Urinary Tract Infection- Causes, Symptom, Diagnosis

Urinary Tract Infection Causes, Symptom, Diagnosis

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Urinary Tract Infection- Causes, Symptom, Diagnosis/ Urinary Tract Infection is a bacterial infection of the bladder and associated structures. These are patients with no structural abnormality and no comorbidities, such as diabetes, immunocompromised, or pregnant. Uncomplicated UTI is also known as cystitis or lower UTI. Forty percent of women in the United States will develop a UTI during their lifetime, making it one of the most common infections in women. UTI is uncommon in circumcised males, and by definition, any male UTI is considered complicated. Many cases of uncomplicated UTI will resolve spontaneously, without treatment, but many patients seek treatment for symptoms. Treatment is aimed at preventing spread to the kidneys or developing into upper tract disease/pyelonephritis, which can cause the destruction of the delicate structures in the nephrons and lead to hypertension.

Treatment of Urinary Tract Infection

Types Urinary Tract Infection

Acute Urethral Syndrome

  • The cardinal symptoms of frequency and dysuria occur in more than 90% of ambulatory patients with acute genitourinary tract infections. However, one-third to one- half of all these patients do not have significant bacteriuria, although most have pyuria.
  • These patients have an acute urethral syndrome which can mimic both bladder and renal infections. Vaginitis, urethritis, and prostatitis are common causes of acute urethral syndrome.[]

Vaginitis

  • The presence of an abnormal vaginal discharge (leucorrhoea) and irritation makes vaginitis the likely cause of dysuria unless a concomitant UTI can be confirmed by culture. Candida albicans, the most common specific cause of vaginitis, can be demonstrated by culture or by finding yeast cells in a Gram-stained smear of vaginal secretions or in a saline preparation with the addition of potassium hydroxide.
  • Trichomoniasis can be documented with a saline preparation that shows the motile protozoa of trichomonas vaginitis. Generally, nonspecific vaginitis is associated with Gardnerella vaginitis. A clue of this diagnosis is the presence of many small Gram-negative bacilli that adhere to vaginal epithelial cells.

Urethritis

  • Acute urinary frequency, dysuria, and pyuria in the absence of vaginal symptoms favor the diagnosis of urethritis or UTI. Chlamydia trachomatis is the common cause of the acute urethral syndrome in women and of nonspecific urethritis in men.
  • Neisseria gonorrhoeae is an important cause of urethritis and dysuria. Herpes simplex virus usually types 2, is another sexually transmitted agent that can cause severe dysuria through ulceration in close proximity to the urethral orifice.
  • The diagnosis of Herpes progenitalis can be confirmed by finding giant multinucleated transformed cells in epidermal scrapings stained with Wright’s stain (Tzanck Smear), by isolating the virus in tissue cultures or by a direct fluorescent antibody test.

Prostatitis

  • Prostatitis is a common problem in men that causes dysuria and urinary frequency in middle-aged and younger men more frequently than urinary tract infection does. Prostate syndromes have classically been divided into four clinical entities
  • Acute bacterial prostatitis
  • Chronic bacterial prostatitis
  • Nonbacterial prostatitis
  • Prostatodynia

Recently, consensus classification of prostatitis syndromes has come up. This classification includes four categories and two subcategories.[]

  • Acute bacterial prostatitis
  • Chronic bacterial prostatitis
  • Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)
  • Asymptomatic inflammatory prostatitis.
  • CP/CPPS has been divided into two sub-categories
  • Inflammatory CP/CPPS; and Non- inflammatory CP/CPPS

Acute Bacterial Prostatitis 

  • The patient often appears acutely ill with the sudden onset of chills and fever, urinary frequency and urgency, dysuria, perineal and low back pain, and constitutional symptoms. Rectal examination should be avoided because of the risk of precipitating sepsis but may disclose a tender, hot and swollen prostate.
  • Microscopic examination of the urine usually displays numerous white cells. Urine culture is usually positive for enteric Gram-negative bacteria and Gram-positive bacteria staphylococci and enterococci are less frequently isolated.

Chronic Bacterial Prostatitis

  • Relapsing UTIs is a hallmark of chronic bacterial prostatitis. Urinary frequency, dysuria, nocturia, and low back and perineal pain are the usual symptoms, although patients may have a minimum of symptoms between UTIs. The patient is often afebrile, does not appear acutely ill, and may have an unremarkable prostate examination. Initially, there is a negative midstream urine examination and culture but after prostate massage, the urine is positive for white blood cells and culture grows a uropathogen.

Nonbacterial Prostatitis

  • This is the most common form of chronic prostatitis. It mimics chronic bacterial prostatitis clinically and displays inflammatory cells on post-prostate massage specimens. However, a bacteriological culture of urine and prostatic secretions are sterile. The etiology is unknown, but some evidence exists for an infectious cause involving organisms that are difficult to culture.

