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Experimental Endocarditis Model of Methicillin Resistant Staphylococcus aureus MRSA in Rat
Published on: June 4, 2012
In vitro exebacase (CF-301) activity against methicillin-susceptible or methicillin-resistant Staphylococcus aureus
María-Alexandra Cañas1, Guillermo Cuervo1,2, Javier García-González1
1Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
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.
Insights
Exebacase demonstrates potent in vitro activity against Staphylococcus aureus and coagulase-negative staphylococci (CoNS) causing infective endocarditis. Its effectiveness is independent of methicillin resistance, suggesting potential as a novel therapeutic agent.
Area of Science:
- Microbiology and Infectious Diseases
- Pharmacology and Therapeutics
- Antimicrobial Resistance
Background:
- Infective endocarditis (IE) is a severe infection frequently caused by Staphylococcus aureus and coagulase-negative staphylococci (CoNS).
- Methicillin-resistant Staphylococcus epidermidis (MRSE) is a significant pathogen in prosthetic valve endocarditis.
- Exebacase is a novel antistaphylococcal lysin with demonstrated rapid bactericidal and antibiofilm properties.
Purpose of the Study:
- To evaluate the in vitro antimicrobial activity of exebacase against Staphylococcus aureus and CoNS isolates from IE patients.
- To compare the efficacy of exebacase with standard IE antibiotics.
- To assess exebacase activity across different staphylococcal species and resistance profiles.
Main Methods:
- Analysis of 211 consecutive IE strains: Staphylococcus aureus (MSSA, MRSA), Staphylococcus epidermidis (MSSE, MRSE), and other CoNS species.
- Determination of minimum inhibitory concentrations (MICs) using broth microdilution.
- Testing exebacase against standard antibiotics including cloxacillin, ceftaroline, vancomycin, daptomycin, gentamicin, and rifampicin.
Main Results:
- Exebacase exhibited potent activity against all Staphylococcus aureus isolates (MIC ≤ 1 mg/L), with geometric mean MICs of 0.56 mg/L for MSSA and 0.49 mg/L for MRSA.
- Activity against Staphylococcus epidermidis showed higher MICs (GM 3.03-3.40 mg/L), while other CoNS species displayed variable susceptibility (GM MICs 0.49-2.59 mg/L).
- Exebacase demonstrated comparable activity to vancomycin and daptomycin, unaffected by methicillin resistance.
Conclusions:
- Exebacase displays significant in vitro activity against Staphylococcus aureus and CoNS, independent of methicillin resistance.
- The lysin was consistently more potent against Staphylococcus aureus compared to Staphylococcus epidermidis.
- Further investigation into lysins, potentially in combination therapy, is warranted for treating staphylococcal infections.
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