Decreasing susceptibility of bacteria to ampicillin/ sulbactam and third generation cephalosporins in urinary tract infections.

Background: Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and have become more difficult to treat over the years. Inappropriate antibiotic use has led to increased antibiotic resistance. Materials and methods: We examined 1921 urine culture samples from a single hospital and analyzed them for bacterial spectrum and antibiotic susceptibility. We further analyzed changes in the rates of detected bacteria and of the sensitivity of these uropathogens to antibiotics over the years. Results: In our hospital-based analysis, cystitis was the most frequently diagnosed UTI in women (76%) and men (79%). Escherichia coli (48%) was the most commonly identified uropathogen. Samples demonstrated an increase in the proportion of E. coli (p < 0.001) and a decrease in Enterococcus faecalis (p < 0.001) over the study time period. Antimicrobial susceptibility analysis showed an increase over time in the number of isolates with resistance to ampicillin/sulbactam (p < 0.001) and to third-generation cephalosporins cefotaxime (p = 0.043) and ceftazidime (p < 0.001). Conclusions: Ampicillin/sulbactam and third-generation cephalosporins are antibiotics frequently used in the treatment of UTIs. When selecting an optimal antimicrobial treatment regimen for patients with UTIs, it is imperative to understand regional and timedependent differences in the prevalence of various uropathogens and antimicrobial resistance patterns. Therefore, continuous surveillance of local pathogen and antimicrobial susceptibility patterns for frequently used antibiotics should be prioritized.

Efficacy of vaccination with StroVac for recurrent urinary tract infections in women: a comparative single-centre study.

PURPOSE: To assess the efficacy of prophylaxis for urinary tract infections (UTI) in a two-year follow-up in women with StroVac compared to a therapy with Nitrofurantoin over three months. MATERIALS AND METHODS: All patients with documented recurrent urinary tract infections (rUTI) were offered vaccination with StroVac or therapy with three months Nitrofurantoin 100 mg once daily for three months at patient's choice. Only patients with a follow-up of at least 24 months were included. All episodes with signs of UTI were documented and urine culture was performed. Success was defined as one or none UTI per 12 months, documented by urine culture. StroVac booster injection was offered 12 months after primary vaccination at patient's choice. RESULTS: 173 patients were included in this study, 124 in the StroVac group, 49 chose Nitrofuratoin. In the first 12 months, 86.8% of patients in the StroVac group and 91.8% in Nitrofurantoin group were successful (p = 0.22). Side effects were noted in 2.3% in the StroVac group causing discontinuation of therapy, whereas in the Nitrofurantoin group 18.4% stopped medication premature, mostly due to mild diarrhoea. In the second year 79.3% of patients in the StroVac group were still successful, most of them had undergone booster injection. In contrast, in the Nitrofurantoin group only 59.2% of patients were still successful (p = 0.03). CONCLUSION: StroVac is an effective and lasting non-antibiotic prophylaxis for rUTI, easy to administer with low rates of adverse events and should be offered to patients with rUTI.

Size does matter: ureteral stents with a smaller diameter show advantages regarding urinary symptoms, pain levels and general health.

OBJECTIVE: To compare the effect of different diameters of ureteral stents (F4.7, F6, and F7) on quality of life regarding the subdomains of the Ureteral Stent Symptom Questionnaire. MATERIALS AND METHODS: All patients undergoing URS between April 2016 and July 2017 were prospectively randomised for ureteral stents F4.7, F6 and F7, respectively. All patients with other pathologies than a ureter stone, ureteral stents on both sides or other therapy than a secondary URS were excluded. Readmitted patients were interviewed using the USSQ. Furthermore, success rates of the second URS were also noted. RESULTS: Between April 2016 to July 2017, 181 patients were included, 48 with a ureteral stent F4.6, 66 with F6 and 67 with F7. No significant differences in age, gender or position of the stones before URS were found (all p > 0.5). Comparing scores of USSQ between F4.7 and F6 or F6 and F7, scores were in favour of the smaller stent, but significance was only reached in "Work performance score" (F6-F7, p = 0.04) and "Urinary index score" (F4.7-F6, p = 0.004). When comparing F4.7 with F7, significant differences in all subgroups in favour of F4.7 were documented (all p < 0.03). Surgical success of the second URS was comparable in all groups (all above 82%, p > 0.15). CONCLUSION: Discomfort and pain increase with the diameter of the indwelling ureter stent, while the success of the following URS is not compromised by a ureter stent with a smaller diameter. Therefore, ureteral stents with a small diameter should be preferred.

Surgical treatment of large volume prostates: a matched pair analysis comparing the open, endoscopic (ThuVEP) and robotic approach.