Prostatodynia

  • This has also been referred to as chronic noninflammatory prostatitis. Clinically, it presents with symptoms similar to other forms of chronic prostatitis. It is distinguished by the absence of inflammatory cells or uropathogens from all specimens.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome

  • The traditional classification suggested that the prostate was the cause for some patients (nonbacterial prostatitis), whereas other problems were responsible in others (prostatodynia). The characteristic symptoms for either group were very poorly defined. CP/ CPPS acknowledges the central role of pain complaints in the syndrome. Also, there is inherent recognition that the prostate gland may not be responsible for every patient’s symptoms.

Its two subcategories are as follows

  1. Inflammatory CP/CPPS – The consensus classification considers symptomatic patients without bacteriuria but who have inflammation in their expressed prostate secretions, their voided bladder 3 (VB3) or their semen fluid analysis (SFA), to have inflammatory CP/CPPS.
  2. Noninflammatory CP/CPPS – Patients without inflammation in their expressed prostate secretions, their voided bladder 3 (VB3) or their semen fluid analysis (SFA) are considered to have noninflammatory CP/CPPS.

Asymptomatic Inflammatory Prostatitis

  • The consensus classification also includes a category for patients with objective evidence of prostatic inflammation noted during histological evaluation of prostatic tissue. This diagnosis commonly occurs in patients who have inflammation documented during evaluation of other urologic conditions, for example, prostatic evaluated for a raised prostate-specific antigen.
  • Another example is seminal fluid inflammation noted during evaluation from an infertile couple. The long-term consequences of such asymptomatic inflammation are unknown. Further, only limited data are available on the relative merits of antimicrobial or other therapies for such asymptomatic patients.

Causes Urinary Tract Infection

  • Atypical organisms causing UTI
  • Recurrent infections despite adequate treatment (multi-drug resistant organisms)
  • Infections are occurring in pregnancy (including asymptomatic bacteriuria)
  • Infections are occurring after instrumentation, nephrostomy tubes, ureteric stents or bladder catheters
  • Infections in renal transplant patients
  • Infections are occurring in patients with impaired renal function
  • Infections following prostatectomies, radiotherapy
  • Dysuria, pollakiuria, nycturia (↑)
  • Present or increased incontinence (↑)
  • Macrohematuria (↑)
  • Suprapubic pain (↑)
  • Offensive” smell, turbid urine (↑)
  • Prior infections of the urinary tract (↑)
  • Changed or new discharge, vaginal irritation (↓).

In addition, risk factors are known which increase the probability of UTI. These include

  • Sexual intercourse within the preceding two weeks ()
  • Contraception with a vaginal diaphragm or spermicide ()
  • Contraception with DMPA (depot medroxyprogesterone acetate) ()
  • Antibiotic administration within the preceding two to four weeks ()
  • Special anatomical features or restrictions (for example, from vesicoureteral reflux, neuropathic bladder, mechanical or functional obstruction) ()
  • Diabetes mellitus ().

Treatment of Urinary Tract Infection

Known and possible age-related risk factors for recurrent urinary tract infection (UTI) in women:()

Young and premenopausal women

  • Sexual intercourse
  • Use of spermicide
  • A new sexual partner
  • A mother with a history of UTI
  • History of UTI during childhood

Postmenopausal and elderly women

  • History of UTI before menopause
  • Atrophic vaginitis due to estrogen deficiency
  • Cystocoele
  • Increased post-void urine volume
  • Blood group antigen urine secretory status
  • Urine catheterization and functional status deterioration in elderly institutionalized women

Possible risk factors for recurrent urinary tract infection

  • Immunodeficiency
  • Diabetes mellitus
  • Organ transplants
  • Chronic renal insufficiency
  • Urinary tract abnormality
  • Urinary calculi
  • Urinary tract obstruction
  • Vesicoureteral reflux
  • Increased residual urinary volume
  • Behavioral factors
  • Spermicide use
  • Voluntary deferral of micturition
  • Drinking soft drinks
  • Estrogen deficiency

