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Health Technology Assessment... May 2022Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking.
OBJECTIVE
To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex; Mylan NV, Canonsburg, PA, USA) compared with current standard care (antibiotic prophylaxis) for recurrent urinary tract infection prevention in adult women.
DESIGN
Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year.
SETTING
Eight UK NHS secondary care sites.
PARTICIPANTS
A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial.
INTERVENTIONS
A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted.
MAIN OUTCOME MEASURES
The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction.
RESULTS
Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in cultured from perineal swabs than participants in the methenamine hippurate arm (39/70; 56%) (-value = 0.05). Urine cultures revealed that during treatment higher proportions of participants and samples from the antibiotic arm grew resistant to trimethoprim/co-trimoxazole and cephalosporins, respectively. Conversely, post treatment, higher proportions of participants in the methenamine hippurate arm (9/45; 20%) demonstrated multidrug resistance in isolated from perineal swabs than participants in the antibiotic arm (2/39; 5%) ( = 0.06). All other secondary outcomes and adverse events were similar in both arms.
LIMITATIONS
This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation.
CONCLUSIONS
This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics.
RECOMMENDATIONS FOR RESEARCH
Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics.
TRIAL REGISTRATION
This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36.
FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 23. See the NIHR Journals Library website for further project information.
Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cost-Benefit Analysis; Escherichia coli; Female; Hippurates; Humans; Male; Methenamine; Trimethoprim; Urinary Tract Infections
PubMed: 35535708
DOI: 10.3310/QOIZ6538 -
Cornea Jan 2015To report a case of caruncular dacryops in a 58-year-old man that was excised in its entirety and to offer an immunohistopathologic analysis.
PURPOSE
To report a case of caruncular dacryops in a 58-year-old man that was excised in its entirety and to offer an immunohistopathologic analysis.
METHODS
Sections stained with hematoxylin and eosin, periodic acid-Schiff, and Grocott methenamine silver (the latter 2 for identification of mucus) were evaluated, and immunohistochemical investigations were performed using cytokeratin (CK) 7, CK14, CK17, and smooth muscle actin.
RESULTS
Histopathologic examination revealed a cystic dilation of the lacrimal gland ducts containing secretory globules. The ducts were composed of double-layered cuboidal epithelium with rare scattered goblet cells and interspersed prominent lobules of lacrimal gland tissue, diagnostic of dacryops. Immunohistochemistry of cystic ducts demonstrated a CK profile identical to that of the conjunctiva including the absence of a myoepithelium.
CONCLUSIONS
This is the first case of an intact caruncular lacrimal ductal cyst (dacryops). A previous report documented a spontaneously collapsed cyst with extrusion of secretory globoid bodies into extracellular space that elicited a foreign body giant cell response.
Topics: Actins; Conjunctiva; Cysts; Goblet Cells; Humans; Immunohistochemistry; Keratins; Lacrimal Apparatus Diseases; Male; Middle Aged; Staining and Labeling
PubMed: 25357082
DOI: 10.1097/ICO.0000000000000287 -
The American Journal of Dermatopathology Jul 2021Cutaneous reactions surrounding abdominal stoma sites are typically irritant, allergic, infectious, traumatic or pathergic in etiology. Pemphigus, which encompasses a... (Review)
Review
Cutaneous reactions surrounding abdominal stoma sites are typically irritant, allergic, infectious, traumatic or pathergic in etiology. Pemphigus, which encompasses a group of vesiculobullous autoimmune skin disorders, is seldom encountered as a peristomal dermatosis. Direct immunofluorescence (DIF) studies of pemphigus generally show continuous intercellular net-like depositions of IgG. However, punctate or dot-like intercellular deposition of IgG can also be seen in cases of pemphigus. The punctuate pattern is underreported in the literature and little is known about its implication. We describe a case of a 58-year-old Caucasian man with a history of bowel obstruction, status postcolostomy, who presented with a sharply demarcated, erythematous, crusted plaque surrounding his abdominal stoma. The patient endorsed persistent pruritus. A punch biopsy of the lesion was performed for clinical suspicion of fungal infection versus irritant dermatitis. Histopathology revealed a predominantly subcorneal acantholytic dermatitis. Periodic acid-Schiff with diastase and Grocott methenamine silver histochemical stains were negative for fungi. DIF was positive for IgG and C3 detected in a punctate intercellular pattern. In conjunction with the patient's clinical presentation and DIF, a diagnosis of peristomal pemphigus foliaceous was rendered. Herein, we describe a case of punctate pemphigus presenting as a peristomal dermatosis and include a review of the literature to raise awareness of this phenomenon.
