North Am. 1997; 11:593-608. [PMID: 9378925] 10. Smaill F, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev. 2007:CD000490. [PMID: 17443502] 11. Fiorante S, Fernndez-Ruiz M, LpezMedrano F, et al. Acute graft pyelonephritis in renal transplant recipients: incidence, risk factors and longterm outcome. Nephrol Dial Transplant. 2011;26:106573. [PMID: 20805254] 12. Fiorante S, LpezMedrano F, Lizasoain M, et al. Systematic screening and treatment of asymptomatic bacteriuria in renal transplant recipients. Kidney Int. 2010;78:774-81. [PMID: 20720526]

6 March 2012

Annals of Internal Medicine

In the Clinic

ITC3-3

2012 American College of Physicians

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

13. Stapleton A, Latham RH, Johnson C, Stamm WE. Postcoital antimicrobial prophylaxis for recurrent urinary tract infection. A randomized, double-blind, placebo-controlled trial. JAMA. 1990; 264:703-6. [PMID: 2197450] 14. Albert X, Huertas I, Pereir II, Sanflix J, Gosalbes V, Perrota C. Antibiotics for preventing recurrent urinary tract infection in non-pregnant women. Cochrane Database Syst Rev. 2004: CD001209. [PMID: 15266443] 15. Perrotta C, Aznar M, Mejia R, Albert X, Ng CW. Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Cochrane Database Syst Rev. 2008:CD005131. [PMID: 18425910] 16. Bent S, Nallamothu BK, Simel DL, Fihn SD, Saint S. Does this woman have an acute uncomplicated urinary tract infection? JAMA. 2002;287:2701-10. [PMID: 12020306] 17. Gupta K, Hooton TM, Roberts PL, Stamm WE. Patient-initiated treatment of uncomplicated recurrent urinary tract infections in young women. Ann Intern Med. 2001;135:9-16. [PMID: 11434727] 18. Hooton TM, Bradley SF, Cardenas DD, et al; Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:625-63. [PMID: 20175247] 19. Huppert JS, Biro F, Lan D, Mortensen JE, Reed J, Slap GB. Urinary symptoms in adolescent females: STI or UTI? J Adolesc Health. 2007;40:41824. [PMID: 17448399]

Symptomatic UTI in women with recurrent episodes can be prevented with antimicrobial prophylaxis. The criterion for the number of episodes of UTI per year that justifies preventive measures is arbitrary, and this decision should be individualized. Postcoital antibiotic prophylaxis has been shown to be highly effective in preventing symptomatic recurrences in women with 3 to 4 episodes of UTI per year, particularly if these are temporally associated with coitus.
A randomized, double-blind, placebocontrolled trial found that among women with at least 2 culture-documented episodes of UTI in the previous year, postcoital use of half of a single-strength tablet of trimethoprim-sulfamethoxazole (TMPSMX) (40 mg TMP plus 200 mg SMX) resulted in an infection rate of 0.3 per patient per year, compared with a rate of 3.6 per patient per year in the control group (13). Side effects were infrequent and minor. In women intolerant of or resistant to TMPSMX, an alternative agent (e.g., nitrofurantoin macrocrystals or a fluoroquinolone) may be as effective for postcoital prophylaxis as TMP-SMX, although clinical evidence specifically related to postcoital use is not available for these agents (13).

patient-initiated therapy. In this approach, women are provided with a course of appropriate antibiotics to take at the onset of symptoms. The advantages of this approach include avoiding long-term use of prophylactic antibiotics. The dosing frequency can be tailored to an individual patients response, with the goal of achieving UTI prevention while minimizing antibiotic exposure. However, rates are decreased only during the active prophylaxis period and return to baseline levels after antimicrobials are discontinued. In postmenopausal women, daily topical application of intravaginal estriol cream may help reduce the frequency of symptomatic episodes. Estrogen therapy is associated with a return of the premenopausal lactobacillus-dominated vaginal flora, an acid vaginal pH, and reduced vaginal colonization with Escherichia coli. Two studies in a 2008 Cochrane systematic review compared vaginal estrogens with placebo and showed that vaginal estrogens reduced the number of UTIs in postmenopausal women. Response varied according to the type of estrogen and treatment duration. Oral estrogens did not reduce UTI compared with placebo. Drug-related events associated with vaginal estrogens can include vaginal itching, burning, discharge, and metrorrhagia (15). A discussion of possible cancer risk should be individualized for each patient.

For women with more frequent recurrences, more frequent coitus, or recurrences temporally unrelated to coitus, continuous (daily, 3 times weekly, or even weekly) prophylaxis may be preferable (14). Another approach, which is appropriate for women with recurrent, uncomplicated UTI unrelated to coitus, is

Screening and Prevention... Inappropriate screening for asymptomatic bacteriuria

can be detrimental because it can lead to unnecessary antibiotic use. Screening and treatment of asymptomatic bacteriuria are not recommended in nonpregnant women, diabetic women, elderly persons, patients with spinal cord injury, or catheterized patients. Screening and treatment of asymptomatic bacteriuria is recommended only in pregnant women and patients about to have an invasive urologic procedure. Consider postcoital antibiotic prophylaxis for women with 2 or more episodes of UTI per year, particularly if these are temporally associated with coitus. Otherwise, daily or thrice-weekly antibiotic prophylaxis can be used to prevent UTIs. Consider topical intravaginal estrogen therapy to prevent symptomatic UTIs for postmenopausal women with recurrent UTIs.

