Urinary Tract Infections

DR-AHMED ALAHNOUMI

Definitions

Urinary tract infection (UTI) is the most common of all bacterial infections; it affects persons throughout their life span. The term UTI reperesent a variety of clinical entities, ranging from asymptomatic bacteriuria to cystitis, prostatitis, and pyelonephritis. UTIs may be further characterized as uncomplicated (occurring without an anatomic or other predisposing reason) or complicated (associated with structural or functional abnormalities of the urinary tract and kidney) and as community acquired or nosocomial (generally, catheter associated).

Recurrent UTI

Complicated infections - underlying abnormality that predisposes patient to UTI or makes UTI more difficult to treat effectively

Recurrent Infections
Relapse - recurrence of infection by same organism after discontinuation of treatment Reinfection - recurrence of infection by a different organism after discontinuation of treatment

Predisposing factors

Sexual activity in females Elderly males: prostatic hypertrophy Young children with inherited defect, e.g. vesico-uretic reflux Pregnancy Catheterisation Surgery, e.g. prostatectomy Diabetes mellitus

Epidemiology and Risk Factors

UTI occurs far more commonly in females than in males, except at the extremes of age ( Table 1 ). During the neonatal period, the incidence of UTI is slightly higher in males than in females because of the greater frequency of congenital anomalies of the urinary tract in male infants. After 50 years of age, the incidence of UTI is almost as high in men as in women, presumably because of obstruction from prostatic hypertrophy. In persons between 1 and about 50 years of age, UTI is predominantly a disease of females.

Women

As many as 50% to 80% of women in the general population acquire at least one UTI during their lifetime; most of these infections are uncomplicated cystitis. Sexually active women are more affected . The incidence of acute uncomplicated pyelonephritis is less common than cystitis . Factors independently associated with pyelonephritis included frequency of sexual intercourse, having a new sexual partner, UTI in the past 12 months, maternal history of UTI, diabetes, and incontinence. Thus, many of the factors predisposing women to cystitis also increase the risk of pyelonephritis.

Young Men

UTI is rare in young men and has traditionally been attributed to the presence of urologic abnormalities. However, it is apparent that uncomplicated UTI can occur in men who acquire uropathogens through direct sexual contact, in the form of unprotected vaginal intercourse with a woman whose vagina is colonized with uropathogens. Lack of circumcision is also associated with an increased risk of UTI, because of an increased incidence of Escherichia coli colonization of the glans and prepuce and the subsequent migration of E. coli to the urinary tract.

Pregnancy

The incidence of asymptomatic bacteriuria in pregnant women is approximately 4% to 10%, which is similar to the rate reported in sexually active nonpregnant women of childbearing age. If not treated, 20% to 40% of pregnant women with bacteriuria in the first trimester will acquire acute pyelonephritis later in pregnancy. Treatment of asymptomatic bacteriuria would lead to approximately a 75% reduction in the incidence of pyelonephritis. Premature births and perinatal mortality are increased in pregnancies complicated by UTI.

Diabetes

The rates of asymptomatic bacteriuria and UTI in diabetic women are twofold to threefold higher than those in nondiabetic women; these differences have not been observed in men. In hospitalized diabetic patients, particularly those with multiple-organ complications, the incidence of infection and true pyelonephritis also appears to be increased, partly because of poor bladder function and urinary catheterization. Other clinical conditions causing obstruction in urinary flow or incomplete voiding also predispose diabetic patients to infection. In addition, impaired cytokine secretion may contribute to asymptomatic bacteriuria in diabetic women.

Etiology

The spectrum of organisms causing UTI varies by clinical syndrome. In acute uncomplicated cystitis, the etiologic agents are highly predictable: E. coli accounts for 75% to 90% of isolates; Staphylococcus saprophyticus accounts for 5% to 15% of isolates (particularly in younger women); and Klebsiella species, Proteus species, enterococci, and other organisms account for 5% to 10% of isolates. The spectrum of agents that cause uncomplicated pyelonephritis is less well studied than, but is similar to, that which causes acute cystitis. In complicated UTIs, E. coli remains the predominant organism. Other aerobic gram-negative rods, such as Klebsiella species, Proteus species, Citrobacter species, Acinetobacter species, Morganella species, and Pseudomonas aeruginosa are also frequently isolated. Gram-positive bacteria, such as enterococci, S. aureus, and S. epidermidis, as well as yeast, are also important pathogens in complicated UTI.

