Efficacy of Antistaphylococcal Lysin LSVT-1701 in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

Huang, David B.; Gaukel, Eric; Kerzee, Nancy; Borroto–Esoda, Katyna; Lowry, Simon; Xiong, Yan Q.; Abdelhady, Wessam; Bayer, Arnold S.

doi:10.1128/aac.00508-21

Cited by 4 publications

(2 citation statements)

References 14 publications

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“…There are also three other phage products, AP-PA02 (NCT04596319), YPT-01 (NCT04684641), and BX004-A (NCT05010577), being evaluated in phase 1/2 trials with cystic fibrosis patients with P. aeruginosa infections. For the phage-derived endolysin tonabacase (N-Rephasin SAL200), a new phase 1 trial has been initiated and it has been renamed LSVT-1701 ( 79 , 80 ).…”

Section: Analysis and Discussionmentioning

confidence: 99%

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed

Butler

Gigante²,

Sati³

et al. 2022

Antimicrob Agents Chemother

174

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There is an urgent global need for new strategies and drugs to control and treat multi-drug resistant bacterial infections. In 2017, the World Health Organization (WHO) released a list of 12 antibiotic-resistant priority pathogens and began to critically analyze the antibacterial clinical pipeline. This review analyzes ‘traditional’ and ‘non-traditional’ antibacterial agents and modulators in clinical development current on 30 June 2021 with activity against the WHO priority pathogens, mycobacteria and Clostridioides difficile. Since 2017, 12 new antibacterial drugs have been approved globally, but only vaborbactam belongs to a new antibacterial class. Also innovative is the cephalosporin derivative cefiderocol, which incorporates an iron-chelating siderophore that facilitates Gram-negative bacteria cell entry. Overall, there were 76 antibacterial agents in clinical development (45 traditional and 31 non-traditional) with 28 in Phase 1, 32 in Phase 2, 12 in Phase 3 and four under regulatory evaluation. Forty-one out of 76 (54%) targeted WHO priority pathogens, 16 (21%) against mycobacteria, 15 (20%) against C. difficile and 4 (5%) are non-traditional agents with broad spectrum effects. Nineteen of the 76 antibacterial agents have new pharmacophores and four of these have new modes of actions not previously exploited by marketed antibacterial drugs. Despite there being 76 antibacterial clinical candidates, this analysis indicated that there were still relatively few clinically differentiated antibacterial agents in late-stage clinical development, especially against critical Priority Pathogens. We believe that future antibacterial R&D should focus on the development of innovative and clinically differentiated candidates that have clear and feasible progression pathways to the market.

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Section: Analysis and Discussionmentioning

confidence: 99%

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed

Butler

Gigante²,

Sati³

et al. 2022

Antimicrob Agents Chemother

174

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“…Both lysin dosage regimens sterilized all target tissues when administered for four daily doses along with daptomycin. These results imply that additional clinical evaluation of LSVT-1701 as an adjuvant therapy for the management of invasive MRSA infections is needed [110].…”

Section: Phage Therapy In Combating S Aureusmentioning

confidence: 99%

Phage Therapy, a Salvage Treatment for Multidrug-Resistant Bacteria Causing Infective Endocarditis

Hetta,

Rashed,

Ramadan

et al. 2023

Biomedicines

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Infective endocarditis (IE) is defined as an infection of the endocardium, or inner surface of the heart, most frequently affecting the heart valves or implanted cardiac devices. Despite its rarity, it has a high rate of morbidity and mortality. IE generally occurs when bacteria, fungi, or other germs from another part of the body, such as the mouth, spread through the bloodstream and attach to damaged areas in the heart. The epidemiology of IE has changed as a consequence of aging and the usage of implantable cardiac devices and heart valves. The right therapeutic routes must be assessed to lower complication and fatality rates, so this requires early clinical suspicion and a fast diagnosis. It is urgently necessary to create new and efficient medicines to combat multidrug-resistant bacterial (MDR) infections because of the increasing threat of antibiotic resistance on a worldwide scale. MDR bacteria that cause IE can be treated using phages rather than antibiotics to combat MDR bacterial strains. This review will illustrate how phage therapy began and how it is considered a powerful potential candidate for the treatment of MDR bacteria that cause IE. Furthermore, it gives a brief about all reported clinical trials that demonstrated the promising effect of phage therapy in combating resistant bacterial strains that cause IE and how it will become a hope in future medicine.

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A Phase 1 Study To Evaluate Safety and Pharmacokinetics following Administration of Single and Multiple Doses of the Antistaphylococcal Lysin LSVT-1701 in Healthy Adult Subjects

Wire

Jun

Jang

et al. 2022

Antimicrob Agents Chemother

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Thirty-two healthy male subjects (8 per cohort) were randomized 6:2 to active:placebo. LSVT-1701, an anti-staphylococcal lysin, was administered intravenously as a 6 mg/kg single dose and as 1.5, 3, and 4.5 mg/kg twice daily for 4 days. LSVT-1701 exposure increased in a greater than dose proportional manner and did not accumulate. Treatment-emergent adverse events (TEAEs) were predominantly of mild intensity. The most common TEAEs were chills, pyrexia, headache, infusion site events, cough, rhinorrhea, and increases in C-reactive protein.

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Efficacy of Antistaphylococcal Lysin LSVT-1701 in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

Cited by 4 publications

References 14 publications

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed

Phage Therapy, a Salvage Treatment for Multidrug-Resistant Bacteria Causing Infective Endocarditis

A Phase 1 Study To Evaluate Safety and Pharmacokinetics following Administration of Single and Multiple Doses of the Antistaphylococcal Lysin LSVT-1701 in Healthy Adult Subjects

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