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Efficacy of Omadacycline against Multidrug-Resistant Enterococcus faecium Strains in a Mouse Peritonitis Model
Kavindra V Singh1,2, Cesar A Arias1,3,4,2,5, Barbara E Murray1,3,2
1Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Abstract:
Omadacycline (OMC) showed better in vitro potency than daptomycin (DAP) or vancomycin (VAN) against Vanr, Ampr, DAP-nonsusceptible, linezolid-resistant, cfr(B)+ Enterococcus faecium strains. In a mouse peritonitis model, OMC also showed significantly better animal survival during the study and at its end than DAP or VAN with these E. faecium strains. However, OMC, DAP, and VAN showed comparable in vitro and in vivo efficacies against a non-vancomycin-resistant, tetracycline-resistant, DAP-susceptible E. faecium strain.
Insights
Omadacycline (OMC) demonstrates superior potency against resistant Enterococcus faecium strains compared to vancomycin (VAN) and daptomycin (DAP). OMC also improved survival in a mouse peritonitis model with these resistant strains.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Enterococcus faecium is a significant cause of hospital-acquired infections.
- Increasing antimicrobial resistance, including to vancomycin and daptomycin, poses a therapeutic challenge.
- Novel antibiotics are needed to combat multidrug-resistant Gram-positive bacteria.
Purpose of the Study:
- To evaluate the in vitro and in vivo efficacy of omadacycline (OMC) against resistant Enterococcus faecium strains.
- To compare OMC's activity with daptomycin (DAP) and vancomycin (VAN).
Main Methods:
- In vitro susceptibility testing against characterized Enterococcus faecium strains.
- Murine peritonitis model to assess in vivo efficacy and survival rates.
- Comparison of omadacycline, daptomycin, and vancomycin.
Main Results:
- Omadacycline exhibited greater in vitro potency than daptomycin and vancomycin against vancomycin-resistant, ampicillin-resistant, daptomycin-nonsusceptible, linezolid-resistant, and cfr(B)+ Enterococcus faecium.
- In a mouse peritonitis model, omadacycline significantly improved animal survival compared to daptomycin and vancomycin against these resistant strains.
- Comparable in vitro and in vivo efficacies were observed for omadacycline, daptomycin, and vancomycin against a susceptible Enterococcus faecium strain.
Conclusions:
- Omadacycline is a promising therapeutic option for infections caused by multidrug-resistant Enterococcus faecium.
- Its efficacy against resistant strains in vivo suggests potential clinical utility.
- Further investigation is warranted for omadacycline's role in treating complex Gram-positive infections.
