Bacteriophages: what role may they play in life after spinal cord injury?

Bacterial infections are the leading cause of death in people with a spinal cord injury (SCI). Bacteriophages (phages) are viruses that solely infect and kill bacteria. The idea of using phages to treat bacterial infections, i.e., phage therapy, is very promising and potentially allows a more specific and personalized treatment of bacterial infections than antibiotics. While multi-drug resistant infections affect individuals from the general population, alternative therapeutic options are especially warranted in high-risk populations, such as individuals with SCI. However, more clinical data must be collected before phage therapy can be implemented in clinical practice, with numerous possible, subsequent applications

Clinical Indications and Compassionate Use of Phage Therapy: Personal Experience and Literature Review with a Focus on Osteoarticular Infections.

The history of phage therapy started with its first clinical application in 1919 and continues its development to this day. Phages continue to lack any market approval in Western medicine as a recognized drug, but are increasingly used as an experimental therapy for the compassionate treatment of patients experiencing antibiotic failure. The few formal experimental phage clinical trials that have been completed to date have produced inconclusive results on the efficacy of phage therapy, which contradicts the many successful treatment outcomes observed in historical accounts and recent individual case reports. It would therefore be wise to identify why such a discordance exists between trials and compassionate use in order to better develop future phage treatment and clinical applications. The multitude of observations reported over the years in the literature constitutes an invaluable experience, and we add to this by presenting a number of cases of patients treated compassionately with phages throughout the past decade with a focus on osteoarticular infections. Additionally, an abundance of scientific literature into phage-related areas is transforming our knowledge base, creating a greater understanding that should be applied for future clinical applications. Due to the increasing number of treatment failures anticipatedfrom the perspective of a possible post-antibiotic era, we believe that the introduction of bacteriophages into the therapeutic arsenal seems a scientifically sound and eminently practicable consideration today as a substitute or adjuvant to antibiotic therapy

Short and oral antimicrobial therapy for diabetic foot infection: a narrative review of current knowledge

Diabetic foot infection is a frequent complication in long-standing diabetes mellitus. For antimicrobial therapy of this infection, both the optimal duration and the route of administration are often based more on expert opinion than on published evidence. We reviewed the scientific literature, specifically seeking prospective trials, and aimed at addressing two clinical issues: (1) shortening the currently recommended antibiotic duration and (2) using oral (rather than parenteral) therapy, especially after the patient has undergone debridement and revascularization. We also reviewed some older key articles that are critical to our understanding of the treatment of these infections, particularly with respect to diabetic foot osteomyelitis. Our conclusion is that the maximum duration of antibiotic therapy for osteomyelitis should be no more than to 4-6 weeks and might even be shorter in selected cases. In the future, in addition to conducting randomized trials and propagating national and international guidance, we should also explore innovative strategies, such as intraosseous antibiotic agents and bacteriophages

Clinical Indications and Compassionate Use of Phage Therapy: Personal Experience and Literature Review with a Focus on Osteoarticular Infections.

The history of phage therapy started with its first clinical application in 1919 and continues its development to this day. Phages continue to lack any market approval in Western medicine as a recognized drug, but are increasingly used as an experimental therapy for the compassionate treatment of patients experiencing antibiotic failure. The few formal experimental phage clinical trials that have been completed to date have produced inconclusive results on the efficacy of phage therapy, which contradicts the many successful treatment outcomes observed in historical accounts and recent individual case reports. It would therefore be wise to identify why such a discordance exists between trials and compassionate use in order to better develop future phage treatment and clinical applications. The multitude of observations reported over the years in the literature constitutes an invaluable experience, and we add to this by presenting a number of cases of patients treated compassionately with phages throughout the past decade with a focus on osteoarticular infections. Additionally, an abundance of scientific literature into phage-related areas is transforming our knowledge base, creating a greater understanding that should be applied for future clinical applications. Due to the increasing number of treatment failures anticipatedfrom the perspective of a possible post-antibiotic era, we believe that the introduction of bacteriophages into the therapeutic arsenal seems a scientifically sound and eminently practicable consideration today as a substitute or adjuvant to antibiotic therapy

Indwelling catheter vs intermittent catheterization: is there a difference in UTI susceptibility?

