Urinary Tract infection- An Evaluation

Ashok Kumar Dept of Biotechnology, Himachal Institute of Life Sciences Rampurghat Road, Paonta Sahib -173025, Himachal Pradesh, INDIA Authors Email: asokumr@gmail.com

Address for Correspondences: Dr. Ashok Kumar C/O Mr. G.K. Rathoure, MAYASHIVRAJ SADAN, Gupta Colony, Railway Ganj Hardoi-241001 (UP) INDIA, Email- asokumr@gmail.com Phone- 05852-223447, Mob- +919450501471, +919548080680

Abstract Urinary Tract Infections (UTIs) are associated with multiplication of organisms in the urinary tract. UTI defined as the microbial invasion of any of the tissues of the urinary tract extending from the renal cortex to the urethral meatus. The urinary tract includes the organs that collect and store urine and release it from the body which include: kidneys, ureter, bladder, urethra and accessory structures. Urine formed in the kidney is a sterile fluid that serves as a good culture medium for proliferation of bacteria. UTI is evident by the presence of 105 microorganisms or of a single strain of bacterium per ml in two consecutive midstream samples of urine. Infections of the urinary tract are the most frequently encountered serious bacteria lillness among febrile infants and children. It is a serious health problem affect in millions of people each year and is the leading cause of Gram-negative bacteremia. The common uropathogen identified in patients with UTI include enteric gram-negative bacteria, with E. coli being the most common followed by Proteus mirabilis, Klebsiella, and Enterococcus. In complicated UTIs, in addition to E. coli, there is a higher prevalence of Pseudomonas, Enterobacter species, Serratia, Acinetobacter, Klebsiella and Enterococcus. Other aerobic gram-negative bacteria of the Enterobacteriaceae family include Citrobacter and Salmonella. The remainder of infections is caused by gram positive coagulase-negative Staphylococcus saprophyticus. UTIs are also the leading cause of morbidity and health care expenditures in persons of all ages. It should be managed by the

Keywords: UTI, renal cortex, bacteremia, uropathogen, health care.

Introduction Urinary tract infection is defined as the colonization of an invasion of the structures in the urinary tract by micro-organisms (Metha et al. 1981). The term UTI refers to infections of the lower urinary tract the bladder and urethra. UTI could be described based on the part of the tract affected, for upper tract it is called Pyelonephritis and the lower part, cystitis (Stamm, 1998). As an anatomical unit, infections of any part can generally spread to its other parts (Roberts, 1967). Urinary tract infection (UTI) is a general term referring to the infection anywhere in the urinary tract. It is generally accepted that infection of the upper urinary tract places the patient at risk for kidney damage, while lower UTI, although a cause of morbidity, does not cause renal damage. There is an estimated 150 million urinary tract infections per annum worldwide. Warren et al., (1990) reported that in the United States, urinary tract infections result in approximately 8 million physician visits per year. Much of this increase has been related to emerging antibiotic resistance in urinary tract pathogens. Urinary Tract Infections (UTIs) is an infection caused by the presence and growth of microorganisms anywhere in the urinary tract. It is perhaps the single most common bacterial infection of mankind (Ebie et al., 2001). (UTIs) are among the most common bacterial infections in humans, both in the community and hospital settings and have been reported in all age groups in both sexes (Hooton et al., 1995). In the United States, it is estimated from surveys of office practices, hospital based clinics and emergency departments that UTIs account for over eight million cases of UTI annually and more than 1 million hospitalizations. The pathogens producing UTI have been said to be mostly derived from the hospital (Tapsal et al., 1975). Although UTIs are not as common in men, they can indicate an obstruction such as a stone or enlarged prostate; they are uncommon in men under age 50. Many women with chronic UTIs are on antibiotics more than off, running the risk of developing dysbiosis and antibiotic resistance.