OBJECTIVE: To compare open simple prostatectomy, endoscopic enucleation and laparoscopic, robot-assisted enucleation of high-volume prostate in terms of operation time, blood loss, transfusion and complication rates and early continence rates. MATERIAL AND METHODS: Patients with BPH treated endoscopically (ThuVEP, Hamburg and Hannover) or robotically (Mainz) were evaluated prospectively for prostate size, free flow and validated questionnaires (IPSS, QoL). 35 patients were matched to patients after open prostatectomy (Mainz) for age, prostate size, IPSS and QoL scores. Operation time was noted from the first cut to the last suture; blood loss was estimated by the drop of haemoglobin preoperatively and one day after surgery. Transfusion rates were documented. Early continence was estimated by pad use over the first 24 h after catheter removal. Statistical analysis was performed with SPSS 22.0. RESULTS: No significant differences in prostate size, age and preoperative questionnaires were found (p > 0.3). Postoperative flow and the results of the questionnaires were significantly improved (all p < 0.05), without difference between the approaches (p > 0.8). Endoscopic surgery showed superiority in operation time (both p < 0.05); blood loss and transfusion rates were significantly lower compared to open surgery (both p < 0.01) and lower than in robotic surgery without reaching significance (p = 0.18, p = 0.36). Similar results were seen in early continence rates. CONCLUSION: Due to our results, endoscopic surgery should be considered as first-line therapy unless there are comorbidities like diverticula and/or bladder calculi that can be easily treated simultaneously by robotic surgery. Against the background of these findings, indications favouring open surgery are getting sparse.

Long-term results of ProACT primary and repeat implantation for treatment of stress urinary incontinence in men.

INTRODUCTION: Urinary incontinence in men after radical prostatectomy affects strongly quality of life. If conservative treatment fails, surgical treatment consists of implantable devices. If the requirement of manual dexterity in the artificial sphincter is to be avoided, the ProACT system offers a readjustable system, which shows good continence, but also high revision rates. Aim of our single-centre, single-surgeon study was to evaluate the success and revision rates of ProACT over long-term follow-up and if repeat ProACT implantation after failure would be a reasonable strategy. MATERIALS AND METHODS: In May 2017, follow-up of all patients who underwent ProACT implantation between 2003 and 2013 was obtained. Parameters were numbers of pads used, filling volume of balloons, and patient-reported satisfaction. Furthermore, revisions were noted. RESULTS: Between 2003 and 2013, 134 patients were implanted a ProACT system. Median age was 71 years; median follow-up was 118 months. 112 implantations were successful (82.6%) and the number of pads used decreased significantly (p < 0.005). 63 patients were revised and 49 were successful (77.8%). No differences in success rate, pads used, or filling volume were seen (all p > 0.8). In a second revision, again, no differences in success rate or pads used were noted (all p > 0.7). Patients' personal satisfaction was high despite the high revision rate. CONCLUSION: In the hands of an experienced surgeon, ProACT is a safe and effective therapy for post-prostatectomy incontinence especially if mayor surgery is to be avoided. Revision rates are high, but the results of ProACT reimplantation are comparable to the results after the first implantation.

Risk-adjusted proposal for >60 months follow up after surgical treatment of organ-confined renal cell carcinoma according to life expectancy.

OBJECTIVES: To determine the long-term oncological outcome of organ-confined (

Incidence of Cardiovascular Events after Nephrectomy - A Single Centre, Matched Pair Analysis between Donor and Tumour Nephrectomy in a Long Term Follow-Up.

INTRODUCTION: The study aimed to compare the incidence of cardiovascular events (CVEs) after donor nephrectomy (DN) and radical tumor nephrectomy (RN), according to an estimated glomerular filtration rate (eGFR), were evaluated over time. MATERIALS AND METHODS: Follow-up was collected for DN who underwent surgery from 1998 to 2007 for CVE and renal function. All DN were matched for age to patients treated by RN or adenoma enucleation (control group), who were eligible for DN. eGFR was estimated using the Cockgroft-Gould formula. Patients with preoperative comorbidities were excluded. RESULTS: Thirty DN (median age 48.9 years) were included with a median follow-up of 138.5 months (interquartile range 119-159). No significant differences in patients' characteristics were found preoperatively (p > 0.5). Four out of 30 DN developed a CVE (3 myocardial infarctions (MI), 1 stroke), 2 of 30 patients in the control group (both MI) and 8 of 30 RN patients (6 MI, 2 strokes, p > 0.05). Arterial hypertension developed in 14 DN (46.7%), in 12 (40%) after RN and in 15 controls. The CVE occurred after a median time of 68 months (5-231) and were related to a drop of ∼30% in the eGFR irrespective of the group. CONCLUSION: Decline of renal function after nephrectomy is the main risk factor for CVE. Close monitoring of renal function and new onset hypertension is warranted.

Concomitant Gleason Score ≥ 7 prostate cancer is an independent prognosticator for poor survival in nonmetastatic bladder cancer patients undergoing radical cystoprostatectomy.