Pathogenesis

Bacteria can establish infection in the urinary tract by traveling from the urethra to the bladder and then up the ureter to the kidney. Abnormal micturition, a significant residual urine volume, or both will promote true infection. There are also acquired and intrinsic host factors, as well as bacterial virulence factors, which increase the likelihood of development of UTI. Bacteria can also gain access to the urinary tract through the bloodstream. Hematogenous spread accounts for fewer than 2% of documented UTIs and usually results from bacteremia caused by relatively virulent organisms, such as Salmonella and S. aureus. Hematogenous infections may produce focal abscesses or areas of pyelonephritis within a kidney and result in positive urine cultures.

Genito-Urinary tract

13

Genetic Factors

There is increasing evidence that genetically determined factors may influence susceptibility to recurrent UTI. Women with recurrent UTI demonstrate a propensity for persistent vaginal colonization with E. coli, even during asymptomatic periods. Vaginal and periurethral mucosal cells from women with recurrent UTI bind threefold more uropathogenic bacteria than do mucosal cells from women without recurrent infection.

Bacterial Virulence

Certain strains of E. coli possess chromosomally encoded virulence determinants that confer the ability to infect the anatomically normal urinary tract and produce acute inflammatory disease (e.g., cystitis and pyelonephritis). Characteristics that have been associated with uropathogenicity are the presence of certain O and K surface antigens (the O antigen is the outer polysaccharide portion of the bacterial envelope, and the K antigen is the antiphagocytic capsular antigen). the presence of the siderophore aerobactin, resistance to the bactericidal activity of serum, the ability to produce toxins such as hemolysin and cytotoxic necrotizing factor, and certain intracellular metabolic capabilities.

Also important is the presence of adhesins on the surface of uropathogenic bacteria that mediate binding to specific receptors on the surface of uroepithelial cells. The best-studied adhesion structure is the P fimbriae, which are hairlike protein structures found on the surface of certain pathogenic strains of E. coli. P fimbriae interact with a specific receptor on epithelial cells. Another adhesion structure is the type 1 pilus (fimbria), which all E. coli strains possess. Type 1 pili are also thought to play a key role in initiating E. coli bladder infection;

Diagnosis
Clinical Presentations and Laboratory Findings

The clinical presentation of UTI is quite variable, ranging from asymptomatic bacteriuria to typical symptomatic cystitis to acute pyelonephritis. In addition, clinical symptoms do not always correlate with the site of infection (bladder versus kidney) or with the degree of bacteriuria. Approximately 30% of patients with lower urinary tract symptoms also have silent infection of the kidney. Despite considerable effort, researchers have been unable to develop a noninvasive technique for differentiating renal infections from bladder infections. The best noninvasive test to delineate the anatomic site of infection appears to be the response to short-course antibiotic therapy .

Radiologic Evaluation to Rule out Functional Abnormalities

A final consideration in the management of UTI is the role of radiologic evaluation. Intravenous pyelography, ultrasonography, or CT should be carried out expeditiously to rule out obstruction in any patient with acute pyelonephritis who does not respond to an effective antimicrobial agent and in any patient in whom a persistent bacteremia has been demonstrated. Contrast-enhanced helical CT is the radiologic study of choice for imaging and evaluation of renal infections. The study should be performed without contrast when renal calculi are suspected. For ambulatory patients who have UTI, guidelines are less clear. Radiographic evaluation, usually with intravenous pyelography and voiding cystourethrography, is carried out for delineation of surgically correctable lesions that might predispose patients to recurrent infection or progressive renal disease. Because congenital anatomic anomalies are particularly prevalent in young children who have a first or second UTI, such studies are obligatory for patients in this age group. In addition, careful prostatic examination and assessment of postvoiding residual urine volume should be considered in males with UTI at any stage of life because such infection is highly unlikely in this population unless anatomic anomalies or specific risk factors are present(see "Young Men"). In women with uncomplicated UTI, the incidence of correctable anatomic lesions is so low that radiologic and urologic evaluation should be restricted to patients who have rapid recurrence of infection or recurrent pyelonephritis despite adequate therapy.

