Corneal Infection Therapy with Topical Bacteriophage Administration

Fadlallah, Ali; Chelala, Elias; Legeais, Jean‐Marc

doi:10.2174/1874364101509010167

Cited by 71 publications

(55 citation statements)

References 6 publications

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“…A recent trial was successfully performed in a patient suffering from an eye infection by Fadlallah et al, in 2015 at the Phage Therapy Center in Tbilisi, Georgia ( 113 ). Many similar trials have achieved success without any harmful side effects ( 114 – 117 ).…”

Section: Phage Therapy and Human Safetymentioning

confidence: 99%

Phage therapy againstEnterococcus faecalisin dental root canals

Khalifa

Shlezinger

Beyth

et al. 2016

Journal of Oral Microbiology

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Antibiotic resistance is an ever-growing problem faced by all major sectors of health care, including dentistry. Recurrent infections related to multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, and vancomycin-resistant enterococci (VRE) in hospitals are untreatable and question the effectiveness of notable drugs. Two major reasons for these recurrent infections are acquired antibiotic resistance genes and biofilm formation. None of the traditionally known effective techniques have been able to efficiently resolve these issues. Hence, development of a highly effective antibacterial practice has become inevitable. One example of a hard-to-eradicate pathogen in dentistry is Enterococcus faecalis, which is one of the most common threats observed in recurrent root canal treatment failures, of which the most problematic to treat are its biofilm-forming VRE strains. An effective response against such infections could be the use of bacteriophages (phages). Phage therapy was found to be highly effective against biofilm and multidrug-resistant bacteria and has other advantages like ease of isolation and possibilities for genetic manipulations. The potential of phage therapy in dentistry, in particular against E. faecalis biofilms in root canals, is almost unexplored. Here we review the efforts to develop phage therapy against biofilms. We also focus on the phages isolated against E. faecalis and discuss the possibility of using phages against E. faecalis biofilm in root canals.

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Section: Phage Therapy and Human Safetymentioning

confidence: 99%

Phage therapy againstEnterococcus faecalisin dental root canals

Khalifa

Shlezinger

Beyth

et al. 2016

Journal of Oral Microbiology

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“…The intravenous and percutaneous administration of personalized therapeutic phage cocktails was shown to rescue a patient from a life-threatening multidrugresistant Acinetobacter baumannii infection (29). With regard to the application of phage therapy to ocular disease, a case of keratitis caused by VAN-resistant S. aureus was effectively treated by phage administration in eyedrops, a nasal spray, and intravenously (30). However, as far as we are aware, phage administration into the vitreous has not yet been described.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis

Kishimoto

Ishida

Fukuda

et al. 2019

Antimicrob Agents Chemother

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Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage ΦEF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of E. faecalis. Phage ΦEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with E. faecalis-related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 × 104 cells) into the vitreous. The number of viable bacteria in the eye increased to >1 × 107 CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of ΦEF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of E. faecalis.

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“…In a recent case study, a woman who had been infected with a persistent vancomycin resistant S. aureus infection exhibited colonization for over 11 years [207]. Despite constant and varied treatment including cyclosporine, pristanamycine, and mupirocin, the infection never successfully cleared [207]. The patent decided to seek treatment at the phage therapy center in Tbilisi Georgia.…”

Section: Phage Therapymentioning

confidence: 99%

“…The patent decided to seek treatment at the phage therapy center in Tbilisi Georgia. Upon treatment with a bacteriophage ATCC PTA-9476 over the course of four weeks, the vancomycin resistant S. aureus infection was successfully cleared [207]. Although such examples highlight the promise of phage therapies, bacterophages are generally highly specific for bacterial strains and thus can exhibit lower efficiency within strains of the same species.…”

Section: Phage Therapymentioning

confidence: 99%

Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics

Kane

Carothers

Lee

2018

CDT

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Background Staphylococcus aureus is a major bacterial pathogen capable of causing a range of infections in humans from gastrointestinal disease, skin and soft tissue infections, to severe outcomes such as sepsis. Staphylococcal infections in humans can be frequent and recurring, with treatments becoming less effective due to the growing persistence of antibiotic resistant S. aureus strains. Due to the prevalence of antibiotic resistance, and the current limitations on antibiotic development, an active and highly promising avenue of research has been to develop strategies to specifically inhibit the activity of virulence factors produced S. aureus as an alternative means to treat disease. Objective In this review we specifically highlight several major virulence factors produced by S. aureus for which recent advances in antivirulence approaches may hold promise as an alternative means to treating diseases caused by this pathogen. Strategies to inhibit virulence factors can range from small molecule inhibitors, to antibodies, to mutant and toxoid forms of the virulence proteins. Conclusion The major prevalence of antibiotic resistant strains of S. aureus combined with the lack of new antibiotic discoveries highlight the need for vigorous research into alternative strategies to combat diseases caused by this highly successful pathogen. Current efforts to develop specific antivirulence strategies, vaccine approaches, and alternative therapies for treating severe disease caused by S. aureus have the potential to stem the tide against the limitations that we face in the post-antibiotic era.

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Corneal Infection Therapy with Topical Bacteriophage Administration

Cited by 71 publications

References 6 publications

Phage therapy againstEnterococcus faecalisin dental root canals

Phage therapy againstEnterococcus faecalisin dental root canals

Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis

Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics

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