Symptoms of Urinary Tract Infection

  • Vaginitis or vulvovaginal infections (for example Gardnerella, Candida albicans, Trichomonas, bacterial vaginosis)—ask about or examine for the presence of vaginal discharge
  • Sexually transmitted diseases (ask about sexual activity, recent change of partner)
  • Urethral syndrome is a complex of symptoms that indicate a urinary tract infection but usually without an underlying infection. It is present in at least one-quarter of patients presenting with lower urinary tract symptoms
  • Interstitial cystitis (chronic pelvic pain syndrome of unknown etiology; bladder wall is inflamed and irritated) is diagnosed by ruling out other diseases. The basic criteria are urinary frequency, urgency, or pain for at least six months without a diagnosable etiology
  • Dysmenorrhoea.
  • Common uropathogenic bacteria, including Escherichia coli, multiply within the cytoplasm of bladder epithelial cells during acute cystitis.
  • In relevant animal models, oral antibiotic therapy for acute cystitis does not completely eradicate E. coli from bladder tissue, perhaps enabling same-strain recurrent cystitis.
  • New therapeutics currently in development aim to target adhesive surface factors of E. coli, such as pili; vaccine targets including pili, siderophores and toxins are also being studied.
  • The bladder, rather than representing a sterile environment, may, in fact, host a “urinary microbiome” of commensal organisms that may influence UTI and other symptomatic urinary tract conditions.
  • Recent laboratory advances now permit the modeling of recurrent UTI, ascending renal abscess formation, and catheter-associated UTI in mice.
  • Infections occurring despite the presence of anatomical protective measures (UTI in males are always complicated UTI)
  • Infections occurring due to anatomical abnormalities, for example, an obstruction, hydronephrosis, renal tract calculi, or colovesical fistula
  • Infections occurring due to an immune compromised state, for example, steroid use, post chemotherapy, diabetes, elderly population, HIV)
  • burning with urination
  • increased frequency of urination without passing much urine
  • increased urgency of urination
  • bloody urine
  • cloudy urine
  • urine that looks like cola or tea
  • urine that has a strong odor
  • pelvic pain in women
  • rectal pain in men
  • A strong, persistent urge to urinate
  • A burning sensation when urinating
  • Passing frequent, small amounts of urine
  • Urine that appears cloudy
  • Urine that appears red, bright pink or cola-colored — a sign of blood in the urine
  • Strong-smelling urine
  • Pelvic pain, in women — especially in the center of the pelvis and around the area of the pubic bone
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Diagnosis of UTI

In 2012 the Society for Healthcare Epidemiology of America (SHEA) updated the surveillance definitions of infections in long-term care facilities, based on the growing body of evidence-based literature on infections in older adults living in long-term care facilities. These guidelines incorporated the acute care hospital surveillance definitions of the Centers for Disease Control and Prevention National Healthcare Safety Network. Major changes were made to the diagnosis of UTI for residents both with and without an indwelling urinary catheter. For residents without an indwelling urinary catheter, the diagnosis of UTI in the revised McGeer criteria includes:

Criteria from both 1 and 2

At least 1 of the following subcriteria of signs or symptoms

  • Acute dysuria or acute pain, swelling, or tenderness of the testes, epididymis, or prostate
Or
Fever or leukocytosis and at least 1 of the following localizing urinary tract subcriteria
  • Acute costovertebral angle pain or tenderness
  • Suprapubic pain
  • Gross hematuria
  • New or marked increase in incontinence
  • New or marked increase in urgency
  • New or marked increase in frequency
In the absence of fever or leukocytosis, then 2 or more of the following localizing urinary tract subcriteria
  • Suprapubic pain
  • Gross hematuria
  • New or marked increase in incontinence
  • New or marked increase in urgency
  • New or marked increase in frequency

One of the following microbiological subcriteria

  • At least 105 cfu/mL of no more than 2 species of microorganisms in a voided urine sample
  • At least 102 of any number of organisms in a specimen collected by in-and-out catheter

Microscopic examination of urine

  • In a centrifuged sediment, patients with significant bacteriuria almost always show bacilli in the urine, whereas only approximately 10% of patients with less than 105 CFU per ml show bacteria. About 60-85% of patients with significant bacteriuria have 10 or more white blood cells per high power field in the segment of mid-stream urine. Also 25% of patients with negative urine cultures also have pyuria, 10 or more white blood cells per high power field and only approximately 40% of patients with pyuria have 105or more bacteria per ml of urine by qualitative cultures.

Pyuria

  • 95% of patients with pyuria have a genitourinary tract infection; however, pyuria cannot distinguish a bacterial UTI from the acute urethral syndrome. Tuberculosis,[] analgesic nephropathy, interstitial nephritis, perinephric abscess, renal cortical abscess, disseminated fungal infection and appendicitis may also result in pyuria.

Gram Stain

  • A simple Gram-stained smear can enhance the specificity of the test because morphology and stain characteristics aid in identifying the likely pathogen and in targeting empiric therapy.

Urine Culture

The diagnosis of UTI from simple cystitis to complicated pyelonephritis with sepsis can be established with absolute certainty only by cultures of urine. The major indications for urine cultures are:

  • Patients with symptoms or signs of UTIs
  • Follow-up of recently treated UTI
  • Removal of indwelling urinary catheter
  • Screening for asymptomatic bacteriuria during pregnancy; and
  • Patients with obstructive uropathy and stasis, before instrumentation.

