A Systematic and Critical Review of Bacteriophage Therapy Against Multidrug-resistant ESKAPE Organisms in Humans

Haddad, Lynn El; Harb, Cynthia P; Gebara, Marc A; Stibich, Mark; Chemaly, Roy F.

doi:10.1093/cid/ciy947

Cited by 116 publications

(90 citation statements)

References 40 publications

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“…However, these treatments alone will not solve the issue of antibiotic resistance. Other therapies including bacteriophage [60,61], lytic enzymes [62], novel cleaning techniques [63], repurposed drugs with antibiotic activity [64], and bacterial byproducts [57] should be further developed. With enough duplicity in treatment options, hopefully physicians will be able to prevent global outbreaks of treatment-resistant infections.…”

Section: Resultsmentioning

confidence: 99%

Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms

Feehan

Garcia‐Diaz

2020

Microorganisms

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Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges.

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Section: Resultsmentioning

confidence: 99%

Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms

Feehan

Garcia‐Diaz

2020

Microorganisms

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“…There is increasing interest in the impact of phages on human immunology. This trend parallels the resurgence of efforts to develop phage therapies to treat chronic/multidrug-resistant bacterial infections (115,116) as well as the rapid expansion of research into endogenous phages residing on and within the human host (117)(118)(119). Much of this work has focused on CF and the viral pathogens of Pa (120,121).…”

Section: Pf Effects On Mammalian Immunitymentioning

confidence: 99%

Pf Bacteriophage and Their Impact on Pseudomonas Virulence, Mammalian Immunity, and Chronic Infections

et al. 2020

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Pf bacteriophage are temperate phages that infect the bacterium Pseudomonas aeruginosa, a major cause of chronic lung infections in cystic fibrosis (CF) and other settings. Pf and other temperate phages have evolved complex, mutualistic relationships with their bacterial hosts that impact both bacterial phenotypes and chronic infection. We and others have reported that Pf phages are a virulence factor that promote the pathogenesis of P. aeruginosa infections in animal models and are associated with worse skin and lung infections in humans. Here we review the biology of Pf phage and what is known about its contributions to pathogenesis and clinical disease. First, we review the structure, genetics, and epidemiology of Pf phage. Next, we address the diverse and surprising ways that Pf phages contribute to P. aeruginosa phenotypes including effects on biofilm formation, antibiotic resistance, and motility. Then, we cover data indicating that Pf phages suppress mammalian immunity at sites of bacterial infection. Finally, we discuss recent literature implicating Pf in chronic P. aeruginosa infections in CF and other settings. Together, these reports suggest that Pf bacteriophage have direct effects on P. aeruginosa infections and that temperate phages are an exciting frontier in microbiology, immunology, and human health.

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“…A recent systematic review has concluded that phage therapy is effective and safe based on the limited publications to date, but more data are needed as challenges in manufacturing and the regulatory process remain. 147,148 Ultimately, all of these therapies need to overcome several obstacles not limited to optimal dosing and delivery and high-quality human trials of safety and comparative effectiveness before they can be incorporated into routine care limiting their current role in clinical practice.…”

Section: Inhaled Antibioticsmentioning

confidence: 99%

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

Strich

Kadri

2019

Semin Respir Crit Care Med

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Antibiotic resistance among gram-negative pathogens is a world-wide problem that poses a constant threat to patients in the intensive care unit and a therapeutic challenge for the intensivist. Furthermore, the substantial economic burden and increased mortality associated with infections due to highly resistant gram-negative pathogens exacerbate these challenges. Understanding the mechanisms, epidemiology, and risk factors for these infections is paramount to the successful control of outbreaks and for guiding therapy which often entails use of antibiotics with suboptimal efficacy and/or toxicity profiles. In this review we will discuss the global epidemiology, burden, risk factors, and treatment of highly resistant gram-negative infections as they apply to the intensive care population.

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A Systematic and Critical Review of Bacteriophage Therapy Against Multidrug-resistant ESKAPE Organisms in Humans

Cited by 116 publications

References 40 publications

Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms

Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms

Pf Bacteriophage and Their Impact on Pseudomonas Virulence, Mammalian Immunity, and Chronic Infections

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

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