Therapeutic strategies for uncomplicated cystitis in women.

Uncomplicated cystitis is affecting many women of all ages and has a great impact on the quality of life, especially in women suffering from recurrent, uncomplicated cystitis. By far the most frequent uropathogen, E. coli, may have acquired increasing resistance against a variety of oral antibiotics, which may differ between countries and regions. Therefore, local resistance data are important to be considered. On the other hand, non-antibiotic therapy has also become an option which should be discussed and offered to the patient. In patients suffering from recurrent uncomplicated cystitis, individual risk factors and possible behavioral changes should first be taken into account. Non-antimicrobial prophylactic strategies shown to be successful in well-designed clinical studies are the next options. Long term antibiotic prophylaxis, however, should only be considered as a last option. For some of those patients self-diagnosis and self-treatment may be suitable, e.g. by using a recognized questionnaire.

Urinary tract infection in patients with diabetes mellitus.

Urinary tract infection occurs with increased frequency and severity in patients with diabetes mellitus. General host factors enhancing risk for urinary tract infection in diabetics include age, metabolic control, and long term complications, primarily diabetic nephropathy and cystopathy. Alterations in the innate immune system have been described and may also contribute. Treatment of asymptomatic bacteriuria in diabetic patients is not indicated. Early diagnosis and prompt intervention is recommended to limit morbidity of symptomatic infection. Clinical studies comparing management of urinary tract infection in persons with diabetes compared to those without as well as diabetic patients with good or poor glucose control will be necessary to improve care of urinary infection in persons with diabetes mellitus.

Urinary tract infections in patients with renal insufficiency and dialysis - epidemiology, pathogenesis, clinical symptoms, diagnosis and treatment.

Epidemiological studies show an increasing number of patients worldwide suffering from chronic kidney diseases (CKD), which are associated with a risk for progression to end-stage kidney disease (ESKD). CKD patients stage 2-5, patients with regular chronic dialysis treatment (hemo- or peritoneal dialysis), and patients suffering from kidney allograft dysfunction are at high risk to develop infections, e.g. urinary tract infections (UTI) and/or sepsis (urosepsis). These groups show metabolic disturbance, chronic inflammation, and impaired immunocompetence. Escherichia coli is still the most common pathogen in UTI. A wide variety of other pathogens may be involved in UTI. Urological interventions, catheterization, as well as repeated courses of antibiotics contribute to an increased challenge of antimicrobial resistance. The diagnosis of UTI in CKD is based on standard clinical and laboratory criteria. Pyuria (≥10 leucocytes/µl) is more often observed in patients with oligoanuria and low bacterial colony counts. The treatment strategies for this population are based on the same principles as in patients with normal renal function. However, drugs cleared by the kidney or by dialysis membranes need dose adjustment. Antimicrobials with potential systemic toxicity and nephrotoxicity should be administered with caution.

Calculated parenteral initial treatment of bacterial infections: Infections of the kidneys and the genito-urinary tract.

This is the eighth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. The chapter deals with the treatment of more severe infections of the kidney and the urogenital tract, including urosepsis. Recommendations for empiric and targeted antibacterial treatment are given.

The interaction of urinary tract infection and renal insufficiency.

Urinary tract infections (UTIs) are among the most common infections caused by microorganisms, and pyelonephritis is the most severe infection of the urogenital tract. The risk of developing chronic renal insufficiency due to a UTI without other risk factors is low. The pathogenicity and virulence of the infective microorganisms as well as the efficiency of local or systemic defence mechanisms determine the course and severity of the disease. Virulence properties (adhesins, toxins, capsule, iron uptake) are encoded by genomic structures and the determination of virulence is influenced by the host situation. In renal insufficiency, a variety of quite different substances (uraemic toxins, betaine, amino acids, creatinine, urea, glucose) influence the microbial environment. Defence factors (Tamm-Horsfall protein, defensin, phagocytic activity of granulocytes) and underlying anatomical lesions as well as pre-existing renal disease determine the severity of UTI and the prognosis of renal insufficiency.

Predictive value of initial histology and effect of plasmapheresis on long-term prognosis of rapidly progressive glomerulonephritis.