Cystitis

The typical symptoms of cystitis are dysuria, urinary frequency, and urgency. Nocturia and suprapubic or back discomfort are also often present. In addition, the urine may be cloudy, malodorous, or bloody. Laboratory : dipstick testing, the presence of leukocyte esterase, nitrite, or both has about 75% to 90% sensitivity and 70% to 82% specificity, PH elevated, blood may be seen. U/S is facultative exam .(to exclude functional abnormality , stones or tumor and to estimate P.V.R.) Urine analysis Urine culture , if not response to antibiotics or in case of recurrent infection .

Pyelonephritis
Clinical presentation :
Patients with pyelonephritis can present with clinical manifestations that range from mild to relatively severe -- from low-grade fever with lower back or costovertebral angle pain to fever, shaking chills, nausea, vomiting, and loin pain . Symptoms are generally acute in onset and may or may not be associated with symptoms of cystitis . Physical examination : The patients have costovertebral angle tenderness on deep palpation. Tachycardia may accompany fever.

Lab. Finding :

Pyuria and bacteriuria are usually demonstrable on urine microscopy and Gram stain. Bacteremia may complicate the course of pyelonephritis. In patients with pyelonephritis, bacteremia is seldom associated with the more serious sequelae of gram-negative infection (i.e., triggering of the complement, clotting, and kinin systems), which may lead to septic shock, disseminated intravascular coagulation, or both. When shock or disseminated intravascular coagulation occurs, the possibility of obstruction must be considered.

Complicated pyelonephritis

In a particularly serious form of obstructive uropathy associated with acute papillary necrosis, the sloughed papillae may obstruct the ureter. This should be suspected in diabetic patients who have severe pyelonephritis and persistent bacteremia despite antibiotic therapy. Papillary necrosis may also be evident in some cases of pyelonephritis complicated by obstruction, sickle cell disease, analgesic nephropathy, or combinations of these conditions. Emphysematous pyelonephritis, which is a particularly severe form of pyelonephritis associated with production of gas in renal and perinephric tissues, occurs almost entirely in diabetic patients.

Renal and Perirenal Abscesses

Two unusual forms of UTI are macroscopic renal and perirenal abscesses. In the past, most of these abscesses were secondary to hematogenous infection with S. aureus. Currently, most of them are secondary to ascending UTI with the usual Enterobacteriaceae organisms . Such infections are often complicated by renal calculi and obstruction of urinary flow from either the kidney or the ureter. Less commonly, preexisting renal cysts become infected and develop into abscesses. In rare instances, there is contiguous spread from a neighboring site of suppuration, such as the colon or overlying rib . The usual presentation of such infections is insidious, with chronic fever, weight loss, night sweats, and anorexia, and is often associated with flank or back pain. When the abscess is under pressure, usually because of obstruction, a more acute presentation with associated bacteremia may occur. Symptoms specific to the urinary tract, such as dysuria, hematuria, and urinary retention, are sometimes noted but are often absent. On physical examination, costovertebral angle tenderness or even a palpable mass may be found; in 30% to 50% of patients, however, this finding is absent.

Routine laboratory tests are of variable value in patients with renal or perirenal abscesses: leukocytosis may be present, anemia is not unusual, and signs of inflammation (e.g., pyuria or proteinuria) may be evident on urinalysis. In more than half of patients with renal or perirenal abscesses, the organism in the abscess may be isolated on urine culture. Definitive diagnosis, however, depends on radiographic detection of a mass lesion. Gallium and ultrasound scans may be helpful, but a computed tomographic or magnetic resonance imaging scan is considered the diagnostic test of choice. If prompt drainage and antibiotic therapy are not provided, renal or perirenal abscesses may extend to the peritoneal cavity, chest, or skin.