CLINICAL BOTTOM LINE

2012 American College of Physicians

ITC3-4

In the Clinic

Annals of Internal Medicine

6 March 2012

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

What signs and symptoms should raise suspicion of UTI? Diagnosis begins with a detailed history because in ambulatory adult women, the history provided by the patient has high predictive value for the presence or absence of cystitis. The most common symptoms in noncatheterized individuals include dysuria, urinary frequency, and urgency.
A meta-analysis of the accuracy of history and physical examination for diagnosing acute, uncomplicated UTI in ambulatory women found that the probability of UTI was approximately 50% in women who presented with 1 or more symptoms of UTI. Specific combinations of symptoms raised the probability to more than 90%. Symptoms that increased the probability were dysuria, hematuria, and costovertebral angle tenderness. A history of vaginal discharge or irritation decreased the probability of UTI (16). Longitudinal studies have shown that ambulatory adult women, particularly those who have had recurrent UTIs, are often able to accurately identify symptoms of UTI (17). A prospective trial enrolled women who had at least 2 episodes of cystitis in the prior 12 months from a university-based primary care clinic. The participants were given urine collection materials and a course of fluoroquinolone antibiotics, both to be used if they developed symptoms of UTI. Overall, 88 of 172 women selfdiagnosed a total of 172 UTIs. Laboratory evaluation showed a uropathogen in 144 cases (84%), sterile pyuria in 19 cases (11%), and no pyuria or bacteriuria in 9 cases (5%). Clinical and microbiological cures occurred in 92% and 96%, respectively, of cultureconfirmed episodes. In this population, the strategy of self-diagnosis and management of acute cystitis was highly effective.

suprapubic pain, or subprapubic tenderness are also compatible with CAUTI (18). 103 colony-forming units/mL of urine or greater is sufficient for the diagnosis of CAUTI with an indwelling or intermittent catheter. By definition, CAUTI can occur with indwelling urethral (Foley) catheters, suprapubic catheters, and condom catheters. Since many of these defining symptoms are nonspecific, other infections and potential causes should be considered before attributing the symptoms to catheter-associated bacteriuria. The distinction between CAUTI and catheter-associated asymptomatic bacteriuria is challenging but clinically relevant, because only the former should be treated with antibiotics. What other disorders should be considered? The main alternative diagnoses to consider in young women presenting with symptoms of cystitis include sexually transmitted urethritis or vaginitis, noninfectious urethritis, and early pyelonephritis (Table 1). Women who are sexually active are at risk for both UTIs and sexually transmitted diseases (STDs). Symptoms of STDs may be subtle, and thus they should always be considered in the differential diagnosis for UTI. A history of vaginal discharge or irritation decreases the probability of UTI and warrants a workup for STDs and other vaginal conditions, such as candidiasis (16).
A cross-sectional study screened 296 sexually active females aged 14 to 22 years who were visiting a teen health center for both UTI (by urine culture) and STD (by vaginal swab and nucleic-acid amplification testing). In this population, the prevalences of UTI and STI were 17% and 33% respectively; 4% had both. The presence or absence of urinary symptoms did not predict STD, indicating that telephone management may not be appropriate for adolescent women with urinary symptoms (19).

Diagnosis and Evaluation

In catheterized patients, signs and symptoms compatible with a CAUTI include new onset or worsening fever, rigors, altered mental status, malaise or lethargy with no other identified cause, flank pain, costovertebral angle tenderness, acute hematuria, or pelvic discomfort. In patients whose catheters have been removed within the past 48 hours, dysuria, urgency, frequent urination,

The treating clinician should also consider whether the patient could

20. Saint S, Scholes D, Fihn SD, Farrell RG, Stamm WE. The effectiveness of a clinical practice guideline for the management of presumed uncomplicated urinary tract infection in women. Am J Med. 1999; 106:636-41. [PMID: 10378621] 21. Lachs MS, Nachamkin I, Edelstein PH, Goldman J, Feinstein AR, Schwartz JS. Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection. Ann Intern Med. 1992;117:135-40. [PMID: 1605428] 22. Geerlings SE. Urinary tract infections in patients with diabetes mellitus: epidemiology, pathogenesis and treatment. Int J Antimicrob Agents. 2008;31 Suppl 1:S547. [PMID: 18054467] 23. Meron M, ReguaMangia AH, Teixeira LM, et al. Urinary tract infections in renal transplant recipients: virulence traits of uropathogenic Escherichia coli. Transplant Proc. 2010;42:483-5. [PMID: 20304171] 24. Nicolle LE. Catheterrelated urinary tract infection. Drugs Aging. 2005;22:627-39. [PMID: 16060714] 25. Ulleryd P, Zackrisson B, Aus G, Bergdahl S, Hugosson J, Sandberg T. Selective urological evaluation in men with febrile urinary tract infection. BJU Int. 2001;88:1520. [PMID: 11446838]

6 March 2012

Annals of Internal Medicine

In the Clinic

ITC3-5

2012 American College of Physicians

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

Table 1. Differential Diagnosis of Acute Cystitis in Women

Condition Pathogens History Symptoms

Vaginitis

Candida, Trichomonas vaginalis, Bacteroides species, Gardnerella vaginalis

Possibly new sex partner or unprotected sexual activity; history of vaginitis

Urethritis

Chlamydia trachomatis, Neisseria gonorrhoeae, or herpes simplex virus None

Irritation

Pyelonephritis

Same as acute cystitis

New sex partner, unprotected sexual activity, history of sexually transmitted diseases or genital herpes simplex No unusual sexual exposure; possible chemical or allergen exposures (e.g., douches, bath products, feminine hygiene products, spermicides) Previous UTI (pyelonephritis or cystitis)

Vaginal discharge, odor, or itching; external dysuria (from urine coming into contact with inflamed and irritated vulvar epithelial surfaces) Gradual onset of symptoms (Chlamydia) vaginal discharge; urinary frequency or urgency Vaginal itching or discharge; usually a diagnosis of exclusion, unless withdrawal of a suspected offending substance resolves symptoms Constitutional symptoms (fever, malaise, sweats, headache), gastrointestinal symptoms (anorexia, nausea, vomiting, abdominal pain), local renal symptoms (back, flank or loin pain), voiding symptoms (as in cystitis)