BACKGROUND Patients with neurogenic lower urinary tract dysfunction (NLUTD) often rely on some type of catheterization for bladder emptying. Intermittent catheterization (IC) is considered the gold standard and is preferred over continuous catheterization, since it is considered to cause fewer urinary tract infections (UTIs) than indwelling catheterization. The main objective of our study was to describe UTI prevalence (at visit) and incidence (within the last 12 months) and urine culture characteristics between patients using an indwelling catheter versus (vs) those performing IC. METHODS In this cross-sectional study, we prospectively evaluated from 02/2020 to 01/2021 patients with NLUTD undergoing urine cultures for prophylactic reasons or due to UTI symptoms. At visit, all patients underwent a standardized interview on current UTI symptoms as well as UTI history and antibiotic consumption within the past year. Patients using an indwelling catheter (n = 206) or IC (n = 299) were included in the analysis. The main outcome was between-group differences regarding UTI characteristics. RESULTS Patients using an indwelling catheter were older (indwelling catheter vs IC: median 66 (Q1-Q3: 55-77) vs 55 (42-67) years of age) and showed a higher Charlson comorbidity index (indwelling catheter vs IC: median 4 (Q1-Q3: 2-6) vs 2 (1-4) (both p < 0·001). A total of 40 patients from both groups were diagnosed with a UTI at visit (indwelling catheters vs IC: 8% (16/206) vs 8% (24/299); p = 0·782), and the number of UTIs within the past 12 months was not significantly different between groups. Overall, Escherichia coli (21%), Enterococcus faecalis (17%), and Klebsiella spp. (12%) were the most frequently detected bacteria. CONCLUSIONS In this cohort of patients with NLUTD, we did not find relevant differences in UTI frequency between groups. These results suggest that UTI-related concerns should not be given undue emphasis when counseling patients for catheter-related bladder emptying methods

Needs assessment to strengthen capacity in water and sanitation research in Africa:experiences of the African SNOWS consortium

Despite its contribution to global disease burden, diarrhoeal disease is still a relatively neglected area for research funding, especially in low-income country settings. The SNOWS consortium (Scientists Networked for Outcomes from Water and Sanitation) is funded by the Wellcome Trust under an initiative to build the necessary research skills in Africa. This paper focuses on the research training needs of the consortium as identified during the first three years of the project

Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine

The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, Enterococcus spp., and Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall, E. coli, Enterococcus spp., and Klebsiella spp. were each detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, 99%), and accuracy (90%, 94%, 98%) at a resolution of ≥10$^{3}$ CFU/ml within 5 h. We further demonstrate how bioluminescence in urine can be used to predict phage antibacterial activity, demonstrating the future potential of reporter phages as companion diagnostics that guide patient-phage matching prior to therapeutic phage application

Interdisciplinary working in public health research: a proposed good practice checklist.

Background: Guidance on how different disciplines from the natural, behavioural and social sciences can collaborate to resolve complex public health problems is lacking. This article presents a checklist to support researchers and principle investigators to develop and implement interdisciplinary collaborations. Methods: Fourteen individuals, representing 10 disciplines, participated in in-depth interviews to explore the strengths and challenges of working together on an interdisciplinary project to identify the determinants of substance use and gambling disorders, and to make recommendations for future interdisciplinary teams. Data were analysed thematically and a checklist was derived from insights offered by participants during interview and discussion among the authors on the implications of findings. Results: Participants identified 18 scientific, interactional and structural strengths and challenges of interdisciplinary research. These findings were used to develop an 18-item BASICS checklist to support future interdisciplinary collaborations. The five domains of the checklist are: (i) Blueprint, (ii) Attitudes, (iii) Staffing, (iv) Interactions and (v) Core Science. Conclusion: Interdisciplinary work has the potential to advance public health science but the numerous challenges should not be underestimated. Use of a checklist, such as BASICS, when planning and managing projects may help future collaborations to avoid some of the common pitfalls of interdisciplinary research

An exploration of the use of simple statistics to measure consensus and stability in Delphi studies

<p>Abstract</p> <p>Background</p> <p>The criteria for stopping Delphi studies are often subjective. This study aimed to examine whether consensus and stability in the Delphi process can be ascertained by descriptive evaluation of trends in participants' views.</p> <p>Methods</p> <p>A three round email-based Delphi required participants (n = 12) to verify their level of agreement with 8 statements, write comments on each if they considered it necessary and rank the statements for importance. Each statement was analysed quantitatively by the percentage of agreement ratings, importance rankings and the amount of comments made for each statement, and qualitatively using thematic analysis. Importance rankings between rounds were compared by calculating Kappa values to observe trends in how the process impacts on subject's views.</p> <p>Results</p> <p>Evolution of consensus was shown by increase in agreement percentages, convergence of range with standard deviations of importance ratings, and a decrease in the number of comments made. Stability was demonstrated by a trend of increasing Kappa values.</p> <p>Conclusion</p> <p>Following the original use of Delphi in social sciences, Delphi is suggested to be an effective way to gain and measure group consensus in healthcare. However, the proposed analytical process should be followed to ensure maximum validity of results in Delphi methodology for improved evidence of consensual decision-making.</p