Case report: Successful treatment of recurrent E. coli infection with bacteriophage therapy for patient suffering from chronic bacterial prostatitis

Background: Chronic Bacterial Prostatitis (CBP) is inflammation of the prostate caused by bacterial infection. An estimated 8.2% of men have prostatitis, most commonly under the age of 50. Antibiotics often fail to treat CBP due to presence of bacterial biofilms and rising antibiotic resistance of pathogenic bacterial strains. The multidrug resistant (MDR) bacterial strains often implicated in cases of CBP include Extended Spectrum Beta Lactam resistant Escherichia coli, Vancomycin resistant Enterococci, Gram-positive bacterial strains like Staphylococci and Streptococci, Enterobacteriaceae like Klebsiella and Proteus, and Pseudomonas aeruginosa. CBP patients experience significant deterioration in quality of life, with impact on mental health comparable with patients of diabetes mellitus and chronic heart failure, leading patients to explore alternatives like phage therapy.Case presentation: We present the case of a patient diagnosed with and exhibiting typical symptoms of CBP. Tests of the prostatic and seminal fluids identified E. coli as the causative pathogen. The patient did not experience favourable long-term treatment outcomes despite repeated antibiotic courses administered over 5 years. This led him to seek phage therapy for treatment of his condition.Methods and outcome: The cultured strain of E. coli was tested against bacteriophage preparations developed by the Eliava Institute, Georgia. Preparations showing lytic activity against the strain were used for the patient’s treatment at the Eliava Phage Therapy Center (EPTC). The patient underwent two courses of treatment with the EPTC. The first treatment course resulted in significant symptomatic improvement, followed by complete resolution of symptoms post the second course of phage therapy. Samples tested during treatment showed declining bacterial growth, corresponding with symptomatic improvement. Post-treatment cultures had no growth of pathogenic bacteria.Discussion: This case illustrates the efficacy of bacteriophages in treating CBP, a condition that is often resistant to antibiotic therapies. Antibiotics such as ofloxacin, Fosfomycin, trimethoprim, nitrofurantoin and ceftriaxone were administered in multiple courses over 5 years, but the infection recurred after each course. After two courses of phage therapy, the patient experienced long-term symptom resolution and substantial reduction in bacterial load. Increasing numbers of such cases globally warrant further research into the potential for bacteriophages for treating MDR and chronic infections

Case Report: Chronic Bacterial Prostatitis Treated With Phage Therapy After Multiple Failed Antibiotic Treatments

Background: Chronic Bacterial Prostatitis (CBP) is an inflammatory condition caused by a persistent bacterial infection of the prostate gland and its surrounding areas in the male pelvic region. It is most common in men under 50 years of age. It is a long-lasting and debilitating condition that severely deteriorates the patient’s quality of life. Anatomical limitations and antimicrobial resistance limit the effectiveness of antibiotic treatment of CBP. Bacteriophage therapy is proposed as a promising alternative treatment of CBP and related infections. Bacteriophage therapy is the use of lytic bacterial viruses to treat bacterial infections. Many cases of CBP are complicated by infections caused by both nosocomial and community acquired multidrug resistant bacteria. Frequently encountered strains include Vancomycin resistant Enterococci, Extended Spectrum Beta Lactam resistant Escherichia coli, other gram-positive organisms such as Staphylococcus and Streptococcus, Enterobacteriaceae such as Klebsiella and Proteus, and Pseudomonas aeruginosa, among others.Case Presentation: We present a patient with the typical manifestations of CBP. The patient underwent multiple courses of antibiotic treatment without any long-term resolution of his symptoms. Testing of prostatic secretion and semen samples revealed pathogenic bacteria in each case, which collectively included members of the Staphylococcal species such as Methicillin resistant Staphylococcus aureus (MRSA) and Staphylococcus haemolyticus, Enterococcus faecalis, and Streptococcus mitis, among others.Methods and Outcome: Bacteriophage preparations from the Eliava Institute were used to treat the patient after establishing phage sensitivity to the pathogenic bacteria. Significant improvements in symptoms and re-testing of samples after bacteriophage treatment indicated a reduction in the bacterial load and resolution of the infection.Discussion: The patient saw significant improvement of symptoms, and positive dynamics in bacterial titers and ultrasound controls after phage therapy. The failure of antibiotic therapy and subsequent success of bacteriophage therapy in treating chronic bacterial prostatitis shows the effectiveness of bacteriophages in controlling chronic infections in areas of low vascularity and anatomical complexity. These cases also highlight the efficacy of phages in overcoming antibiotic-resistant infections as well as biofilm infections

