Phage Therapy

Almost immediately after the discovery of bacteriophages by Frederik Twort and Félix d'Hérelle in 1915 and 1917, their potential for antibacterial therapy and prophylaxis in humans was recognized and applied. Bacteriophages provide the optimal conditions for this: High specificity, low toxicity, and self-maintaining and amplifying character. Renewed attention to the therapeutic potential of phages reflects growing concern about the emergence of antibiotic resistance and the prospect of a post-antibiotic era. However, modern phage therapy products must compete with today’s antimicrobial drugs, which includes the regulatory requirements for clinical use.

Recently, compassionate use of phages in cases, lacking therapeutic options (bacteria multiresistant against antibiotics) for serious or life-threatening infections has been used and occasionally published. Although there are currently few reference laboratories for the selection and testing of phages for clinical isolates, on-site testing is particularly advantageous in urgent cases. At the PCR new molecular tests to facilitate personalized phage therapy are developed.

Pathogen (MDRO)	Nosocomial infections/year (Germany)	Mortality rate (per 100,000 inhabitants)
MRSA (Methicillin-resistant S. aureus)	~11,000	~4.0
VRE (Vancomycin-resistant enterococci)	~4,000	~3.4
Multidrug-resistant E. coli	~8,000	~7.9
Multidrug-resistant K. pneumoniae	~2,000	~2.2
Multidrug-resistant P. aeruginosa	~4,000	~1.6

MDRO infections impose substantial additional costs on the healthcare system. They often prolong hospital stays (by about five days on average), require more expensive treatments, and necessitate isolation measures. Studies estimate additional treatment costs of €5,000 to €20,000 per hospital-acquired MDRO infection. MRSA infections, for instance, incur costs nearly three times higher than comparable MSSA infections. An analysis by the Techniker Krankenkasse (TK) reported average excess costs of ~€17,500 per MDRO case. Recent calculations estimate even higher costs — up to €27,000 per patient — due to increasingly complex resistance patterns. This represents a 41% increase compared to 2018 and corresponds to an overall burden of ~€1.1 billion annually for German hospitals alone. Including all direct and indirect costs (rehabilitation, isolation, personnel, etc.), the total economic impact is estimated at €4 billion per year.

No approved medicinal product: Currently, no phage preparations are approved in Germany. Since phages are classified as medicinal products, they would require extensive clinical trial data on pharmaceutical quality, efficacy, and safety. Due to their host specificity, these requirements are difficult to meet.
Compassionate use only: In the absence of approval, phage therapy is currently only available via individual treatment attempts (compassionate use). This allows physicians to use phages when standard options fail, but such use is not intended for systematic data collection. There are no formal treatment guidelines; each application is experimental and requires utmost caution.
Manufacturing and quality standards: Phages must be produced under GMP conditions. There are very few approved production facilities for phages in Germany. An alternative is the production of patient-specific phage formulations by pharmacies ("magistral formula"), as is regulated in Belgium. While theoretically allowed in Germany, this pathway lacks infrastructure and clear regulatory support. The BfArM has signaled openness but demands high quality standards.
Lack of reimbursement: Without official approval and early benefit assessment, there is no legal entitlement to reimbursement by statutory health insurance. Currently, funding occurs only in exceptional cases — often via research projects or case-by-case decisions. Billing codes are also lacking in the outpatient setting. This uncertain reimbursement situation significantly limits access.
Stance of authorities and policymakers: Both regulatory agencies and professional societies acknowledge these hurdles. The BfArM has emphasized the need for new approval pathways or exemptions. The German Bundestag recommends further development of phage therapy as a response to antibiotic resistance — including support for clinical research, regulatory adaptation, and transitional solutions like magistral formulations.
Guidelines on phage therapy ("AWMF S2k Leitlinie Phagentherapie") in Germany are not expected to be published until November 2025