UTI has become the most common hospital-acquired infection, accounting for as many as 35% of nosocomial infections, and it is the second most common cause of bacteremia in hospitalized patients (Kolawole et al., 2009). Numerous reports have also suggested that UTI can occur in both males and females of any age, with bacterial counts as low as 100 colony forming units (CFU) per millimeter in urine (Akinyemi et al., 1997). This is common in patients with symptoms of acute urethral syndrome, males with chronic prostitutes and patients with in dwelling catheters (Karen et al., 1994). Females are however believed to be more affected than males except at the extremes of life. Untreated upper UTI

in pregnancy carries well documented risks of morbidity and rarely, mortality to the pregnant women (Nice, 2003). Sexually active young women are disproportionately affected. An estimated 40% of women reported having had a UTI at some point in their lives (Kunin, 1994).

Usually, a UTI is caused by bacteria that can also live in the digestive tract, in the vagina, or around the urethra, which is at the entrance to the urinary tract. Women tend to have UTIs more often than men because bacteria can reach the bladder more easily in women. This is partially due to the short and wider female urethra and its proximity to anus. Bacteria from the rectum can easily travel up the urethra and cause infections (Kolawole et al., 2009). Moreover, the main factors predisposing married womento bacteriuria are pregnancy and sexual intercourse (NIH, 2004). Sexual activity increases the chances of bacterial contamination of female urethra. Having intercourse may also cause UTIs in women because bacteria can be pushed into the urethra. This anatomical relationship of the female urethra to the vagina makes it liable to trauma during sexual intercourse as well as bacteria being massaged up the urethra into the bladder during pregnancy/child birth (Duerden et al., 1990). UTI is the second most common clinical indication for empirical antimicrobial treatment in primary and secondary care and urine samples constitute the largest single category of specimens examined in most medical microbiology laboratories (Morgan and McKenzie, 1993). Proteus mirabilis is the microorganism, after E. coli, most frequently associated with urinary tract infection (UTI), particularly in the elderly (Senior, 1979). However, E. coli which is usually confined to the bladder, P. mirabilis appears to have a special predilection for the upper urinary tract (Fairley, 1971). This may lead to stone formation and acute Pyelonephritis. Certain strains of P. mirabilis of a particularproticine sensitivity (p/s) type have been found to be associated more frequently with upper urinary tract infections than bladder infections.

Proteus mirabilis strains also invade the blood stream and give rise to septicemia. This is usually a consequence of a prior urinary tract infection or as a result of catheterization or other surgical manipulation. Proteus bacteraemia are difficult to treat and have a mortality rate of 15- 48 % depending on the severity of the underlying disease. It is not known if P. mirabilis strains which invade the blood stream have special virulence properties and if so, whether these are similar to or different from those associated with upper urinary tract infections. Proteus species, members of the family Enterobacteriaceae are motile Gram

negative enteric bacteria; they are important pathogens of the urinary tract and are the primary infectious agent in patients with indwelling urinary catheters (Warren et al., 1982). The genus originally had four species: Proteus mirabilis, Proteus rettgeri, Proteus morganii and Proteus vulgaris which are the typespecies. The genus is a frequent cause of urinary tract infections, but is not usually a nosocomial pathogen. Individuals suffering from urinary tract infections caused by Proteus mirabilis often develop bacteriuria, cystitis, kidney and bladder stones, catheter obstruction due to stone encrustation, acute Pyelonephritis and fever (Burall et al., 2004). In addition strains of Proteuspenneri can also cause urinary tract infection (Krajden et al., 1984). Several potential virulence actors of Proteus had been studied in relation to its virulence and pathogen city of urinary tract, including hydrolysis of urea byurease, cell invasiveness, cytotoxicity induced by hemolysins, cleavage of IgA and IgG by proteolytic enzyme and adherence to the uroepitheliu mmediated by fimbriae (Coker et al., 2000). Microbial invasion could be facilitated by virulence factors, microbial adherence and resistance to antimicrobials. There are many proposed mechanisms and influencing factors for the invasive properties of P. mirabilis (Korn et al., 1995).

