Treatment of bacterial urinary tract infections: presence and future

Bacterial urinary tract infections (UTIs) are frequent infections in the outpatient as well as in the nosocomial setting. The stratification into uncomplicated and complicated UTIs has proven to be clinically useful. Bacterial virulence factors on the one side and the integrity of the host defense mechanisms on the other side determine the course of the infection. In uncomplicated UTIs Escherichia coli is the leading organism, whereas in complicated UTIs the bacterial spectrum is much broader including Gram-negative and Gram-positive and often multiresistant organisms. The therapy of uncomplicated UTIs is almost exclusively antibacterial, whereas in complicated UTIs the complicating factors have to be treated as well. There are two predominant aims in the antimicrobial treatment of both uncomplicated and complicated UTIs: (i) rapid and effective response to therapy and prevention of recurrence of the individual patient treated; (ii) prevention of emergence of resistance to antimicrobial chemotherapy in the microbial environment. The main drawback of current antibiotic therapies is the emergence and rapid increase of antibiotic resistance. To combat this development several strategies can be followed. Decrease the amount of antibiotics administered, optimal dosing, prevention of infection and development of new antibiotic substances. The aim of this review is to highlight the current and to describe future treatment options for UTIs.     

May we go on with antibacterial prophylaxis for urinary tract infections?

Recurrent urinary tract infections (UTIs), with or without vesicoureteric reflux (VUR), are by far the most frequent reason for long-term antibacterial prophylaxis in infants and children today. However, the strategies of antibacterial prophylaxis for the prevention of recurrent urinary tract infection are no longer universally accepted. In infants and children at risk, the benefits of antibacterial prophylaxis definitively are not yet proven by evident data. To put antibacterial prophylaxis in its place, risk groups for recurrent symptomatic infections, ascending UTI and permanent renal damage have to be defined and the efficacy of prophylaxis in these groups has to be proved by prospective randomised studies. Nevertheless, until the results of these studies are available, antibacterial prophylaxis will remain one of the most frequently practised methods to protect risk patients from pyelonephritic damage and UTI recurrences.     

The office management of recurrent urinary tract infection and vesicoureteral reflux in children

Recurrent urinary tract infections (UTIs) and vesicoureteral reflux are common diagnosis' in infants and children who are referred to a urologist. Recurrent UTIs in these patients can be challenging, especially when radiographic evaluation reveals no structural abnormality. Prophylaxis and correction of voiding and bowel dysfunction are important treatment strategies. Febrile UTIs are commonly associated with reflux and should be treated aggressively to avoid renal scarring and its sequelae. Based on a comprehensive survey of the literature, long-term treatment strategies for children with reflux are now available.     

Advances in the understanding and treatment of urinary tract infections in young women

Despite relative ease of management, the high rate of urinary tract infections (UTI) among young women presents substantial problems for the health care community. Although the majority of UTIs in young women are simple and uncomplicated, the rate of recurrence is substantial. Each treatment of UTI recurrence brings greater antibiotic resistance, requiring the use of broader spectrum and more expensive antibiotic therapy. Moreover, infection in patients with underlying urinary tract or systemic diseases can lead to serious medical and financial consequences. A better understanding of antibiotic resistance, particularly in regard to beta-lactamase-producing pathogens, has allowed us to develop more appropriate criteria for selecting antibiotics as well as the duration of therapy. The overall cost for treating UTIs in young women is a substantial health care expenditure, and requires an ongoing examination of new information concerning pathogenesis and available antibiotic therapies.     