26. Abarbanel J, Engelstein D, Lask D, Livne PM. Urinary tract infection in men younger than 45 years of age: is there a need for urologic investigation? Urology. 2003;62:27-9. [PMID: 12837416] 27. Gupta K, Hooton TM, Naber KG, et al; Infectious Diseases Society of America. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52:e103-20. [PMID: 21292654] 28. Gupta K, Hooton TM, Roberts PL, Stamm WE. Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women. Arch Intern Med. 2007; 167:2207-12. [PMID: 17998493]

have pyelonephritis (or in men, prostatitis) before initiating therapy for acute cystitis. The recommended duration of therapy for pyelonephritis is longer than that of cystitis; treatment of incipient pyelonephritis with a short-course regimen for cystitis could predispose the patient to relapse. Pyelonephritis may or may not be associated with symptoms of cystitis, which in some patients may overshadow the renal or systemic manifestations. In patients presenting with symptoms of acute cystitis, confirm the absence of fever, nausea, vomiting, rigors, and flank pain. In men with urinary symptoms and fever, consider both acute infectious prostatitis and/or pyelonephritis in the differential. What tests should be done to diagnose UTI? Urine culture is generally not required in suspected cases of acute, uncomplicated cystitis because the spectrum of causative organisms is predictable and urine culture results are often not available until after completion of short-course empirical treatments. The role of urine culture is 2-fold: to provide retrospective confirmation of the presence of bacteriuria, which in the correct clinical setting confirms the diagnosis of UTI, and to provide specific information about the

organism and its antimicrobial susceptibility. It is appropriate to obtain a culture (with susceptibility testing) of a pretreatment urine sample for women with suspected cystitis if the diagnosis is not clear from the history and physical examination, if an unusual or antimicrobial-resistant organism is suspected, if the episode represents a suspected relapse or treatment failure, or if the patients therapeutic options are limited by medication intolerance. Pretreatment urine culture is also considered standard of care in pregnant women and men. Women presenting with classic symptoms of cystitis (dysuria, frequency) who do not have symptoms of possible alternative diagnoses or underlying complicating conditions may be treated for UTI without further testing. For such women, self-initiated therapy or telephone clinic provider-guided presumptive therapy may be appropriate (20). In a woman presenting with symptoms of acute cystitis, a positive urine dipstick result can help to confirm the diagnosis, but a negative dipstick result cannot rule out the diagnosis in a woman with a high pretest probability of cystitis (16, 21). Thus, a dipstick test is not necessary if the history is clearly diagnostic of UTI (particularly in

2012 American College of Physicians

ITC3-6

In the Clinic

Annals of Internal Medicine

6 March 2012

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

women with symptoms akin to previous episodes). If the diagnosis is not clear-cut or if further complicating factors or alternative diagnoses emerges from the history, a more thorough and broad-based diagnostic evaluation should be conducted. Blood tests (including cultures) are not indicated in women with suspected cystitis unless they are needed to screen for alternative diagnoses suggested by the history or physical examination or to assess the status of a known underlying medical condition (e.g., diabetes mellitus). Up to 30% of women with acute pyelonephritis may have secondary bacteremia, and identification of the organism by blood culture can be helpful in cases where antibiotics are started in advance of the urine culture. Diabetic women and renal transplant recipients have a higher incidence of secondary bacteremia with UTI (22, 23). What organisms are generally found in UTI? Escherichia coli is the pathogen isolated in more than 90% of patients with uncomplicated cystitis and pyelonephritis. Other coliforms, including Klebsiella and Proteus, are less common. Staphylococcus saprophyticus is a coagulase-negative staphylococcus that causes uncomplicated cystitis and pyelonephritis in a small proportion (5%10%) of otherwise-healthy women. Escherichia coli is still a predominant pathogen in complicated UTI, but other coliforms and enterococci are also common. CAUTI in patients with short-term catheters can be caused by E. coli as well as by a spectrum of typical hospitalacquired pathogens, including Klebsiella, Citrobacter, Enterobacter, Pseudomonas, coagulase-negative staphylococci, enterococci, and Candida. Patients with long-term catheters typically have polymicrobial infections; in addition to the

pathogens above, Proteus, Morganella, and Providencia are common (24). Interpretation of urine culture depends on the clinical context and the urinalysis findings; the threshold of bacteriuria required for the diagnosis of acute cystitis is not absolute. Even a low concentration (102 colony-forming units/mL) of coliform bacteria in a urine sample from a woman with acute dysuria and pyuria often represents true (i.e., from within the urinary tract) bacteriuria. Such organisms should not be dismissed as contaminants in a clinical setting suggestive of cystitis (e.g., a patient with irritative voiding symptoms plus pyuria). On the other hand, even high concentrations (>105 colony-forming units/mL) of nonpathogens may not reflect true bacteriuria if the urine specimen was not collected properly or was allowed to stand at room temperature before processing. Organisms other than coliform bacilli, S. saprophyticus, and Enterococcus (e.g., lactobacilli, alpha streptococci, and coagulase-negative staphylococci other than S. saprophyticus) are usually considered contaminants in urine cultures from women with uncomplicated cystitis, whereas in complicated UTI almost any organism can be causative and must be considered seriously if the patient is symptomatic. Is there a role for diagnostic imaging in diagnosing UTI? For uncomplicated bladder infections, expert consensus is that imaging studies (abdominal radiographs, ultrasonography, computed tomography, and excretory urography) add little or no benefit but increase cost, cause delays, and carry some potential risk for the patient. Such studies should be done only if the pretest suspicion is high for an alternative diagnosis or an anatomical problem (such as bladder obstruction or stone) that would require intervention. Although men with acute

29. Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE. Fosfomycin for the treatment of multidrug-resistant, including extendedspectrum betalactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis. 2010;10:43-50. [PMID: 20129148] 30. Falagas ME, Kotsantis IK, Vouloumanou EK, Rafailidis PI. Antibiotics versus placebo in the treatment of women with uncomplicated cystitis: a metaanalysis of randomized controlled trials. J Infect. 2009;58:91102. [PMID: 19195714] 31. Little P, Moore MV, Turner S, et al. Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial. BMJ. 2010;340:c199. [PMID: 20139214]

6 March 2012

Annals of Internal Medicine

In the Clinic

ITC3-7

2012 American College of Physicians

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

cystitis should be considered for further evaluation for urologic abnormalities, imaging studies for acute cystitis in men younger than 45 years or in older men without any symptoms of voiding difficulties or hematuria may not be fruitful. Unfortunately, the evidence base for male cystitis is limited (25).
A prospective study of UTI was done in 29 consecutive men younger than

45 years who were hospitalized for febrile UTI but were otherwise healthy. Significant urethral stricture was excluded in all patients by insertion of a 16-French urethral catheter. Ultrasonography and intravenous (IV) urography were normal in all patients. Ten patients with hematuria had cystoscopy, and the urinary tract was healthy in all 10. One patient (3%) had bladder outflow obstruction detected by uroflowmetry (26).

