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

Samaee, Hamid Reza; Eslami, Gohar; Rahimzadeh, Golnar; Saeedi, Majid; Badabi, Alireza Davoudi; Asare-Addo, Kofi; Nokhodchi, Ali; Roozbeh, Fatemeh; Moosazadeh, Mahmood; Ghasemian, Roya; Alikhani, Ahmad; Rezai, Mohammad Sadegh

doi:10.1016/j.jddst.2023.104486

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…These are all as found in situ while treating infections caused by what are typically somewhat uncharacterized bacterial strains and, in many cases, also in combination with antibiotics [ 41 , 57 , 86 , 87 , 88 , 89 ], which can have antagonistic impacts on phage infection abilities [ 41 , 51 , 85 , 90 ]. In particular for the latter, note that of 18 clinical phage therapy studies that I was able to obtain—published in 2023 or, at the time of writing, which are published but still online ahead of print—at least 16 indicate treatments using phages in combination with antibiotics [ 57 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ]. See also [ 109 ], where 79 of the 114 clinical phage treatments reported “were administered in combination with standard-of-care antibiotics”.…”

Section: Discussionmentioning

confidence: 99%

Automating Predictive Phage Therapy Pharmacology

Abedon

2023

Antibiotics

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Viruses that infect as well as often kill bacteria are called bacteriophages, or phages. Because of their ability to act bactericidally, phages increasingly are being employed clinically as antibacterial agents, an infection-fighting strategy that has been in practice now for over one hundred years. As with antibacterial agents generally, the development as well as practice of this phage therapy can be aided via the application of various quantitative frameworks. Therefore, reviewed here are considerations of phage multiplicity of infection, bacterial likelihood of becoming adsorbed as a function of phage titers, bacterial susceptibility to phages also as a function of phage titers, and the use of Poisson distributions to predict phage impacts on bacteria. Considered in addition is the use of simulations that can take into account both phage and bacterial replication. These various approaches can be automated, i.e., by employing a number of online-available apps provided by the author, the use of which this review emphasizes. In short, the practice of phage therapy can be aided by various mathematical approaches whose implementation can be eased via online automation.

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Section: Discussionmentioning

confidence: 99%

Automating Predictive Phage Therapy Pharmacology

Abedon

2023

Antibiotics

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“…A number of phage characteristics make them amenable to potential therapeutic use: (1) high species specificity, thereby enabling pathobiont targeting while minimising microbiome disruption [ 158 ]; (2) ability to penetrate and disrupt biofilms [ 159 ]; (3) ability to kill antibiotic-resistant persister cells [ 160 ]; (4) ability to re-sensitise bacteria to existing antibiotics [ 161 ]; and (5) generally good tolerability in clinical trials [ 162 , 163 ]. Clinical trials of phage therapy for pulmonary infections are scarce [ 164 , 165 ], with no trials specific to PBB or bronchiectasis. However, phage therapy candidates are being investigated against common respiratory pathobionts, including NTHi, S. pneumoniae , M. catarrhalis , and P. aeruginosa [ 13 , 166 ].…”

Section: Emerging Therapeutic Approachesmentioning

confidence: 99%

The Respiratory Microbiome in Paediatric Chronic Wet Cough: What Is Known and Future Directions

Atto,

Anteneh,

Bialasiewicz

et al. 2023

JCM

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Chronic wet cough for longer than 4 weeks is a hallmark of chronic suppurative lung diseases (CSLD), including protracted bacterial bronchitis (PBB), and bronchiectasis in children. Severe lower respiratory infection early in life is a major risk factor of PBB and paediatric bronchiectasis. In these conditions, failure to clear an underlying endobronchial infection is hypothesised to drive ongoing inflammation and progressive tissue damage that culminates in irreversible bronchiectasis. Historically, the microbiology of paediatric chronic wet cough has been defined by culture-based studies focused on the detection and eradication of specific bacterial pathogens. Various ‘omics technologies now allow for a more nuanced investigation of respiratory pathobiology and are enabling development of endotype-based models of care. Recent years have seen substantial advances in defining respiratory endotypes among adults with CSLD; however, less is understood about diseases affecting children. In this review, we explore the current understanding of the airway microbiome among children with chronic wet cough related to the PBB–bronchiectasis diagnostic continuum. We explore concepts emerging from the gut–lung axis and multi-omic studies that are expected to influence PBB and bronchiectasis endotyping efforts. We also consider how our evolving understanding of the airway microbiome is translating to new approaches in chronic wet cough diagnostics and treatments.

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Bacteriophages in Infectious Diseases and Beyond—A Narrative Review

2023

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The discovery of antibiotics has revolutionized medicine and has changed medical practice, enabling successful fighting of infection. However, quickly after the start of the antibiotic era, therapeutics for infectious diseases started having limitations due to the development of antimicrobial resistance. Since the antibiotic pipeline has largely slowed down, with few new compounds being produced in the last decades and with most of them belonging to already-existing classes, the discovery of new ways to treat pathogens that are resistant to antibiotics is becoming an urgent need. To that end, bacteriophages (phages), which are already used in some countries in agriculture, aquaculture, food safety, and wastewater plant treatments, could be also used in clinical practice against bacterial pathogens. Their discovery one century ago was followed by some clinical studies that showed optimistic results that were limited, however, by some notable obstacles. However, the rise of antibiotics during the next decades left phage research in an inactive status. In the last decades, new studies on phages have shown encouraging results in animals. Hence, further studies in humans are needed to confirm their potential for effective and safe treatment in cases where there are few or no other viable therapeutic options. This study reviews the biology and applications of phages for medical and non-medical uses in a narrative manner.

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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

Cited by 4 publications

References 38 publications

Automating Predictive Phage Therapy Pharmacology

Automating Predictive Phage Therapy Pharmacology

The Respiratory Microbiome in Paediatric Chronic Wet Cough: What Is Known and Future Directions

Bacteriophages in Infectious Diseases and Beyond—A Narrative Review

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