Prostatitis

A common complication of UTI in men is prostatitis. Bacterial prostatitis is usually caused by the same gram-negative bacilli that cause UTI in females; 80% or more of such infections are caused by E. coli. The pathogenesis of this condition is poorly understood. Antibacterial substances in prostatic secretions probably protect against such infections. Classifying prostatitis into three syndromes: acute bacterial prostatitis, chronic bacterial prostatitis, and chronic pelvic pain syndrome (CPPS). Acute bacterial prostatitis is a febrile illness characterized by chills; dysuria; urinary frequency and urgency; and perineal, back, or pelvic pain. Bladder outlet obstruction may occur. On physical examination, the prostate is found to be enlarged, tender, and indurated. Pyuria is present, and urine cultures generally grow E. coli or another typical uropathogen.

Chronic bacterial prostatitis is a clinically more occult disease and may be manifested only as recurrent bacteriuria or variable low-grade fever with back or pelvic discomfort. Urinary symptoms usually relate to the reintroduction of infection into the bladder, with both pyuria and bacteriuria being present; a chronic prostatic focus is the most common cause of recurrent UTI in men. CPPS describes the large group of men who present with minimal signs on physical examination but have a variety of irritative or obstructive voiding symptoms; perineal, pelvic, or back pain; and sexual dysfunction. These men can be divided into those with and those without inflammation (defined as > 10 white blood cells per highpower field in expressed prostatic secretions). The etiology and appropriate management in these patients, regardless of inflammatory status, is unknown.

ACUTE EPIDIDYMITIS

Reflux of sterile urine from the urethra through the vasdeferent is the common cause anther factor is trauma. It can be divided in 2 groups.. sexually transmitted disease (C.trachomatis and N.gonorrhoe ) primirly not sexually transmitted form associated with U.T.I. and prostatitis ( the most pathogens are intero bacteriacea or pseudomonas ) clinical finding:the epididumitis may follow sever physical strain ( e.g. lifting a heavy object ) or considerable sexual excitement. History of urethritis or prostatitis or after urethral instrumentation, prostatic surgery sever pain develop suddenly in the scrotum and may radiate a long the spermatic cord and even reach the flank . swolling and redness of the scrotum, fever may reach 40 degree C. LABORATORY FINDING: Hemogram ----- leukocytosis Urine analysis and urine culture are positive.

TREATMENT:

IN sexual transmitted epididymitis ceftriaxon 250 mg i.m. single dose + doxycycline 100mg 2/d for 21dys For gono, epid. Ciproflxacine 500mg twice /d for 21days.

Management of U.T.I. Antimicrobial Therapy

In general, antimicrobial therapy is warranted for any symptomatic infection of the urinary tract. The choice of antimicrobial agent, dose, and duration of therapy depends on the site of infection and the presence or absence of complicating conditions. Therefore, each category of UTI merits a different approach on the basis of the particular clinical syndrome that is present.

Treatment Regimens for Acute Uncomplicated Cystitis*

*Characteristic pathogens are Escherichia coli (85% to 90%) and Staphylococcus saprophyticus (5% to 15%); other organisms, which account for < 5% of cases, are Proteus mirabilis, Klebsiella pneumoniae, and Enterococcus species. Treatments listed are those to be prescribed before the etiologic agent is known (Gram stain can be helpful); regimens can be modified once the agent has been identified. Optimal empirical regimen may differ among settings because of differences in the antimicrobial susceptibility profiles of uropathogens. Fluoroquinolones should not be used in pregnancy. Although TMP-SMX is classified as pregnancy category C, it is widely used; however, avoid use of this drug in the first and third trimesters of pregnancy. TMP-SMX = trimethoprim-sulfamethoxazole

