Phage Therapy in Germany—Update 2023

Abstract

Bacteriophage therapy holds promise in addressing the antibiotic-resistance crisis, globally and in Germany. Here, we provide an overview of the current situation (2023) of applied phage therapy and supporting research in Germany. The authors, an interdisciplinary group working on patient-focused bacteriophage research, addressed phage production, phage banks, susceptibility testing, clinical application, ongoing translational research, the regulatory situation, and the network structure in Germany. They identified critical shortcomings including the lack of clinical trials, a paucity of appropriate regulation and a shortage of phages for clinical use. Phage therapy is currently being applied to a limited number of patients as individual treatment trials. There is presently only one site in Germany for large-scale good-manufacturing-practice (GMP) phage production, and one clinic carrying out permission-free production of medicinal products. Several phage banks exist, but due to varying institutional policies, exchange among them is limited. The number of phage research projects has remarkably increased in recent years, some of which are part of structured networks. There is a demand for the expansion of production capacities with defined quality standards, a structured registry of all treated patients and clear therapeutic guidelines. Furthermore, the medical field is still poorly informed about phage therapy. The current status of non-approval, however, may also be regarded as advantageous, as insufficiently restricted use of phage therapy without adequate scientific evidence for effectiveness and safety must be prevented. In close coordination with the regulatory authorities, it seems sensible to first allow some centers to treat patients following the Belgian model. There is an urgent need for targeted networking and funding, particularly of translational research, to help advance the clinical application of phages.

Attitudes to phage therapy among Australian infectious diseases physicians

“…The sample size lacked power for further sub-analysis. Furthermore, uncertainty in replies regarding prioritisation of some clinical syndromes (for example, infections in cystic fibrosis and burns patients) was higher than that regarding prioritisation of microorganisms, suggesting limited exposure to phage therapy and an understanding of its role in polymicrobial infections, as observed in other countries [20] . With most Australian physician being hospital based, and phage therapy currently requiring close follow-up during its administration period, rural and remote medicine aspects were not fully considered in this study.…”

Inhalation phage therapy as a new approach to preventing secondary bacterial pneumonia in patients with moderate to severe COVID-19: A double-blind clinical trial study

“…Generally, patients with COVID-19 suffer from pneumonia and secondary respiratory infection with high hospitalization and mortality rates [ [17] , [18] , [19] , [20] ]. The development of multi-drug-resistant (MDR) bacteria recommends that phage therapy could be another option to treat pulmonary infections [ 8 , [21] , [22] , [23] , [24] ]. Phage therapy through the inhalation route has long been employed and is in practice in Eastern European countries [ 25 ].…”

“…They are multiplied at the site of infection and, unlike antibiotics, do not require dose adjustment. Phages are self-replicating and their production is fast and economically viable [ [7] , [8] , [9] ]. In Georgia, Herelle'd Félix with the collaboration of Eliava commercially produced the first phage product against gram-negative bacteria that caused gastrointestinal infections in 1931.…”

Current Clinical Landscape and Global Potential of Bacteriophage Therapy

“…For phages to be effectively and efficiently transported between countries and regions, there must be a well-established, regulated, and frequently updated resource detailing both the full scope of isolated phages stored in various banks around the world as well as their respective host ranges. Currently, national and institutional updates are published sporadically in a variety of scientific journals, and there is no single standardized outlet for combining all current phage information [195,196]. While databases such as the Phage Directory exist, contribution to the site is voluntary and independently motivated, which results in an under-approximation of the global scale of phage labs and phageoriented scientists.…”