Urine specimens must be cultured promptly within 2h or can be preserved by refrigeration or a suitable chemical additive (boric acid-sodium formate). Acceptable methods of collection are:

  • Midstream urine after careful washing
  • Urine obtained by single catheterization
  • Urine obtained by suprapubic needle aspiration; and
  • Sterile needle aspiration of urine from the tube of a closed catheter drainage system.

Micro-organisms in young men are similar to the organisms that cause uncomplicated infections in women. Enterococci and coagulase-negative staphylococci are more common in elderly men; most likely representing recent instrumentation or catheterization. C. albicans is rarely encountered except in patients with indwelling catheters, nosocomial UTIs or relapsing infections after multiple courses of antibiotics. Although the likely organism and usual susceptible patterns are sufficient to guide initial empiric therapy of uncomplicated UTI, adequate treatment of acute bacterial pyelonephritis and complicated UTIs necessitates precise therapy based on isolation of the causative bacterium and its antimicrobial susceptibility.[]

Imaging Studies

  • In general, imaging should be done 3-6 weeks after cure of acute infection to identify abnormalities predisposing to infection or renal damage or which may affect management.[] Rarely, imaging is carried out in the acute phase, particularly where there is severe loin pain, to identify possible sepsis (pyonephrosis or abscess) or to differentiate acute pyelonephritis from ureteric colic. It is important to recognize that abnormalities will be found in less than 5% of unselected cases.

Plain X-ray of the Abdomen

  • These are used to show the presence and extent of calcification in the urinary tract. They are less sensitive in the detection of ureteric calculi. Plain films are of value in monitoring change in position, size and number of calculi.

Ultrasound

  • Ultrasound (USG) combined with plain X-ray has become the imaging method of choice in patients with recurrent infections. It is a sensitive detector of pelvicalyceal dilatation, indicative of possible obstruction. Echoes within a dilated pelvicalyceal system, either diffuse or layered, suggest the presence of pyonephrosis. Drainage of an obstructed kidney can be guided by ultrasonography. It provides accurate renal length measurements and identifies the majority of renal scars, abscesses and perinephric fluid collections.[]
  • Ultrasound may show short segments of dilated ureter adjacent to the renal pelvis, at pelvic brim level or behind the full bladder. It can also assess the bladder for wall thickness, calculi, diverticula and emptying as well as assess prostate size.

Intravenous Urography

  • Intravenous urography (IVU) provides anatomical detail of the calyces, pelvis and ureter not obtained from ultrasonography. Calyceal detail is essential to diagnose papillary necrosis and medullary sponge kidney and careful assessment of the calyces and overlying parenchyma is necessary to diagnose reflex nephropathy.
  • Gram-negative bacilli have the ability to impede ureteral peristalsis and transient abnormalities of the IVU are common with acute pyelonephritis. These include hydroureter,vesicoureteric reflux, diminished pyelogram, loss of renal outline and renal enlargement. IVU should also be avoided for the first 6-12 weeks after pregnancy to allow resolution of the physiological dilatation of the pelvicalyceal system and ureter.

Computed Tomography

  • CT is the most common method of detecting renal and ureteric calculi, including calculi that are lucent on plain radiographs. It is a sensitive detector of pelvicalyceal dilatations, renal abscesses and perinephric collections than US. Contrast enhanced CT is very sensitive for acute pyelonephritis.[]
  • However, CT involves more radiation than even IVU, the potential risks of contrast media and is more expensive and less readily available than US. Therefore, it should be reserved as a second-line investigation for patients with severe infection not responding to appropriate treatment or for diagnostic problems not resolved by IVU or US.

Static Renal Scintigraphy

Di-mercapto-succinic acid (DMSA) scintigraphy is a sensitive detector of renal parenchymal infection in children.

Indications and Choice of Renal Imaging

Acute infection

  • Patients who have severe loin pain or whose infection does not settle on treatment should have US and plain X-ray to exclude pyonephrosis, intrarenal or perinephric sepsis or calculi. CT may be undertaken if no abnormality is seen on US in such patients. If ureteric colic is suspected, IVU or spiral CT should be used.[]

Imaging After Treatment of Infection

  • In women, there is no indication for imaging following a single or infrequent infection. Recurrent attacks more often than 2 per 6 months should be investigated by USG and plain KUB. In men, UTI is much less common than in women, and imaging is indicated after the first documented bacteriuria to exclude predisposing factors especially impaired bladder emptying. USG and plain film are the best first choice.[]
  • Imaging should be considered if urinary infection is slow to resolve, if there is relapse or if there are risk factors for papillary necrosis. IVU is the method of choice to check for papillary necrosis, medullary sponge kidney or reflux nephropathy. IVU is also indicated in all patients over the age of 40 who have gross hematuria because of the risk of associated cancer.
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Micturating Cystourography

  • MCU is not usually indicated in adults with urinary infection unless they have loin or abdominal pain during voiding, suggestive of reflux or as part of the investigation of impaired bladder emptying.