PURPOSE: In bladder cancer (BCa) patients undergoing radical cystoprostatectomy (RCPx), concomitant prostate cancer (PCa) is a common finding. Up to now there is no clear evidence to suggest that concomitant PCa is a predictor of outcome in these patients. Aim of this study was to assess incidence and clinicopathologic characteristics of concomitant PCa in RCPx specimen and correlate it to survival parameters from a single-centre material over two decades. METHODS: All men who had undergone RCPx for BCa at our institution between 1994 and 2013 were included in this study. Clinicopathologic parameters for BCa and PCa were evaluated and correlated with outcome parameters. Survival analysis was performed for the subgroup of nonmetastatic organ-confined BCa to evaluate the role of concomitant Gleason Score (GS) ≥7 PCa. RESULTS: Of 945 men who had undergone RCPx for BCa, concomitant PCa was present in 237 patients (25.1 %). There was a significant increase in PCa incidence from 18.9 to 32.3 % between 1994 and 2013 (p = 0.009). Concomitant PCa represented a more aggressive phenotype at the end of the study (p = 0.037). In nonmetastatic organ-confined BCa, concomitant GS ≥7 PCa (HR 3.09; p = 0.0001) and age > 68 (HR 1.80; p = 0.0004) were independent negative predictors for overall survival. CONCLUSIONS: Concomitant PCa in RCPx specimen of BCa patients is a common finding. The incidence of concomitant PCa has significantly increased within 2 decades, presenting a more aggressive phenotype. Age and in particular concomitant GS ≥7 PCa are independent prognosticators for poor survival in patients with nonmetastatic organ-confined BCa.

Pancreatic Fistulae after Urologic Surgery - A Single Centre Experience.

INTRODUCTION: To evaluate incidence, symptoms and management of postoperative pancreatic fistula (POPF) after urologic surgery based on our experience. MATERIAL AND METHODS: Database was searched for clinically evident POPF after urologic surgery between 1998 and 2014. Fistulae were graded using the POPF classification. Clinical course of every POPF patient was evaluated. RESULTS: During this time, 3,200 surgeries for renal, adrenal and retroperitoneal pathologies were performed. Twelve POPF occurred postoperatively in this series. Eight fistulae were POPF grade A, 3 POPF grade B and one POPF grade C. POPF became clinically evident after a median of 3 days (IQR 2-3). In all POPF grade A/B patients, secretion from the pancreatic fistula completely subsided under conservative therapy. In one POPF grade C patient with positive surgical margins of urothelial cancer, conservative treatment failed and the patient died due to POPF-related sepsis. CONCLUSIONS: POPF is a rare complication after urologic surgery. Conservative therapy is the first choice of treatment and will be successful in the majority of cases. Pancreatic fistula after surgery of recurrent malignancy may have a poor outcome.

Pregnane X receptor and yin yang 1 contribute to the differential tissue expression and induction of CYP3A5 and CYP3A4.

The hepato-intestinal induction of the detoxifying enzymes CYP3A4 and CYP3A5 by the xenosensing pregnane X receptor (PXR) constitutes a key adaptive response to oral drugs and dietary xenobiotics. In contrast to CYP3A4, CYP3A5 is additionally expressed in several, mostly steroidogenic organs, which creates potential for induction-driven disturbances of the steroid homeostasis. Using cell lines and mice transgenic for a CYP3A5 promoter we demonstrate that the CYP3A5 expression in these organs is non-inducible and independent from PXR. Instead, it is enabled by the loss of a suppressing yin yang 1 (YY1)-binding site from the CYP3A5 promoter which occurred in haplorrhine primates. This YY1 site is conserved in CYP3A4, but its inhibitory effect can be offset by PXR acting on response elements such as XREM. Taken together, the loss of YY1 binding site from promoters of the CYP3A5 gene lineage during primate evolution may have enabled the utilization of CYP3A5 both in the adaptive hepato-intestinal response to xenobiotics and as a constitutively expressed gene in other organs. Our results thus constitute a first description of uncoupling induction from constitutive expression for a major detoxifying enzyme. They also suggest an explanation for the considerable tissue expression differences between CYP3A5 and CYP3A4.

The unique complexity of the CYP3A4 upstream region suggests a nongenetic explanation of its expression variability.

OBJECTIVE: The individually variable and unpredictable expression of CYP3A4 compromises therapies with 50% of contemporary drugs. Gene variants explain only a fraction of this variability. METHODS: We investigated the evolution of CYP3A4 transcriptional regulation by nuclear receptors such as the xenobiotics sensors PXR and CAR. RESULTS: The combination of a proximal ER6 element with XREM and CLEM represents the original scheme of CYP3A regulation by nuclear receptors in placental mammals. Among human CYP3A genes, this scheme is retained only in CYP3A4, whereas non-CYP3A4 genes lost these elements to a variable extent during primate evolution. In parallel, the number of elements outside XREM and CLEM potentially responsive to PXR and CAR increased in primate CYP3A4 orthologs, which led to enhanced CYP3A4 inducibility. Additions to the other primate CYP3A genes were more restricted and specific, as exemplified by a CYP3A5 DR4 site responsive to CAR, but not to PXR. All these changes resulted in human CYP3A4 having a much more complex upstream regulatory region in comparison to its paralogs. CONCLUSION: Instead of gene variants, the intraindividual CYP3A4 expression variability in humans may be primarily caused by particular sensitivity of this gene to endogenous and exogenous PXR and CAR ligands conferred by the unique complexity of its upstream regulatory region.