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BJU International Nov 2022To compare recurrent urinary tract infection (rUTI) guidelines from major urological and non-urological organisations internationally and identify areas of consensus and... (Review)
Review
OBJECTIVE
To compare recurrent urinary tract infection (rUTI) guidelines from major urological and non-urological organisations internationally and identify areas of consensus and discrepancy.
METHODS
PubMed, Google Scholar and the official webpages of major urological, gynaecological, infectious diseases and general practice organisations were searched for rUTI guidelines in March 2022. Nine guidelines were included for review: European Association of Urology, National Institute for Health and Care Excellence (NICE), Society of Obstetricians and Gynaecologists of Canada, American Academy of Family Physicians, Mexican College of Gynaecology and Obstetrics Specialists, Swiss Society of Gynaecology and Obstetrics, Spanish Society of Infectious Diseases and Clinical Microbiology, German Association of Scientific Medical Societies, and the combined American Urological Association/Canadian Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction.
RESULTS
The definition and evaluation of rUTIs, and antibiotic prophylaxis strategies, were mostly consistent across guidelines, and emphasised the importance of obtaining urine cultures and limiting cystoscopy and upper tract imaging in women without risk factors. Variable recommendations were noted for symptomatic treatment, self-initiated antibiotics, and antibiotic-sparing preventative strategies such as cranberry, vaginal oestrogen, immunoactive prophylaxis with OM-89, intravesical glycosaminoglycan instillation, and phytotherapeutics. Recent randomised evidence supports the use of methenamine hippurate. Either continuous or post-coital prophylactic antibiotics were supported by all guidelines. None of the guidelines were tailored to the management recurrent complicated UTI.
CONCLUSION
Multiple rUTI guidelines were identified and mostly limited their recommendations to otherwise healthy non-pregnant women with uncomplicated cystitis. Variation was noted, particularly in antibiotic-sparing preventative strategies. Some conflicting recommendations are due to more recent guidelines including updated evidence. Future guidelines should consider recommendations to assist management of complex patient groups, such as recurrent complicated UTI.
Topics: Pregnancy; Female; Humans; Canada; Urinary Tract Infections; Antibiotic Prophylaxis; Cystitis; Anti-Bacterial Agents
PubMed: 35579121
DOI: 10.1111/bju.15756 -
The Brazilian Journal of Infectious... 2020Urinary tract infection (UTI) is a common condition in women. There is an increased concern on reduction of bacterial susceptibility resulting from wrongly prescribing...
Joint report of SBI (Brazilian Society of Infectious Diseases), FEBRASGO (Brazilian Federation of Gynecology and Obstetrics Associations), SBU (Brazilian Society of Urology) and SBPC/ML (Brazilian Society of Clinical Pathology/Laboratory Medicine): recommendations for the clinical management of...
Urinary tract infection (UTI) is a common condition in women. There is an increased concern on reduction of bacterial susceptibility resulting from wrongly prescribing antimicrobials. This paper summarizes the recommendations of four Brazilian medical societies (SBI - Brazilian Society of Infectious Diseases, FEBRASGO - Brazilian Federation of Gynecology and Obstetrics Associations, SBU - Brazilian Society of Urology, and SBPC/ML - Brazilian Society of Clinical Pathology/Laboratory Medicine) on the management of urinary tract infection in women. Asymptomatic bacteriuria should be screened at least twice during pregnancy (early and in the 3rd trimester). All cases of significant bacteriuria (≥10CFU/mL in middle stream sample) should be treated with antimicrobials considering safety and susceptibility profile. In women with typical symptoms of cystitis, dipsticks are not necessary for diagnosis. Urine cultures should be collected in pregnant women, recurrent UTI, atypical cases, and if there is suspicion of pyelonephritis. First line antimicrobials for cystitis are fosfomycin trometamol in a single dose and nitrofurantoin, 100mg every 6hours for five days. Second line drugs are cefuroxime or amoxicillin-clavulanate for seven days. During pregnancy, amoxicillin and other cephalosporins may be used, but with a higher chance of therapeutic failure. In recurrent UTI, all episodes should be confirmed by urine culture. Treatment should be initiated only after urine sampling and with the same regimens indicated for isolated episodes. Prophylaxis options of recurrent UTI are behavioral measures, non-antimicrobial and antimicrobial prophylaxis. Vaginal estrogens may be recommended for postmenopausal women. Other non-antimicrobial prophylaxis, including cranberry and immunoprophylaxis, have weak evidence supporting their use. Antimicrobial prophylaxis may be offered as a continuous or postcoital scheme. In pregnant women, options are cephalexin, 250-500mg and nitrofurantoin, 100mg (contraindicated after 37 weeks of pregnancy). Nonpregnant women may use fosfomycin trometamol, 3g every 10 days, or nitrofurantoin, 100mg (continuous or postcoital).