Virulence factors assisted pathogens in invasion and resistance of host defenses. Bacterialproteins with enzymatic activity e.g. protease, hyaluronidase, neuraminidase, elastase, collagenase facilitated local tissue spread. Microbial adherence tosurfaces helps microorganismsestablish a base to penetrate tissues.The adhesive properties in the Entero bacteriaceae were generally mediated by different types of pili (Ofek and Doyle, 1994). Urease could facilitate the colonization of the urinary tract in a mouse model (Jones et al., 1990). The ability of P. mirabilis to express virulence factors, including urease and haemolysin and to invade human urothelial cells is coordinately regulated with swarming differentiation (Liaw et al., 2000, 2001 and 2004). Swarming cell differentiation is thought to be important for thevirulence of P. mirabilis duringurinary tract infections (UTIs) since several virulence factors, including flagellin, urease, the hemolysin HmpA, and the IgA metalloprotease ZapA, are up regulated in the differentiated swarmer cell compared to swimmer cells (Fraser et al., 2002). Extended spectrum -lactamases (ESBLs) that compromise the efficacy of all -lactams byhydrolysis of the -lactam ring (Coque et al., 2008). The genes encoding ESBLs were usually locatedon plasmids that were highly mobileand can harbour resistance genes to several other unrelated classes of antimicrobials (Canton and Coque, 2006).

In the developing countries, the disease has more prevalence due to poor personal hygiene, life style, mal-nutrition and environmental condition. The disease is caused by variety of micro-organisms and at different location of urinary tract system. The urethra and urinary bladder are most frequent sites of infection with in the urinary tract, with the resulting infections referred to as urethritis and cystitis. The kidney is also subject to microbial infections leading to Pyelonephritis. Urinary Tract Infection affects as many as 50% women at least once during their lifetime and 25% of those who acquire UTI, will have recurrent infection within the following six months. Urine located within the urinary tract, excluding the distal region of the urethra is considered sterile in healthy individuals, as indicated by the absence of cultivable bacterial cells. Uropathogenic E. coli is responsible for approximately 85% of community acquired infections, besides Proteus, Klebsiella and Pseudomonas. UTI in pregnancy may be associated with an increase in neonatal mortality and it can also be a source for Gram negative septicemia, which so frequently proves fatal. These infections leave their mark from cradle to the grave and are responsible for many complications. Hence, it is important to diagnose and treat UTI before it produce symptoms, since this would offer the prospect of reducing morbidity.

Infection of the urinary tract is an extremely common clinical problem. The urinary tract can be invaded by a variety of organisms from the normal flora micro organisms in the urinary tract is termed as urinary tract infection, UTI which act as opportunists and by pathogenic species as well. UTI can be categorized in terms of different criteria. Uncomplicated UTI is an infection of the bladder or kidney without any structural or functional abnormality of the urinary tract. Complicated UTI may be developing in patient with diabetes, mellitus, pregnancy, a transplanted kidney or other metabolic or immunogenic illness. Asymptomatic bacteriuria refers to significant bacteriuria in patient without symptoms attributable to the urinary tract. Symptomatic bacteriuria refers to significant in patients with symptoms attributable to the urinary tract. The causes of urinary tract infection are related to poor perineal hygiene, sexual intercourse, pregnancy, urinary tract obstruction, urethral reflux, catheterization, instrumentation and neurogenic bladder but in many instances the pathogenesis is equivalent. Woman with continuous colonization with bacteria were more likely to develop symptomatic infection than those with intermittent or no colonization (O` Grady et al., 1970). Microbiological studies have demonstrated that the urethra, per urethral region and vaginal vestibule of women with recurrent UTIs tend to be more commonly colonized with coliforms bacteria (Flower and Stamey, 1977).

