A Review of Bacteriuria and Urinary Tract Infection

Educational Objectives

The goal of this program is to improve management of urinary tract infection (UTI). After hearing and assimilating this program, the clinician will be better able to:

1. Select medications for treatment of UTI.
2. Integrate considerations for antibiotic resistance into treatment decision-making for UTI.
3. Advise patients on preventive therapies for UTI.

Summary

Urinary tract infection (UTI): comprised of 4 major syndromes, ie, asymptomatic bacteriuria (ASBU), cystitis, recurrent UTI (rUTI), and complicated UTI (cUTI), which includes pyelonephritis

Antibiotic resistance (ABR) in UTI: overuse of antibiotics leads to ABR; no new classes of antibiotics have been developed since 2000; ABR is projected to surpass cancer as the leading cause of death worldwide, according to the World Health Organization; UTIs remain the first or second cause of morbidity in patients seen by internists; the North American Urinary Tract Infection Collaborative Alliance reports on ABR in treatment of UTI; bacteria which cause UTI are resistant to ampicillin, trimethoprim-sulfamethoxazole (TMP-SMZ), and fluoroquinolones; resistance to ceftriaxone has been increasing; currently, carbapenem (broad spectrum) and nitrofurantoin (narrow spectrum) are the only reliable drugs for use in patients with UTI; the hypervirulent Escherichia coli subtype ST131 accounts for 25% of E coli infections and is resistant to fluoroquinolones and β-lactams; carbapenem and nitrofurantoin may treat ST131

Diagnosis: precisely diagnosing the type of UTI allows for the best evidence-based guideline-concordant care to be provided to patients; patients are overtreated for cUTI when the more precise diagnosis is ASBU, rUTI, or acute simple cystitis (ASC); in cUTI, the risk for complications is high; patients with rUTI have urinary symptoms which are confined to the bladder with >2 occurrence in 6 mo; isolated urinary symptoms occur in patients with ASC

ASC: ≈80% of cases seen in clinic are for ASC; the risk for progression to pyelonephritis is ≈0.5%; symptoms include dysuria, urgency, frequency, suprapubic pain, and hematuria; vaginal symptoms and upper urinary tract symptoms (eg, flank pain, nausea and vomiting, fever) are absent; urinalysis, physical examination, or imaging is not required for a diagnosis of ASC in first or isolated episodes; a first-line antibiotic may be prescribed; management goals include relief of symptoms and avoiding adverse events; a short-course narrow-spectrum antibiotic is recommended because symptoms resolve on their own in 50% of cases; nitrofurantoin and fosfomycin concentrate in the bladder and kill uropathogens, with a low risk for ABR or adverse effects (eg, Clostridioidesdifficile infection); the cure rate with nitrofurantoin and fosfomycin is non-inferior to broader spectrum drugs; TMP-SMZ is no longer a first-line drug (>20% resistance); second-line treatment — hydration is recommended; therapy is delayed until results of urine culture and sensitivity are available; β-lactams and fluoroquinolones should be reserved for serious infections because of unwanted adverse effects (eg, C difficile infection, ABR, hypersensitivity reactions)

rUTI: occurrence of cystitis >2 times in the last 6 mo and >3 times in a year; typically characterized by irritative voiding symptoms; patients should be given a urine culture test because of the high risk for resistance; pelvic imaging may be required if vaginal irritative symptoms, incontinence, or voiding issues are present; specialty referral may be considered for recurrent extended-spectrum β-lactamase UTI; relapse — occurs days to weeks after treatment; typically indicates the same infection and the presence of a nidus (eg, stone, stent); reinfection — occurs months after treatment and typically indicates the presence of modifiable risk factors (eg, uncontrolled diabetes) which permit reinfection

Management: therapy should be delayed until results of culture and sensitivity tests are available; patients should be advised on the importance of hydration; non-antibiotic methods for prevention of future episodes should be attempted; clinical evidence supports the strengthening of protective mechanisms and mitigation of predisposing factors; increased fluid intake (2L/day) increases urine flow which washes away the bladder slough (ie, bladder epithelial cells and mucus which entrap bacteria); in postmenopausal women, vaginal estrogen replacement therapy restores microbiome and decreases local inflammation, dyspareunia, vaginal pruritus, and dryness (atrophic vaginitis mimics rUTIs); methenamine is converted to formaldehyde in the urine, which sterilizes the bladder slough; clinical evidence is mixed for the efficacy of vaginal probiotic suppositories, cranberry juice, and D-mannose; clinicians should educate patients that UTI may recur after completion of antibiotic therapy; antibiotic administration may be postcoital or continuous; nitrofurantoin is preferred to be used first; fluoroquinolones should be avoided; most complaints of rUTIs may turn out to be miscellaneous diagnoses (eg, dyspareunia, ASBU)