Topics: Anti-Bacterial Agents; Female; Humans; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Infectious; Societies, Medical; Urinary Tract Infections
PubMed: 32360431
DOI: 10.1016/j.bjid.2020.04.002 -
Nature Microbiology May 2023Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We...
Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, that impacts susceptibility to recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from mice with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, elucidating evidence of molecular imprinting that involved epigenetic changes, including differences in chromatin accessibility, DNA methylation and histone modification. Epigenetic marks in USCs from chronically infected mice enhanced caspase-1-mediated cell death upon UPEC infection, promoting bacterial clearance. Increased Ptgs2os2 expression also occurred, potentially contributing to sustained cyclooxygenase-2 expression, bladder inflammation and mucosal wounding-responses associated with severe recurrent cystitis. Thus, UPEC infection acts as an epi-mutagen reprogramming the urothelial epigenome, leading to urothelial-intrinsic remodelling and training of the innate response to subsequent infection.
Topics: Mice; Animals; Uropathogenic Escherichia coli; Trained Immunity; Urinary Tract Infections; Urinary Bladder; Escherichia coli Infections
PubMed: 37037942
DOI: 10.1038/s41564-023-01346-6 -
Clinical Cancer Research : An Official... Jan 2023Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective...
PURPOSE
Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus.
PATIENTS AND METHODS
We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either unresponsive to or patients were unable to tolerate standard antiviral therapies. Fifty-eight adult and pediatric patients were enrolled and treated.
RESULTS
Posoleucel was well tolerated, with no cytokine release syndrome or other infusion-related toxicities; two patients (3.4%) developed Grade 2 and one patient (1.7%) Grade 3 GvHD during the trial. The overall response rate 6 weeks after the first posoleucel infusion was 95%, with a median plasma viral load reduction of 97%. Of the 12 patients who had two or more target viral infections identified at study entry, 10 (83%) had a clinical response for all evaluable viruses. Of the 23 patients treated for refractory BKV-associated hemorrhagic cystitis, 74% had resolution of symptoms and macroscopic hematuria by 6 weeks post-infusion.
CONCLUSIONS
In this open-label trial, treatment of refractory viral infections/disease in allo-HCT recipients with posoleucel was feasible, safe, and effective.
Topics: Adult; Child; Humans; Antiviral Agents; Cell- and Tissue-Based Therapy; Epstein-Barr Virus Infections; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Virus Diseases
PubMed: 36628536
DOI: 10.1158/1078-0432.CCR-22-2415 -
BMJ Case Reports Jan 2022This case study discusses a patient who presented with severe lower urinary tract symptoms and pain after commencing immunotherapy for eosinophilic asthma. Initial...
This case study discusses a patient who presented with severe lower urinary tract symptoms and pain after commencing immunotherapy for eosinophilic asthma. Initial aetiology was presumed to be infective but cultures were negative. Cross-sectional imaging showed extensive perivesical and periprostatic stranding and inflammation. He was initially treated with antibiotics and anti-inflammatories but a lack of clinical improvement led to a rigid cystoscopy which identified an inflamed, oedematous urothelium which was biopsied. Histology demonstrated extensive, full thickness superficial detrusor inflammation, with marked congestion, oedema and a mixed inflammatory infiltrate in keeping with a severe active chronic non-infectious cystitis, possibly secondary to benralizumab therapy. His benralizumab was stopped and his symptoms completely settled. We believe this is the first described case of severe non-infective cystitis which may be secondary to benralizumab. This case adds to the isolated reports of this rare side effect of some of the newer biological agents in use.
Topics: Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Cystitis; Disease Progression; Humans; Immunotherapy; Male
PubMed: 35039341
DOI: 10.1136/bcr-2021-244733 -
Frontiers in Immunology 2021Parasitic helminths, comprising the flatworms (tapeworms and flukes) and nematodes (roundworms), have plagued humans persistently over a considerable period of time. It... (Review)
Review
Parasitic helminths, comprising the flatworms (tapeworms and flukes) and nematodes (roundworms), have plagued humans persistently over a considerable period of time. It is now known that the degree of exposure to these and other pathogens inversely correlates with the incidence of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. Accordingly, there has been recent increased interest in utilizing active helminth worm infections and helminth-derived products for the treatment of human autoimmune and inflammatory diseases and to alleviate disease severity. Indeed, there is an accumulating list of novel helminth derived molecules, including proteins, peptides, and microRNAs, that have been shown to exhibit therapeutic potential in a variety of disease models. Here we consider the blood-dwelling schistosome flukes, which have evolved subtle immune regulatory mechanisms that promote parasite survival but at the same time minimize host tissue immunopathology. We review and discuss the recent advances in using schistosome infection and schistosome-derived products as therapeutics to treat or mitigate human immune-related disorders, including allergic asthma, arthritis, colitis, diabetes, sepsis, cystitis, and cancer.
