Proof-of-Concept Standardized Approach Using a Single-Disk Method Analogous to Antibiotic Disk Diffusion Assays for Routine Phage Susceptibility Testing in Diagnostic Laboratories.

Application of bacteriophages is increasingly being implemented in clinical therapies. Prior susceptibility testing should be regarded as mandatory, but standards are lacking. The objective of this research was to develop a highly standardized methodology to facilitate phage susceptibility testing (PST) in clinical microbiology routine laboratories. Therefore, EUCAST methods established for single disk-based antibiotic susceptibility testing (AST) were adapted. In a first step, basic parameters were evaluated using well-studied Escherichia phage T4-Escherichia coli combinations. In addition, test results were compared to those from conventional spot test and efficiency of plating (EOP) approaches. In a second step, the applicability of the methodology and the most promising test parameters were demonstrated for five other frequently isolated clinical bacterial species and their corresponding phages. At present, the method predominantly leads to qualitative rather than quantitative results. This disk-based approach provides a standardized, easy-to-handle, reproducible and reliable PST protocol by relying on well-established routine procedures in diagnostic laboratories. IMPORTANCE Application of bacteriophages in clinical therapies is attractive due to increasing rates of isolation of multidrug-resistant bacteria worldwide. As the phage effect is highly specific, prior susceptibility testing of target bacteria is mandatory. Of note, established standards are lacking. In this research, we adapted the single-disk method for antibiotic susceptibility testing to phage susceptibility testing (PST) in order to provide a standardized, easy-to-handle, reproducible, and reliable PST protocol for application in diagnostic routine laboratories.

Treatment Complexity in Primary Open-Angle Glaucoma (POAG): Perspectives on Patient Selection in Micro-Invasive Glaucoma Surgery (MIGS) Using Stents. / Versorgungskomplexität beim primären Offenwinkelglaukom (POWG): Perspektiven zur Patientenauswahl in der mikroinvasiven Glaukomchirurgie (MIGS) mit Stents.

BACKGROUND: Primary open-angle glaucoma (POAG) is still one of the most common causes of impaired vision worldwide, despite the further development of therapy options, and can lead to blindness. Micro-invasive glaucoma surgery (MIGS) using stents aims at reducing intraocular pressure (IOP), as it is the main risk factor. With regard to adherence and adverse drug reactions it also aims at reducing the drug burden on patients. The study investigates under everyday conditions the criteria according to which ophthalmologists in Germany select patients for MIGS using stents. In addition, it will be investigated which patients (could) benefit most from the therapy. MATERIAL AND METHODS: In this qualitative study, 11 narrative interviews were conducted between May 2017 and July 2018 with ophthalmologists working in the hospital or in a private practice. They were interviewed on their experiences in the treatment of POAG with microstents. The interviews were analysed by an interdisciplinary team using the qualitative content analysis. RESULTS: The stages of therapy escalation form the frame of reference for patient selection in MIGS using stents. Only if the IOP cannot be sufficiently reduced by drop therapy or when this causes drug-related side effects that are intolerable for the patients, stents are apparently used as the next higher escalation stage. The intensive post-operative medication and the frequent check-up appointments are perceived as barriers by the interviewees, especially for people with or without disabilities, who are dependent on external help and/or those living in rural areas. The active cooperation of the patients in the demanding aftercare seems to be indispensable for the ophthalmologists. In addition, necessary revisions are sometimes stressful for patients (physical/psychological) and doctors (work organisation/therapy). Against the background of the organisational and economic challenges in the outpatient spectrum of tasks, especially physicians in private practice seem to weigh up carefully for which patients microstent therapy would be reasonable. CONCLUSION: In view of the therapeutic requirements, the current microstent therapy seems to be used in a selected, adherent patient group. Further qualitative and quantitative studies (in other health care regions and structures) are necessary to verify and extend the available results.

Bacteriophages for the Treatment of Graft Infections in Cardiovascular Medicine.

Bacterial infections of vascular grafts represent a major burden in cardiovascular medicine, which is related to an increase in morbidity and mortality. Different factors that are associated with this medical field such as patient frailty, biofilm formation, or immunosuppression negatively influence antibiotic treatment, inhibiting therapy success. Thus, further treatment strategies are required. Bacteriophage antibacterial properties were discovered 100 years ago, but the focus on antibiotics in Western medicine since the mid-20th century slowed the further development of bacteriophage therapy. Therefore, the experience and knowledge gained until then in bacteriophage mechanisms of action, handling, clinical uses, and limitations were largely lost. However, the parallel emergence of antimicrobial resistance and individualized medicine has provoked a radical reassessment of this approach and cardiovascular surgery is one area in which phages may play an important role to cope with this new scenario. In this context, bacteriophages might be applicable for both prophylactic and therapeutic use, serving as a stand-alone therapy or in combination with antibiotics. From another perspective, standardization of phage application is also required. The ideal surgical bacteriophage application method should be less invasive, enabling highly localized concentrations, and limiting bacteriophage distribution to the infection site during a prolonged time lapse. This review describes the latest reports of phage therapy in cardiovascular surgery and discusses options for their use in implant and vascular graft infections.