Florian Wagenlehner

Infective Complications After Prostate Biopsy: Outcome of the Global Prevalence Study of Infections in Urology (GPIU) 2010 and 2011, A Prospective Multinational Multicentre Prostate Biopsy Study

BACKGROUND Infection is a serious adverse effect of prostate biopsy (P-Bx), and recent reports suggest an increasing incidence. OBJECTIVE The aim of this multinational multicentre study was to evaluate prospectively the incidence of infective complications after P-Bx and identify risk factors. DESIGN, SETTING, AND PARTICIPANTS The study was performed as an adjunct to the Global Prevalence Study of Infections in Urology (GPIU) during 2010 and 2011. Men undergoing P-Bx in participating centres during the 2-wk period commencing on the GPIU study census day were eligible. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Baseline data were collected and men were questioned regarding infective complications at 2 wk following their biopsy. The Fisher exact test, Student t test, Mann-Whitney U test, and multivariate regression analysis were used for data analysis. RESULTS AND LIMITATIONS A total of 702 men from 84 GPIU participating centres worldwide were included. Antibiotic prophylaxis was administered prior to biopsy in 98.2% of men predominantly using a fluoroquinolone (92.5%). Outcome data were available for 521 men (74%). Symptomatic urinary tract infection (UTI) was seen in 27 men (5.2%), which was febrile in 18 (3.5%) and required hospitalisation in 16 (3.1%). Multivariate analysis did not identify any patient subgroups at a significantly higher risk of infection after P-Bx. Causative organisms were isolated in 10 cases (37%) with 6 resistant to fluoroquinolones. The small sample size per participating site and in compared with other studies may have limited the conclusions from our study. CONCLUSIONS Infective complications after transrectal P-Bx are important because of the associated patient morbidity. Despite antibiotic prophylaxis, 5% of men will experience an infective complication, but none of the possible factors we examined appeared to increase this risk. Our study confirms a high incidence of fluoroquinolone resistance in causative bacteria.

Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI)

BACKGROUND Treatment of complicated urinary-tract infections is challenging due to rising antimicrobial resistance. We assessed the efficacy and safety of ceftolozane-tazobactam, a novel antibacterial with Gram-negative activity, in the treatment of patients with complicated lower-urinary-tract infections or pyelonephritis. METHODS ASPECT-cUTI was a randomised, double-blind, double-dummy, non-inferiority trial done in 209 centres in 25 countries. Between July, 2011, and September, 2013, hospital inpatients aged 18 years or older who had pyuria and a diagnosis of a complicated lower-urinary-tract infection or pyelonephritis were randomly assigned in a 1:1 ratio to receive intravenous 1·5 g ceftolozane-tazobactam every 8 h or intravenous high-dose (750 mg) levofloxacin once daily for 7 days. The randomisation schedule was computer generated in blocks of four and stratified by study site. The next allocation was obtained by the study site pharmacist via an interactive voice-response system. The primary endpoint was a composite of microbiological eradication and clinical cure 5-9 days after treatment in the microbiological modified intention-to-treat (MITT) population, with a non-inferiority margin of 10%. This study is registered with ClinicalTrials.gov, numbers NCT01345929 and NCT01345955. FINDINGS Of 1083 patients enrolled, 800 (73·9%), of whom 656 (82·0%) had pyelonephritis, were included in the microbiological MITT population. Ceftolozane-tazobactam was non-inferior to levofloxacin for composite cure (306 [76·9%] of 398 vs 275 [68·4%] of 402, 95% CI 2·3-14·6) and, as the lower bound of the two-sided 95% CI around the treatment difference was positive and greater than zero, superiority was indicated. Adverse event profiles were similar in the two treatment groups and were mainly non-serious. INTERPRETATION Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis. FUNDING Cubist Pharmaceuticals.

A Pollen Extract (Cernilton) in Patients with Inflammatory Chronic Prostatitis–Chronic Pelvic Pain Syndrome: A Multicentre, Randomised, Prospective, Double-Blind, Placebo-Controlled Phase 3 Study

BACKGROUND National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists. OBJECTIVES To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS. DESIGN, SETTING, AND PARTICIPANTS We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres. INTERVENTION Participants were randomised to receive oral capsules of the pollen extract (two capsules q8h) or placebo for 12 wk. MEASUREMENTS The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post-prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk. RESULTS AND LIMITATIONS In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract (n=70) or placebo (n=69). The individual domains pain (p=0.0086) and quality of life (QoL; p=0.0250) as well as the total NIH-CPSI score (p=0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% (p=0.0141), respectively. Adverse events were minor in all patients studied. CONCLUSIONS Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.

Spectrum and antibiotic resistance of uropathogens from hospitalised patients with urinary tract infections: 1994–2005

From 1994-2005, all uropathogens cultured from the urine of hospitalised urological patients were identified and their sensitivity was tested against the most important antibiotics for the treatment of urinary tract infection (UTI). Duplicate isolates were eliminated. The following results were obtained: (i) there was no general trend of increase in resistance; (ii) certain uropathogens developed resistance to some antibiotics; (iii) vancomycin- or linezolid-resistant staphylococci or enterococci did not play a role; (iv) the lowest overall rates of resistance were found with piperacillin/tazobactam; and (v) ciprofloxacin and trimethoprim/sulfamethoxazole showed the next favourable overall activity. Adequate initial antibiotic therapy is critical in the treatment of severe UTI. Therefore, ongoing surveillance of antibiotic resistance must be performed in every institution. Additionally, it reflects antibiotic and hospital infection policies in a defined department or institution.

Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program.