If a patient is still symptomatic after therapy, urine culture is necessary (Figure 2). If the culture is negative, a 2-day course of the urinary tract analgesic phenazopyridine, 200 mg three times daily after meals, can be prescribed. A pelvic exam for evaluation of alternative diagnoses such as chlamydial, gonococcal, or herpetic infection should be considered, and close clinical follow-up is recommended. If testing shows pyuria but not bacteriuria, pelvic examination for alternative diagnoses should be performed. If the patient has both pyuria and bacteriuria, the antimicrobial susceptibility of the infecting strain should be assessed for resistance and an alternative agent should be given. Finally, a patient who is symptomatic after a short-course regimen and has persistent infection with a uropathogen that is sensitive to the antibiotic used should be regarded as having covert renal infection. In this circumstance, a 14-day course of a fluoroquinolone or TMP-SMX is indicated.

Figure 2.Clinical Approach to Uncomplicated Cystitis. Clinical approach to acute uncomplicated cystitis in a woman

Treatment of Relapsing Infection.

The approach to the minority of patients with relapsing infection, as evidenced by finding the same bacterial strain in a UTI that occurs within 2 weeks after completion of antimicrobial therapy, is very different from the management of reinfection. Two factors may contribute to the pathogenesis of relapsing infection in women: deep-tissue infection of the kidney that is suppressed but not eradicated by a 14-day course of antibiotics, and structural abnormality of the urinary tract, particularly calculi. Patients with true relapsing UTIs should undergo radiologic or urologic evaluation and should be considered for longer-term therapy.

Acute Uncomplicated Pyelonephritis

Two requirements guide the initial choice of antimicrobial regimens for pyelonephritis: the probability that the infecting organism is sensitive to the regimen should be at least 99%, and therapeutic blood levels should be quickly achievable. Depending on the severity of illness and the presence of comorbid conditions, pyelonephritis can be initially managed with oral outpatient therapy or with parenteral inpatient therapy. Patients with mild disease (low-grade fever and no signs of sepsis) who are otherwise healthy and do not have significant nausea or vomiting can be managed as outpatients with an oral fluoroquinolone or TMP-SMX (see Figure 3 and Table 4 ).

Figure 3.Clinical approach to acute uncomplicated pyelonephritis in a woman

Table 4. Treatment Regimens for Acute Pyelonephritis

UTI During Pregnancy

There are three major differences between the approach to UTI in pregnant women and that in nonpregnant women. First, in pregnant women, asymptomatic bacteriuria is actively sought and is as aggressively treated and followed as symptomatic infection; this is clearly not the case in nonpregnant women, for whom screening for asymptomatic bacteriuria is not recommended. Second, although short-course therapy is also the cornerstone of treatment during pregnancy for patients with uncomplicated cystitis (as well as those with asymptomatic bacteriuria), the drugs that can be safely used are far more limited for pregnant women. Third, follow-up of patients with bacteriuria during pregnancy is more intense, with a more rapid deployment of prophylactic strategies in pregnant women with recurrent bacteriuria.

Nitrofurantoin, ampicillin, and the cephalosporins have been considered relatively safe in early pregnancy. Nitrofurantoin, ampicillin, and the cephalosporins have been used most extensively in pregnancy and are the regimens of choice for the treatment of asymptomatic or minimally symptomatic UTI ( Table 3 ). For pregnant women with overt pyelonephritis, admission to the hospital for parenteral therapy should be the standard of care; lactams with or without aminoglycosides are the cornerstone of therapy. Prevention of UTI, including pyelonephritis, can be accomplished during pregnancy with nitrofurantoin or cephalexin taken prophylactically after coitus or at bedtime without relation to coitus. Such prophylaxis should be considered for patients who have had acute pyelonephritis during pregnancy, patients with bacteriuria during pregnancy who have had a recurrence after a course of treatment, and patients who had recurrent UTI before pregnancy that required prophylaxis.

