Immunomodulation therapy offers new molecular strategies to treat UTI.

Innovative solutions are needed for the treatment of bacterial infections, and a range of antibacterial molecules have been explored as alternatives to antibiotics. A different approach is to investigate the immune system of the host for new ways of making the antibacterial defence more efficient. However, the immune system has a dual role as protector and cause of disease: in addition to being protective, increasing evidence shows that innate immune responses can become excessive and cause acute symptoms and tissue pathology during infection.

Immunomodulation-A Molecular Solution to Treating Patients with Severe Bladder Pain Syndrome?

Background: Patients with bladder pain syndrome experience debilitating pain and extreme frequency of urination. Numerous therapeutic approaches have been tested, but as the molecular basis of disease has remained unclear, specific therapies are not available.

Objective: Recently, a systematic gene deletion strategy identified interleukin-1 (IL-1) hyperactivation as a cause of severe cystitis in a murine model.

Active bacterial modification of the host environment through RNA polymerase II inhibition.

Unlike pathogens, which attack the host, commensal bacteria create a state of friendly coexistence. Here, we identified a mechanism of bacterial adaptation to the host niche, where they reside. Asymptomatic carrier strains were shown to inhibit RNA polymerase II (Pol II) in host cells by targeting Ser2 phosphorylation, a step required for productive mRNA elongation.

Biomarkers in urinary tract infections - which ones are suitable for diagnostics and follow-up?

Urinary tract infections (UTIs) are one of the most common infections worldwide. Under special circumstances, clinicians must rely on laboratory findings, which might have a weak predicting value, misguiding the practitioners and leading to incorrect diagnosis and overuse of antibiotics. Therefore, there is an urgent need for reliable biomarkers in UTIs.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury.

Fimbriae reprogram host gene expression - Divergent effects of P and type 1 fimbriae.

Pathogens rely on a complex virulence gene repertoire to successfully attack their hosts. We were therefore surprised to find that a single fimbrial gene reconstitution can return the virulence-attenuated commensal strain Escherichia coli 83972 to virulence, defined by a disease phenotype in human hosts. E.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury.

Transurethral Resection of the Prostate: are We Following the Guidelines? - Outcomes from the Global Prevalence of Infections in Urology (GPIU) Study.

Transurethral resection of the prostate (TURP) is one of the most common urological procedures. With the increasing rate of multiresistant infections including urosepsis, it is essential for all surgeons to adhere to the relevant international guidelines to prevent infectious complications. The aim of this prospective, multinational, multicentre study was to evaluate compliance with recommended infection control measures regarding TURP procedures.

Neuroepithelial control of mucosal inflammation in acute cystitis.

The nervous system is engaged by infection, indirectly through inflammatory cascades or directly, by bacterial attack on nerve cells. Here we identify a neuro-epithelial activation loop that participates in the control of mucosal inflammation and pain in acute cystitis. We show that infection activates Neurokinin-1 receptor (NK1R) and Substance P (SP) expression in nerve cells and bladder epithelial cells in vitro and in vivo in the urinary bladder mucosa.

Asymptomatic Bacteriuria is Harmless and Even Protective: Don't Treat if You Don't Have a Very Specific Reason.

Symptom-free bacterial colonization of the lower urinary tract in an otherwise healthy individual was long misunderstood. Our current understanding is based on solid research proving that asymptomatic bacteriuria (ABU) is harmless and even protective against symptomatic urinary tract infection episodes. Thus, ABU should not be treated in patients with the exception of before endosurgery and, until we have accumulated more knowledge, in pregnant women.

Benefits and Harms of Treatment of Asymptomatic Bacteriuria: A Systematic Review and Meta-analysis by the European Association of Urology Urological Infection Guidelines Panel.

Unlabelled: People with asymptomatic bacteriuria (ABU) are often unnecessarily treated with antibiotics risking adverse effects and antimicrobial resistance. We performed a systematic review to determine any benefits and harms of treating ABU in particular patient groups. Relevant databases were searched and eligible trials were assessed for risk-of-bias and Grading of Recommendations, Assessment, Development and Education quality.

Social and economic burden of recurrent urinary tract infections and quality of life: a patient web-based study (GESPRIT).

Background: Uncomplicated lower urinary tract infections (UTIs) occur in approximately 50% of women, and 20-30% experience recurrent UTI. Data on UTIs and quality of life (QoL) in Europe are limited.

Methods: This was an anonymous, self-administered web-based survey conducted in 5 countries (Germany, Switzerland, Poland, Russia and Italy), on adult women who had experienced recurrent UTI and were affected by acute UTI currently or within 4 weeks of study entry.

The Global Prevalence of Infections in Urology (GPUI) Study: A Worldwide Surveillance Study in Urology Patients.

The GPIU study is currently the only study registering health care-associated urogenital tract infections, especially in urology patients, in an ongoing surveillance protocol that can help to deliver data on adequate empirical antibiotic therapy in hospitalised urology patients according to guideline recommendations. The annual GPIU study will continue to be performed in November of each year under the URL http://gpiu.esiu.

Triggered Urine Interleukin-6 Correlates to Severity of Symptoms in Nonfebrile Lower Urinary Tract Infections.

