exebacase (CF-301) / ContraFect - LARVOL DELTA

In vitro exebacase (CF-301) activity against methicillin-susceptible or methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci strains isolated from patients with infective endocarditis. (PubMed, J Antimicrob Chemother) - "Exebacase activity was independent of methicillin resistance and consistently higher against S. aureus than S. epidermidis. Further research is warranted to explore lysins in combination against staphylococcal infections."

Journal • Preclinical • Cardiovascular • Infectious Disease

CF301. Perioperative Challenges in Patients with Diabetes Mellitus: More Meds, More Problems? (1 CME) (ASA 2025) - "Finally, the risk of perioperative euglycemic ketoacidosis with SGLT2 inhibitors will be addressed. SessionLearningObjective1: Upon completion of this learning activity, participants should be able to explain the perioperative management of GLP-1 agonists.SessionLearningObjective2: Upon completion of this learning activity, participants should be able to describe the potential role for gastric ultrasound in assessing aspiration risk in patients with diabetes mellitus.SessionLearningObjective3: Upon completion of this learning activity, participants should be able to recognize the risk factors for perioperative euglycemic ketoacidosis associated with SLGT2 inhibitors."

Clinical • Diabetes • Metabolic Disorders

CF301. Challenges and Controversies in Trauma Management (ASA 2024) - "Learning Objective 2 Evaluate different means of triage and prioritization in the mass casualty scenario.. Learning Objective 3 Describe difficulties in organizational capabilities when dealing with mass casualties"

Mood Disorders • Obstetrics

Bacteriophages as a potential substitute for antibiotics: A comprehensive review. (PubMed, Cell Biochem Funct) - "Many commercially available endolysins such as Staphefekt SA.100, Exebacase (CF-301), and N-Rephasin®SAL200 are used in biofilm penetration and treating plant diseases. Although obtaining commercial approval may be time-consuming, it will be beneficial in the postantibiotic era. This review provides an overview of the significance of phage therapy as a potential alternative to antibiotics in combating resistant bacterial strains and its application to various fields and emphasizes the importance of safeguarding and ensuring treatment efficacy."

Journal • Review • Infectious Disease

Lysin exebacase demonstrates potent bactericidal activity against intraosteoblastic Staphylococcus aureus (ECCMID 2024) - No abstract available

Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT). (PubMed, Clin Infect Dis) - "Exebacase + antibiotics failed to improve clinical response at Day 14 in patients with MRSA bacteremia/endocarditis. This result was unexpected based on phase 2 data that established proof-of-concept for exebacase + antibiotics in patients with MRSA bacteremia/endocarditis. In the antibiotics alone group, the clinical response rate was higher than that seen in phase 2. Heterogeneity within the study population and a relatively small sample size in either the phase 2 or phase 3 studies may have increased the probability of imbalances in the multiple components of Day 14 clinical outcome. This study provides lessons for future superiority studies in S. aureus bacteremia/endocarditis."

Clinical • Head-to-Head • Journal • P3 data • Cardiovascular • Immunology • Infectious Disease

Efficacy of the lysin exebacase in addition to vancomycin in a rabbit lung infection model caused by a cystic fibrosis methicillin resistant Staphylococcus aureus (CF-MRSA) clinical isolate (NACFC 2023) - "Treatment with exebacase alone significantly reduced CFU counts of a CF-MRSA isolate in infected rabbit lungs. Exebacase activity in infected lungs was significantly enhanced when combined with vanco-mycin. Moreover, exebacase plus vancomycin significantly reduced metastatic infection in kidneys and spleen."

Clinical • Preclinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

CF301. Fascial plane blocks--Bring your clinical challenges and we will help you solve them--Ask the experts! (ASA 2023) - "What is the best way to provide analgesia or anesthesia to a particularly challenging patient? We will have experts in ESP, Pecs, ITM, and QL block discuss approaches to their challenging cases and offer advice and options to the audience members who are dealing with their own."

Clinical • Anesthesia • Pain

In vitro activity of exebacase against methicillin-resistant Staphylococcus aureus biofilms on orthopedic Kirschner wires. (PubMed, BMC Res Notes) - "Daptomycin showed significant biofilm reduction, although non-bactericidal, at all time points for 0.98 and 9.8 mg/ml and at 4 and 8 h with 0.098 mg/ml (P < 0.0495). This study supports further evaluation of local administration of exebacase as a potential treatment for orthopedic implant infections."

Journal • Preclinical • Infectious Disease • Orthopedics

Rapid bacteriolysis of Staphylococcus aureus by lysin exebacase. (PubMed, Microbiol Spectr) - "Rapid reductions in optical density were likewise observed in exebacase-treated cultures, which were visually consistent with microscopic observations of rapid lysis. Overall, exebacase provides a novel antimicrobial modality against S. aureus, characterized by a rapid cidal and lytic activity."

Journal

Lysin exebacase exerts potent in vitro bactericidal activity against Staphylococcus aureus strains associated with pulmonary exacerbations (PExs) of cystic fibrosis (CF) (ECCMID 2023) - No abstract available

Preclinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

The Lysin Exebacase Has a Low Propensity for Resistance Development in Staphylococcus aureus and Suppresses the Emergence of Resistance to Antistaphylococcal Antibiotics. (PubMed, Microbiol Spectr) - "For comparator antibiotics also tested, oxacillin MICs increased by 32-fold with ATCC 29213 and daptomycin and vancomycin MICs increased by 16- and 8-fold, respectively, with MW2. No changes in susceptibility to exebacase were observed over the 28-day period for multiple replicates of two S. aureus strains, indicating a low propensity for resistance development. Interestingly, while high-level resistance to commonly used antistaphylococcal antibiotics was readily obtained using the same method, the added presence of exebacase acted to suppress antibiotic resistance development."