The urinary tract is especially vulnerable to infection during pregnancy because the altered secretions of steroid sex hormones and the pressure exerted by the gravid uterus and bladder cause hypotonic and congestion and predispose to uretero-vesical reflux. Urinary retention after delivery may also initiate or aggravate urinary tract infection (Cunningham, 1990). Almost 10% of the pregnant women suffer from urinary tract infection (Bear, 1976). Dysuria is a common complaint in young women but only 50% to 60% of all dysuria women have bacterial urinary tract infections (Leibavi et al. 1989). In some women, the vaginal introits contain a heavy flora resembling that of the perineum and perianal area. This may be a predisposing factor in recurrent urinary tract infection. Manifestations include burning pain on urination after with turbid foul smelling or dark urine, frequency, and suprapubic or lower abdominal discomfort. There are usually no positive physical findings unless the upper tract is involved also (Culpapper and Andreoli, 1983).

Cystitis is an inflammation of the urinary bladder and is very common, especially among females. Symptoms often include dysuria, difficult or painful urination and pyuria, the presence of leukocytes in the urine). Dysuria and frequency often related to UTI may be produced by mechanical or chemical irritation without any relationship to infection of may be related to infection in the urethra only. Over 40% of symptomatic patients had sterile urine on insignificant bacteria. Cystitis may progress to Pyelonephritis, an inflammation of one or both kidneys. The disease is generally a complication of infection elsewhere in the body. The causative agent is E. coli in about 75% of the cases. Indiscriminate use of drugs and antimicrobial therapy may alter per urethral flora of colonization with enteric organisms. Analgesic nephropathy may produce papillary necrosis and may also mimic bacterial Pyelonephritis on radiography.

Despite the presence of this diverse normal flora, urine usually remains sterile. When pathogens gain access of the system, they can establish infection. The most common aerobic members causing UTI are Escherichia coli, Klebsiella spp., Enterobacter sp., Pseudomonas spp., and Proteus spp. Other bacteria such as Staphylococcus saprophyticus occasionally appear in spontaneous urinary infection. It has been observed that only a small number of serologically distinct strains are responsible for the infections caused by E. coli. It has been observed that the greater dominance of E. coli in outpatient population is serologically distinct strains responsible for the UTI. Many investigators previously described that the

property in 90% of the E. coli strain from patients with Pyelonephritis and demonstrated the ability of mannose resistant hemagglutination only in 41% of the cases. The bacteriuria persisted usually throughout pregnancy and was present six months after delivery in about a 1/3 of the patients (Smith and Bullen, 1965). 78.8% of the E. coli infection in the urine was found in women by Haque et al., (1995). Nahar and Selim (1989) screened the urine samples of adult women. They reported that 70.9% organism was found to be the E. coli. Moreover, in accordance with the previous reports E. coli was found to be the predominant organism. UTI is much more common in women than in men, due to anatomic and physiological reasons (Fihn, 2003). By virtue of its position urinogenital tract is more vulnerable to bacterial infections caused by both internal and external flora. It is not always possible to trace the mode of entry of bacteria into the urinary tract. Many authors have suggested four possibilities which are ascending infection, haematogenous spread and lymphogenous spread and direct extension from another organ. UTI with increased risk include infants, pregnant women and the elderly, as well as those with in dwelling catheters, diabetes and underlying urologic abnormalities (Foxman and Brown, 2003). Incidence of urogenital tract infection in hospital environment is on the rise due to cross infection and lowered immune status of the patients. Furthermore indiscriminate use of antibiotics has resulted in the emergence of drug resistant pathogens. Even though several different microorganisms can cause UTIs, including protozoan parasites, fungi and viruses, bacteria are the major causative organisms and are accountable for more than 95% of UTI cases (Bonadio et al., 2001). Common pathogens that have been implicated in UTIs are primarily gram-negative organisms with Escherichia coli having a more prevalence than other gram-negative pathogens include Klebsiella pneumonia, Enterobacter spp., Proteus mirabilis, Pseudomonas aeruginosa and Citrobacter spp. (Blair, 2007). Some enteric organisms such as Pseudomonas also adhere to the urinary catheter andform a biofilm on the surface, which then acts as are savoir for growth (Shigemura et al., 2006). Anaccurate and prompt diagnosis of UTI is important in shortening the disease course and for preventing the ascent of the infection to the upper urinary tract and renal failure. This problem of persistent urotract infection is more pronounced in rural environment due to insanitary condition, lack of knowledge of personal hygiene, non availability of clinical diagnostic facilities and lack of patients compliance.
rd