Intensive immunosuppressive therapy has improved the outcome of patients with rapidly progressive glomerulonephritis (RPGN), which progresses to end-stage renal failure in 90% of patients without intervention. However, it remains unclear which patients benefit most from immunosuppressive therapy and whether plasmapheresis improves long-term outcome. This prospective multicenter study randomized 39 patients with biopsy-proven RPGN (Couser type II, n = 6; pauci-immune type III, n = 33) to undergo either immunosuppressive therapy with prednisone and cyclophosphamide (n = 18) or plasmapheresis in addition to immunosuppression (n = 21). Patients were observed for a mean of 127 months or until reaching the end points of hemodialysis or death. Six of 11 patients who were initially dialysis dependent recovered renal function; however, 2 of those patients required dialysis therapy again after 10 and 105 months. Overall, 15 of 39 patients reached end-stage renal failure after a mean of 25 months, and 4 patients died before requiring hemodialysis therapy. Plasmapheresis had no significant effect on renal or patient survival in type II or pauci-immune (type III) RPGN, independently of age, sex, or serum creatinine level at the time of diagnosis. Overall, probabilities of dialysis-free survival were 0.80, 0.67, 0.55, and 0.48 after 12, 24, 60, and 120 months, respectively. Histological characteristics at the time of diagnosis predicted the effect of immunosuppression on renal outcome. All patients were dialysis dependent within 24 months if more than one third of glomeruli were totally sclerosed on the initial histological examination. Interstitial fibrosis also correlated significantly with the risk for progression to renal failure. Conversely, long-term dialysis-free survival was significantly more likely in patients with a greater number of crescents than in those with a low number of crescents. In conclusion, plasmapheresis does not add to the improvement in outcome reached by immunosuppression alone. Crescents on initial histological examination correlate with a favorable outcome. However, 90% of patients who initially have glomerular sclerosis present become dialysis dependent. Overall, approximately 50% of patients are alive and off dialysis therapy 10 years after the diagnosis of type II or type III RPGN using immunosuppression with cyclophosphamide and prednisone.

Cyclosporine A and chlorambucil in the treatment of idiopathic focal segmental glomerulosclerosis.

BACKGROUND: The therapy of nephrotic syndrome in focal segmental glomerulosclerosis (FSGS) is still a matter of controversy. METHODS: We performed a prospective randomized study of the treatment of nephrotic syndrome due to FSGS. We compared 2 specific treatment protocols to assess the effect of treatment on proteinuria and renal function. Fifty-seven patients were randomly assigned to 2 groups: group 1 (n = 34) received steroids and cyclosporine, and group 2 (n = 23) received steroids and chlorambucil for 6 months. When treatment was refractory to chlorambucil, the patients in this group were treated with cyclosporine. Creatinine, blood urea nitrogen, proteinuria, lipids, and arterial hypertension were monitored at regular intervals. RESULTS: Patients showed a mean serum creatinine of 1.5 +/- 0.2 mg/dL (132.6 +/- 17.7 micromol/L) and proteinuria of 4.8 +/- 2.8 g/24 h with no differences between the groups. At the end of the chlorambucil therapy, patients in group 2 had creatinine levels of 1.8 +/- 0.6 mg/dL (159.1 +/- 53 micromol/L) and proteinuria levels of 3.4 +/- 1 g/24 h. All patients in this group were given cyclosporine. After 4 years the mean creatinine level in group 1 was 1.7 +/- 0.4 mg/dL (150.3 +/- 35.4 micromol/L) and the proteinuria level was 2.5 +/- 1 g/24 h. In group 2, the mean creatinine level was 1.9 +/- 0.6 mg/dL (168 +/- 53 micromol/L) (not significant [NS]) and the mean proteinuria level was 2.3 +/- 1.1 g/24 h (NS). Full remission occurred in 23% of the patients in group 1 (n = 8) and 17% of the patients in group 2 (n = 4; NS). Partial remission was observed in 38% of the patients in group 1 (n = 13) and 48% in group 2 (n = 11; NS). The number of patients who developed end-stage renal disease was comparable in both groups: 4 of 34 patients in group 1 after 2.5 +/- 0.8 years, and 5 of 23 patients in group 2 (NS). CONCLUSION: Additional treatment with chlorambucil was found to be ineffective in FSGS. Patients responded to treatment with steroids or cyclosporine, but additional treatment with chlorambucil did not improve the patient's outcome. Future studies must focus on the long-term prognosis of these patients.

[Nephrology update. Kidney protection with antihypertensive drugs: I]. / Update Nephrologie. Renoprotektion durch Antihypertensiva: Teil I.

Diabetes has become the most common single cause of end-stage renal disease in many countries. The coexistence of diabetes mellitus and hypertension dramatically increases the risk of developing target organ complications including renal disease. There are good arguments that ESRD in the patient with diabetes is largely preventable with the interventions currently available. For type 2 diabetes the UK Prospective Diabetes Study Group Trial clearly documented that the frequency of microangiopathic sequelae can be diminished by glycaemic control and even more impressively by intensified antihypertensive treatment. An analysis of recent randomized long-term clinical trials that evaluated the rate of decline in renal function demonstrated that the lower the blood pressure within the range of normotensive values, the greater the preservation of renal function. Since the 1994 Working Group Report on Hypertension and Diabetes suggested a goal blood pressure of 130/80 mmHg should be achieved in patients with diabetes and/or renal insufficiency; lower blood pressure levels, i.e. less than 125/75 mmHg are recommended for patients with proteinuria > 1 g/d and renal insufficiency regardless of etiology. Antihypertensive regimens should include an ACE inhibitor or an AT1-receptor blocker in order to provide maximum renal benefits in diabetic and non-diabetic renal diseases. Such low blood pressure are virtually impossible to achieve with monotherapy. In most cases the combination of two and more antihypertensive drugs is necessary. The purpose of this report is to update the previous recommendations with a focus on level of blood pressure control, proteinuria reduction and retarding the progression of renal disease.

[Fever after travel to the tropics]. / Fieber nach Tropenaufenthalt.

BACKGROUND: Fever in travellers returning from the tropics may be caused not only by tropical infection but also by travel associated non-specific infections and cosmopolitan infective diseases. DIAGNOSTIC PROCEDURE: A rational out-patient step by step procedure needs clinical data and a small account of laboratory investigations. A parasitological screening is mandatory. The results refer to parasitological, bacterial or viral diseases. Epidemiological aspects of the travelled country and incubation periods of tropical or other diseases have to be considered. CONCLUSIONS: Plasmodium falciparum infection has to be excluded first because of vital damage. Following malaria (30%) respiratory infections (11%) are common. Fever as a symptom of non-infective disease occurred in 9%. Other diseases (typhus, Dengue fever, tuberculosis) are rare but have to be considered.

[Nephrology-part 3: Urinary tract infections]. / Nephrologie-Teil 3Harnwegsinfektionen.

Urinary tract infections are one of the most common bacterial infectious diseases in humans. Depending on the localization and the effectiveness of pathogenetic factors, various clinical pictures (lower urinary tract infection, pyelonephritis, asymptomatic bacteriuria) have to be differentiated. There are virulence factors of microorganisms on the one hand and defense mechanisms on the other, which influence the manifestation and the course of disease. The process of bacterial attachment to the epithelial cells of the boundary layer, the internalization and invasion of bacteria could be important for acute and chronic disease. Disturbances of local defense mechanisms, such as increased urinary glucose concentration in diabetes or variations of Tamm-Horsfall protein and defensin levels, may influence the course of infection. On the basis of microbiological and laboratory findings as well as the results of clinical and ultrasound procedures, the decision on the therapeutic strategy should be made. There are different treatment recommendations for acute uncomplicated and complicated cases as well as for chronic diseases. Future investigations should focus on effective therapeutic options for special immunocompromised patients in relation to the microbiological aspects and defense mechanisms of the host.

Uncomplicated urinary tract infections.

BACKGROUND: Urinary tract infections (UTIs) are among the most common types of bacterial infection in outpatient medicine. Rising rates of antibiotic resistance and a better understanding of the ecological adverse effects (collateral damage) of antibiotics warrant a reevaluation of the treatment recommendations for uncomplicated UTI. The new S3 guideline contains updated recommendations. METHODS: The new S3 guideline is based on a review of publications on uncomplicated UTI retrieved by a systematic search of the Medline and Cochrane Library databases. Guidelines from abroad were also considered in the review. RESULTS: Uncomplicated UTI is classified as either uncomplicated cystitis (UC) or uncomplicated pyelonephritis (UP). The choice of a suitable antibiotic is determined by the following main criteria: the patient's individual risk profile and prior antibiotic treatment, if any; the spectrum of pathogens and antibiotic susceptibility; the proven efficacy of the antibiotic; the ecological adverse effects (collateral damage) of antimicrobial therapy; the side effects for the patient under treatment. On the basis of these criteria, co-trimoxazole/trimethoprim and fluoroquinolones can no longer be recommended as first-line empirical treatment for UC. Rather, the new recommended treatment of first choice consists of fosfomycin-trometamol, nitrofurantoin, or pivmecillinam. High-dose fluoroquinolones are still recommended, however, as first-line oral treatment for UP. Asymptomatic bacteriuria should only be treated in exceptional situations such as pregnancy or before urological procedures that will probably injure the mucosa of the urinary tract. CONCLUSION: The new S3 guideline on uncomplicated UTI incorporates a forward-looking approach to the use of antibiotics in treating this common type of infection. It is intended to bring about a sustained improvement in the quality of care.