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Urinary tract infection (UTI)

Most common bacterial infection.

Estimated to cause approximately 8 million office each year in the US, along with an additional 1million ED visits and 100,000 hospitalizations.

UTIs are associated with substantial mobility, mortality, and economic burden.

Estimated 11 million office visits in the United States, 2-3,000,000 emergency department visits, 400,000 hospitalizations in approximately $2.3 billion in healthcare costs annually in the US.

Number of office visits for UTIs twice as common among women of all ages compared with men.

Uncomplicated UTIs are the most one of the most commonly treated types of infections in primary care settings.
The majority of patients with uncomplicated UTI or pre-menopausal women who are not pregnant and have a few or no comorbidities.
Women are at greatest risk with the lifetime incidence approaching 50%, and approximately 33% rate of recurrence.

Half of all women report at least one UTI by 32 years of age.

Second most common infection among community dwelling older patients.

50% of females and 40% of male nursing home residents have reported a urinary tract infection during their admission.

Defined as an infection of the urinary system and may involve lower urinary tract or the lower and upper urinary tracts together.

Pathogenesis of UTI starts from periurethral mucosal colonization of pathogens that ascends to the urethra to the bladder.

Obstruction of urine flow is the most important etiology of UTI.

Enteric organisms like E. coli are the most common organisms.

Enterobacteriaceae are the most common causes of complicated UTIs, and multi drug resistance within this family is a global concern.

Patients with multidrug resistant UTIs are three times as likely to receive inappropriate empirical antibiotic therapy as patients who do not have multidrug resistant infections.

Patients with multidrug resistant UTIs have longer hospital stays, incur higher hospital costs and have a higher risk of septic shock and death.

Has a spectrum of conditions ranging from asymptomatic bacteria, to symptomatic UTI, to sepsis requiring hospitalization.

Pyuria and bacteriuria are diagnostic.

Asymptomatic bacteria in women is defined as the presence of at least 10 to the fifth CFU/mL of the same uropathogen in two consecutive clean catch midstream urine samples in patients without symptoms or signs of a UTI.

Asymptomatic bacteria in women does not indicate an infection that requires treatment, but is a colonization state.

Asymptomatic bacteria incidence increases with age.

The incidence is asymptomatic bacteria increases from 3.5% in the general population to 16-80% in women older than 70 years.

Asymptomatic bacteria affects 50% of older women and is generally benign in this group of patients.

A symptomatic UTI is one that requires a patient to have symptoms and signs of a UTI and laboratory confirmation of bacteria of 10 to the fifth CFU per mill and pyuria of 10 white blood cells per high-powered field.

Uncomplicated symptomatic UTI refers to a symptomatic bladder infection with fever, urinary urgency or frequency, dysuria, suprapubic tenderness, CVA pain or tenderness and no recognized cause, and laboratory tests revealing UTI.

Most common form is acute uncomplicated cystitis with acute onset of dysuria, frequency, or urgency in a healthy, nonpregnant woman without functional or anatomical abnormalities of the urinary tract.

Symptomatic UTI localized to the bladder is usually not associated with fever.

Complicated UTI refers to a symptomatic UTI in patients with the functional or structural abnormality, having had urinary instrumentation, having systemic diseases such as renal insufficiency, diabetes, or immune impairment.

UTIs of the most common reason for antimicrobial prescriptions in nursing homes and responsible for 28-60% of systemic antibiotic courses among nursing home residents.

Accounts for 25% of all infections in older adults.

Pyuria refers to the presence of leukocytes in the urine.

11 percent of women have a UTI each year and more than half of women have such an infection during their lifetime.

Incidence in women 0.5/person/yr and 27% to 48% of healthy women with 1 infection will experience recurrent infection.

3-5 % of women have recurrent UTI’s.

Approximately 20-30% of women who have had an infection experience a recurrence with concurrent short term morbidity.

Hallmark of UTIs the presence of bladder bacteria.

Tx uti in women

Urinary Tract Infection in Women Clinical Practice Guidelines (2019)

Women presenting with recurrent lower urinary tract infections should undergo a complete patient history and pelvic examination.

A diagnosis of recurrent UTI must be based on documented positive urine culture results in association with prior symptomatic episodes.

Patients presenting with recurrent UTI should not routinely undergo upper tract imaging and cystoscopy.