Diagnosis and Evaluation... Diagnosis of UTI begins with a detailed history. In ambulatory adult women, the history provided by the patient has high predictive value for the presence or absence of cystitis. Consider the diagnosis of pyelonephritis (or in men, prostatitis) before starting therapy for acute cystitis. Consider complicating factors, namely underlying medical or urologic conditions that may predispose to treatment failure, infection with antibiotic-resistant organisms, or infectious complications that would affect the appropriate diagnostic workup and course of therapy. Use urinalysis via dipstick, microscopy, or automated microscopy to confirm the diagnosis in women with suspected UTI when the history alone is not diagnostic. Always culture the urine of patients with pyelonephritis, complicated UTI, men, pregnant women, or those with a history of failure of initial therapy. Initiate empirical therapy and make adjustments based on the results of the urine culture, if done.

CLINICAL BOTTOM LINE

Treatment and Management

32. Stapleton AE, Dziura J, Hooton TM, Cox ME, YarovaYarovaya Y, Chen S, et al. Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Injesting Cranberry Juice Daily: A Randomized Controlled Trial. Mayo Clin Proc. 2012;87:143-50. [PMID:22305026] 33. Barbosa-Cesnik C, Brown MB, Buxton M, Zhang L, DeBusscher J, Foxman B. Cranberry juice fails to prevent recurrent urinary tract infection: results from a randomized placebo-controlled trial. Clin Infect Dis. 2011;52:23-30. [PMID: 21148516] 34. Beerepoot MA, ter Riet G, Nys S, et al. Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women. Arch Intern Med. 2011;171:12708. [PMID: 21788542

What are the preferred treatments for UTI? Women with cystitis should be treated with an appropriate antimicrobial agent. Before selecting a treatment regimen for women with presumed cystitis, ask about factors that may influence the choice of antimicrobial agent, including pregnancy and breast-feeding, other medications being taken, drug allergy history, recent antibiotic therapy, other recent infections or positive cultures, and recent travel. Also, whether there are any complicating factors should be determined because management of uncomplicated cystitis and pyelonephritis differs from that of complicated UTI. The IDSA has recently published updated guidelines for treatment of uncomplicated cystitis and pyelonephritis, specifically in premenopausal, nonpregnant women with no known urologic abnormalities or comorbid conditions (27).

In addition to the usual concerns for efficacy and safety, the 2010 IDSA treatment recommendations for acute cystitis and pyelonephritis were guided by 2 important principles: the increasing prevalence of resistant organisms, and the potential for propagation of resistance (collateral damage) among normal host flora with the use of broadspectrum antibiotics. No single agent was designated as the preferred regimen. Instead, agents are listed as recommended for first-line therapy (nitrofurantoin, TMP-SMX, pivemecillinam, and fosfomycin trometamol) and alternative agents (fluoroquinolones and betalactams). Treatment regimens for cystitis and pyelonephritis are listed in Tables 2 and 3, respectively. Each agent has its own caveats. Nitrofurantoin concentrates in the urine but has little tissue penetration and thus should be avoided if there is any possibility of pyelo-nephritis.

2012 American College of Physicians

ITC3-8

In the Clinic

Annals of Internal Medicine

6 March 2012

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

Table 2. Treatment Regimens for Acute Uncomplicated Cystitis

Drug Dose and Duration Common Side Effects Comments

Recommended agents Nitrofurantoin monohydrate/ macrocrystals Trimethoprimsulfamethoxazole Fosfomycin trometamol Alternative agents Fluoroquinolones

100 mg twice daily for 5 days 160/800 mg (one DS tablet) twice daily for 3 days 3-g single-dose sachet Dose varies by agent; 3day regimen Dose varies by agent; 57 day regimen

Nausea, headache

Resistance rare to date; cost varies; usually well-tolerated; generally safe in pregnancy Excellent efficacy if local resistance less than 20%; resistance prevalence is increasing; inexpensive; extensive clinical experience; avoid during pregnancy, particularly first and third trimesters May be useful for multidrug-resistant pathogens; may be less effective than other agents; safe in pregnancy Prevalence of resistance increasing; cost varies; excellent efficacy; high collateral damage; better reserved for more serious conditions; avoid in pregnancy; tendon inflammation and rupture have been reported with use of quinolone antibiotics Resistance varies by agent; increased adverse effects compared with other options; safe during pregnancy

Rash, urticaria, nausea, vomiting, hematologic Diarrhea, nausea, headache Nausea, vomiting, diarrhea, headache, drowsiness, insomnia Diarrhea, nausea, vomiting, rash, urticaria

Beta-lactams

A 5-day course of nitrofurantoin was as effective as a 3-day course of TMP-SMX in terms of both clinical and microbiological cure in a randomized trial (28). The main limitation to the use of TMP-SMX is the rising rate of resistance among uropathogens, especially outside the United States, and consistent evidence that in vitro resistance correlates with bacterial and clinical failures in at least 50% of women. However, the 4 studies reviewed by the IDSA guidelines committee showed that TMP-SMX remains an appropriate empirical treatment for acute uncomplicated cystitis in women when the local rate of resistance is known or expected to be < 20%. Fosfomycin is available in the United States but is rarely used. The recommended 3-g single dose may not be as efficacious as other recommended agents, and it should be not be used if pyelonephritis is suspected. Susceptibility data are not routinely reported for this drug, but surveys demonstrate that it retains activity against multidrug resistant uropathogens, such as extended-spectrum beta-lactamaseproducing gramnegative organisms (29). Pivmecillinam, which is currently unavailable in the United States, is an extended-spectrum penicillin that is active against gram-negative organisms

but is used only for treatment of UTI. Although efficacy rates are lower than those of the other recommended agents, its low resistance rates have made it a popular firstline choice in some European countries. The fluoroquinolones, ofloxacin, ciprofloxacin, and levofloxacin, are all highly efficacious in 3-day regimens but are recommended as alternative agents because they have a high propensity for collateral damage of the normal fecal flora. Increasing rates of fluoroquinolone resistance in certain areas suggest that these agents should be reserved for conditions other than acute cystitis. Beta-lactams in general have inferior efficacy, high collateral damage, and greater rates of adverse effects than other UTI antimicrobials and thus are also considered alternative agents. Pyelonephritis is a tissue-invasive disease, and the initial empirical regimen should be broad enough to ensure in vitro activity against the uropathogen. In all suspected cases, a urine culture would ideally be obtained for susceptibility testing before starting therapy so the initial empirical therapy can be tailored appropriately. The decision points in managing acute pyelonephritis include ruling out complicated infection (pregnancy, nephrolithiasis,

