Resistance to Mecillinam and Nine Other Antibiotics for Oral Use in Escherichia coli Isolated from Urine Specimens of Primary Care Patients in Germany, 2019/20

Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Escherichia coli is by far the leading cause of community-acquired UTIs. Pivmecillinam, the oral prodrug of the penicillin derivative mecillinam (amdinocillin), was re-introduced in Germany in March 2016 for first-line treatment of acute uncomplicated cystitis. This study aimed to evaluate the prevalence of resistance to mecillinam in comparison to nine other antibiotics used for oral treatment in E. coli urine isolates after the re-introduction of pivmecillinam. A total of 460 isolates were collected at 23 laboratories of clinical microbiology between October 2019 and March 2020. Forty-six isolates (10.0%) produced an extended-spectrum β-lactamase (ESBL) of the CTX-M family. Resistance to amoxicillin (43.3%) was most widespread, followed by resistance to trimethoprim-sulfamethoxazole (27.0%), amoxicillin-clavulanic acid (18.0%), cefuroxime (11.3%), and ciprofloxacin (11.1%). Twenty-four E. coli isolates (5.2%) were resistant to mecillinam. The concentrations of mecillinam needed to inhibit 50/90% of the ESBL-producing isolates and the remaining isolates were 1/4 mg/L and 0.5/4 mg/L, respectively. The findings support the recommendation to regard pivmecillinam as a first-line option for the treatment of uncomplicated lower UTIs.Peer Reviewe

Metagenomics in diagnosis and improved targeted treatment of UTI

INTRODUCTION: The genomic revolution has transformed our understanding of urinary tract infection. There has been a paradigm shift from the dogmatic statement that urine is sterile in healthy people, as we are becoming forever more familiar with the knowledge that bacterial communities exist within the urinary tracts of healthy people. Metagenomics can investigate the broad populations of microbial communities, analysing all the DNA present within a sample, providing comprehensive data regarding the state of the microenvironment of a patient's urinary tract. This permits medical practitioners to more accurately target organisms that may be responsible for disease-a form of 'precision medicine'. METHODS AND RESULTS: This paper is derived from an extensive review and analysis of the available literature on the topic of metagenomic sequencing in urological science, using the PubMed search engine. The search yielded a total of 406 results, and manual selection of appropriate papers was subsequently performed. Only one randomised clinical trial comparing metagenomic sequencing to standard culture and sensitivity in the arena of urinary tract infection was found. CONCLUSION: Out of this process, this paper explores the limitations of traditional methods of culture and sensitivity and delves into the recent studies involving new high-throughput genomic technologies in urological basic and clinical research, demonstrating the advances made in the urinary microbiome in its entire spectrum of pathogens and the first attempts of clinical implementation in several areas of urology. Finally, this paper discusses the challenges that must be overcome for such technology to become widely used in clinical practice

Cost-effectiveness analysis of ceftazidime/avibactam compared to imipenem as empirical treatment for complicated urinary tract infections

Abstract Ceftazidime/avibactam (CAZ-AVI) is a novel, fixed-dose combination antibiotic that has been approved in Europe and the United States for patients with complicated urinary tract infections (cUTIs) based on results of a Phase III, randomized, comparative study (RECAPTURE study). The present analysis evaluated cost-effectiveness of CAZ-AVI as an empirical treatment for hospitalized patients with cUTIs from the Italian publicly funded healthcare (third-party payer) perspective. A sequential, patient-level simulation model was developed that followed the clinical course of cUTI and generated 5000 pairs of identical patients (CAZ-AVI or imipenem as empirical treatment). The model included additional impact of resistant pathogens; patients who did not respond to empirical treatment were switched to second-line treatment of colistin+high dose carbapenem in both groups. The time horizon of the model was five years, with an annual discount rate of 3% applied to both costs and quality-adjusted life-years (QALYs). The analysis demonstrated that an intervention sequence (CAZ-AVI followed by colistin+high dose carbapenem) compared with a comparator sequence (imipenem followed by colistin+high dose carbapenem) was associated with a net incremental cost of €1015 per patient but provided better health outcomes in terms of clinical cure (97.65% vs. 91.08%; ∆ = 6.57%), shorter hospital stays (10.65 vs. 12.55 days; ∆ = 1.90 days), and QALYs gained per patient (4.190 vs. 4.063; ∆ = 0.126). The incremental cost-effectiveness ratio was €8039/QALY, which is well below the willingness-to-pay threshold of €30 000/QALY in Italy. The results showed that CAZ-AVI is expected to be a cost-effective treatment compared with imipenem for cUTI in Italy

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients: Part 1

Objectives: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Materials and Methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, ­EMBASE, and the Cochrane Library to identify literature published in 2010–2015. Results: We provide 75 recommendations and 68 statements in the updated evidence- and consensus-based national clinical guideline. The diagnostics part covers practical recommendations on cystitis and pyelonephritis for each defined patient group. Clinical examinations, as well as laboratory testing and microbiological pathogen assessment, are addressed. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients. Part II: Therapy and Prevention