Urodynamic Studies

  • These may be necessary in patients with unexplained impairment of bladder emptying.

Treatment of Urinary Tract Infection

For effective management of UTI, the following principles must be recognized.

  • Asymptomatic patients should have colony counts greater than or equal to 105 per ml on at least 2 occasions before treatment is considered.
  • Unless symptoms are present, no attempt should be made to eradicate bacteriuria until catheters, stones or obstructions are removed.
  • Selected patients with chronic bacteriuria may benefit from suppressive therapy.
  • A patient who develops bacteriuria as a result of catheterization should be treated to re-establish sterile urine.
  • Efficacy of treatment should be evaluated by urine culture, one week after completion of therapy except in nonpregnant adult women with uncomplicated cystitis and uncomplicated pyelonephritis who respond to therapy.
  • Uncomplicated infections can be diagnosed and treated based on symptoms alone.[rx] Antibiotics taken by mouth such as trimethoprim/sulfamethoxazole (TMP/SMX), nitrofurantoin, or fosfomycin are typically first line.[rx] Cephalosporins, amoxicillin/clavulanic acid, or a fluoroquinolone may also be used.[rx] However, resistance to fluoroquinolones among the bacterial that cause urinary infections has been increasing.[rx]

Antimicrobial prophylaxis regimens and recommend doses from the current guidelines

Antimicrobial agentsContinuous prophylaxis (daily dose) (mg)Postcoital prophylaxis (one-time dose) (mg)
  • Cephalexin
125-250250
125125
  • Nitrofurantoin
50-10050-100
  • Trimethoprim/sulfamethoxazole
40/20040/200-80/400
200200
Oral therapy for mild to moderate infection
First-line drugs (A)*4Daily doseDuration
  • Ciprofloxacin
500–750 mg 2 × daily7–10 days
  • Ciprofloxacin ER
1000 mg 1 × daily7–10 days
  • Levofloxacin
(250–) 500 mg 1 × daily7–10 days
750 mg 1 × daily5 days
Second-line drugs (B) (same clinical efficacy, bacteriologically not as effective as fluoroquinolones)
  • Cefpodoxime proxetil
200 mg 2 × daily10 days
  • Ceftibuten
400 mg 1 × daily10 days
In cases of known pathogen sensitivity (B) (not for empirical treatment)
  • Co-trimoxazole
160/800 mg 2 × daily14 days
  • Amoxicillin/clavulanate
0.875/0.125 g 2 × daily14 days
  • Amoxicillin/clavulanate
0.5/0.125 g 3 × daily14 days
Initial parenteral therapy in severe infection
  • After clinical improvement, in cases with known pathogen sensitivity, oral follow-on treatment using one of the treatment regimes given above may be started. Total treatment duration is 1 to 2 weeks; for this reason, no duration is given for the parenteral antibiotic treatment.
First-line drugs (A)Daily dose
  • Ciprofloxacin
400 mg 2 × daily
  • Levofloxacin
(250–) 500 mg 1 × daily
  • Levofloxacin
750mg 1 × daily
Second-line drugs (B)
  • Cefepime
1–2 g 2 × daily
  • Ceftazidime
1–2 g 3 × daily
  • Ceftriaxone
1–2 g 1 × daily
  • Cefotaxime
2 g 3 × daily
  • Amoxicillin/clavulanate
1/0.2 g 3 × daily
  • Ampicillin/sulbactam
1/0.5 g 3 × daily
  • Piperacillin/tazobactam
2/0.5–4/0.5 g 3 × daily
  • Amikacin
15 mg/kg 1 × daily
  • Gentamicin
5 mg/kg 1 × daily
  • Doripenem
0.5 g 3 × daily
  • Ertapenem
1 g 1 × daily
  • Imipenem/cilastatin
0.5/0.5 g 3 × daily
  • Meropenem
1 g 3 × daily

Asymptomatic Bacteriuria

Pregnancy

  • Pregnancy increases the risk of UTI complications. The rate of prematurity in children born to women who have bacteriuria during pregnancy is increased, and 20-40% of these patients develop pyelonephritis. Successful therapy of these patients with bacteriuria decreases the risk of symptomatic infection by 80-90%.
  • Therefore, all women should be screened twice during pregnancy for asymptomatic bacteriuria. All bacteriuric patients should be treated for seven days, with follow-up cultures to identify relapses. In selecting therapy, risk to foetus should be considered. Amoxicillin or cephalexin usually suffice.[]

Children

  • Asymptomatic bacteriuria in young children and school-aged girls may signify underlying vesicoureteral reflux. Therefore, asymptomatic bacteriuria should be treated with follow-up urologic evaluation after six weeks.