35. Talan DA, Stamm WE, Hooton TM, et al. Comparison of ciprofloxacin (7 days) and trimethoprimsulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial. JAMA. 2000;283:1583-90. [PMID: 10735395] 36. Saint S, Meddings JA, Calfee D, Kowalski CP, Krein SL. Catheter-associated urinary tract infection and the Medicare rule changes. Ann Intern Med. 2009;150:87784. [PMID: 1952856784] 37. Warye KL, Murphy DM. Targeting zero health care-associated infections [Editorial]. Am J Infect Control. 2008; 36:683-4. [PMID: 19084162]

6 March 2012

Annals of Internal Medicine

In the Clinic

ITC3-9

2012 American College of Physicians

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

Table 3. Oral Treatment Regimens for Acute Uncomplicated Pyelonephritis*

Drug Dose and Duration Comments Other

Fluoroquinolones Ciprofloxacin Ciprofloxacin XR Levofloxacin

500 mg twice daily for 7 d 1000 mg once daily for 7 d 750 mg once daily for 5 d

If local resistance prevalence is < 10%

Trimethoprimsulfamethoxazole Beta-lactams

160/800 mg (one DS tablet) twice daily for 14 days Dose varies by agent; 10- to 14-d regimen

If pathogen known to be susceptible; otherwise give an initial IV agent Oral beta-lactams are less effective and should be used cautiously only when other agents cannot be used

Consider adding an initial 1-time IV dose of a longacting parenteral antimicrobial (such as 1 g of ceftriaxone or a single 24-h dose of an aminoglycoside) if the patient is borderline for oral therapy but not meeting admission criteria or if there may be a delay in starting oral therapy Same as above Give an initial IV dose of a long-acting parenteral antimicrobial when using oral beta-lactams

* For pyelonephritis, urine culture and susceptibility testing should always be done, with empirical treatment modified based on the results.

obstruction) and then determining whether the patient can take oral antibiotics as an outpatient. If oral therapy is feasible, oral ciprofloxacin in a 7-day regimen is the preferred regimen if local resistance rates to the fluoroquinolones do not exceed 10%. The extended-release formulation of ciprofloxacin for 7 days or a oncedaily dose of levofloxacin for 5 days can also be used, albeit the evidence is not as robust (27). TMP-SMX is also effective if the pathogen is susceptible, but in the absence of evidence to support short-course therapy a 14-day course is the official recommendation. If susceptibility of the uro-pathogen is not known, an initial single IV dose of ceftriaxone or a long-acting aminoglycoside is recommended before outpatient oral therapy. In a study comparing ciprofloxacin to TMPSMX, an initial dose of IV ceftriaxone resulted in improved outcomes in women receiving TMP-SMX who had a resistant uropathogen. Oral beta-lactam agents are not recommended for treatment of pyelonephritis given inferior efficacy rates. In women being admitted for IV therapy, a broad-spectrum agent should be given until the susceptibilities of the organism are known. This can be achieved with a carbapenem agent, an aminoglycoside with or without ampicillin, or extended spectrum betalactam with or without an aminoglycoside, or another regimen chosen on the basis of local resistance patterns.

Urinary analgesics for acute cystitis are appropriate in certain situations to speed resolution of bladder discomfort. The analgesic phenazopyridine is widely used but may cause nausea. Combination analgesics containing urinary antiseptics (methenamine, methylene blue), a urine-acidifying agent (sodium phosphate), and an antispasmodic agent (hyoscamine) are also available. Because these analgesics can mask the symptoms of antimicrobial failure, they are best used in patients with a clear diagnosis of cystitis. Patients with underlying complicating conditions are more likely to have a drug-resistant organism, to exhibit a poor response to antimicrobial therapy even when the urine organism is susceptible, and to develop complications if initial therapy for UTI is suboptimal. Broaderspectrum empirical therapy with agents to which resistance is least common and longer treatment durations are measures intended to blunt the negative effects of host compromise on treatment outcomes. In clinical trials of therapy for complicated UTI, oral fluoroquinolones were as effective as traditional iv regimens and as or even more effective than oral TMP-SMX or TMP (particularly for organisms resistant to TMP-SMX). However, resistance to fluoroquinolones among uropathogens is increasing worldwide. If the local prevalence

of fluoroquinolone resistance exceeds 10%, another broad-spectrum antimicrobial should be considered, including an extended-spectrum cephalosporin with or without an aminoglycoside or a carbapenem. Combinations of a beta-lactam and a beta-lactamase inhibitor (e.g., ampicillin-sulbactam, ticarcillinclavulanate, and piperacillintazobactam) could also be considered. The IDSA has issued evidence-based guidelines on the diagnosis, prevention, and treatment of CAUTI (18). The goal of limiting exposure to antimicrobial therapy and thus limiting selection pressure for resistant organisms is balanced by the awareness that microbial eradication requires a longer duration of therapy in patients with a urinary catheter. Seven days is the recommended duration of antimicrobial treatment for patients whose symptoms resolve promptly, and 10 to 14 days is recommended for patients with a delayed response. For those with CAUTI who are not severely ill, a 5-day regimen of levofloxacin may be considered (18). In pregnant women with symptomatic UTI, a urine culture and susceptibility testing should be performed. Empirical therapy with an oral antimicrobial agent that is safe for use in pregnancy should be given for 3 to 7 days for cystitis or 7 to 14 days for pyelonephritis. Antibiotic therapy should be adjusted on the basis of culture results.