Urinary tract infections in the frail elderly: Issues for diagnosis,treatment and prevention

Urinary tract infections (UTIs) are among the most common infections in frail elderly adults, whether they are community dwelling, live in long term care facilities (LTCFs) or are hospitalized. UTIs cause substantial morbidity and mortality in frail elderly men and women. While many major risk factors in these individuals may not be modifiable, improved attention to incontinence management, judicious use of antimicrobials and urinary catheters, and, in women, appropriate use of topical estrogen may be useful in reducing UTIs. Future strategies may also include the appropriate use of new urinary catheter technology and emerging vaccines.Presented in part at the 7th International Conference on Geriatric Nephrology and Urology, October 9–12, 2003, Atlanta, GA     

Phase 2 clinical trial of a vaginal mucosal vaccine for urinary tract infections

PURPOSE: Recurrent urinary tract infections (UTIs) in susceptible women remain a common urological condition. With an increasing number of UTIs being caused by antibiotic resistant bacteria there is a need for alternatives to antibiotics. We determined whether multiple doses of a vaginal mucosal vaccine are effective for increasing long-term resistance to recurrent UTIs. MATERIALS AND METHODS: A total of 54 women were entered into a double-blind, placebo controlled, phase 2 clinical trial using a vaginal vaccine containing 10 heat killed uropathogenic bacteria. Patients were withdrawn from prophylactic antibiotics and randomly assigned to 1 of 3 treatment groups, namely placebo only, primary immunization or primary plus booster immunizations. Subjects received treatments at 0, 1, 2, 6, 10 and 14 weeks. Placebo treated patients received suppositories without bacteria. The primary immunization group received vaccine suppositories, followed by 3 doses of placebo. Patients receiving booster immunizations were given 6 vaccine suppositories. All women were followed for 6 months to determine the time until first recurrence, number of infections and adverse reactions. RESULTS: Women receiving 6 vaccine doses remained free of infections for a significantly longer period than those receiving placebo or primary immunizations. Of patients receiving 6 immunizations 55% did not experience an infection, whereas 89% of placebo treated women had UTIs. No women had significant adverse effects. CONCLUSIONS: This study demonstrates that vaginal mucosal vaccine given for a 14-week period increased the time to re-infection in UTI susceptible women. The infrequent, minimal adverse reactions confirm previous observations on the safety of this vaginal mucosal immunization regimen.     

Evaluation of the diagnostic workup in young women referred for recurrent lower urinary tract infections

Objectives. To evaluate the current practice of the diagnostic workup in The Netherlands and the clinical relevancy of the outcome of various diagnostic procedures in young women referred for recurrent lower urinary tract infections (UTIs).Methods. A questionnaire was sent to all urologic departments in The Netherlands (n = 104) inquiring about the diagnostic procedures used for recurrent lower UTIs. Furthermore, we performed a prospective study in 100 consecutive young female patients (18 to 40 years old) referred for evaluation of recurrent lower UTIs. All patients underwent a standardized workup: questionnaire, voiding diary, physical examination, urinalysis and culture, abdominal x-ray with ultrasound or intravenous urography, and cystoscopy.Results. The response rate to the questionnaires was 92%. The standard procedures were laboratory blood tests in 56%, cystoscopy in 69%, plain abdominal x-ray in 91%, and abdominal ultrasound in 59%. Only 18% of the urologists asked every patient to make a voided urine frequency volume chart. In our group of patients, the radiologic procedures revealed only one relevant abnormality. Cystoscopy confirmed cystitis in 22 patients, but never revealed relevant findings. None of these diagnostic procedures ever contributed to the diagnosis. The 24-hour urine output was less than 1.5 L in 43 patients, which was considered insufficient. The individual self-reports of fluid intake were unreliable.Conclusions. Many Dutch urologists perform an extensive routine workup in patients referred for recurrent lower UTIs. The results of our study revealed that the yield of most diagnostic procedures in these patients is low. The focus in evaluating these patients should be directed toward the behavioral aspects. Thus, the routine workup can be restricted to a voiding diary, urinalysis, and urine culture.     

Value of urologic investigation in a targeted group of women with recurrent urinary tract infections.

According to the conclusions of clinical studies, excretory urography and cystoscopy are of no value in managing the majority of women who have a history of recurrent urinary tract infection (UTI). Of 475 women with recurrent UTIs, 186 were prospectively targeted for evaluation by cystoscopy and ultrasonography or excretory urography from selection criteria based on the degree of complicating factors, to determine the value of urologic investigation. Thirty-nine patients had significant detectable abnormalities, and 20 of them required surgical intervention. Definite indications for urologic evaluation include hematuria (gross hematuria and persistent microscopic hematuria between infections), pyelonephritis and a presentation that is not typical for simple uncomplicated UTIs (obstructive symptoms, infection with urea-splitting bacteria, clinical impression of persistent infection or urinary calculi). Diabetes itself does not warrant urologic evaluation. The findings from this study suggest that cystoscopy and upper urinary tract evaluation do play a role in the management of a selected group of women with UTIs.     