General Population

  • Asymptomatic bacteriuria in men and nonpregnant women, a common condition in the elderly,[] does not appear to cause renal damage in the absence of obstructive uropathy or vesicoureteral reflux and therefore it should not be treated.
  • Instrumentation of genitourinary tract should be avoided in patients with asymptomatic bacteriuria or, if necessary done under the cover of prophylactic antibiotic therapy. Selected high-risk patients (renal transplantation or neutropenia) may benefit from therapy for asymptomatic bacteriuria.

Diabetis Mellitus

  • Patients with asymptomatic bacteriuria who have conditions predisposing to papillary necrosis such as diabetis mellitus must be considered at risk of potentially harmful extension of infection to the kidney which may accelerate interstitial damage. Treatment is similar to that used for sysmptomatic patients.

Uncomplicated Cystitis

  • This is almost exclusively a disease of sexually active women mostly between the ages of 15 and 45 years. Although reinfection is common, complications are rare.

Common Treatment Options for Uncomplicated Cystitis

AntibioticMechanismDosageNotes
  • Nitrofurantoin monohydrate/macrocrystals
Inhibits protein, DNA, RNA, and cell wall synthesis100 mg orally, twice daily for 5 dLow resistance rates and risk of adverse side effects. Similar efficacy compared to a 3-d regimen of trimethoprim-sulfamethoxazole
  • Trimethoprim- sulfamethoxazole
Inhibits nucleic acid synthesis by folate synthesis inhibition160 mg/800 mg (1 double-strength tablet), twice daily for 3 dOnly for use when local resistance rates do not exceed 20% and in patients who do not have sulfa drug allergies
  • Fosfomycin trometamol
Blocks cell wall synthesis by inactivating enolpyruvyl transferase3 g in a single doseMinimal resistance and risk of collateral damage. Inferior efficacy compared to other regimens
  • Pivmecillinam
Disrupts synthesis of cell wall by inhibiting formation of peptidoglycan cross-links400 mg, once daily for 3–7 dLow resistance rates and risk of adverse side effects. Not available in North America

Short Course Therapy

  • Infections truly confined to bladder or urethra respond as well to single-dose or short-course (3 day) therapy as to conventional therapy for 10-14 days. However, it has been observed that three- day therapy is more effective than single-dose therapy.[] A three-day regimen of amoxillin-clavulinate was found to be significantly less effective than a three-day regimen of ciprofloxacin in treating uncomplicated UTIs in women.[]
  • However, resistance has increased to various antimicrobials and more than one quarter of E. coli strains causing acute cystitis are resistant to amoxicillin, sulfa drugs and cephalexin and resistance to co-trimoxazole is now approaching these levels. Resistance to fluoroquinolones is also rising. Thus, knowledge of local resistance pattern is needed to guide empirical therapy.[]

Seven-Day Regimen

  • A longer course of therapy for cystitis should be given to patients with complicating factors that lead to lower success rates and a higher risk of relapse. These factors include a history of prolonged symptoms (more than seven days), recent UTI, diabetes, age above 65 years and use of a diaphragm. Importantly, both elderly and diabetic women frequently have concurrent renal infection, thus short course therapy should not be used in them.

Recurrent Cystitis (re-infections)

Some women especially whose periurethral and vaginal epithelial cells avidly support attachment of coli-form bacteria suffer from recurrent episodes of cystitis in the absence of recognized structural abnormalities of the urinary tract. Management in such women include the following:

  • Post-coital prophylaxis
  • Continuous low dose prophylaxis and
  • Self-administered therapy.

Postcoital prophylaxis is the most helpful for patients who associate recurrent UTIs with sexual intercourse. In these women, a single dose of an antimicrobial after sexual intercourse significantly reduces the frequency of UTIs. Women with recurrent UTIs (more than three UTIs per year) benefit from thrice weekly bed time antibiotic therapy. Such therapy significantly reduces the frequency of episodes of cystitis from an average of 3 per patient-year to 0.1 per patient-year.[] This regimen is known as continues low dose prophylaxis.

Women with fewer than three UTIs per year can be offered self-administered treatment. At the first sign/symptom of a UTI, such women should take a single-dose regimen of TMP-SMX or a fluoroquinolone. This is both effective and well tolerated.[]

  • Several prospective studies have demonstrated the efficacy of either nitrofurantoin 50 mg or nitrofurantoin macrocrystals 100 mg at bed time for prophylaxis against recurrent reinfection of urinary tract. Such a regimen has little if any effect on the faecal flora and presumably acts by providing intermittent urinary antibacterial activity.
  • Perhaps, the most popular prophylactic regimen currently used in women susceptible to recurrent UTI is low-dose TMP-SMX; as little as half a tablet (trimethoprim, 40 mg, sulfamethoxazole, 200 mg) three times weekly at bed-time is associated with an infection frequency of less than 0.2 per patient-year.
  • The efficacy of this prophylactic regimen appears to remain unimpaired even after several years. Similar to TMP-SMX, the fluoroquinolones may be used in a low-dose prophylactic regimen. The efficacy of these regimens is further delineated by their potency in preventing UTI in the far challenging population of kidney transplant recipients.

