Endolysin treatment against Staphylococcus aureus in adults with atopic dermatitis: A randomized controlled trial

Wit, Jill de; Totté, J.E.E.; Mierlo, Minke M.F. van; Veldhuizen, Joyce van; Doorn, Martijn van; Schuren, Frank; Willemsen, Sten P.; Pardo, Luba M.; Pasmans, Suzanne G.M.A.

doi:10.1016/j.jaci.2019.05.020

Cited by 37 publications

(31 citation statements)

References 9 publications

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“…Lysins are featured by a rapid and highly bactericidal action upon exogenous addition [2]. They are under clinical development as an adjunctive therapy to standard-of-care antibiotics, but only target Gram-positive Staphylococcus aureus in ongoing (phase 3) or completed clinical trials [3][4][5]. Gram-negative pathogens have been long considered a no go zone based on the simple logic that lysins are too large to pass the additional outer membrane (OM) barrier present in Gram-negative bacteria.…”

Section: Introductionmentioning

confidence: 99%

Lysins breaking down the walls of Gram-negative bacteria, no longer a no-go

Gutiérrez

Briers

2021

Current Opinion in Biotechnology

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Section: Introductionmentioning

confidence: 99%

Lysins breaking down the walls of Gram-negative bacteria, no longer a no-go

Gutiérrez

Briers

2021

Current Opinion in Biotechnology

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“…Commercially, the recombinant endolysins Staphefekt SA.100 and Staphefekt XDR.300 (Micreos Human Health BV, Netherlands) which act on S. aureus (including MRSA) are available for use. A few clinical studies have been conducted with Staphefekt SA.100 and all have demonstrated remission and/or improvement of chronic S. aureus skin infections (folliculitis, rosacea, and eczema) [57,58], reinforcing the utility of this therapeutic resource. Moreover, it is believed that endolysins may be better therapeutic alternatives than bacteriophages themselves since bacteria have the possibility to develop resistance to the phage.…”

Section: Commercial Phage Products Anti-staphylococcalmentioning

confidence: 99%

Bacteriophages as Anti-Methicillin Resistant Staphylococcus aureus Agents

Picoli¹,

Röhnelt²,

Schenkel³

2021

Insights Into Drug Resistance in Staphylococcus Aureus

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Staphylococcus aureus is a colonizing microorganism of the nasal region of both humans and animals and represents an important opportunistic pathogen. The acquisition of the mecA and mecC genes by S. aureus led to the emergence of methicillin resistance (MRSA), becoming a public health problem in both human and animal areas. In addition to resistance to β-lactam antibiotics, MRSA strains have multidrug resistance to antimicrobials, significantly limiting therapeutic options, making it crucial to have effective alternatives for treating staphylococcal infections. In this context, the use of lytic bacteriophages, which are viruses that infect and lyse bacteria, as well as the use of their by-products, such as endolysins, has shown potential in the control of S. aureus, including MRSA. Due to the specificity of bacteriophages to infect particular prokaryotic hosts, these viruses represent an antibacterial resource for the control of public health relevant microorganisms, especially antibiotic-resistant bacteria.

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“…A clinical trial examining the effect of Staphefekt on atopic dermatitis was recently performed (NCT02840955). The results of the twelve-week treatment showed that Staphefekt was well tolerated by patients ( de Wit et al, 2019 ). Endolysin XZ.700, which is active against S. aureus , is a product that is also being developed by Micreos which has undergone pre-clinical trials ( Herpers et al, 2016 ) and has successfully moved onto phase I/IIa clinical trial (NL8876).…”

Section: Phage Lysinsmentioning

confidence: 99%

Efficacy of Phage- and Bacteriocin-Based Therapies in Combatting Nosocomial MRSA Infections

Walsh

Johnson

Hill

et al. 2021

Front. Mol. Biosci.

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Staphylococcus aureus is a pathogen commonly found in nosocomial environments where infections can easily spread - especially given the reduced immune response of patients and large overlap between personnel in charge of their care. Although antibiotics are available to treat nosocomial infections, the increased occurrence of antibiotic resistance has rendered many treatments ineffective. Such is the case for methicillin resistant S. aureus (MRSA), which has continued to be a threat to public health since its emergence. For this reason, alternative treatment technologies utilizing antimicrobials such as bacteriocins, bacteriophages (phages) and phage endolysins are being developed. These antimicrobials provide an advantage over antibiotics in that many have narrow inhibition spectra, enabling treatments to be selected based on the target (pathogenic) bacterium while allowing for survival of commensal bacteria and thus avoiding collateral damage to the microbiome. Bacterial resistance to these treatments occurs less frequently than with antibiotics, particularly in circumstances where combinatory antimicrobial therapies are used. Phage therapy has been well established in Eastern Europe as an effective treatment against bacterial infections. While there are no Randomized Clinical Trials (RCTs) to our knowledge examining phage treatment of S. aureus infections that have completed all trial phases, numerous clinical trials are underway, and several commercial phage preparations are currently available to treat S. aureus infections. Bacteriocins have primarily been used in the food industry for bio-preservation applications. However, the idea of repurposing bacteriocins for human health is an attractive one considering their efficacy against many bacterial pathogens. There are concerns about the ability of bacteriocins to survive the gastrointestinal tract given their proteinaceous nature, however, this obstacle may be overcome by altering the administration route of the therapy through encapsulation, or by bioengineering protease-resistant variants. Obstacles such as enzymatic digestion are less of an issue for topical/local administration, for example, application to the surface of the skin. Bacteriocins have also shown impressive synergistic effects when used in conjunction with other antimicrobials, including antibiotics, which may allow antibiotic-based therapies to be used more sparingly with less resistance development. This review provides an updated account of known bacteriocins, phages and phage endolysins which have demonstrated an impressive ability to kill S. aureus strains. In particular, examples of antimicrobials with the ability to target MRSA strains and their subsequent use in a clinical setting are outlined.

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Endolysin treatment against Staphylococcus aureus in adults with atopic dermatitis: A randomized controlled trial

Cited by 37 publications

References 9 publications

Lysins breaking down the walls of Gram-negative bacteria, no longer a no-go

Lysins breaking down the walls of Gram-negative bacteria, no longer a no-go

Bacteriophages as Anti-Methicillin Resistant Staphylococcus aureus Agents

Efficacy of Phage- and Bacteriocin-Based Therapies in Combatting Nosocomial MRSA Infections

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