In patients with recurrent UTI , urinalysis, urine culture, and sensitivity should be performed for each symptomatic acute cystitis episode.

Surveillance urine testing, including urine culture, should not be performed in asymptomatic patients with recurrent UTI.

Asymptomatic bacteriuria should not be treated.

Symptomatic UTIs in women should be treated with first-line therapy (ie, nitrofurantoin, TMP-SMX,) and should depend on local antibiogram.

The duration of antibiotic therapy for recurrent UTI in patients should be short as is reasonable, and typically no longer than 7 days.

Recurrent UTI in patients with acute cystitis that has shown resistance to oral antibiotics on urine culture may be treated with culture-directed parenteral antibiotics for as short a course as is reasonable, typically no longer than 7 days.

In a randomized clinical trial that included 272 men with presumes symptomatic UTI, resolution of symptoms by 14 days after completion of active anabiotic therapy was the same in a seven day group and in a 14 day group.

Posttreatment urinalysis or urine culture to test for cure should not be performed in asymptomatic patients.

UTI symptoms that persist after antimicrobial therapy should prompt repeat urine culture to guide further treatment.

Vaginal estrogen therapy with no contraindications should be recommended to perimenopausal and postmenopausal women with rUTIs to reduce the risk of future UTI.

The usual urine collection for culture is the midstream portion of voided urine.

Dipstick testing is useful to assess the presence of leukocyte esterase and nitrates.

Leukocyte esterase is in enzyme released by leukocytes and represents the presence of pyuria.

Nitrates are metabolic products converted from nitrites by enteric organisms.

Enterococcus and Candida species do not produce nitrates.

Urine culture testing is performed to determine the presence of bacteriuria and anti-microbial susceptibility.

Midstream urine cultures may be incorrectly interpreted because of the potential for contamination of specimens by periurethral microorganisms.

Early studies suggest bacterial culture counts of 10 to the 5th colony forming units per millimeter or higher in midstream urine cultures is predictive of bladder bacteria in asymptomatic women and women with pyelonephritis, while lower counts are more likely to be associated with contamination.

Other studies have shown in patients with symptoms of cystitis proven bacteria with urinary colform-colony counts as low as 10 to the second power CFU per millimeter.

Colony counts of E. coli as low as 10 to 2nd power CFU per milliliter midstream urine is sensitive and specific for the presence of E. coli in symptomatic women (Hooten TM et al).

In the above study enterococci and group B streptococci only rarely caused acute uncomplicated cystitis and was felt to be contaminants of the mid stream collection process.

Majority of nursing home residents with pyuria or bactiuria documented on urinalysis do not manifest symptoms of infection (Nicolle LE et al).

Increased frequency with first-degree relatives with UTI, in non-secretors of blood group substances, with increased frequency of sexual intercourse and increased use of spermicide and diaphragm use.

E. Coli responsible for 80-85% of infections, Staph saprophyticus 5-10% of infections and Proteus mirabilis and Klebsiella responsible for most of the remaining infections.

E. Coli bacteria have P fimbriae that facilitate uro epithelial attachment, even with adequate urine flow.

When bacteria invade the kidney a localized inflammation develops that triggers immune mechanisms through multiple pathways.

Toll-like receptor signaling occurs in the kidney after recognizing the presence of bacteria initiating an immune response involving nuclear factor KappaB and the production of cytokines and chemokines.

Limited renal parenchymal infection is associated with full recovery, however, continued inflammation can lead to scarring.

Infectious Diseases Society of America (IDSA) and the American Medical Directors Association suggest asymptomatic UTIs should not be treated, taking into account the high likelihood of recolonization, potential complications of treatment, including increased incidence of Clostridium difficile, and the risks of causing antibiotic resistance.

IDSA guidelines recommend nitrofurantoin, trimethoprim-sulfamethoxazole and fosfomycin as the first line regimen.

Almost all of the above agents have good clinical efficacy, approximately 90 percent, with relatively favorable adverse effect profiles.

In patients with impaired renal function nitrofurantoin may be a poor choice, since its efficacy diminishes with declining creatinine clearance.

With decreased renal function TMP-SMX should be used judiciously because the antibiotic may induce hyperkalemia.

The previous mainstays of empirical antibiotic therapy for complicated UTIs, such as fluoroquinolones and cephalosporins, are presently not widely recommended because of concerns about resistance.

