Antiphage Activity of Sera During Phage Therapy in Relation to its Outcome

Łusiak-Szelachowska, Marzanna; Żaczek, Maciej; Weber‐Dąbrowska, Beata; Międzybrodzki, Ryszard; Letkiewicz, Sławomir; Fortuna, Wojciech; Rogóż, Paweł; Szufnarowski, Krzysztof; Jończyk‐Matysiak, Ewa; Olchawa, Ewa; Walaszek, K; Górski, Andrzej

doi:10.2217/fmb-2016-0156

Cited by 75 publications

(59 citation statements)

References 17 publications

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“…Normal antibody responses to this antigen are consistently defective in patients with HIV67, genetic immunodeficiencies68 and receiving immunosuppressing treatments69. In a clinical study of patients treated with phage therapy for bacterial infections, in which 50% of the patients were immunocompromised, 60% of patients given local administration of phage demonstrated low antibody neutralization in serum70. This is interesting because in our study we chose to test phage treatment of a bacterial infection within the context of immunosuppression, which is when patients are most at risk of these opportunistic ExPEC infections.…”

Section: Discussionmentioning

confidence: 99%

Bacteriophages from ExPEC Reservoirs Kill Pandemic Multidrug-Resistant Strains of Clonal Group ST131 in Animal Models of Bacteremia

Green

Kaelber

et al. 2017

Sci Rep

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Multi-drug resistant (MDR) enteric bacteria are of increasing global concern. A clonal group, Escherichia coli sequence type (ST) 131, harbors both MDR and a deadly complement of virulence factors. Patients with an immunocompromised system are at high risk of infections with these E. coli and there is strong epidemiologic evidence that the human intestinal tract, as well as household pets, may be a reservoir. Here, we examine if phages are an effective treatment strategy against this clonal group in murine models of bacteremia that recapitulate clinical infections. Bacteriophages isolated from known E. coli reservoirs lyse a diverse array of MDR ST131 clinical isolates. Phage HP3 reduced E. coli levels and improved health scores for mice infected with two distinct ST131 strains. Efficacy was correlated to in vitro lysis ability by the infecting phage and the level of virulence of the E. coli strain. Importantly, it is also demonstrated that E. coli bacteremia initiated from translocation across the intestinal tract in an immunocompromised host is substantially reduced after phage treatment. This study demonstrates that phage, isolated from the environment and with little experimental manipulation, can be effective in combating even the most serious of infections by E. coli “superbugs”.

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Section: Discussionmentioning

confidence: 99%

Bacteriophages from ExPEC Reservoirs Kill Pandemic Multidrug-Resistant Strains of Clonal Group ST131 in Animal Models of Bacteremia

Green

Kaelber

et al. 2017

Sci Rep

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“…Interestingly, the level of antibody responses was not correlated with the outcome of therapy. What is more, high antibody levels were detected in 43% of patients treated with phage cocktails versus only in 17% of patients on monotherapy [23,24]. The S. aureus phage cocktails were composed of three phages: S. aureus A5/80, S. aureus P4/6409 and S. aureus 676/Z.…”

Section: • Phage Interactions With Lymphocytesmentioning

confidence: 99%

“…Phages vary in their immunogenicity, and the humoral response also depends on the route of administration, dose and the patient's immune status [23,24]. Recently, we presented a vision to develop and establish a bank of phages specific to the most threatening pathogens and armed with homing peptides enabling their selective localization in infected tissues and stable eradication of infection [25].…”

Section: • Phage Interactions With Lymphocytesmentioning

confidence: 99%

“…The rate of phage inactivation (K) less than 5 was estimated as weak phage neutralization, between 5 and 18 as a medium level. K above 18 (≥50% neutralization at serum dilution ≥1:800) was associated with high phage neutralization [23]. Recently, Jain et al have demonstrated that Brucella abortus phage lysate absorbed on aluminum gel elicits strong humoral and cell-mediated immune responses in guinea pigs and protection comparable to a standard vaccine.…”

Section: • Phage Interactions With Lymphocytesmentioning

confidence: 99%

“…However, neither experimental nor clinical data available so far corroborate this hypothesis, and -as stated earlier -the data of Barr et al [15] strongly suggest the protective role of phages present on epithelial surfaces. Moreover, it is well known that oral phage administration in mice and man allowing for subsequent phage-epithelial surface interactions in the gut induces only very weak antibody production [21,23,24].…”

Section: • Phages and Inflammationmentioning

confidence: 99%

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Phages and Immunomodulation

et al. 2017

Self Cite

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In the past years, the microbiome and its role in the pathophysiology of diseases have gained great interest. The progress of our knowledge in this field opens completely novel prospects for treating disorders, including those which are most challenging to medicine today. Of special interest are studies on the interactions of the microbiome with the immune system. Only recently has the presence of bacteriophages in the microbiome been highlighted, and their potential role in maintaining normal immunity has gained increasing attention. We summarize the available data pointing to the potential impact of phages in maintaining immunological homeostasis.

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Reapproaching Old Treatments: Considerations for PK/PD Studies on Phage Therapy for Bacterial Respiratory Infections

Schmalstig

Freidy

Hanafin

et al. 2021

Clin Pharma and Therapeutics

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Antibiotic resistant bacterial respiratory infections are a significant global health burden, and new therapeutic strategies are needed to control the problem. For bacterial respiratory infections, this need is emphasized by the rise in antibiotic resistance and a lean drug development pipeline. Bacteriophage (phage) therapy is a promising alternative to antibiotics. Phage are viruses that infect and kill bacteria. Because phage and antibiotics differ in their bactericidal mechanisms, phage are a treatment option for antibiotic-resistant bacteria. Here, we review the history of phage therapy and highlight recent preclinical and clinical case reports of its use for treating antibiotic-resistant respiratory infections. The ability of phage to replicate while killing the bacteria is both a benefit for treatment and a challenge for pharmacokinetic (PK) and pharmacodynamic (PD) studies. In this review, we will discuss how the phage lifecycle and associated bidirectional interactions between phage and bacteria can impact treatment. We will also highlight PK/PD considerations for designing studies of phage therapy to optimize the efficacy and feasibility of the approach.

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Antiphage Activity of Sera During Phage Therapy in Relation to its Outcome

Abstract: The analysis of the association between AAS level and clinical results indicated that the level of AAS is not correlated with the outcome of PT.

Cited by 75 publications

References 17 publications

Bacteriophages from ExPEC Reservoirs Kill Pandemic Multidrug-Resistant Strains of Clonal Group ST131 in Animal Models of Bacteremia

Bacteriophages from ExPEC Reservoirs Kill Pandemic Multidrug-Resistant Strains of Clonal Group ST131 in Animal Models of Bacteremia

Phages and Immunomodulation

Reapproaching Old Treatments: Considerations for PK/PD Studies on Phage Therapy for Bacterial Respiratory Infections

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