Acute Bacterial Pyelonephritis

  • In this setting, blood and urine cultures should be obtained.

Out-Patient Therapy

  • For uncomplicated acute pyelonephritis, a fluoroquinolone or co-trimoxazole is the drug of choice for initial therapy. After culture results are available, a full 10-14 day course of the antimicrobial to which the organism is susceptible should be instituted.[]
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In-Patient Therapy

  • Patients who require admission to the hospital should be treated initially with a third-generation cephalosporin or a fluoroquinolone and gentamicin 4-7 mgs every 24 h if the urine shows Gram-negative bacilli on microscopy. If gram-positive cocci are seen in the urine, intra-venous ampicillin 1g every 4 hours should be given in addition to gentamicin, to cover the possibility of enterococcal infection. If no complications ensue and patient becomes afebrile, the remaining two-week course can be completed with oral therapy.

Recurrent Renal Infections (Relapses)

  • Chronic bacterial pyelonephritis is one of the most refractory problems as relapse rates are as high as 90% occur.

Acute Symptomatic Infection

  • The treatment of acute symptoms and signs of UTI in a patient with chronic renal bacteriuria is the same as for patients with acute bacterial pyelonephritis.

Prolonged Treatment

  • Some patients with relapsing bacteriuria respond to six weeks of antimicrobial therapy. This is especially true of patients with no underlying structural abnormality and of men with the normal prostatic examination.

Suppressive Therapy

  • Patients who fail the longer therapy, who have repeated episodes of symptomatic infection or who have progressive renal disease despite corrective measures, are candidates for suppressive antibiotic therapy. These patients should have two to three days of specific high-dose antimicrobial therapy to which their infecting bacteria are susceptible to reduce the colony counts in their urine. The preferred agent for long-term suppression is methenamine mandelate. Alternative therapy is cotrimoxazole, two tablets twice daily or nitrofurantoin 50-100 mg twice daily.[]

Prostatitis

Acute bacterial prostatitis

  • The drug of choice is cotrimoxazole or fluoroquinolone. However, treatment must be ultimately based on an accurate microbiological diagnosis and continued for 30 days to prevent chronic bacterial prostatitis. Urethral catheterization should be avoided. If acute urinary retention develops, drainage should be by supra-public needle aspiration or if prolonged bladder drainage is required by a suprapubic cystostomy tube.

Chronic bacterial prostatitis

  • The hallmark of chronic bacterial prostatitis is relapsing UTI. It is most refractory to treatment. Although erythromycin with alkalinization of urine is effective against susceptible Gram-positive pathogens, most instances of chronic bacterial prostatitis are caused by gram-negative enteric bacilli. Cotrimoxazole or fluoroquinolone is the drug of choice.
  • Approximately 75% of patients improve and 33% are cured with 12 weeks of cotrimoxazole therapy. For patients who cannot tolerate cotrimoxazole or a fluoroquinolone, nitrofurantoin 50 or 100 mg once or twice daily can be used for long-term (6-12 months) suppressive therapy.[]

Nonbacterial chronic prostatitis

  • Therapy is difficult because an exact etiology has not been identified. Owing to a concern for C. trachomatis, Ureaplasma urealyticum and other fastidious and difficult to culture organism, many experts recommended a six- week trial of tetracycline or erythromycin. Symptomatic therapy with NSAIDs and alpha-receptor blockers has also been used.

Catheter-Associated Infection

  • Urinary catheters are valuable devices for enabling drainage of the urinary bladder but their use is associated with an appreciable risk of infection. For a single (in-and-out) catheterization, the risk is small (12%), though this prevalence is much higher in diabetic and elderly women. However, bacteriuria occurs in virtually all patients with indwelling catheters within three to four days unless placement is done under sterile conditions and a sterile, closed drainage system is maintained. The use of a neomycin-polymyxin irrigate does not prevent catheter-associated infection.
  • Catheter-associated bacteriuria should only be treated in the symptomatic patient. When the decision to treat is made, removal of the catheter is an important aspect of therapy, because if an infected catheter remains in place, relapsing infection is very common. The interaction between the organisms and catheter cause the organism to form a biofilm, an area in which antibiotics are unable to completely eradicate these organisms. The empiric therapy of these infections is similar to that of complicated UTIs. Patients who rapidly respond to the therapy may be treated only for seven days.
  • The use of catheters impregnated with antimicrobial agents reduces the incidence of asymptomatic bacteriuria in patients catheterized for less than two weeks. Despite precautions, the majority of patients catheterized for more than two weeks eventually develop bacteriuria.[]