Topics: Acantholysis; Aged; Biopsy; Colostomy; Fluorescent Antibody Technique, Direct; Humans; Male; Pemphigus; Skin
PubMed: 33156025
DOI: 10.1097/DAD.0000000000001845 -
Pathology Mar 2022The evolution of the diagnosis of infectious diseases began with the observation of the morphological characteristics of organisms such as ascaris and whipworms,... (Review)
Review
The evolution of the diagnosis of infectious diseases began with the observation of the morphological characteristics of organisms such as ascaris and whipworms, followed by the use of the microscope and haematoxylin and eosin stains, which allowed recognition of microscopic characteristics undetectable with the naked eye, such as the viral cytopathic changes of herpes and the presence of fungi. Patterns of acute and chronic granulomatous inflammation were also observed; these were not specific to the exact aetiology of the disease, which led to the introduction of special methenamine stains for fungi and Ziehl-Neelsen for fungi and mycobacteria. Later, the use of immunohistochemistry was introduced, which acknowledged the use of antibodies to classify microorganisms and detect cases that were either difficult to interpret or in the midst of severe inflammatory processes. Currently, the use of molecular biology has made it possible to reach diagnoses that would have been very difficult to obtain through traditional methods; these techniques show key specific characteristics and facilitate the diagnosis of various infectious pathologies. These new techniques are based on the detection of antigens and nucleic acids of microorganisms, an important advance in the diagnosis of infectious diseases.
Topics: Histocytological Preparation Techniques; Humans; Infections; Microbiological Techniques; Sensitivity and Specificity
PubMed: 35063292
DOI: 10.1016/j.pathol.2021.10.004 -
Infectious Disease Clinics of North... Jun 2024Urinary tract infections (UTIs) are common in women; more than 50% of women will be diagnosed with a UTI in her lifetime. Many of these women will go on to develop... (Review)
Review
Urinary tract infections (UTIs) are common in women; more than 50% of women will be diagnosed with a UTI in her lifetime. Many of these women will go on to develop recurrent UTI. Nevertheless, evidence-based prevention of recurrent UTI is under-utilized. Here, the authors provide detailed practical advice on UTI prevention with a thorough review of the evidence. Non-antibiotic prevention measures discussed include increased fluid intake, vaginal estrogen therapy, methenamine, and cranberry. Antibiotic prophyalxis for carefully selected patients is also discussed.
Topics: Humans; Urinary Tract Infections; Female; Risk Factors; Recurrence; Anti-Bacterial Agents; Secondary Prevention
PubMed: 38599896
DOI: 10.1016/j.idc.2024.03.010 -
International Journal of Toxicology 2017
Topics: Aerosols; Consumer Product Safety; Cosmetics; Formaldehyde; Humans; Methenamine; Risk Assessment
PubMed: 29025332
DOI: 10.1177/1091581817717643 -
Journal of Clinical Neuroscience :... Jul 2016Fungal infection should be considered in the differential diagnosis of a pituitary or sellar mass, albeit fungal infections involving the pituitary gland and sella are a...