Background: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. Materials and Methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010–2015. Results: For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients

Clinical and microbiological outcomes of ceftazidime-avibactam treatment in adults with Gram-negative bacteremia: A subset analysis from the phase 3 clinical trial program

INTRODUCTION: This exploratory analysis assessed efficacy and safety outcomes in patients with Gram-negative bacteremia treated with ceftazidime-avibactam or comparator across five phase 3, randomized, controlled, multi-center trials in adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI)/pyelonephritis, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). METHODS: In each trial, RECLAIM and RECLAIM 3 (cIAI; NCT01499290/NCT01726023), REPRISE (cIAI/cUTI; NCT01644643), RECAPTURE (cUTI; NCT01595438/NCT01599806), and REPROVE (HAP/VAP; NCT01808092), patients were randomized 1:1 to intravenous ceftazidime-avibactam (plus metronidazole for those with cIAI) or comparators (carbapenems in \u3e 97% patients) for 5-21 days. Efficacy assessments included clinical and microbiological responses at the test-of-cure visit in the pooled Gram-negative extended microbiologically evaluable (GNeME) population (bacteremia subset). Safety outcomes were summarized for patients with positive bacterial blood culture(s) at baseline who received ≥ 1 dose of study treatment. RESULTS: The overall safety population included 4050 patients (ceftazidime-avibactam, n = 2024; comparator, n = 2026). The GNeME population (bacteremia subset) comprised 101 patients (ceftazidime-avibactam, n = 54; comparator, n = 47). Clinical cure rates (all indications combined) were 47/54 (87.0%) for ceftazidime-avibactam and 39/47 (83.0%) for comparators; favorable microbiological response rates were 43/54 (79.6%) and 32/47 (68.1%), respectively. Clinical and microbiological responses in the bacteremia subset were generally similar to those in the overall set. The pattern of adverse events in patients with bacteremia was similar between treatment groups and was consistent with the known safety profile of ceftazidime-avibactam. CONCLUSION: This analysis provides supportive evidence of the efficacy and safety of ceftazidime-avibactam in patients with Gram-negative bacteremia associated with cIAI, cUTI/pyelonephritis, or HAP/VAP

Systematic review and meta-analysis provide no guidance on management of asymptomatic bacteriuria within the first year after kidney transplantation

Producción Científica(1) Background: Urinary tract infections (UTIs) are among the most frequent complications in kidney transplant (KT) recipients. Asymptomatic bacteriuria (ASB) may be a risk factor for UTIs and graft rejection. We aimed to evaluate available evidence regarding the benefit of screening and treatment of ASB within the first year after KT. (2) Evidence acquisition: A systematic literature search was conducted in MEDLINE, the Cochrane Library CENTRAL and Embase. Inclusion criteria were manuscripts in English addressing the management of ASB after KT. The PICO questions concerned Patients (adults receiving a KT), Intervention (screening, diagnosis and treatment of ASB), Control (screening and no antibiotic treatment) and Outcome (UTIs, sepsis, kidney failure and death). (3) Evidence synthesis: The systematic review identified 151 studies, and 16 full-text articles were evaluated. Seven were excluded because they did not evaluate the effect of treatment of ASB. There was no evidence for a higher incidence of lower UTIs, acute pyelonephritis, graft loss, or mortality in patients not treated with antibiotics for ASB. Analysis of comparative non-randomized and observational studies did not provide supplementary evidence to guide clinical recommendations. We believe this lack of evidence is due to confounding risk factors that are not being considered in the stratification of study patients

Non-antibiotic strategies for the prevention of infectious complications following prostate biopsy : A Systematic Review and Meta-analysis

Acknowledgments Emma Smith from the EAU Guidelines Office assisted with the systematic review, and Robert Pickard (deceased), Newcastle upon Tyne, United Kingdom, initiated this review.Peer reviewedPostprin

Asymptomatic bacteriuria in clinical urological practice : preoperative control of bacteriuria and management of recurrent UTI

Asymptomatic bacteriuria (ABU) is a common clinical condition that often leads to unnecessary antimicrobial use. The reduction of antibiotic overuse for ABU is consequently an important issue for antimicrobial stewardship and to reduce the emergence of multidrug resistant strains. There are two issues in everyday urological practice that require special attention: the role of ABU in pre-operative prophylaxis and in women affected by recurrent urinary tract infections (rUTIs). Nowadays, this is the time to think over our practice and change our way of thinking. Here, we aimed to summarize the current literature knowledge in terms of ABU management in patients undergoing urological surgery and in patients with rUTIs. In the last years, the approach to patient with ABU has changed totally. Prior to all surgical procedures that do not enter the urinary tract, ABU is generally not considered as a risk factor, and screening and treatment are not considered necessary. On the other hand, in the case of all procedures entering the urinary tract, ABU should be treated in line with the results of a urine culture obtained before the procedure. In patients affected by rUTIs, ABU can even have a protective role in preventing symptomatic recurrence, particularly when Enterococcus faecalis (E. faecalis) has been isolated