Journal

DISRUPT: Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase (clinicaltrials.gov) - P3 | N=249 | Terminated | Sponsor: ContraFect | Active, not recruiting ➔ Terminated; The independent DSMB recommended that the study be stopped for futility following interim efficacy analysis.

Trial termination • Cardiovascular • Infectious Disease

Locally delivered antistaphylococcal lysin exebacase or CF-296 is active in methicillin-resistant Staphylococcus aureus implant-associated osteomyelitis. (PubMed, J Bone Jt Infect) - "CF-296 with daptomycin was more active than either CF-296 alone ( ) or daptomycin alone ( ) based on bone cultures. Local delivery of either exebacase or CF-296 offers a promising complement to conventional antibiotics in implant-associated infections."

Journal • Infectious Disease • Inflammation • Orthopedics

"$CFRX ContraFect Announces Publication on Exebacase and CF-296 Demonstrating Potent In Vivo Antimicrobial Activity in Implant-Associated MRSA Osteomyelitis https://t.co/nlUQfI8XII" (@stock_titan)

Preclinical • Inflammation

CF301. Trauma Anesthesiology: Perioperative Care of the Multi-trauma Patient (ASA 2022) - "Discuss anesthetic considerations for unknown polysubstance intoxication during major trauma. Recognize the injury patterns seen following gunshot wounds."

Clinical • Anesthesia

DISRUPT: Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase (clinicaltrials.gov) - P3 | N=249 | Active, not recruiting | Sponsor: ContraFect | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Infectious Disease

Activity of Exebacase (CF-301) against Biofilms Formed by Staphylococcus epidermidis Strains Isolated from Prosthetic Joint Infections. (PubMed, Antimicrob Agents Chemother) - "Exebacase can be considered a promising therapy in addition to rifampicin, vancomycin, or daptomycin in the context of PJI. Further in vitro studies are needed to understand its mechanism of action on S. epidermidis biofilms and in vivo investigations are required to confirm these data."

Journal • Infectious Disease

Lysin Exebacase Has a Low Propensity for Resistance Development and Suppresses the Emergence of Resistance to Anti-Staphylococcal Antibiotics (ASM Microbe 2022) - "For single-agent resistance studies, daily passages were performed with a two-fold dilution series of exebacase or comparator antibiotics vancomycin, daptomycin and oxacillin (MSSA only). Exebacase shows a low propensity for decreased susceptibility development and has the capacity to suppress the emergence of antibiotic resistance for anti-staphylococcal antibiotics when used together. These features may be important considerations for the use of exebacase in addition to standard-of-care antibiotics to treat S. aureus BSI including IE."

Cardiovascular • Infectious Disease

Locally Delivered Antistaphylococcal Lysins Exebacase or CF-296 is Active in Methicillin-Resistant Staphylococcus Aureus Implant-Associated Osteomyelitis (ASM Microbe 2022) - "Using a rabbit model of implant-associated osteomyelitis (IAO), we tested the activity of EXE and CF-296 delivered locally, with and without daptomycin (DAP). Lysins, administered locally in addition to traditional therapies, may offer a potential strategy for combatting S. aureus implant-associated infections."

Infectious Disease • Inflammation • Orthopedics

Assessment of exebacase MIC reproducibility: thirty S. aureus isolates tested at three sites using three different commercial media lots (ECCMID 2022) - No abstract available

Evaluation of the broth microdilution MIC method for exebacase against 100 beta-haemolytic streptococci (ECCMID 2022) - No abstract available

In vitro activity of exebacase against contemporary beta-haemolytic streptococci recovered from US patients with bloodstream infections (ECCMID 2022) - No abstract available

Preclinical • Infectious Disease

Direct Lytic Agents: Novel, Rapidly Acting Potential Antimicrobial Treatment Modalities for Systemic Use in the Era of Rising Antibiotic Resistance. (PubMed, Front Microbiol) - "Lysins were originally described as having activity against Gram-positive pathogens and of those, exebacase, is the first to have advanced into Phase 3 of clinical development. Importantly, novel DLAs targeting Gram-negatives, including the lysin CF-370 and the amurin peptides, are active in biological matrices (blood/serum) and, as such, offer promise for therapeutic use as systemically administered agents for the treatment of life-threatening invasive infections. In this review, DLAs are discussed as potential new classes of antimicrobial biologics that can be used to treat serious systemic infections."

Journal • Review • Infectious Disease • Pneumonia

Exebacase: A Novel Approach to the Treatment of Staphylococcal Infections. (PubMed, Drugs R D) - "Lysins are bacteriophage-derived enzymes that degrade essential components of bacteria. Exebacase (Lysin CF-301) is an attractive antimicrobial agent because it demonstrates rapid bacteriolytic activity against staphylococcal species, including Staphylococcus aureus, has a low resistance profile, eradicates biofilms, and acts synergistically with other antibiotics. Combinations including exebacase and standard of care antibiotics represent an alternative to antibiotic monotherapies currently used to treat invasive staphylococcal infections. This manuscript reviews what is known about exebacase and explores how this novel agent may be used in the future to treat human bacterial pathogens."

Journal • Review • Infectious Disease