The XMM Cluster Survey: X-ray analysis methodology

The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMM-Newton Science Archive. Its main aims are to measure cosmological parameters and trace the evolution of X-ray scaling relations. In this paper we describe the data processing methodology applied to the 5,776 XMM observations used to construct the current XCS source catalogue. A total of 3,675 > 4-sigma cluster candidates with > 50 background-subtracted X-ray counts are extracted from a total non-overlapping area suitable for cluster searching of 410 deg^2. Of these, 993 candidates are detected with > 300 background-subtracted X-ray photon counts, and we demonstrate that robust temperature measurements can be obtained down to this count limit. We describe in detail the automated pipelines used to perform the spectral and surface brightness fitting for these candidates, as well as to estimate redshifts from the X-ray data alone. A total of 587 (122) X-ray temperatures to a typical accuracy of < 40 (< 10) per cent have been measured to date. We also present the methodology adopted for determining the selection function of the survey, and show that the extended source detection algorithm is robust to a range of cluster morphologies by inserting mock clusters derived from hydrodynamical simulations into real XMM images. These tests show that the simple isothermal beta-profiles is sufficient to capture the essential details of the cluster population detected in the archival XMM observations. The redshift follow-up of the XCS cluster sample is presented in a companion paper, together with a first data release of 503 optically-confirmed clusters.Comment: MNRAS accepted, 45 pages, 38 figures. Our companion paper describing our optical analysis methodology and presenting a first set of confirmed clusters has now been submitted to MNRA

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The Context and Impact of Being Wrongly Accused of Abuse in Occupations of Trust

In recent years, there has been rising concern that allegations of sexual abuse, particularly non‐recent abuse, have not received an appropriate response. From this has emerged a new determination to correct past and prevent further injustices, with police operations focusing considerable resources on the identification and prosecution of child abusers. Police and other services have reached out to encourage reporting, and developments in the trial process related to the rules of evidence have eroded due process protections for suspects. This article considers this changed legal and social context, and the processes entailed in responding to allegations of abuse, before presenting original empirical data, gathered from the accounts of 30 men and women who were wrongly accused of abuse related to their employment in occupations of trust. It demonstrates the considerable and lasting harms done to those who face allegations of such heinous crimes

Phage Therapy in a 16-Year-Old Boy with Netherton Syndrome

Netherton syndrome (NS) is a rare autosomal recessive disorder, characterized by a classical triad of clinical features, including congenital ichthyosiform erythroderma, trichorrhexis invaginata, and atopic diathesis coupled with frequent bacterial infections (1). The genetic basis for the disease has been recently identified with mutations in gene SPINK5, which is involved in the regulation of formation of skin barriers. We report on a 16-year-old male with all the typical manifestations of NS, including atopic diathesis and ongoing serious staphylococcal infections and allergy to multiple antibiotics whose family sought help at the Eliava Phage Therapy Center when all other treatment options were failing. Treatment with several antistaphylococcal bacteriophage preparations led to significant improvement within 7 days and very substantial changes in his symptoms and quality of life after treatment for 6 months, including return visits to the Eliava Phage Therapy Center after 3 and 6 months of ongoing use of phage at home

A ‘train the trainers’ approach to infection prevention and control training in pandemic conditions

Background: The first wave of the SARS-CoV-2 global pandemic in early 2020 required a rapid roll-out of infection prevention and control (IPC) training for healthcare workers (HCW), including use of appropriate personal protective equipment (PPE). Education about respiratory droplet and aerosol transmission was of paramount importance to ensure safe working practices and improve confidence. Methods: A joint working group of Infectious Diseases and IPC staff developed a ‘train the trainers’ programme, to be rapidly deployed over a three-week period. This model utilised a snowballing approach, training selected staff with the intention that they would train their teams, facilitating swift cascading of information. Targeted invitations prompted staff from diverse departments of the hospital to attend. Pre- and post-session questionnaires evaluated staff confidence with regard to appropriate PPE use. Results: The programme trained 130 HCW over a three week period, was well received and led to increased confidence with PPE use amongst staff. Real-time evaluation ensured content could be adapted to the specific needs of HCW involved. We highlight perceived gaps in training despite existing and enhanced training structures. Conclusion: Provision of face-to-face training in transmission-based precautions, including PPE use, is required to maintain confidence in safe and appropriate IPC amongst hospital staff. We highlight the importance of including non-clinical staff in PPE educational programmes, recognising that these roles are vital for patient care and are frequently patient-facing. We recommend adopting the train the trainers model to facilitate rapid dissemination of education, with interactive multidisciplinary training in future outbreaks to improve HCW confidence and effective IPC