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

Background: Infective endocarditis (IE) is a severe infection mainly caused by Staphylococcus aureus, Enterococcus faecalis and viridans streptococci. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are major pathogens in prosthetic valves and devices. Exebacase is a first-in-class, antistaphylococcal lysin with rapid bactericidal and antibiofilm activity. Objective: To assess the in vitro activity of exebacase and standard IE antibiotics against S. aureus and CoNS isolates from IE patients in a university hospital (2010-2020). Methods: A total of 211 consecutive strains were analysed: S. aureus [n = 103 (82 MSSA, 21 MRSA)], S. epidermidis [n = 76 (20 MSSE, 56 MRSE)] and other CoNS species (n = 32, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus schleiferi, Staphylococcus caprae, Staphylococcus pasteuri). Broth microdilution MICs were determined for exebacase and comparators (cloxacillin, ceftaroline, vancomycin, daptomycin, gentamicin, rifampicin). Results: Exebacase inhibited all S. aureus at ≤1 mg/L. Geometric mean (GM) MICs were 0.56 mg/L for MSSA and 0.49 mg/L for MRSA, with MIC50/90 of 0.5/1 mg/L. For S. epidermidis, GM MICs were 3.03 mg/L (MSSE) and 3.40 mg/L (MRSE), with MIC50/90 of 4/16 and 4/8 mg/L, respectively. Other CoNS showed GM MICs ranging from 0.49 mg/L (S. capitis) to 2.59 mg/L (S. lugdunensis), with intermediate values for S. haemolyticus (1.15), S. hominis (1.0) and S. schleiferi (0.79). Exebacase activity was comparable to β-lactams, vancomycin and daptomycin and remained unaffected by resistance. Conclusions: 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.