Combination Therapy With Lysin CF-301 and Antibiotic Is Superior to Antibiotic Alone for Treating Methicillin-Resistant Staphylococcus aureus–Induced Murine Bacteremia

Abstract

Lysins are bacteriophage-derived enzymes that degrade bacterial peptidoglycans. Lysin CF-301 is being developed to treat Staphylococcus aureus because of its potent, specific, and rapid bacteriolytic effects. It also demonstrates activity on drug-resistant strains, has a low resistance profile, eradicates biofilms, and acts synergistically with antibiotics. CF-301 was bacteriolytic against 250 S. aureus strains tested including 120 methicillin-resistant S. aureus (MRSA) isolates. In time-kill studies with 62 strains, CF-301 reduced S. aureus by 3-log10 within 30 minutes compared to 6–12 hours required by antibiotics. In bacteremia, CF-301 increased survival by reducing blood MRSA 100-fold within 1 hour. Combinations of CF-301 with vancomycin or daptomycin synergized in vitro and increased survival significantly in staphylococcal-induced bacteremia compared to treatment with antibiotics alone (P < .0001). Superiority of CF-301 combinations with antibiotics was confirmed in 26 independent bacteremia studies. Combinations including CF-301 and antibiotics represent an attractive alternative to antibiotic monotherapies currently used to treat S. aureus bacteremia.

Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent

“…We previously demonstrated antibiofilm activity for CF-301 against S. aureus strain BAA-42 (43). This analysis was extended here to show that CF-301 (at the MIC of 32 g/ml) can disrupt BAA-42 biofilms on 24-well polystyrene plates within 2 h and prevent regrowth over 24 h (Fig.…”

“…Aggressive antibiotic therapies can reduce biofilms and control dispersed planktonic bacteria; however, eradication is difficult because of the high antibiotic concentrations that must be sustained (50,(52)(53)(54). To avoid the limitations of antibiotics, a promising new strategy was proposed based on the emerging understanding of bacteriophage lysins as antibiofilm agents (32,43). Lysins can potentially destroy biofilms, kill constituent bacteria, and resensitize released planktonic bacteria to antibiotics and immune surveillance, and, in doing so, provide effective standalone or adjunctive therapies to treat biofilm infections.…”

Efficacy of Artilysin Art-175 against Resistant and Persistent Acinetobacter baumannii

“…Combinations of endolysins and antibiotics have been reported to be superior to antibiotics alone (42). To evaluate the potential of Art-175 as a supplement to existing antibiotic therapies, Art-175 was combined with ciprofloxacin and tobramycin, and its effect was compared to that of monotherapy.…”

Platelet Lysate-Loaded Photocrosslinkable Hyaluronic Acid Hydrogels for Periodontal Endogenous Regenerative Technology

“…Carlson et al 43 suggested that the bacteriostatic effect of HA may be due to the saturation of the bacterial hyaluronate lyase by the excess HA, which prevents the bacteria from maintaining elevated levels of tissue permeability and penetrating the physical defenses of the host. This would enhance the ability of the host's immune system to eradicate MRSA involved β-lysin, which is responsible for blood clotting found after platelets activation [44][45] . β-lysin, which is one of the most abundant compound found in PL after activation 46 has been described to act against bacteria cell-wall, rapidly killing and stopping bacteria reproduction [44][45] , which could explain the results from this study.…”

“…This would enhance the ability of the host's immune system to eradicate MRSA involved β-lysin, which is responsible for blood clotting found after platelets activation [44][45] . β-lysin, which is one of the most abundant compound found in PL after activation 46 has been described to act against bacteria cell-wall, rapidly killing and stopping bacteria reproduction [44][45] , which could explain the results from this study. In addition, other PL-derived molecules with antibacterial properties against Gram+ bacteria could be involved in this response, such as neutrophil activating protein-2 demonstrated capacity to kill Gram-positive and Gram-negative bacteria [47][48] .…”