Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

Phage therapy is a promising alternative treatment of bacterial infections in human and animals. Nevertheless, despite the appearance of many bacterial strains resistant to antibiotics, these drugs still remain important therapeutics used in human and veterinary medicine. Although experimental phage therapy of infections caused by Salmonella enterica was described previously by many groups, those studies focused solely on effects caused by bacteriophages. Here, we compared the use of phage therapy (employing a cocktail composed of two previously isolated and characterized bacteriophages, vB_SenM-2 and vB_Sen-TO17) and antibiotics (enrofloxacin and colistin) in chickens infected experimentally with S. enterica serovar Typhimurium. We found that the efficacies of both types of therapies (i.e. the use of antibiotics and phage cocktail) were high and very similar to one another when the treatment was applied shortly (one day) after the infection. Under these conditions, S. Typhimurium was quickly eliminated from the gastrointestinal tract (GIT), to the amount not detectable by the used methods. However, later treatment (2 or 4 days after detection of S. Typhimurium in chicken feces) with the phage cocktail was significantly less effective. Bacteriophages remained in the GIT for up to 2-3 weeks, and then were absent in feces and cloaca swabs. Interestingly, both phages could be found in various organs of chickens though with a relatively low abundance. No development of resistance of S. Typhimurium to phages or antibiotics was detected during the experiment. Importantly, although antibiotics significantly changed the GIT microbiome of chickens in a long-term manner, analogous changes caused by phages were transient, and the microbiome normalized a few weeks after the treatment. In conclusion, phage therapy against S. Typhimurium infection in chickens appeared as effective as antibiotic therapy (with either enrofloxacin or colistin), and less invasive than the use the antibiotics as fewer changes in the microbiome were observed.

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“…The analysis was performed in accordance to protocols described by Łusiak-Szelakowska et al. (2014) and Letkiewicz et al. (2021) .…”

Section: Methodsmentioning

confidence: 99%

“…The analysis was performed in accordance to protocols described by Łusiak-Szelakowska et al ( 2014) and Letkiewicz et al (2021). Briefly, chicken blood plasma was diluted from 1:10 to 1:1000.…”

Section: Phage Plate Neutralization Testmentioning

confidence: 99%

Biological aspects of phage therapy versus antibiotics against Salmonella enterica serovar Typhimurium infection of chickens

Kosznik-Kwaśnicka

Podlacha

Grabowski

et al. 2022

Front. Cell. Infect. Microbiol.

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“…The immunogenicity of phages and the emergence of phage-neutralising antibodies seem to depend, at least partially, on the route of administration [ 62 , 63 ], as parenteral application induces a stronger response compared to topical or enteral routes. Repeated parenteral administration of phages over a 6-week period in rabbits [ 64 ] resulted in complete neutralisation of phages 3–5 weeks after immunisation.…”

Section: Lessons Learned From Clinical Applications and Key Considera...mentioning

confidence: 99%

Phage therapy for pulmonary infections: lessons from clinical experiences and key considerations

et al. 2022

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Lower respiratory tract infections lead to significant morbidity and mortality. They are increasingly caused by multidrug-resistant pathogens, notably in individuals with cystic fibrosis, hospital-acquired pneumonia and lung transplantation. The use of bacteriophages (phages) to treat bacterial infections is gaining growing attention, with numerous published cases of compassionate treatment over the last few years. Although the use of phages appears safe, the lack of standardisation, the significant heterogeneity of published studies and the paucity of robust efficacy data, alongside regulatory hurdles arising from the existing pharmaceutical legislation, are just some of the challenges phage therapy has to overcome. In this review, we discuss the lessons learned from recent clinical experiences of phage therapy for the treatment of pulmonary infections. We review the key aspects, opportunities and challenges of phage therapy regarding formulations and administration routes, interactions with antibiotics and the immune system, and phage resistance. Building upon the current knowledge base, future pre-clinical studies using emerging technologies and carefully designed clinical trials are expected to enhance our understanding and explore the therapeutic potential of phage therapy.

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“…In this case, liquid phage suspensions are typically used, normally prepared in aqueous buffers suitable for inoculation [64,72]. (e) Intravesical instillation of liquid phage preparations has also been used to treat genitourinary tract infections [77,78].…”

Section: Formulation and Administrationmentioning

confidence: 99%

Essential Topics for the Regulatory Consideration of Phages as Clinically Valuable Therapeutic Agents: A Perspective from Spain

Vázquez

Díez-Martínez²,

Domingo‐Calap

et al. 2022

Microorganisms

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Antibiotic resistance is one of the major challenges that humankind shall face in the short term. (Bacterio)phage therapy is a valuable therapeutic alternative to antibiotics and, although the concept is almost as old as the discovery of phages, its wide application was hindered in the West by the discovery and development of antibiotics in the mid-twentieth century. However, research on phage therapy is currently experiencing a renaissance due to the antimicrobial resistance problem. Some countries are already adopting new ad hoc regulations to favor the short-term implantation of phage therapy in clinical practice. In this regard, the Phage Therapy Work Group from FAGOMA (Spanish Network of Bacteriophages and Transducing Elements) recently contacted the Spanish Drugs and Medical Devices Agency (AEMPS) to promote the regulation of phage therapy in Spain. As a result, FAGOMA was asked to provide a general view on key issues regarding phage therapy legislation. This review comes as the culmination of the FAGOMA initiative and aims at appropriately informing the regulatory debate on phage therapy.

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Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

Cited by 9 publications

References 18 publications

Biological aspects of phage therapy versus antibiotics against Salmonella enterica serovar Typhimurium infection of chickens

Biological aspects of phage therapy versus antibiotics against Salmonella enterica serovar Typhimurium infection of chickens

Phage therapy for pulmonary infections: lessons from clinical experiences and key considerations

Essential Topics for the Regulatory Consideration of Phages as Clinically Valuable Therapeutic Agents: A Perspective from Spain

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