2012 American College of Physicians

ITC3-10

In the Clinic

Annals of Internal Medicine

6 March 2012

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

Is there a role for nonpharmcologic therapies in treating UTI, including alternative therapies? There is no defined role for nondrug therapy in managing acute cystitis. Patients may have heard of supposed adjunctive or alternative measures to UTI therapy, and may want guidance on their use. Advise patients that increased fluid intake, consumption of cranberry juice, acupuncture, and other nondrug approaches to the management of cystitis are of no known benefit. Patients should be counseled that relying on nondrug therapies to treat acute cystitis is essentially similar to treating the condition with a placebo. A meta-analysis of 5 trials of placebo vs. antibiotic therapy for uncomplicated cystitis showed that antibiotic therapy was clearly superior for achieving symptom resolution (OR,
4.8; CI, 2.59.2) and microbio-logical cure (OR, 10.7; CI, 2.9638.4) (30). A randomized, controlled trial of 5 approaches to management of UTI in nonpregnant adult women found that all approaches achieved similar symptom control, but women who delayed the start of antibiotics had a longer duration of symptoms. The 5 strategies tested were immediate antibiotics, delayed empirical antibiotics for persistent symptoms, antibiotics based on a symptom score, antibiotics based on dipstick results, and antibiotics based on a positive urine culture result (31). This finding is in accord with the meta-analysis of Bent and colleagues (16), which found that women who present with symptoms of UTI have a high pretest probability of UTI and will probably require treatment for UTI unless another explanation for their symptoms is found.

well as a reduction in urinary P-fimbriated E. coli; however, the study was underpowered to reach statistical significance for either outcome (32). Another recent, randomized, controlled trial of twice-daily cranberry juice consumption versus placebo did not find a difference in the rate of UTI recurrence between the groups (33). Another randomized study compared cranberry capsules with TMP-SMX and showed that the antibiotic was more effective at preventing recurrent UTI, albeit at the expense of promoting antibiotic resistance (34). At this point there is no definitive evidence that commercially available cranberry products can be used for treating or preventing UTI.

The patient may raise the issue of cranberry products to prevent or to treat UTI. Cranberries contain substances that inhibit certain adhesins of uropathogenic E. coli, thereby preventing the bacteria from adhering to human cells. However, these in vitro findings have not yet been proven to have clinical relevance.
A recent randomized trial attempted to address this issue and found a potentially protective effect on recurrent UTI with cranberry products compared with placebo as

When should patients be hospitalized for UTI? Uncomplicated cystitis by definition does not require hospitalization, but complicated cystitis or pyelonephritis may require inpatient management. Factors for which hospitalization may be necessary include serious comorbid conditions, including pregnancy. Patients with a high fever, dehydration, high leukocyte count, or other evidence of sepsis may require inpatient supervision, as do those who are vomiting and thus unable to take oral therapy. Another consideration is whether the patient has an upper urinary tract condition that would require drainage or surgical intervention, including abscesses, emphysematous pyelonephritis, papillary necrosis, or xanthogranulomatous pyelonephritis. On rare occasions, a patient will have a multidrug-resistant urine organism that is susceptible only to parenterally administered antimicrobial agents or is intolerant of agents that can be given orally. However, many women with pyelonephritis can be managed successfully at home, as treatment trials have shown the efficacy of oral therapy with a fluoroquinolone for mild, acute pyelonephritis in this group (35). Clinical judgment is required to determine which patients are appropriate for outpatient management, and a period of observation in the emergency department may be warranted.

What are the usual reasons for failure of UTI therapy? Underlying medical conditions that increase the risk for delayed or incomplete response to therapy, relapse, or infectious complications include pregnancy, poorly controlled diabetes mellitus, and immunosuppression. Advanced age, recent UTIs, recent antibiotic use, previous infection with resistant organism, prolonged duration of symptoms before presentation (>3 d), and recent travel to an area with a high prevalence of antibiotic-resistant uropathogens all increase the risk for resistant infection. Urologic complications that can put the patient at risk for treatment failure include urinary tract stones, voiding disorders, indwelling catheters, stents, urinary obstruction, duplicated collecting system or other anatomical abnormalities, or vesicoureteral reflux. The combination of obstruction and infection puts the patient at increased risk for upper UTI (pyelonephritis), sepsis, and perinephric or intrarenal abscess. In particular, patients with CAUTI who do not promptly respond to appropriate antibiotic therapy may have obstruction or stones in the upper urinary tract. Effective urine drainage reduces intraluminal pressure and restores the flow of urine. When should clinicians consider consultation with a specialist? Consultation is rarely needed for acute, uncomplicated cystitis in ambulatory women but can be helpful in complicated UTI, particularly in patients with indwelling bladder catheters, those hospitalized because of upper tract disease, and men with UTI. Consider consulting an infectious disease specialist when the organisms isolated in the urine are resistant to standard antibiotics. Consultation with an infectious diseases specialist or a urologist may also be necessary in patients with possible upper urinary tract involvement who do not respond to appropriate antibiotic therapy within 72 hours. A surgically correctable lesion may be

6 March 2012

Annals of Internal Medicine

In the Clinic

ITC3-11

2012 American College of Physicians

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

present in men who report voiding difficulties or acute urine retention or who have early recurrent UTI or persistent microscopic hematuria. Stones, strictures, and occult cancer are among the differential diagnoses for men with these symptoms. How should patients treated for UTI be followed? In uncomplicated cystitis, no specific follow-up is required as long as symptoms resolve. In pregnant women, obtain urine cultures after treatment to confirm eradication of bacteriuria, and obtain repeated urinalyses or urine cultures at intervals to confirm sterility of the urine through the time of delivery. The rationale for repeated screening is that pregnant women who have already had bacteriuria during their pregnancy are at increased risk for recurrence and need closer monitoring than do women who had sterile urine on initial screening. However, more evidence is needed to define the appropriate frequency of follow-up cultures and retreatment strategies (10). It seems prudent to monitor patients with complicated UTI during and after therapy, because failure of therapy for cystitis in the presence of underlying complicating conditions is both more probable and more likely to produce significant morbidity than in patients without complicating conditions. Because complicated UTI is an extremely heterogenous disorder, the approach to monitoring during and after therapy must be individualized. Patients who are more fragile, are infected with more difficult-to-treat organisms, have more severe symptoms at the outset,

multiple predisposing conditions, or multiple medication allergies need closer follow-up than do patients with only mild symptoms, an easily-treated organism, a single minor predisposing condition, and otherwise good health status. Patients with complicated UTI should be followed clinically for symptomatic resolution and be reevaluated if symptoms do not improve within 24 to 48 hours, worsen, or recur quickly after therapy. In CAUTI, it is important to monitor response to therapy by the patients symptoms rather than by repeated urine cultures, as recurrent bacteriuria is the norm in patients whose indwelling catheter remains in place. What is the correct approach to secondary prevention in patients who have a history of UTI? Recurrent UTI is very common, estimated to occur in up to 50% of women within 1 year of an initial UTI (3). Other than the antimicrobial prophylaxis recommended in the Prevention section above, there are few measures that women can take to prevent recurrent UTI. As for the often-cited behavioral risk factors for recurrent UTI, a large casecontrol study in premenopausal women did not find any associations between risk for recurrent UTI and pre- and postcoital voiding, frequency of urination, wiping patterns, douching, use of hot tubs, frequent use of pantyhose or tights, or daily fluid consumption (2). Women with recurrent UTI should be counseled about the true risk factors for UTI so they do not blame themselves or make unnecessary behavioral changes.