Urinary Tract Infection, commonly known as UTI, affects as many as 50% women at least once during their lifetime and 25% of those who acquire UTI have recurrent infection

within the following six months. Urine located within the urinary tract, excluding the distal region of the urethra is considereds terile in healthy individuals, as indicated by the absence of cultivable bacterial cells. Urinary tract infection describes a condition in which there aremicro-organisms established and multiplying within theurinary tract. It is most often due to bacteria (95%), but may also include fungal and viral infection (Cattell, 1996). In general UTI is characterized by the presence of bacteria in bladder urine. Uropathogenic E. coli is responsible for approximately 85% of community acquired infections, besides Proteus, Klebsiella and Pseudomonas. On the basis of the work done by Kass, 105 Colony Forming Units (CFU) of a single species per ml in a clean catch midstream sample of urine is considered as significant bacteriuria (Domann, 2003).

UTI in pregnancy may be associated with an increase in neonatal mortality and it can also be a source for Gram negative septicemia, which so frequently proves fatal (Acharya, 1980). These infections leave their mark from cradle to the grave and are responsible for many complications. Hence it is important to diagnose and treat UTI before it produces symptoms, since this would offer the prospect of reducing morbidity and decrease the work load of costly dialysis and transplant units. The empirical choice of an effective treatment is becoming more difficult as urinary pathogens are increasingly becoming resistant to commonly used antibiotics (Zhanel, 2003).

Urinary tract infection (UTI) is the second most common infectious presentation in community medical practice. Worldwide, about 150 million people are diagnosed with UTI each year, and UTI are classified as uncomplicated or complicated (Stamm, 2001). Uncomplicated UTIs occur in sexually active healthy female patients with structurally and functionally normal urinary tracts. Complicated UTIs are those that are associated with co morbid conditions that prolong the need for treatment or increasethe chances for therapeutic failure. These conditions include abnormalities of theurinary tract that impede urine flow, theexistence of a foreign body e.g., indwelling catheter, stone or infection with multidrugresistant pathogens. UTIs in malepatients are considered complicated.Despite involvement of the upper urinarytract; Pyelonephritis can be considered uncomplicated when it occurs in a healthy patient (Stapleton, 2003). Urinary tract infection may in volveonly the lower urinary tract or both the upper and the lower tracts. The term cystitishas been used to describe the syndrome involving dysuria, frequency, and occasionally suprapubic tenderness. Acute Pyelonephritis describes the clinical syndrome characterized by flank pain or

tenderness or both and fever, often associated with dysuria, urgency and frequency. More than 95% of urinarytract infections are caused by a single bacterial species. E. coli is the mostfrequent infecting organism in acute infection (Jellheden, 1996). Klebsiella, Staphylococci, Enterobacter, Proteus, Pseudomonas and Enterococcus species are more often isolated from inpatients, whereas there is a greater preponderance of E. coli in an out patient population. Corynebacterium urealyticum has been recognized as an important nosocomial pathogen (Soriano, 1990). Anaerobic organisms are rarely pathogens in the urinary tract (Jacobs, 1996). Coagulase negative Staphylococci are a common cause of urinary tract infection in some reports (Mandell, 2005) Staphylococci saprophyticus tends to cause infection in young women of a sexually active age (Schneider, 1996). Despite advances in antimicrobial therapy, UTIs remain a significant cause of morbidity. The