Fungal Urinary Tract Infection

  • The most common form of fungal infection of urinary tract is that caused by Candida species. Such infections usually occur in patients with indwelling catheters who have been receiving broad-spectrum antibiotics, particularly if diabetes mellitus is also present or corticosteroids are being administered.
  • Although most of these infections remain limited to the bladder and clear with the removal of the catheter, cessation of antibiotics and control of diabetes mellitus, the urinary tract is the source of approximately 10% of episodes of candidemia, usually in association with urinary tract manipulation or obstruction.[] Spontaneously occurring lower UTI caused by Candida species is far less common, although papillary necrosis, caliceal invasion and fungal ball obstruction have all been described as resulting from ascending candidal UTI that is not related to catheterization.

Antimicrobial prophylaxis regimens and recommend doses from the current guidelines

Oestrogen

  • Oestrogen use stimulates the proliferation of lactobacillus in the vaginal epithelium, reduces pH and avoids vaginal colonization by uropathogens. After the menopause, estrogen levels and lactobacilli numbers drop; this plays a significant role in the development of bacteriuria and makes post-menopausal women susceptible to UTIs.
  • Vaginal estrogen use reduces RUTIs by 36–75% and has minimal systemic absorption. Based on a Cochrane review in post-menopausal women with RUTIs, when compared to a placebo, vaginal estrogens were found to prevent RUTIs, but oral estrogen did not have the same effect.,
  • Local estrogen cream twice a week and an Oestradiol-releasing vaginal ring are both effective in reducing RUTI attacks.,, They restore vaginal flora, reduce pH and therefore reduce UTIs; however, the reappearance of vaginal lactobacilli takes at least 12 weeks when using an estrogen vaginal ring. Although the evidence does not support using a particular type or form of vaginal estrogen topical creams are cheaper than an Oestradiol-releasing vaginal ring but have more side effects.,,,

Cranberry Juice and Tablets

  • Cranberry juice and tablets have been shown to reduce RUTIs as they contain a compound called tannin, or proanthocyanidin, which reduces E. coli vaginal colonization., Although earlier, smaller studies have shown that consuming cranberry juice or tablets can prevent RUTIs, an updated Cochrane review showed that evidence for its benefit in preventing UTIs is small; therefore, cranberry juice cannot be recommended any longer for UTI prevention.,

Acupuncture

  • Recent studies indicate that the rate of cystitis among cystitis-prone women treated with acupuncture was one-third the rate of that among untreated women and half the rate among women treated by sham acupuncture. Therefore, acupuncture may prevent RUTIs in healthy adult women.,,

Probiotics

  • Probiotics are beneficial microorganisms that could protect against UTIs. Lactobacilli strains are the best-known probiotics and are found in fermented milk products, mainly yogurt. Other probiotics include Lactobacilli bifidobacteriarhamnosuscaseiplanetariumbulgaricus and salivarius; Streptococcus thermophiles and Enterococcus faecium.
  • Reid et al. showed in vitro that lactobacillus can prevent uropathogen infections., Other trials have showed that L. rhamnosus gr-1 and L. fermentum rc-14 can colonise the vagina, which could subsequently prevent UTIs. Nevertheless, more clinical studies need be carried out to determine their role in RUTI prevention.

Immunoprophylaxis

  • Immunoprophylaxis taken orally may prove an effective alternative to antibiotics in the prevention of RUTIs. A meta-analysis of 5 studies showed that oral immunoprophylaxis with the Uro-Vaxom E. coliextract (Terra-Laba, Zagreb, Croatia) taken for a period of 3 months was effective in preventing RUTIs over a period of 6 months. Another double-blind study has confirmed that E. coli extracts are efficient and well-tolerated in the treatment of UTIs, reducing the need for antibiotics and preventing RUTIs.

Other Therapies

  • Methenamine hippurate is used for prophylaxis and treatment of RUTIs. Methenamine is hydrolysed to ammonia and formaldehyde when in acidic urine, which act as a bactericide to some strains of bacteria.
  • They are well-tolerated and have mild adverse effects, such as gastrointestinal upsets, rashes, anorexia, and stomatitis. Patients should be informed regarding adequate hydration, adverse effects and the need to avoid milk products and antacids to help keep the urine acidic.
  • A recent Cochrane review on the use of methenamine hippurate concluded that short-term use is effective in preventing RUTIs in patients with a normal renal tract. Nevertheless, it is not effective in women who have urinary tract abnormalities or a neuropathic bladder.,

References

Urinary Tract Infection Causes, Symptom, Diagnosis

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