Treatment and Management... The IDSA has recently released new standard-ofcare guidelines for treatment of acute, uncomplicated cystitis; acute uncomplicated pyelonephritis; and catheter-associated UTI. Nonpharmacologic therapies for acute cystitis do not have proven benefits and may lead to adverse outcomes. Posttreatment follow-up should include monitoring the response to therapy rather than repeated urine cultures, except in pregnant women.

CLINICAL BOTTOM LINE

2012 American College of Physicians

ITC3-12

In the Clinic

Annals of Internal Medicine

6 March 2012

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

What measures do U.S. stakeholders use to evaluate the quality of care for patients with UTI? The recent guidelines on acute uncomplicated cystitis and pyelonephritis published by the IDSA in 2011 identified several performance measures as appropriate indicators for management of acute uncomplicated UTI in women. Use an available recommended antimicrobial for treatment of uncomplicated cystitis and uncomplicated pyelonephritis if the patient is not allergic. Use fluoroquinolones for acute uncomplicated cystitis only when a recommended antimicrobial cannot be used. Obtain a pretherapy urine culture in cases of acute uncomplicated pyelonephritis; start empirical therapy and modify according to culture results. In other words, fluoroquinolone antibiotics should not be the first choice agents for acute, uncomplicated cystitis, and urine culture results should be used to guide therapy in pyelonephritis (27). CAUTI has been in the spotlight recently because of several important social changes. On 1 October 2008, the Centers for Medicare & Medicaid Services stopped reimbursing U.S. hospitals for several complications of hospitalization, including CAUTI that develops during hospitalization. Although the rule has provoked controversy over whether CAUTI is truly preventable, the increased focus on prevention of this disorder, particularly through decreasing unnecessary use of urinary catheters, is likely to be beneficial (36). Around the same time, the focus of infection control agencies shifted from control of hospitalacquired infections to prevention, as summarized in the mission statement of the Targeting Zero campaign of the Association for Professionals in Infection Control and Epidemiology (37). The other

important social change affecting CAUTI research and prevention efforts has been the upsurge in public reporting of hospital qualityof-care data. Although CAUTI is not among the standard outcome of care measures, prevention of CAUTI has been announced as a 2012 National Patient Safety Goals by the Joint Commission. Therefore, monitoring for appropriate urinary catheter care and use is rapidly becoming standard hospital policy. What do professional organizations recommend regarding care of patients with UTI? Professional organizations in both the United States and internationally have released practice guidelines concerning UTI that address 3 categories of UTI: acute cystitis, CAUTI, and asymptomatic bacteriuria. The IDSA published the Guidelines for Antimicrobial Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women in 2011. These guidelines focus on treatment of women with acute uncomplicated cystitis and pyelonephritis, and their recommendations are limited to premenopausal, nonpregnant women with no known urologic abnormalities or comorbid conditions. An important and unifying theme in these guidelines is that the issues of in vitro resistance prevalence and the potential for collateral damage by various antimicrobial agents are taken into account in the recommended treatment choices. CAUTI has received considerable press lately. Guidelines concerning management and prevention of this condition have been released by the Centers for Diseases Control Healthcare Infection Control Practices Advisory Committee, by the Association for Professionals in Infection Control and Epidemiology in its Compendium of Strategies to Prevent Healthcare-Associated

Practice Improvement

6 March 2012

Annals of Internal Medicine

In the Clinic

ITC3-13

2012 American College of Physicians

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

Infections in Acute Care Hospitals, and also by the IDSA. This topic is also addressed in the very comprehensive European Association of Urologists Guidelines on Urological Infections released in 2009. Asymptomatic bacteriuria guidelines were published by the IDSA in 2005. Abundant evidence supports nontreatment of asymptomatic bacteriuria (with the exceptions of pregnant women and patients undergoing urologic

procedures). These IDSA guidelines recommendations were reviewed and endorsed by the U.S. Preventive Services Task Force in 2008. Specifically, the Task Force recommended against screening for asymptomatic bacteriuria in men and nonpregnant women and recommended for screening for asymptomatic bacteriuria with urine culture for pregnant women at 12 to 16 weeks gestation or at the first prenatal visit, if later.

Tool Kit
Urinary Tract Infection

http://pier.acponline.org/physicians/diseases/d162/d162.html PIER module on UTI from the American College of Physicians (ACP). PIER modules provide evidence-based, updated information on current diagnosis and treatment in an electronic format designed for rapid access at the point of care.

Patient Information
www.annals.org/intheclinic/toolkit-uti.html Patient information that appears on the next page for duplication and distribution to patients. www.nlm.nih.gov/medlineplus/ency/article/000483.htm www.nlm.nih.gov/medlineplus/spanish/ency/article/000483.htm Information on catheter-associated UTIs from the National Institutes of Healths MedlinePLUS, in English and Spanish. http://familydoctor.org/online/famdocen/home/women/ gen-health/190.html Frequently asked questions on UTIs in women from the American Academy of Family Physicians. http://kidney.niddk.nih.gov/kudiseases/pubs/uti_ez/ (English) http://kidney.niddk.nih.gov/spanish/pubs/uti_ez/ (Spanish) A handout titled What I need to know about Urinary Tract Infection from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in English and Spanish.