Urinary tract infections in cystic fibrosis patients

Improved understanding of non-respiratory infections in cystic fibrosis (CF) patients will be vital to sustaining the increased life span of these patients. To date, there has not been a published report of urinary tract infections (UTIs) in CF patients. We performed a retrospective chart review at a major academic medical center during 2010-2020 to determine the features of UTIs in 826 CF patients. We identified 108 UTI episodes during this period. Diabetes, distal intestinal obstruction syndrome (DIOS), and nephrolithiasis were correlated with increased risk of UTIs. UTIs in CF patients were less likely to be caused by Gram-negative rods compared to non-CF patients and more likely to be caused by Enterococcus faecalis. The unique features of UTIs in CF patients highlight the importance of investigating non-respiratory infections to ensure appropriate treatment.     

Urinary tract infections: what's new?

PURPOSE: This review provides practicing urologists with important basic information about urinary tract infections (UTIs) that can be applied to everyday clinical problems. MATERIALS AND METHODS: A review is presented of provocative and controversial concepts in the current literature. RESULTS: Bacterial virulence mechanisms are critical for overcoming the normal host defenses. Increasing antimicrobial resistance of uropathogens has led to reconsideration of traditional treatment recommendations in many areas. For effective patient management the first issue is to define complicating urological factors. Managing complicated urinary tract infections, particularly in urology, is determined by clinical experience to define the pertinent anatomy and to determine the optimal interventions. New clinical data are summarized on UTIs in long-term care patients, behavioral risks for UTI in healthy women and anatomical differences associated with an increased risk for UTI. The rationale is presented for UTI prophylaxis using cranberry juice, immunization and bacterial interference. Current treatment trends for UTI include empiric therapy (without urine culture and sensitivity testing), short-course therapy, patient-administered (self-start) therapy and outpatient therapy for uncomplicated pyelonephritis. CONCLUSIONS: Recommendations for treating patients with UTIs have changed based on basic science and clinical experience.     

Postoperative cystography and endoscopic treatment of low-grade vesicoureteral reflux

INTRODUCTION: The endoscopic subureteral injection of tissue-bulking agents has become an established alternative to long-term antibiotic prophylaxis and open surgery with a high success rate, especially for low-grade reflux (>90%). Though it is recognized that a routine postoperative voiding cystourethrography (VCUG) is unnecessary following a ureteroneocystostomy, most teams perform one after an endoscopic treatment. MATERIALS AND METHODS: In this paper, we report on our experience with the endoscopic correction of vesicoureteral reflux in 72 ureteral units, for whom no routine postoperative cystography was performed. DISCUSSION: Two children presented with postoperative recurrent febrile urinary tract infections (UTIs), which were not correlated with cystography findings. Postoperative VCUGs after a ureteroneocystostomy are invasive and expose the child to radiation, they are associated with a substantial cost, and most of all, they do not allow the identification of those patients at risk of recurrent febrile UTIs. Further, the endoscopic subureteral injection of tissue-bulking agents have been used for several years, and numerous studies, set in various clinical settings, have since been published, confirming excellent long-term results for low-grade reflux. CONCLUSIONS: We feel that postoperative cystograms should be reserved for children who present with recurrent UTIs, new sonographic abnormalities, or who were treated for high-grade reflux.     

Recurrent Urinary Tract Infections in Females and the Overlap with Overactive Bladder

Purpose of Review

There are an estimated 33 million men and women with overactive bladder (OAB) in the USA. Despite the prevalence of OAB, it remains a frequently misdiagnosed condition. OAB has shared symptomatology with other common urologic conditions, namely recurrent urinary tract infections (UTIs). Here, we will review key distinguishing features of OAB that aid in establishing an accurate diagnosis and recent advances in OAB management.

