Bacteriophage Therapy Increases Complement-Mediated Lysis of Bacteria and Enhances Bacterial Clearance After Acute Lung Infection With Multidrug-Resistant Pseudomonas aeruginosa

El‐Aziz, Abeer M. Abd; Elgaml, Abdelaziz; Ali, Youssif M

doi:10.1093/infdis/jiy678

Cited by 60 publications

(42 citation statements)

References 43 publications

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“…Although phages appear to induce only weak antibody responses, antiphage antibody responses may lead to the activation of the complement system. 121 Human blood from recipients of phage therapy was found to contain antiphage IgG, IgM, and IgA antibodies in vitro. However, no correlation was found between the induction of phageneutralizing antibodies and the outcome of phage therapy.…”

Section: Drug-related Problemsmentioning

confidence: 99%

Phage Therapy in the Resistance Era: Where Do We Stand and Where Are We Going?

Luong

Salabarria

Roach

2020

Clinical Therapeutics

171

107

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Purpose: Widespread antibiotic-resistant bacteria are threatening the arsenal of existing antibiotics. Not only are antibiotics less likely to be effective today, but their extensive use continues to drive the emergence of multidrug-resistant pathogens. A newold antibacterial strategy with bacteriophages (phages) is under development, namely, phage therapy. Phages are targeted bacterial viruses with multiple antibacterial effector functions, which can reduce multidrug-resistant infections within the human body. This review summarizes recent phage therapy clinical trials and patient cases and outlines the fundamentals behind phage treatment strategies under development, mainly through bench-to-bedside approaches. We discuss the challenges that remain in phage therapy and the role of phages when combined with antibiotic therapy. Methods: This narrative review presents the current knowledge and latest findings regarding phage therapy. Relevant case reports and research articles available through the Scopus and PubMed databases are discussed. Findings: Although recent clinical data suggest the tolerability and, in some cases, efficacy of phage therapy, the clinical functionality still requires careful definition. The lack of well-controlled clinical trial data and complex regulatory frameworks have driven the most recent human data generation on a singlepatient compassionate use basis. These cases often include the concomitant use of antibiotics, which makes it difficult to draw conclusions regarding the effectiveness of phages alone. However, human data support using antibiotics as phage potentiators and resistance breakers; thus, phage adjuvants are a promising avenue for near-term clinical development. Current knowledge gaps exist on the appropriate routes of administration, phage selection, frequency of administration, dosage, phage resistance, and pharmacokinetic and pharmacodynamic properties of the phages. In addition, we highlight that some phage therapies have mild adverse effects in patients. Implications: Although more translational research is needed before the clinical implementation is feasible, phage therapy may well be pivotal in safeguarding humans against antibiotic-resistant infections.

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Section: Drug-related Problemsmentioning

confidence: 99%

Phage Therapy in the Resistance Era: Where Do We Stand and Where Are We Going?

Luong

Salabarria

Roach

2020

Clinical Therapeutics

171

107

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“…Roach et al (2017) showed that neutrophils are an essential part of controlling both phagesensitive and emergent phage-resistant bacterial variants as a means of ensuring effective treatment. Work by Abd El-Aziz et al (2019) showed that the addition of phages to a mixture of human serum and bacteria enhanced serum killing activity. Multiple studies provide evidence that the immune system generates antibodies against bacteriophages (Biswas et al, 2002;Wang et al, 2006a;Shivshetty et al, 2014), though this likely would impair rather than bolster activity against bacterial infection.…”

Section: Pneumoniamentioning

confidence: 99%

Animal Models of Phage Therapy

2021

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Amidst the rising tide of antibiotic resistance, phage therapy holds promise as an alternative to antibiotics. Most well-designed studies on phage therapy exist in animal models. In order to progress to human clinical trials, it is important to understand what these models have accomplished and determine how to improve upon them. Here we provide a review of the animal models of phage therapy in Western literature and outline what can be learned from them in order to bring phage therapy closer to becoming a feasible alternative to antibiotics in clinical practice.

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“…A variety of animal studies were able to show that phages can be used to eliminate MDR bacteria, including MDR P. aeruginosa, A. baumannii, and VRE. [97][98][99] A number of smaller randomized controlled trials assessing the efficacy of phages in the treatment of bacterial infections have been published. While none of these studies reported any problems with respect to safety, response to treatment was inconsistent between studies.…”

Section: Phage-mediated Therapiesmentioning

confidence: 99%

The role of the human gut microbiota in colonization and infection with multidrug-resistant bacteria

et al. 2021

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About 100 years ago, the first antibiotic drug was introduced into health care. Since then, antibiotics have made an outstanding impact on human medicine. However, our society increasingly suffers from collateral damage exerted by these highly effective drugs. The rise of resistant pathogen strains, combined with a reduction of microbiota diversity upon antibiotic treatment, has become a significant obstacle in the fight against invasive infections worldwide.Alternative and complementary strategies to classical "Fleming antibiotics" comprise microbiotabased treatments such as fecal microbiota transfer and administration of probiotics, livebiotherapeutics, prebiotics, and postbiotics. Other promising interventions, whose efficacy may also be influenced by the human microbiota, are phages and vaccines. They will facilitate antimicrobial stewardship, to date the only globally applied antibiotic resistance mitigation strategy.In this review, we present the available evidence on these nontraditional interventions, highlight their interaction with the human microbiota, and discuss their clinical applicability.

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Bacteriophage Therapy Increases Complement-Mediated Lysis of Bacteria and Enhances Bacterial Clearance After Acute Lung Infection With Multidrug-Resistant Pseudomonas aeruginosa

Cited by 60 publications

References 43 publications

Phage Therapy in the Resistance Era: Where Do We Stand and Where Are We Going?

Phage Therapy in the Resistance Era: Where Do We Stand and Where Are We Going?

Animal Models of Phage Therapy

The role of the human gut microbiota in colonization and infection with multidrug-resistant bacteria

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