Uropathogenic Escherichia coli (UPEC) is a causative agent in the vast majority of urinary tract infections (UTIs), including cystitis and pyelonephritis, and infectious complications, which may result in acute renal failure in healthy individuals as well as in renal transplant patients. UPEC expresses a multitude of virulence factors to break the inertia of the mucosal barrier. In response to the breach by UPEC into the normally sterile urinary tract, host inflammatory responses are triggered leading to cytokine production, neutrophil influx, and the exfoliation of infected bladder epithelial cells. Several signaling pathways activated during UPEC infection, including the pathways known to activate the innate immune response, interact with calcium-dependent signaling pathways. Some UPEC isolates, however, might possess strategies to delay or suppress the activation of components of the innate host response in the urinary tract. Studies published in the recent past provide new information regarding how virulence factors of uropathogenic E. coli are involved in activation of the innate host response. Despite numerous host defense mechanisms, UPEC can persist within the urinary tract and may serve as a reservoir for recurrent infections and serious complications. Presentation of the molecular details of these events is essential for development of successful strategies for prevention of human UTIs and urological complications associated with UTIs.

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Role of Uropathogenic Escherichia coli Virulence Factors in Development of Urinary Tract Infection and Kidney Damage.

BACKGROUND Acute pyelonephritis is a potentially severe disease for which there are few population-based studies. We performed a population-based analysis of trends in the incidence, microbial etiology, antimicrobial resistance, and antimicrobial therapy of outpatient and inpatient pyelonephritis. METHODS A total of 4887 enrollees of Group Health Cooperative, based in Seattle, Washington, who received an International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis of acute pyelonephritis from 1997 through 2001 were identified using computerized records. Diagnoses were linked to urine culture and antibiotic prescription data. Case patients (n=3236) included subjects who had received an inpatient or culture-confirmed outpatient diagnosis of acute pyelonephritis. RESULTS Among the female population, annual rates of outpatient and inpatient pyelonephritis were 12-13 cases per 10,000 population and 3-4 cases per 10,000 population, respectively; among the male population, the rates were 2-3 cases per 10,000 population and 1-2 cases per 10,000 population, respectively. Rates were relatively stable from year to year. Incidence was highest among young women, followed by infants and the elderly population. The ratio of outpatient to inpatient cases was highest among young women (ranging from 5 : 1 to 6 : 1). Escherichia coli caused 80% of cases of acute pyelonephritis in women and 70% of cases in men and was less dominant in older age groups. Among E. coli strains, the rate of ciprofloxacin resistance increased from 0.2% of isolates to 1.5% of isolates (P=.03), and the rate of trimethoprim-sulfamethoxazole resistance decreased from 25% of isolates to 13% of isolates (P<.01) from 1997 to 2001. Among outpatient cases, the rate of fluoroquinolone use increased from 35% to 61%, whereas the rate of trimethoprim-sulfamethoxazole use decreased from 53% to 32% over the 5-year period (P<.01). CONCLUSIONS This comprehensive, population-based analysis adds to our limited knowledge of the epidemiology of acute pyelonephritis, especially among outpatients, in whom the majority of cases now occur.

Population-Based Epidemiologic Analysis of Acute Pyelonephritis

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. Disproportionately affecting women, UTIs exact a substantial public burden each year in terms of direct medical expenses, decreased quality of life, and lost productivity. Increasing antimicrobial resistance among strains of extraintestinal pathogenic E. coli challenges successful treatment of UTIs. Community-acquired UTIs were long considered sporadic infections, typically caused by the patients’ native gastrointestinal microbiota; however, the recent recognition of UTI outbreaks with probable foodborne origins has shifted our understanding of UTI epidemiology. Along with this paradigm shift come new opportunities to disrupt the infection process and possibly quell increasing resistance, including the elimination of nontherapeutic antimicrobial use in food-animal production.

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Foodborne urinary tract infections: a new paradigm for antimicrobial-resistant foodborne illness.

Prevalence of urinary tract infection in febrile infants

OBJECTIVE: Urinary tract infections (UTIs) in childhood are considered a risk for chronic kidney disease (CKD), but this association is poorly verified. We wanted to determine the etiologic fraction of UTIs in childhood as a cause of CKD. METHODS: A systematic literature search on the association between childhood UTIs and CKD was conducted, and data for patients with CKD in the area of 1 tertiary care hospital were reviewed. RESULTS: In our literature search, we found no patients among the 1576 reviewed cases for whom childhood UTIs were the main cause of subsequent CKD. However, there were 3 patients with childhood UTIs for whom the results of kidney imaging studies were not reported. Of the 366 patients with CKD who were monitored in the Oulu University Hospital, 308 had a specific noninfectious cause of CKD. Of the remaining 58 patients, 13 had a history of UTIs in childhood. In their first imaging studies, all of those 13 patients demonstrated kidney tissue abnormalities, which could have been observed through ultrasonography. Recurrent UTIs in childhood were possibly the cause of CKD in 1 case; therefore, the etiologic fraction of recurrent childhood UTIs as a main cause of CKD was, at most, 0.3%. CONCLUSIONS: In the absence of structural kidney abnormalities evident in imaging studies after the first childhood UTI, the etiologic fraction of recurrent childhood UTIs as a main cause of CKD seems to be small. A child with normal kidneys is not at significant risk of developing CKD because of UTIs.

Childhood Urinary Tract Infections as a Cause of Chronic Kidney Disease

Acute pyelonephritis (APN) may produce permanent renal damage (PRD), which can subsequently lead to diverse complications. We prospectively evaluated 147 females and 122 males (mean age 3.5 years) with APN in order to analyze the relationship between the presence of PRD, at the time of cortical renal scintigraphy, and age, gender, episodes of urinary tract infection (UTI), and presence of vesicoureteral reflux (VUR). There were 152 children studied after the first proven UTI. VUR was present in 150 children. PRD was observed in 170 children. There were no significant differences between boys and girls. PRD was found in 36.4% of children younger than 1 year and in 70.1% of those older than 1 year (P<0.0001). Of children with VUR, 72% had PRD compared with 52% of children without VUR (P<0.0001). Of children with a first episode of UTI, 55.9% developed PRD as did 72.6% of those with recurrent UTI (P=0.004). Our results showed that PRD in children with APN is important, especially in the presence of VUR, recurrent UTI, and older age.

Dilip Kumar

Papers

Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux