Prospective multicentre randomized double-blind placebo-controlled parallel group study on the efficacy and tolerability of StroVac® in patients with recurrent symptomatic uncomplicated bacterial urinary tract infections.

PURPOSE: To evaluate efficacy and safety of vaccination with StroVac compared to placebo in patients with recurrent urinary tract infections (rUTI). MATERIAL AND METHODS: We performed a prospective, double-blinded, placebo-controlled study in patients with uncomplicated rUTI. Patients received three single intramuscular injections with StroVac every two weeks. Primary endpoint was the number of bacterial urinary tract infections (UTI) over 13.5 months after randomization and adjusted by the respective "baseline" value when comparing verum and placebo group. Secondary endpoints were the number of patients with non-recurrence, time to first recurrence, frequency of recurrences, and patients' self-assessment of quality of life using a validated questionnaire. RESULTS: 376 patients were randomized to both groups between January 2012 and March 2015. Mean age was 44.4 years. Patients were mainly female (98.4%). In the StroVac group (n = 188), the number of UTIs was reduced from 5.5 to 1.2, in the placebo group (n = 188) from 5.4 to 1.3 (p = 0.63). In patients with ≥ 7 UTIs prior to study inclusion, StroVac was statistically significantly superior to placebo (p = 0.048). However, in all other secondary endpoints, no statistical differences between the two groups could be seen (all p > 0.3). CONCLUSION: StroVac reduced the number of clinically relevant UTIs like in former studies but did not show statistically significant better results than the chosen placebo. Most likely, that was due to a, since confirmed, prophylactic effect of the chosen placebo itself. Therefore, placebo-controlled and double-blinded studies using a different ineffective placebo preparation are needed to determine the importance of StroVac in prophylaxis of rUTI.

[Uncomplicated urinary tract infections : Use of mustard oils]. / Unkomplizierte Harnwegsinfektionen : Senföle zeigen Effizienz.

BACKGROUND: Increasing rates of multidrug resistant bacteria demand a change in managing infectious diseases. New ways of antibiotic-free treatment in uncomplicated urinary tract infections (UTI) saving antibiotics for severe infections should be chosen. OBJECTIVES: Beside analgesics for purely symptomatic treatment, herbal medicine can be used for uncomplicated UTI instead of antibiotics. MATERIALS AND METHODS: Anti-infectious phytodrugs like isothiocyanates (ITC) from horseradish and cress (nasturtium) have been thoroughly examined scientifically. RESULTS: ITC showed multitarget effects in many pharmacological studies. Beside anti-inflammatory effects, a broad spectrum of species, including multiresistant bacteria were covered. Positive results and good compatibility are documented in several studies for therapy of uncomplicated UTI and respiratory infections with horseradish and cress as well as for prophylaxis in recurrent UTI (recommendation in the German S3 guideline for uncomplicated urinary tract infections, AWMF registry 043/044, statement 8.1.d.4 on prophylaxis). CONCLUSION: Using isothiocyanates (ITC) for therapy and prophylaxis in uncomplicated urinary tract infections is a rational approach and helps to save antibiotics. Even after long-term use, development of resistance has not yet been observed and is not probable due to the multimodal mechanism of action of ITC.

[Diagnosis and treatment of interstitial cystitis (IC/PBS) : S2k guideline of the German Society of Urology]. / Diagnostik und Therapie der interstitiellen Zystitis (IC/BPS) : S2k-Leitlinie der Deutschen Gesellschaft für Urologie.

In this review article, the authors describe all relevant aspects of the new S2k guideline from the German Society of Urology (Deutschen Gesellschaft für Urologie, DGU) for the diagnosis and treatment of IC/PBS (interstitial cystitis/painful bladder syndrome). A list of necessary and optional examinations and the necessity of diagnosis of exclusion are summarized and evaluated. The treatment options listed (ranging from conservative, oral drug, and complementary medicine to interventional surgical procedures) also give the reader a good overview of the contents of the guideline and possible therapeutic approaches. Finally, the recommendations including consensus of the guideline group are also summarized in various information boxes.

[Management of multiresistant bacteria in urology]. / Management multiresistenter Erreger in der Urologie.

Contamination and infection with extensive drug resistant (XDR) bacteria are increasing in urology with the exception of methicillin resistant Staphylococcus aureus (MRSA) (stabilization). They often lead to logistic and therapeutical problems. Only 30-50% of XDR cases are of exogenous origin. To slow this trend, screening, hygiene programs, isolation, decontamination, targeted therapy of symptomatic infections, education programs, and success controls should be applied. Furthermore, all regulatory and legal instructions should be followed. Local hygiene networks help to find apt measures for XDR control. It is important to balance hygiene measures against hygiene hysteria. To prepare urological instruments, a local instrument preparation plan that takes into consideration all legal instructions should be followed. The efforts in health system general prophylactic measures should be supported. Only with consistent implementation in all areas of daily life (health care, local environment, animal husbandry, and soil contaminated within the framework of animal husbandry) can a substantial reduction of XDR bacteria be achieved in the long term.

[Epidemiology, diagnostics, therapy, prevention and management of uncomplicated bacterial outpatient acquired urinary tract infections in adult patients : Update 2017 of the interdisciplinary AWMF S3 guideline]. / Epidemiologie, Diagnostik, Therapie, Prävention und Management unkomplizierter, bakterieller, ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten : Aktualisierung 2017 der interdisziplinären AWMF S3­Leitlinie.

BACKGROUND: Update of the 2010 published evidence-based S3 guideline on epidemiology, diagnostics, therapy and management of uncomplicated, bacterial, outpatient-acquired urinary tract infections in adult patients. The guideline contains current evidence for the rational use of antimicrobial substances, avoidance of inappropriate use of certain antibiotic classes and development of resistance. METHODOLOGY: The update was created under the leadership of the German Association of Urology (DGU). A systematic literature search was conducted for the period 01 January 2008 to 31 December 2015. International guidelines have also been taken into account. Evidence level and risk of bias were used for quality review. RESULTS: Updated information on bacterial susceptibility, success, collateral damage and safety of first- and second-line antibiotics was given. For the treatment of uncomplicated cystitis the first line antibiotics are fosfomycin trometamol, nitrofurantoin, nitroxoline, pivmecillinam, trimethoprim (with consideration of the local resistance rates). Fluoroquinolones and cephalosporins should not be used as first choice antibiotics. In the case of uncomplicated pyelonephritis of mild to moderate forms, preferably cefpodoxime, ceftibuten, ciprofloxacin or levofloxacin should be used as oral antibiotics. CONCLUSION: The updated German S3 guideline provides comprehensive evidence- and consensus-based recommendations on epidemiology, diagnostics, therapy, prevention and management of uncomplicated bacterial outpatient acquired urinary tract infections in adult patients. Antibiotic stewardship aspects have significantly influenced the therapeutic recommendations. A broad implementation in all clinical practice settings is necessary to ensure a foresighted antibiotic policy and thus t improve clinical care.

[Social medical/public health assessment of the ability to work regarding urological and urooncological diseases]. / Sozialmedizinische Begutachtung der Arbeits- und Erwerbsfähigkeit bei urologischen/uroonkologischen Erkrankungen.

The primary objectives of modern urooncological treatment concepts are quality of life, reintegration and participation. Urological rehabilitation supports the overcoming of side effects of disease and treatment, which is necessary for the timely return to work life. Social medical assessment reflects the individual overall results of the entire treatment process concerning oncological prognosis, physical and mental capacity and resilience.

[Social medicine assessment after surgical and targeted treatment of renal cell cancer]. / Sozialmedizinische Begutachtung nach operativer und zielgerichteter Therapie des Nierenzellkarzinoms.

In Germany, renal cell cancer counts for 2.5 % of all carcinomas in women and 3.5 % in men. Curative therapy ensures good chances of recovery. But there might be permanent complications like renal insufficiency, pain, incisional hernia, flank muscle relaxation, and paresis. In addition, targeted therapy is associated with several potential side effects. In both therapy groups, severe psychological problems may occur. Still employed patients with these problems must be examined by an expert to estimate the possibilities of returning to working (positive scope of work) and occupations which can not be performed anymore (negative scope of work).

[Social medical/public health assessment of bladder cancer after curative and adjuvant therapy]. / Sozialmedizinische Begutachtung nach kurativer und adjuvanter Therapie des Harnblasenkarzinoms.

Radical cystectomy and urinary diversion are a challenge for patients. Requirements for the successful participation of the patient are sufficient urinary diversion management and recuperation/recovery as the result of urological rehabilitation. A social medical assessment reviews the individual oncological prognosis and the rehabilitation results to determine the return to work.

[Social medicine assessment of patients with prostate cancer]. / Sozialmedizinische Begutachtung bei Patienten mit Prostatakarzinom.

Due to the increasing incidence of prostate cancer in social-medicine-relevant age groups, a correct subject-specific evaluation of the professional capacity of these patients with all stages of disease is required. A concluding assessment is only significant when based on concrete functional deficits.

[Bacteriuria after Radical Prostatectomy: Importance of Bacterial Count]. / Bakteriurie nach radikaler Prostatektomie - Stellenwert der Keimzahl.

MATERIAL AND METHODS: 100 consecutive cases after radical prostatectomy with a bacterial count of 10(4) CFU/ml in midstream urine were followed during urological inpatient rehabilitation without antibiotic treatment. Before discharge, a follow-up examination with a urine dipstick and a second urine culture were performed. RESULTS: No symptomatic urinary tract infections (UTI) occurred during the average follow-up period of 15.2 days. Patients with unremarkable urine dipstick findings at follow-up (no leukocyturia and no haematuria and no nitrituria) had no relevant bacteriuria (≥10(5) CFU/ml).54 of urine culture controls before discharge were negative, 31 showed insignificant bacterial growth (≤10(4) CFU/ml) and 15 had a bacterial count≥10(5) CFU/ml. 4 patients (27%) with > 10(5) CFU/ml were successfully treated with antibiotics for clear signs of infection (fever, chills, leukocytosis); the other 11 patients were just followed further. CONCLUSIONS: Even though almost all patients after radical prostatectomy continue to suffer from some discomfort that might be due to UTI, patients with 10(4) CFU/ml in midstream urine samples should not receive antibiotic treatment unless they have clear systemic symptoms of an infection, e. g. fever, chills or leukocytosis. Unremarkable urine dipstick findings during the follow-up period (no leukocyturia and no erythrocyturia and no nitrituria) rule out a relevant bacteriuria (≥10(5) CFU/ml). Clear systemic signs of infection during follow-up only occurred in 4 patients, who were successfully treated with test-adapted antibiotics.

[Specialist uro-oncological rehabilitation after treatment for prostate cancer--update 2015. Position statement of the working group on "rehabilitation of urological and nephrological diseases" of the German Society of Urology with respect to current S3 guidelines]. / Fachspezifische uroonkologische Rehabilitation nach Therapie des Prostatakarzinoms--Update 2015. Positionsbestimmung des Arbeitskreises "Rehabilitation urologischer und nephrologischer Erkrankungen" der DGU vor dem Hintergrund der aktuellen S3-Leitlinie.

After uro-oncological primary therapy of prostate cancer the quality of life of patients is often limited. The adequate and prompt treatment of specific urological functional, physical and mental deficits has a decisive influence on the quality of life. These deficits can be recorded using instruments for measuring the quality of life, in particular the QLQ-C30 of the European Organization for Research and Treatment of Cancer (EORTC) and the SF-36 questionnaires. The quality of life is the most important parameter for quality assurance of the results. The primary objectives are the therapy of postoperative functional disorders, in particular urinary incontinence and erectile dysfunction in addition to overcoming the disease. The "urological triad" plays a central role in recovering the quality of life and patient satisfaction.

[Prophylaxis of recurrent urinary tract infections]. / Prophylaxe rezidivierender Harnwegsinfektionen.

BACKGROUND: Recurrent urinary tract infections (rUTI), defined as ≥ 3 UTIs per year, mostly affect young and postmenopausal women. Treatable predisposing factors are rare. METHODS: General recommendations to reduce rUTIs lower the recurrence rate by up to approximately two thirds. Continuous long-term prophylaxis (LP) with low dose antibiotics or single postcoital doses can reduce the recurrence rate of rUTIs to as low as 5%. According to the European Association of Urology guidelines nitrofurantoin, trimethoprim and co-trimoxazole are the first-line drugs and cephalosporins or fluoroquinolones should be restricted to specific indications. Oral and parenteral immunotherapy were found to be effective in several controlled studies for prevention of rUTIs and can be combined with acute antibiotic therapy. CONCLUSIONS: Vaginal prophylaxis with estriol has proven its positive effect without serious gynecological side effects and there is also increasing evidence that cranberries prevent rUTIs but the exact mode of this therapy remains to be defined. There are also other promising modalities, such as phytotherapeutics, mannose, urine acidification, influencing bacterial intestinal and vaginal flora and the general immune response by e.g. acupuncture and inpatient rehabilitation, the therapeutic value of which still has to be proven.

[Prostatitis - diagnostics and therapy]. / Prostatitis: Diagnostik und Therapie.

The prostatitis syndrome is a frequent and complex disease. During the last 40 years the scientific perception has shifted between sometimes success and sometimes disappointment. Whereas acute prostatitis is most frequently considered an infectious disease, in only about 10% of cases with a chronic prostatitis syndrome can pathogens be identified. The bacterial spectrum is similar to that of complicated urinary tract infections with mainly Gram-negative pathogens. In some studies atypical pathogens, such as Chlamydia trachomatis and mycoplasmas, can be found in a considerable proportion. In most cases, however, a multifactorial aetiology is discussed. This has lead to a phenotyping directed multimodal treatment approach, considering the main symptoms. In prostatitis of microbial origin antibiotics, particulary fluorquinolones, are still the therapy of first choice. In the other cases multimodal treatment strategies are used considering evidence-based monotherapeutic studies. The evidence for multimodal combination treatment is still sparse.

Prevention of recurrent urinary tract infections.

Urinary tract infections (UTI) are among the most frequent bacterial infections in the community and health care setting. Mostly young and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI) defined as ≥3 UTI/year or ≥2 UTI/half year. In contrast, rUTI is rare in healthy men. On the other hand, rUTI are frequently found in female and male patients with complicating urological factors, e.g. urinary catheters, infection stones. Remediable predisposing factors in uncomplicated rUTI in women are rare. In complicated rUTI the success depends mainly on the possibility to eliminate or at leastimprove the complicating risk factors. Continuous antibiotic prophylaxis or postcoital prophylaxis, if there is close correlation with sexual intercourse, are most effective to prevent rUTI. Nitrofurantoin, trimethoprim (or cotrimoxazole), and fosfomycin trometamol are available as first-line drugs. Oral cephalosporins and quinolones should be restricted to specific indications. Antibiotic prophylaxis reduces the number of uropathogens in the gut and/or vaginal flora and reduces bacterial "fitness". Given the correct indication, the recurrence rate of rUTI can be reduced by about 90%. Due to possible adverse events and the concern of selecting resistant pathogens, according to the guidelines of the European Association of Urology antimicrobial prophylaxis should be considered only after counselling, behavioural modification and non-antimicrobial measures have been attempted. In postmenopausal patients vaginal substitution of oestriol should be started first. Oral or parenteral immunoprophylaxis is another option in patients with rUTI. Other possibilities with varying scientific evidence are prophylaxis with cranberry products, specific plant combinations or probiotics. The prophylaxis of catheter-associated UTI should employ strategies which result in a reduction of frequency and duration of catheter drainage of the urinary tract. The currently available catheter materials have only little influence on reducing catheter-associated rUTI.

Activity of the antiseptic polyhexanide against meticillin-susceptible and meticillin-resistant Staphylococcus aureus.

Staphylococcus aureus is one of the most important pathogens, with increasing emergence of meticillin-resistant S. aureus (MRSA) strains. This is associated not only with multiresistance to antibiotics but also with increasing resistance to topical antibiotics and antiseptics. As the antiseptic polyhexanide has only a low risk of emergence of resistant strains, the aim of the study was to obtain data on the sensitivity of S. aureus towards polyhexanide. The effect of polyhexanide was tested against 80 meticillin-susceptible S. aureus (MSSA) and 80 MRSA strains from sporadic cases as well as against 6 MRSA outbreak strains. The clonal diversity of the 166 strains was proven by pulsed-field gel electrophoresis (PFGE). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined by the serial broth microdilution technique according to DIN 58940. Time-kill studies were performed for reference strains MSSA ATCC 29213 and MRSA ATCC 33591. MICs and MBCs in the range of 0.5-2mg/L were found. According to a created epidemiological cut-off (ECOFF) value of 4mg/L, all strains were regarded as susceptible to polyhexanide, including MRSA epidemic strains and MSSA and MRSA sporadic strains with various antibiotic susceptibility patterns. Addition of up to 4% albumin to the test medium did not change the MICs and MBCs. Time-kill studies showed reduction rates of 4log10CFU/mL for 200mg/L and 5log10CFU/mL for 400mg/L polyhexanide within 5-30min. It is concluded that polyhexanide is suitable for topical eradication of S. aureus.

[Primary and secondary prevention of urinary tract infections]. / Primär- und Sekundärprävention von Harnwegsinfektionen.

Urinary tract infections (UTI) are among the most frequent bacterial infections in the community and health care setting. Mostly young and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI) defined as ≥3 UTI/year. On the other hand rUTI are frequently found in patients with complicating urological factors, e.g. urinary catheters. Modifiable predisposing factors in uncomplicated rUTI in women are rare. Continuous antibiotic prophylaxis or postcoital prophylaxis, if there is close correlation with sexual intercourse, are most effective to prevent rUTI. Nitrofurantoin, trimethoprim (or cotrimoxazole), and fosfomycin trometamol are available as first-line drugs. Oral cephalosporins and quinolones should be restricted to specific indications. Antibiotic prophylaxis reduces the number of uropathogens in the gut and/or vaginal flora and reduces bacterial"fitness". Given the correct indication, the recurrence rate of rUTI can be reduced by about 90%. In postmenopausal patients vaginal substitution of oestriol should be started first. Oral or parenteral immunoprophylaxis is another option in patients with rUTI. Other possibilities with varying scientific evidence are prophylaxis with cranberries or probiotics. The prophylaxis of catheter-associated UTI or asymptomatic bacteriuria should employ strategies which result in a reduction of frequency and duration of catheter drainage of the urinary tract. The currently available catheter materials have only little influence on reducing catheter-associated rUTI.