Carbapenims, have traditionally been reserved for the treatment of multiresistant infections are increasingly being used to treat complicated UTIs.

As the incidence of multidrug resistantance continue to increase and now includes Carbapenim resistance, alternative treatment options are required.

Aminoglycosides are alternative treatment for complicated UTI’s that are caused by multidrug resistant organisms, such as extended spectrum beta lactamase producing Enterobacteriaceae or carbopenem resistant Enterobacteriaceae.

Bacterial strains that are resistant to cephalosporins and carbapenems commonly produce aminoglycoside modifying enzymes, which resulted in resistance to many aminoglycosides.

Asymptomatic bacteriuria should not be treated with antibiotics, except in patients undergoing urologic manipulation and in pregnant women.

Current management in women with uncomplicated infections is empirical use of antibiotics without the use of urine cultures or susceptibility testing.

The current drug of choice in the U.S. for empirical therapy for uncomplicated UTI in women is trimethoprim-sulfamethoxazole.

Urine cultures and sensitivity studies are reserved for patients who are pregnant, or who had symptoms of upper tract disease, have a high risk factor for resistant organisms, or experience therapeutic failure or early relapse.

The management of a complicated infection, demands a thorough evaluation of the urinary tract, to exclude structural or functional abnormalities of clinical importance.

Affects 2% of boys and 8% of girls by age 7 (Hellstrom A).

A prevalence of greater than 3% in febrile infants and children younger than two years.

White girls 10 times more likely to harbor infection than nonwhite girls, and uncircumcised boys almost 8 times more likely to have infection than circumcised boys.

In children UTI associated with long-term morbidity with renal damage in about 5% of cases (Coulthard MG).

Approximately 1/3 of children with a unique key on any have vesicoureteral reflux causes urine flow to be retrograde from the bladder, toward the kidneys during micturition.

Standard practice in evaluation of children with UTI includes voiding cystourethrography to rule out vesicoureteral reflux and treat with daily antibiotics for years.

For children at risk for recurrent UTI, without reflux, long term antibiotics is also recommended.

Long-term risks of infection related scarring in children with previously healthy kidneys is incompletely understood: a few prospective studies show low rate of long-term consequences, while retrospective studies suggest high rates of chronic kidney disease up to 20%, hypertension, 20-40%, and preeclampsia 10 to 20%.

Diabetes is associated with an increased risk of clinically apparent UTI in postmenopausal women.

A combination of dysuria, and urinary frequency without vaginal discharge as a 96% positive prediction value in diagnosing a UTI, and a urinalysis or urine culture can be eliminated.

Bacteria colonize the vagina, perineum and periurethral tissues and ascend to the bladder, commonly after sexual intercourse.

There the bladder invasion by bacteria may lead to a symptomatic urinary tract infection depending upon genetic, biological, and behavioral factors.

Bacteriuria occurs in 10%-15% of hospitalized patients with indwelling catheters.

The risk of urinary tract infection is 3%-5% per day of catheterization.

Symptomatic cystitis is associated with abrupt onset of dysuria, urinary frequency, and urinary urgency.

The likelihood that a patient may experiencing UTI is increased by the presence of hematuria, suprapubic pain, turbid urine, malodorous urine, incontinence, recent intercourse, and recent antibiotic administration.

In a review of 27 randomized clinical trial’s, six systemic reviews, and 11 observational studies: acute uncomplicated cystitis in women can be diagnosed without an office visit or urine culture (Grigoryan L et al).

In the above studies immediate anti-microbial therapy with trimethoprim-sulfamethoxazole, nitrofurantoin or fosfomycin is indicated for acute cystitis in adult women.

Current recommendations for treatment of male urinary tract infections is for 7 to 14 days of antibiotics.

In a study of urinary tract infections in men longer duration of treatment, that is greater than seven days, for outpatients was associated with no reduction in early or late recurrence compared to patients treated with seven days or fewer of antibiotics (Drekonja DM et al).

Prevention strategies include: increased water intake, frequent voiding intervals, low-dose vaginal estrogen in women, and postcoital or chronic antibiotic suppression in women.
Some women attribute UTIs to sexual activity in these patients a single dose of low dose, postcoital antibiotics  as a preventive strategy is effective.

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