Recent Findings

Recent studies have shown that among women presenting with lower urinary tract symptoms, the majority were diagnosed with UTIs and treated without performing a urine culture as routine care. The authors found that when urine cultures were obtained, less than half of women had a positive urine culture, suggesting that empiric treatment of UTIs without cultures commonly led to a misdiagnosis of UTI. The symptoms of OAB have overlap with other common conditions, most notably UTI, BPH, and bladder cancer/carcinoma in situ. Despite the shared symptomatology of OAB and UTI, the timing of symptom onset is usually very different between the two. UTI symptoms are generally acute, whereas those of OAB are generally chronic. OAB and UTI share the common features of urgency, frequency, and nocturia. However, dysuria and hematuria are not features of OAB, while they are frequently seen in UTI. Of note, urgency, frequency, and nocturia are rarely seen in bladder cancer/carcinoma in situ; when these symptoms do occur, it is generally in the setting of microhematuria. One study of patients with carcinoma in situ found that 41% had macroscopic hematuria and 44% had microscopic hematuria at presentation. In patients with lower urinary tract symptoms, it is important to perform a urinalysis (UA) to evaluate for microhematuria to rule out the possibility of malignancy. First-line treatment of OAB (outside the setting of UTI) involves behavioral modification, including bladder training, fluid management, and pelvic floor exercises. Numerous studies have supported behavioral modification strategies as the most efficacious initial step in treatment. Although routinely given for recurrent UTIs and vaginal atrophy in postmenopausal women, several review articles have shown that vaginal estrogen is an effective treatment of lower urinary tract symptoms.

Summary

The importance of distinguishing OAB from other conditions presenting with similar symptoms is key in preventing misdiagnosis, treatment delays, and antibiotic overuse. Here, we have reviewed key parameters distinguishing OAB from UTI, the most commonly misdiagnosed condition among those presenting with lower urinary tract symptoms (LUTS). Given that UTI is the most commonly misdiagnosed condition among women with OAB, we recommend relying on urine cultures and the constellation of acute-onset dysuria, frequency, and urgency as more important diagnostic factors in distinguishing these conditions.

     

Urinary tract infections in the elderly

The elderly population is now increasing in the world. A higher incidence of bacteriuria and urinary tract infection (UTI) is observed in elderly patients, in both long-term care facilities and at home. The management of elderly patients with UTI is increasing in clinical significance. Almost all of UTI in the elderly is complicated UTI. Control of the underlying diseases in the urinary tract is quite important in the management of UTIs in elderly patients. For pyelonephritis, switch therapy using aminoglycosides and fluoroquinolones, carbapenems, third-generation cephalosporines, or penicillins are selections of choice. The recommended duration of treatment for patients with pyelonephritis is 14 days. Seven to 10 days of treatment using fluoroquinolones or trimethoprim-sulfamethoxazole is recommended for the treatment of elderly patients with symptomatic cystitis. Although asymptomatic bacteriuria is quite common in the elderly population, antibiotic treatment has no benefit for such patients. Intravaginal estrogen replacement is one of choice for the prevention of recurrent UTIs in postmenopausal women.     

Uncomplicated urinary tract infections in women

Uncomplicated urinary tract infections, such as acute uncomplicated cystitis and pyelonephritis, are common infections in otherwise healthy women. Although severe complications are rare, the high prevalence of these infections contributes to significant costs to health care systems. The present review addresses recent publications that concern the epidemiology, pathogenesis, aetiology, diagnosis, treatment and prevention of uncomplicated urinary tract infections and recurrent urinary tract infections in women.     

Nephrogenic Adenoma Complicating Renal Transplantation: A Case Report and Discussion

Nephrogenic adenoma (NA) is a benign adenomatous lesion of the urinary tract. Long considered to be a rare phenomenon, case series from the renal transplant population suggest that it may be much more common within this group. Although NA is considered to be a lesion with low premalignant potential, hematuria, lower urinary tract symptoms, and recurrent urinary tract infections (UTIs) are frequently observed in the context of NA. Furthermore, after resection of NA, lesion recurrence and persistent symptoms are frequently observed. Here we present the case of a 69-year-old male renal transplant recipient with NA and associated recurrent UTIs despite cystoscopic resection of the primary lesion. This case is illustrative of the clinical impact of NA and the need for ongoing work into the development of strategies to manage this problematic phenomenon.     