Fungal infection should be considered in the differential diagnosis of a pituitary or sellar mass, albeit fungal infections involving the pituitary gland and sella are a rare occurrence. We report a case of Aspergillus infection involving the pituitary gland and sellar region discovered in a 74-year-old man. The patient had a history of hypertension, chronic renal disease, autoimmune hemolytic anemia and presented with right eye pain, headaches and worsening hemiparesis. Imaging studies revealed a right internal carotid artery occlusion and an acute right pontine stroke along with smaller infarcts in the right middle cerebral artery distribution. Clinically, the patient was thought to have vasculitis. An infectious etiology was not identified. He developed respiratory distress and died. At autopsy, necrotizing meningitis was discovered. A predominantly chronic inflammatory cell infiltrate consisting of benign-appearing lymphocytes, plasma cells and macrophages was accompanied by acute angle branching, angioinvasive hyphae which were highlighted on Gomori methenamine silver staining and were morphologically consistent with Aspergillus species. In previously reported cases of Aspergillus infection involving the pituitary or sella, most presented with headaches or impaired vision and were not immunocompromised. A transsphenoidal surgical approach is recommended in suspected cases in order to minimize the risk of dissemination of the infection. Some patients have responded well to antifungal medications once diagnosed.
Topics: Aged; Anemia, Hemolytic, Autoimmune; Aspergillosis; Comorbidity; Diagnosis, Differential; Fatal Outcome; Humans; Hypertension; Immunocompromised Host; Male; Pituitary Diseases; Renal Insufficiency, Chronic
PubMed: 26896907
DOI: 10.1016/j.jocn.2016.01.010 -
Seminars in Diagnostic Pathology Nov 2017Fungal pneumonias can be a diagnostic problem. However, their recognition is important as they can pose a significant health risk, especially in the immunocompromised... (Review)
Review
Fungal pneumonias can be a diagnostic problem. However, their recognition is important as they can pose a significant health risk, especially in the immunocompromised host. While many of these infections are accompanied by necrotizing or non-necrotizing granulomas, some might be characterized by cellular interstitial pneumonia, intra-alveolar frothy material or only minimal inflammatory change. Much of the tissue reaction is dependent on the immune status of the patient and the type of fungal organism. While many of the fungi can be identified in tissue, especially if using histochemical stains such as Grocott's Methenamine Silver (GMS) stain and/or Periodic Acid Schiff (PAS) stain, in some cases, these stains are negative and the organisms can only be identified in cultures or using special techniques such as PCR or fungal serology. Some fungi can be accurately identified in tissue based on morphologic features; others require culture for exact classification. Knowledge about immune status, geographic region and social history of the patient are helpful in identifying the fungus and, therefore, detailed clinical and travel histories are important. In this manuscript we aim to describe the most common fungal infections that occur in the lung, their morphologic features, and differential diagnoses.
Topics: Biopsy; Fungi; Host-Pathogen Interactions; Humans; Immunocompromised Host; Lung; Lung Diseases, Fungal; Microbiological Techniques; Opportunistic Infections; Predictive Value of Tests
PubMed: 28684133
DOI: 10.1053/j.semdp.2017.06.002 -
Medical Mycology Apr 2019Aspergillosis is more common among immunocompromised patients with neutropenia or immunosuppression due to corticosteroid use, and infections are typically of the lung... (Review)
Review
Aspergillosis is more common among immunocompromised patients with neutropenia or immunosuppression due to corticosteroid use, and infections are typically of the lung or sinuses. For diagnosis, broncholaveolar lavages (BALs) and lung biopsies are the specimens of choice. Culture and microscopic examinations are a must have and laboratory results should immediately be reported to the clinic. Fungal elements (hyphae) display the proof of an infection if present in primarily steril specimens, independent of culture results. Microscopy should be performed preferably using optical brighteners and histopathology using Gomori's methenamine silver stain or Periodic acid-Schiff. Serum and BAL galactomannan assays are recommended as markers for the diagnosis of invasive aspergillosis, PCR should be considered in conjunction with other diagnostic tests. Antifungal treatment decreases GM sensitivity. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates.
Topics: Aspergillus; Biopsy; Bronchoalveolar Lavage Fluid; Diagnostic Tests, Routine; Galactose; Histocytochemistry; Humans; Invasive Pulmonary Aspergillosis; Lung; Mannans; Microbiological Techniques; Microscopy; Polymerase Chain Reaction
PubMed: 30816965
DOI: 10.1093/mmy/myy103