ASBU: a positive urine culture for bacteriuria is likely common among the general population; screening and overtreatment should be avoided; diagnosis must be consistent with presenting symptoms; urine studies are not recommended, unless the patient is symptomatic, pregnant, or about to undergo cystoscopy with biopsy; 2% to 5% of premenopausal healthy women, 10% to 25% of women with diabetes, and 25% to 50% of people >65 yr of age have ASBU; each day an indwelling catheter is placed, the rate of bacteriuria increases by 5% to 7%; evidence — supports treating ASBU in pregnancy (the incidence of pyelonephritis is ≤30% in untreated individuals) or prior to invasive urologic procedures (≤60% of untreated patients develop bacteremia); antibiotics do not confer benefits in terms of, eg, preventing symptomatic UTI, pyelonephritis, sepsis, reducing hospitalizations or mortality; ≤33% of patients who receive antibiotics without indication develop resistance, C difficile infection, or hypersensitivity; Harding et al (2002) randomized patients with diabetes with ASBU to antibiotics or placebo and found no improvement in the incidence of symptomatic UTI, pyelonephritis, and hospitalizations; no mortality benefit was observed; increasing use of antibiotics increases rates of adverse effects; patients with ASBU should be assessed for a cause that is consistent with their symptoms (eg, polypharmacy, hyponatremia, hypernatremia, hepatic encephalopathy, uremia)

cUTIs and pyelonephritis: guidelines for treatment are not available; the mortality rate for patients with bacteremia who require admission to the intensive care unit or require urologic intervention is 10% to 33%; symptoms include flank pain, back pain, nausea, vomiting, fever, and sepsis; a urine culture test is mandatory; management — early empiric antibiotics should be used and a culture-guided transition to oral administration employed; patients who present with mild pyelonephritis or cUTI (eg, flank pain, mild fever) without vomiting and can tolerate oral administration, may be triaged by prescribing an oral fluoroquinolone which may include intramuscular ceftriaxone or gentamicin; ABR — for treatment of E coli infection, resistance to ceftriaxone is at 15%, ciprofloxacin is at 30%, and TMP-SMZ is at >40%; ceftriaxone, ciprofloxacin, and TMP-SMZ are not suitable for treatment of cUTI; carbapenem is indicated for patients with cUTI with recent history of hospitalization, antibiotic treatment, or travel to places where E coli ST131 is endemic, or in patients with sepsis

Readings

Chwa A, Kavanagh K, Linnebur SA, Fixen DR. Evaluation of methenamine for urinary tract infection prevention in older adults: a review of the evidence. Ther Adv Drug Saf. 2019;10:2042098619876749. Published 2019 Sep 23. doi:10.1177/2042098619876749; DeMarsh M, Bookstaver PB, Gordon C, et al. Prediction of trimethoprim/sulfamethoxazole resistance in community-onset urinary tract infections. J Glob Antimicrob Resist. 2020;21:218-222. doi:10.1016/j.jgar.2019.10.023; Herness J, Buttolph A, Hammer NC. Acute pyelonephritis in adults: rapid evidence review. Am Fam Physician. 2020;102(3):173-180; Harding GK, Zhanel GG, Nicolle LE, et al; Manitoba diabetes urinary tract infection study group. Antimicrobial treatment in diabetic women with asymptomatic bacteriuria. N Engl J Med. 2002;347(20):1576-1583. doi:10.1056/NEJMoa021042; Gebremedhin KB, Alemayehu H, Medhin G, Amogne W, Eguale T. Maternal complications and adverse pregnancy outcomes among pregnant women who acquired asymptomatic bacteriuria in Addis Ababa, Ethiopia. Biomed Res Int. 2021;2021:5254997. Published 2021 Aug 13. doi:10.1155/2021/5254997; Grigoryan L, Trautner BW, Gupta K. Diagnosis and management of urinary tract infections in the outpatient setting: a review. JAMA. 2014;312(16):1677-1684. doi:10.1001/jama.2014.12842; Qureshi ZA, Doi Y. Escherichia coli sequence type 131: epidemiology and challenges in treatment. Expert Rev Anti Infect Ther. 2014;12(5):597-609. doi:10.1586/14787210.2014.899901; Scott AM, Clark J, Mar CD, Glasziou P. Increased fluid intake to prevent urinary tract infections: systematic review and meta-analysis. Br J Gen Pract. 2020;70(692):e200-e207. Published 2020 Feb 27. doi:10.3399/bjgp20X708125; Welker S, Boutin S, Miethke T, et al. Emergence of carbapenem-resistant ST131 Escherichia coli carrying blaOXA-244 in Germany, 2019 to 2020. Euro Surveill. 2020;25(46):2001815. doi:10.2807/1560-7917.ES.2020.25.46.2001815; Zhanel GG, Hisanaga TL, Laing NM, et al. Antibiotic resistance in outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA). Int J Antimicrob Agents. 2005;26(5):380-388. doi:10.1016/j.ijantimicag.2005.08.003.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Reynoso was recorded at the 32nd Annual Essentials in Internal Medicine Conference, held April 14-15, 2023, in Galveston, TX, presented by the University of Texas Medical Branch at Galveston. For information about upcoming CME activities from this presenter, please visit https://www.utmb.edu/internalmedicine/. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

UR470801

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.