There is an urgent need for new strategies to reduce carbapenem consumption. Ceftazidime-avibactam was highly effective for empiric treatment of complicated urinary tract infection, including in patients with ceftazidime-nonsusceptible pathogens, and may offer an alternative to carbapenems in this setting.

Update on biofilm infections in the urinary tract

PurposeBiofilm infections have a major role in implants or devices placed in the human body. As part of the endourological development, a great variety of foreign bodies have been designed, and with the increasing number of biomaterial devices used in urology, biofilm formation and device infection is an issue of growing importance.MethodsA literature search was performed in the Medline database regarding biofilm formation and the role of biofilms in urogenital infections using the following items in different combinations: “biofilm,” “urinary tract infection,” “bacteriuria,” “catheter,” “stent,” and “encrustation.” The studies were graded using the Oxford Centre for Evidence-based Medicine classification.ResultsThe authors present an update on the mechanism of biofilm formation in the urinary tract with special emphasis on the role of biofilms in lower and upper urinary tract infections, as well as on biofilm formation on foreign bodies, such as catheters, ureteral stents, stones, implants, and artificial urinary sphincters. The authors also summarize the different methods developed to prevent biofilm formation on urinary foreign bodies.ConclusionsSeveral different approaches are being investigated for preventing biofilm formation, and some promising results have been obtained. However, an ideal method has not been developed. Future researches have to aim at identifying effective mechanisms for controlling biofilm formation and to develop antimicrobial agents effective against bacteria in biofilms.

Use of the UPOINT Chronic Prostatitis/Chronic Pelvic Pain Syndrome Classification in European Patient Cohorts: Sexual Function Domain Improves Correlations

PURPOSE Patients with chronic prostatitis-chronic pelvic pain syndrome are difficult to treat due to the unknown etiology and complex clinical presentation. Clinical phenotyping may better correlate with multimodal treatment concepts than a current diagnosis. We evaluated a novel clinical phenotyping system in a database of patients with chronic prostatitis-chronic pelvic pain syndrome at 2 European institutions and correlated it with patient symptoms. We also investigated the addition of a sexual dysfunction domain in regard to symptom correlation and system internal consistency. MATERIALS AND METHODS We retrospectively classified 937 patients from Milan, Italy, and 290 from Giessen, Germany, with chronic prostatitis-chronic pelvic pain syndrome into a 6-domain phenotyping system, consisting of urinary, psychosocial, organ specific, infection, neurological and muscle tenderness domains, termed UPOINT. Symptom severity was assessed by the National Institutes of Health Chronic Prostatitis Symptom Index and the International Prostate Symptom Score. RESULTS There was significant correlation between the number of positive UPOINT domains and Chronic Prostatitis Symptom Index/International Prostate Symptom Score symptoms in the total and Italian cohorts but not in the German cohort. After adding a sexual dysfunction domain to create the modified UPOINTS system phenotypic domains also correlated significantly with Chronic Prostatitis Symptom Index symptoms in the German cohort. CONCLUSIONS Consistency of the UPOINT chronic prostatitis-chronic pelvic pain syndrome clinical phenotyping system was generally confirmed by our study and further refined by adding a sexual dysfunction domain. The treatment effect of clinical phenotyping with UPOINT(S) must be extensively evaluated in prospective treatment studies.

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 patients 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.

Preoperative assessment of the patient and risk factors for infectious complications and tentative classification of surgical field contamination of urological procedures

PurposeTo assess the patient and identify the risk factors for infectious complications in conjunction with urological procedures and suggest a model for classification of the procedures.MethodReview of literature, critical analysis of data and tentative model for reducing infectious complications.ResultsRisk factors are bound to the patient and to the procedure itself and are associated with the environment where the healthcare is provided. Assuming a clean environment and sterile operation field, a five-level assessment ladder related to the patient and type of surgery is useful, considering: (1) the ASA score, (2) the general risk factors, (3) the individual endogenous and exogenous risk factors, (4) the class of surgery and the potential bacterial contamination burden and (5) the level of severity and difficulty of the surgical intervention. A cumulative approach will identify the level of risk for each patient and define preventive measures, such as the type of antibiotic prophylaxis or therapeutic measures before surgery. There are data suggesting that the higher the ASA score, the higher is the risk of infectious complication. Age, dysfunction of the immune system, hypo-albuminaemia/malnutrition and overweight, uncontrolled blood glucose level and smoking are independent general risk factors, whilst bacteriuria, indwelling catheter treatment, urinary tract stone disease, urinary tract obstruction and a history of urogenital infection are specific urological risk factors. There is inconclusive evidence for most other reported risk factors. The level of contamination of the surgical field is of utmost importance as are the procedure-related factors, and the sum of these have to be reflected on for the subsequent perioperative management of the patient.ConclusionsIt is essential to identify and control risk factors to minimize infectious complications in conjunction with urological procedures. Our knowledge is limited and clinical research and quality registries analysing risk factors must be undertaken. We propose a working basis for assessment of patients’ risk factors and classification of urological procedures.

An update on uncomplicated urinary tract infections in women.

Purpose of review Urinary tract infections (UTIs) in women comprise uncomplicated and complicated UTIs. Uncomplicated UTIs, such as acute uncomplicated cystitis and pyelonephritis, are very common infections in otherwise healthy women, with a high tendency to recur. Although severe complications are rare, their high prevalence causes remarkable costs in the healthcare systems. Recent findings As most scientific evidence has been gathered in uncomplicated UTI, this study focuses on recent developments in epidemiology, pathogenesis, cause, diagnosis, treatment and prevention of uncomplicated UTI and recurrent UTI in women. Summary A remarkable increase of antibiotic resistance is also noted in uncomplicated UTI. Therefore, prudent use of antibiotic substances in uncomplicated UTI is increasingly important.