Topics: Animals; Biological Products; Disease Management; Disease Models, Animal; Humans; Immune System Diseases; Immunologic Factors; Immunomodulation; Mice; Recombinant Proteins; Schistosoma
PubMed: 33692793
DOI: 10.3389/fimmu.2021.619776 -
Frontiers in Immunology 2022Urinary tract infection (UTI) caused by uropathogens is the most common infectious disease and significantly affects all aspects of the quality of life of the patients.... (Review)
Review
Urinary tract infection (UTI) caused by uropathogens is the most common infectious disease and significantly affects all aspects of the quality of life of the patients. However, uropathogens are increasingly becoming antibiotic-resistant, which threatens the only effective treatment option available-antibiotic, resulting in higher medical costs, prolonged hospital stays, and increased mortality. Currently, people are turning their attention to the immune responses, hoping to find effective immunotherapeutic interventions which can be alternatives to the overuse of antibiotic drugs. Bladder infections are caused by the main nine uropathogens and the bladder executes different immune responses depending on the type of uropathogens. It is essential to understand the immune responses to diverse uropathogens in bladder infection for guiding the design and development of immunotherapeutic interventions. This review firstly sorts out and comparatively analyzes the immune responses to the main nine uropathogens in bladder infection, and summarizes their similarities and differences. Based on these immune responses, we innovatively propose that different microbial bladder infections should adopt corresponding immunomodulatory interventions, and the same immunomodulatory intervention can also be applied to diverse microbial infections if they share the same effective therapeutic targets.
Topics: Anti-Bacterial Agents; Cystitis; Humans; Immunity; Quality of Life; Urinary Bladder; Urinary Tract Infections
PubMed: 36081496
DOI: 10.3389/fimmu.2022.953354 -
Frontiers in Immunology 2022Inflammatory macrophages play a pivotal role in the progression of inflammatory cystitis. Formation of NOD-, LRR- and PYD domains-containing protein 3 (NLRP3)...
Inflammatory macrophages play a pivotal role in the progression of inflammatory cystitis. Formation of NOD-, LRR- and PYD domains-containing protein 3 (NLRP3) inflammasome triggers the activation of caspase-1/IL-1β signaling cascades to mediate inflammatory response. However, it is not known whether NLRP3 activation in macrophages during cystitis may differ in normal or diabetic setting as well as the importance of it. In this study, we found that NLRP3 levels significantly increased in bladder macrophages in diabetic mice that underwent cystitis. Moreover, bladder macrophages from diabetic mice appeared to have increased their potential of growth, migration and phagocytosis. Furthermore, specific depletion of NLRP3 in macrophages alleviated the severity of cystitis in diabetic mice, but not in non-diabetic mice. Together, our data suggest that NLRP3 depletion in macrophages may be a promising strategy for treating diabetic cystitis.
Topics: Mice; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Mice, Inbred NOD; Macrophages; Diabetes Mellitus; Cystitis
PubMed: 36405726
DOI: 10.3389/fimmu.2022.1057746 -
Journal of Clinical Oncology : Official... Aug 2021BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of...
PURPOSE
BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option.
METHODS
We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed.
RESULTS
Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement.
CONCLUSION
Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.
Topics: Adolescent; Adult; Aged; Cystitis; Female; Hemorrhagic Disorders; Humans; Male; Middle Aged; Prospective Studies; T-Lymphocytes, Cytotoxic; Vascularized Composite Allotransplantation; Young Adult
PubMed: 33929874
DOI: 10.1200/JCO.20.02608 -
Journal of Cellular and Molecular... Feb 2022Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by several symptoms of higher sensitivity of the lower urinary tract, such as bladder... (Review)
Review
Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by several symptoms of higher sensitivity of the lower urinary tract, such as bladder pain/discomfort, urgency, urinary frequency, pelvic pain and nocturia. Although the pathophysiology of IC/BPS is not fully understood, the hypothesis suggests that mast cell activation, glycosaminoglycan (GAG) layer defects, urothelium permeability disruption, inflammation, autoimmune disorder and infection are potential mechanisms. Mesenchymal stem cells (MSCs) have been proven to protect against tissue injury in IC/BPS by migrating into bladders, differentiating into key bladder cells, inhibiting mast cell accumulation and cellular apoptosis, inhibiting inflammation and oxidative stress, alleviating collagen fibre accumulation and enhancing tissue regeneration in bladder tissues. In addition, MSCs can protect against tissue injury in IC/BPS by secreting various soluble factors, including exosomes and other soluble factors, with antiapoptotic, anti-inflammatory, angiogenic and immunomodulatory properties in a cell-to-cell independent manner. In this review, we comprehensively summarized the current potential pathophysiological mechanisms and standard treatments of IC/BPS, and we discussed the potential mechanisms and therapeutic effects of MSCs and MSC-derived exosomes in alleviating tissue injury in IC/BPS models.
Topics: Cystitis, Interstitial; Exosomes; Humans; Mesenchymal Stem Cells; Pelvic Pain; Urinary Bladder
PubMed: 34953040
DOI: 10.1111/jcmm.17132