Enterobacteriaceae, were the most frequent pathogens detected, causing 84.3% of the UTIs (Gales et al., 2000). Escherichia coli cause about 85% of community-acquired UTIs, 50%of nosocomial UTI and more than 80% of cases of uncomplicated Pyelonephritis (Bergeron, 1995). A vacuolating cytotoxin expressed by Uropathogenic E. coli, elicits defined damage to kidney epithelium (Guyer et al., 2002). The medically equally important Klebsiella account for6 to 17% of all nosocomial UTIs and show an even higher incidence in specific groups of patients at risk (Bennett et al., 1995). Multiple antimicrobial resistances among gramnegative organisms have been a long term and well-recognized problem with urinary tract infections. Resistance has been observed in multiple genera including Escherichia, Enterobacter, Klebsiella, Proteus, Salmonella, Serratia, and Pseudomonas (Cohen, 1992). Fosfomycin is routinely and effectively used for the treatment of uncomplicated lower urinary tract infections. The frequency of gram-negative enteric bacilli causing urinary tract infections was 41/56 Escherichia coli (73%), 9/56 Klebsiella pneumoniae (16%) and 6/56 Proteus species (11%).Organisms responsible for UTI include Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Staphylococcus and Pseudomonas (Ali, 2000). Nosocomial infections are a problem for the successful therapeutic treatments (Lyon and Skurray, 1987). About 50% of all nosocomialinfections caused by Enterobacteriaceae pertain to urinary tract (Zaman et al., 1999). Previous studies have also demonstrated that Escherichia coli are the most frequent community and hospital acquired UTIs (Brosnema et al., 1993, Weber et al., 1997). Gram negative enteric constitutes a serious problem in urinary tract infection in many parts of the world. UTI has become the most common hospital-acquired infection, accounting for as many as 35% of nosocomial infections, and it is the second most common cause of bacteremia in hospitalized patients (Stamm, 2002). UTI accounts for a significant part of the

work load in clinical microbiology laboratories and enteric bacteria (E. coli) remain the most frequent cause of UTI, although the distribution of pathogens that cause UTI is changing (Ojiegbe and Nworie, 2000). There are several factors and abnormalities of UTI that interfere with its natural resistance to infections. These factors include sex and age disease, hospitalization and obstruction (Epoke et al., 2000). Females are however believed to be more affected than males except at the extremes of life (Akinkugbe et al., 1973). This is as a result of shorter and wider urethra. The anatomical relationship of the females urethra and the vagina make it liable to trauma during sexual intercourse as well asbacteria been massaged up the urethra into the bladder during pregnancy/child birth (Duerdenet al., 1990). UTI is challenging, not only because of the large number of infections that occur each year, but also because the diagnosis of UTI is not always straight forward. Bacterial infections of the urinary tract (UTI) whether hospital acquired or community acquired, occur in all age groups in both genders, and usually require urgent treatment. In males, the prevalence of UTI is about 0.3%, but increases (1340%) in the older age group ( 65 years) because of prostatic diseases and urologic manipulations (Nicolle, 2001). Among young men who develop UTI, homosexuality, as a result of exposure of the urethra to micro-organisms (E. coli) during receptive rectal intercourse, lack of circumcision and human immunodeficiency virus (HIV) infection is recognized risk factors (Spach, 1992). In sexually active women between the ages of 1635years, the prevalence of UTI is between 2050% (Bukharie, 2001), and the major risk factors among this age group appear to besexual intercourse and the use of contraceptive devices such as the diaphragm and spermicide (Strom, 1987). Among elementary school boys, UTI is rare, but among school girls, it is approximately one percent (Gillenwater, 1979). Urinary pathogens from hospitalized and community patients have included strains that are resistant to many commonly prescribed antimicrobials.

Acknowledgments The author is thankful to K.P. Rathoure (Mrs) for valuable comments and technical support.