Treatment of Men With UTI

It is uncommon for men to have UTI that is analogous to acute uncomplicated cystitis in women. Even when seemingly uncomplicated UTI does occur, men should never be treated with short-course therapy, because of a high rate of early relapse. Instead, 7- to 14-day regimens of a fluoroquinolone should be prescribed. TMP-SMX is the best alternative drug, assuming susceptibility of the strain.

In men older than 50 years with UTI, bacterial invasion of the prostate and possibly the kidneys should be considered, even in the absence of overt signs of infection at these sites. Acute bacterial prostatitis should be treated with a fluoroquinolone for 2 weeks or with TMP-SMX for at least 4 weeks. Recurrence is common and usually connotes a sustained focus in the prostate that has not been eradicated. Several factors make eradication of prostatic foci difficult. In view of these factors, intensive therapy for at least 4 to 6 weeks is recommended for chronic bacterial prostatitis. The drugs of choice for this purpose are the fluoroquinolones. The best alternative agent is TMP-SMX. Most therapeutic failures result from either anatomic factors or infection by Enterococcus faecalis or P. aeruginosa ; these two organisms are particularly likely to cause relapse after treatment with the antimicrobial agents currently recommended. Relapses should be treated for 12 weeks. If this therapy fails, long-term antimicrobial suppression or repeated treatment courses for each relapse are often needed.

Complicated UTI

Complicated UTI occurs in a heterogeneous group of patients with a wide variety of structural and functional abnormalities of the urinary tract and kidneys. The range of microbial species and their susceptibility to antimicrobial agents are likewise heterogeneous. As a consequence, therapy for patients with complicated UTI requires individualization, although the following guidelines appear to be useful.

As a rule, only symptomatic UTI requires therapy. If symptoms of UTI are present, a urine culture and susceptibilities should always be obtained. If the antimicrobial susceptibilities of the infecting organism are not known and symptomatic infection requires immediate therapy, consideration of previous microbiology or recent antimicrobial exposures can help guide initial empirical therapy. In patients with mild disease (see "Pyelonephritis"), an oral regimen with a fluoroquinolone, or possibly TMP-SMX, is appropriate and can be given in the outpatient or inpatient setting depending on other patient factors. In patients who cannot take oral regimens or who have more severe disease, intravenous therapy with fluoroquinolones or broad-spectrum agents such as ampicillin plus gentamicin, imipenem-cilastatin, or piperacillin-tazobactam should be considered until the susceptibilities of the invading organism are identified ( Table 4 ). Whenever possible, every effort should be made to correct the underlying complicating factor in conjunction with the antimicrobial therapy.

Genito-urinary tract Candida

The appearance of Candida in the urine is an increasingly common complication of indwelling catheterization, particularly for patients in the intensive care unit, on broad-spectrum antimicrobials, or with underlying diabetes mellitus. C. albicans is still the most common isolate, although C. glabrata and other non- albicans species are also frequently isolated. The clinical presentation can vary from an asymptomatic laboratory finding to sepsis. In asymptomatic patients, removal of the urethral catheter results in resolution of the candiduria in as many as one third of cases. For patients with symptomatic candiduria (fever with or without cystitis symptoms), oral fluconazole, 200 mg/day for 7 to 14 days, has been shown to be highly effective. For more severely ill patients, the possibility of pyelonephritis and candidemia should be evaluated, and systemic antifungal therapy with fluconazole, 6 mg/kg/day, or amphotericin, 0.6 mg/kg or more a day, should be instituted.

Asymptomatic Bacteriuria

Bacteriuria detected in the absence of symptoms referable to the urinary tract does not warrant antimicrobial therapy except in specific settings. These include during pregnancy, before surgery or instrumentation of the urinary tract, and after renal transplantation. Treatment of asymptomatic bacteriuria in patients who are immunosuppressed because of transplantation other than renal (i.e., other solid organ or bone marrow) or because of neutropenia has not been well studied and is not currently recommended as standard practice. In women with diabetes and asymptomatic bacteriuria, no need treatment .