Clinical Guidelines
www.annals.org/content/149/1/W-20.full Recommendation statement on screening for asymptomatic bacteriuria in adults from the U.S. Preventive Services Task Force. http://cid.oxfordjournals.org/content/50/5/625.full International clinical practice guidelines from the Infectious Diseases Society of America on the diagnosis, prevention, and treatment of catheter-associated UTI in adults, released in 2009.

Diagnostic Tests and Criteria

http://pier.acponline.org/physicians/diseases/d162/tables/d162-tlab.html Table listing laboratory and other studies for acute cystitis in women.

Quality of Care Guidelines

http://qualitymeasures.ahrq.gov/browse/by-topic-detail.aspx? id=13254&ct=1&term=urinary AHRQ quality indicators for UTI, including measures on the hospital admission rate of UTI and the percentage of nursing home residents with UTI. www.annals.org/content/144/2/116.full Systematic review on antimicrobial urinary catheters to prevent catheter-associated UTI in hospitalized patients published in Annals of Internal Medicine in 2006.

2012 American College of Physicians

ITC3-14

In the Clinic

Annals of Internal Medicine

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

In the Clinic
6 March 2012

In the Clinic

PIER Module

THINGS YOU SHOULD KNOW ABOUT URINARY TRACT INFECTION

What is a urinary tract infection (UTI)?
A UTI is a common infection of the urinary system (i.e., urethra, bladder, ureters, and kidneys). It occurs when bacteria at the opening of the urethra ascend to the bladder. Infection limited to the urethra is called urethritis. Infection that moves from the urethra to the bladder is called cystitis. Infection that moves further up the urinary tract to the kidneys is called pyelonephritis.

In the Clinic Annals of Internal Medicine

What factors increase the risk for UTI?

Being a sexually active adult woman. Using a diaphragm or spermicide. Having an abnormality of the urinary tract that obstructs the flow of urine (such as a kidney stone or enlarged prostate gland). Having a catheter (a tube inserted in the urethra and bladder of people who cannot pass urine or who lack bladder control). Having poorly controlled diabetes in postmenopause.

What are common symptoms?

Painful urination and feeling an urgent need to urinate frequently. Urine that contains blood or looks cloudy. Discomfort in the lower abdomen and pain in the back or pelvic area. Fever may develop. If you have recurrent or resistant infection, your doctor may order tests to determine if your urinary system is normal.

How is it treated?
Your doctor will prescribe an oral antibacterial drug. It is important to take the full course of treatment even if your symptoms disappear. Patients with severe kidney infections may need to be hospitalized and receive IV treatments. If you have recurring infection, you may be advised to take low doses of an antibiotic daily for many months or to take a single dose of an antibiotic after sexual intercourse to prevent infection.

How is it diagnosed?
Your doctor may diagnose UTI based on your symptoms or may do additional tests. Your urine is checked for evidence of infection with a test called a urinalysis or dipstick. A urine culture for bacteria if you are pregnant or are likely to have a kidney infection or resistant bacteria.

For More Information

www.urologyhealth.org/urology/index.cfm?article=47

Information on urinary tract infections in adults from the American Urological Association.
http://familydoctor.org/online/famdocen/home/women/ gen-health/284.html

Answers to questions about painful urination, from the American Academy of Family Physicians.
http://womenshealth.gov/publications/our-publications/fact-sheet/ urinary-tract-infection.cfm

Urinary tract infection fact sheet from the U.S. Department of Health and Human Services Office on Womens Health.

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012

Patient Information

CME Questions

1. A 64-year-old woman is evaluated for symptoms of a urinary tract infection (UTI). She has had 3 UTIs in the past 2 years. She is not sexually active. She has no other medical problems and takes no medications. A pelvic examination reveals pale, dry vaginal epithelium that is smooth and shiny with loss of most rugation. Urinalysis reveals 2+ leukocyte esterase, leukocytes too numerous to count, and 10 to 20 erythrocytes/hpf. Urine culture grows escherichia coli. In addition to treating the current UTI, which of the following is the most reasonable management option for this patient?

3. An otherwise-healthy 28-year-old woman has had 2 episodes of acute cystitis within the past 6 months. The patient is sexually active and has intercourse with her husband on average 2 times per week and says her cystitis does not seem to be intercourse-related. Each time, symptoms remit after a single course of trimethoprimsulfamethoxazole. The patient is currently asymptomatic but will be traveling abroad for the next 2 months and is concerned about recurrent infections. Her only medication is an oral contraceptive for birth control. She reports no allergies. Which of the following is the most appropriate management?

4. A 32-year-old sexually active woman with type 1 diabetes mellitus is evaluated because of recurrent UTIs. She has had 3 episodes this year. The most recent episode occurred 2 weeks ago. Physical examination, including vital signs, is normal. Urinalysis is normal except for the microscopic examination, which shows 4+ bacteria. Which of the following management strategies is most appropriate at this time?

A. Continuous antibiotic prophylaxis B. CT imaging of the abdomen and pelvis C. Topical estrogen therapy D. Vaginal lubricants
2. A 65-year-old woman is evaluated because a screening urine culture for an insurance policy grows greater than 105 colony-forming units/mL of E. coli. She does not have fever, dysuria, urinary frequency, or other symptoms. Medical history is unremarkable. She has no allergies and takes no medications. Physical examination findings are normal. Which of the following is the most appropriate treatment?

A. Ciprofloxacin after intercourse B. Ciprofloxacin for 10 days when symptoms develop C. Trimethoprim chronic suppressive therapy D. Trimethoprim-sulfamethoxazole for 3 days when symptoms develop

A. Patient-initiated empiric antibiotic therapy B. Continuous standard-dose antibiotic therapy C. Urinalysis and culture at the onset of dysuria D. Postcoital empiric antibiotic therapy

A. Amoxicillin B. Ciprofloxacin C. Trimethoprim-sulfamethoxazole D. No treatment

Questions are largely from the ACPs Medical Knowledge Self-Assessment Program (MKSAP, accessed at http://www.acponline.org/products_services/mksap/15/?pr31). Go to www.annals.org/intheclinic/ to complete the quiz and earn up to 1.5 CME credits, or to purchase the complete MKSAP program.

2012 American College of Physicians

ITC3-16

In the Clinic

Annals of Internal Medicine

6 March 2012

Downloaded From: http://annals.org/ by Jose Roel on 09/12/2012