Evidence-based medicine and vesicoureteral reflux

Vesicoureteral reflux (VUR) remains one of the most controversial subjects in paediatric urology. Much literature has been published on VUR, making the understanding of this anomaly and its treatments quite opaque. Evidence-Based Medicine (EBM) should be helpful to clarify the various VUR approaches contained in the 6224 titles found on Medline using the keywords "vesicoureteral reflux" and "vesicoureteric reflux". These articles were critically reviewed and graded according to EBM scorings, with regard to their methodological designs. This review of VUR literature suggests that most of our knowledge is based on publications with a low level of evidence, and that EBM lacks arguments to support recommendations for VUR diagnostic and treatment. It appears yet that antenatal dilatation of the urinary tract and symptomatic urinary tract infections (UTI) justify VUR screening. Surgery should be discussed in recurrent UTIs or deterioration of renal function. There is no consensus in case of persistent asymptomatic VUR regarding indication and duration of antibio-prophylaxis, and selection of radical treatment.     

Vesicoureteral reflux: why we can't agree on its management! An evidence based approach

Vesicoureteral reflux remains one of the most controversial subjects in paediatric urology. The flooding of publications on reflux makes the understanding of this anomaly and its treatments quite opaque. Evidence Based Medicine might be a helpful tool to clarify the various approaches of reflux reflected in 6.715 publications found on Medline with the key-words "vesicoureteral reflux" and "vesicoureteric reflux". These articles were critically reviewed and graded according to EBM scorings, with regard to their methodological designs. It appears clearly after this review of literature concerning VUR that most of our beliefs are based on low evidence publications and that EBM has not sufficient arguments to establish recommendations for diagnostic and treatment of VUR. It appears yet that antenatal dilatation of the urinary tract and symptomatic UTIs justify looking for VUR. Surgery should be discussed in recurrent UTIs or deterioration of renal function. There is no consensus in the case of persistent asymptomatic VUR, indication and duration of antibioprophylaxis, and choice of radical treatment.     

Infectious disease complications of simultaneous pancreas kidney transplantation

BACKGROUND: Although technical success rate of simultaneous pancreas kidney (SPK) transplantation in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy has improved, morbidity remains high due to infection and rejection. The purpose of this study was to analyse infections encountered in our series of SPK transplants, using a restrictive antibiotic prophylaxis policy. METHODS: We reviewed all infectious diseases after 66 consecutive bladder-drained SPK transplantations in 64 IDDM patients with end-stage renal disease due to diabetic nephropathy. During follow-up, the perioperative antibiotic regimen was altered (from 5 days preemptive therapy with multiple drugs to 1 day prophylaxis with cefamandole), and long-term viral prophylaxis (high-dose aciclovir) was introduced. For post-operative urinary tract or opportunistic infection, no prophylaxis was given. RESULTS: Overall mean infection rate was 2.9 infections/ patient/year after a mean follow-up of 2.3 years. Surgical site infections (SSI) were seen in 30% of the patients, with Enterococci present in 47%. Logistic regression showed one day cefamandole prophylaxis to be associated with SSI, but there was no significant influence of SSI on either graft or patient survival. Forty-eight percent of all infections were lower urinary tract infections (UTI). There were 59 first UTIs (89%), probably related to long-term Foley catheter use, and 47 second UTIs (71%). Subsequent UTIs were not microbiologically related to first UTIs. Cytomegalovirus (10 patients) and other opportunistic agents did not cause mortality or graft loss. Five grafts were lost due to infection (SSI three times, post-transplant lymphoproliferative disease twice). Only one patient died because of infection (2%). CONCLUSIONS: Infectious diseases after SPK transplantation caused significant morbidity but did not influence either patient or graft survival. A change in prophylactic policy for both SSI as well as recurrent UTI, combined with earlier Foley removal, may lower incidences of these infections.