Purpose: Objective diagnosis of symptomatic urinary tract infections in patients prone to asymptomatic bacteriuria is compromised by local host responses that are already present and the positive urine culture. We investigated interleukin-6 as a biomarker for nonfebrile urinary tract infection severity and diagnostic thresholds for interleukin-6 and 8, and neutrophils to differentiate between asymptomatic bacteriuria and urinary tract infection.

Materials And Methods: Patients with residual urine and neurogenic bladders due to spinal lesions included in a long-term Escherichia coli 83972 asymptomatic bacteriuria inoculation trial were monitored for 2 years.

Molecular Basis of Acute Cystitis Reveals Susceptibility Genes and Immunotherapeutic Targets.

Unlabelled: Tissue damage is usually regarded as a necessary price to pay for successful elimination of pathogens by the innate immune defense. Yet, it is possible to distinguish protective from destructive effects of innate immune activation and selectively attenuate molecular nodes that create pathology. Here, we identify acute cystitis as an Interleukin-1 beta (IL-1β)-driven, hyper-inflammatory condition of the infected urinary bladder and IL-1 receptor blockade as a novel therapeutic strategy.

Deliberate Establishment of Asymptomatic Bacteriuria-A Novel Strategy to Prevent Recurrent UTI.

We have established a novel strategy to reduce the risk for recurrent urinary tract infection (UTI), where rapidly increasing antibiotic resistance poses a major threat. Epidemiologic studies have demonstrated that asymptomatic bacteriuria (ABU) protects the host against symptomatic infections with more virulent strains. To mimic this protective effect, we deliberately establish ABU in UTI-prone patients, who are refractory to conventional therapy.

Bacterial Suppression of RNA Polymerase II-Dependent Host Gene Expression.

Asymptomatic bacteriuria (ABU) is a bacterial carrier state in the urinary tract that resembles commensalism at other mucosal sites. ABU strains often lack the virulence factors that characterize uropathogenic Escherichia coli (E. coli) strains and therefore elicit weak innate immune responses in the urinary tract.

Susceptibility to Urinary Tract Infection: Benefits and Hazards of the Antibacterial Host Response.

A paradigm shift is needed to improve and personalize the diagnosis of infectious disease and to select appropriate therapies. For many years, only the most severe and complicated bacterial infections received more detailed diagnostic and therapeutic attention as the efficiency of antibiotic therapy has guaranteed efficient treatment of patients suffering from the most common infections. Indeed, treatability almost became a rationale not to analyze bacterial and host parameters in these larger patient groups.

Asymtomatic Bacteriuria as a Model to Study the Coevolution of Hosts and Bacteria.

During asymptomatic bacteriuria (ABU), bacteria colonize the urinary tract for extended periods of time without causing symptoms of urinary tract infection. Previous studies indicate that many Escherichia coli (E. coli) strains that cause ABU have evolved from uropathogenic E.

Antimicrobial resistance in urosepsis: outcomes from the multinational, multicenter global prevalence of infections in urology (GPIU) study 2003-2013.

Objective: Primary objective was to identify the (1) relationship of clinical severity of urosepsis with the pathogen spectrum and resistance and (2) appropriateness of using the pathogen spectrum and resistance rates of health-care-associated urinary tract infections (HAUTI) as representative of urosepsis. The secondary objective was to provide an overview of the pathogens and their resistance profile in patients with urosepsis.

Population And Methods: A point prevalence study carried out in 70 countries (2003-2013).

Predictive value of urinary interleukin-6 for symptomatic urinary tract infections in a nursing home population.

Objectives: To study urinary interleukin-6, interleukin-8 and pyuria during episodes of asymptomatic bacteriuria and symptomatic urinary tract infection in the institutionalized elderly, and to investigate the role of interleukin-6 as a biomarker for differential diagnosis.

Methods: Levels of interleukin-6, interleukin-8 and pyuria were assessed in 35 older adults with asymptomatic bacteriuria and symptomatic urinary tract infection to define possible diagnostic thresholds. In a two-phase intervention study, the antibiotic treatment for urinary tract infection before and after introduction of urinary interleukin-6 as a biomarker was then assessed.

Antibiotic stewardship challenges in the management of community-acquired infections for prevention of escalating antibiotic resistance.

Community-acquired infections, including respiratory tract infections (RTIs) and urinary tract infections (UTIs), represent a major burden for most healthcare systems, partially due to ineffective or inappropriate antibiotic treatment leading to clinical failure, which often requires alternative antibiotics for cure. Appropriate antimicrobial use not only maximises clinical success in the treatment of community-acquired infections, but also minimises unintended consequences such as resistance development or collateral damage. This article outlines a range of antibiotic stewardship strategies and other preventative approaches that support the management of community-acquired infections, based on existing antibiotic use for community-acquired infections and the current resistance patterns among common RTI and UTI pathogens.

Rare emergence of symptoms during long-term asymptomatic Escherichia coli 83972 carriage without an altered virulence factor repertoire.

Purpose: Asymptomatic bacteriuria established by intravesical inoculation of Escherichia coli 83972 is protective in patients with recurrent urinary tract infections. In this randomized, controlled crossover study a total of 3 symptomatic urinary tract infection episodes developed in 2 patients while they carried E. coli 83972.