Synergistic bactericidal effects of phage-enhanced antibiotic therapy against MRSA biofilms.
Autor: | Kunz Coyne AJ; Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA., Stamper K; Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA., Bleick C; Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA., Kebriaei R; Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA., Lehman SM; Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA., Rybak MJ; Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.; Department of Pharmacy Services, Detroit Receiving Hospital, Detroit Medical Center, Detroit, Michigan, USA.; Department of Medicine, Division of Infectious Diseases, Wayne State University, Detroit, Michigan, USA. |
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Jazyk: | angličtina |
Zdroj: | Microbiology spectrum [Microbiol Spectr] 2024 Apr 02; Vol. 12 (4), pp. e0321223. Date of Electronic Publication: 2024 Feb 27. |
DOI: | 10.1128/spectrum.03212-23 |
Abstrakt: | Methicillin-resistant Staphylococcus aureus (MRSA) causes biofilm-related medical device infections. Phage-antibiotic combinations offer potential therapy due to proven in vitro antibiofilm efficacy. We evaluated phage-antibiotic synergy against biofilms using modified checkerboard and 24-h time-kill assays. Humanized-simulated daptomycin (DAP) (10, 8, and 6 mg/kg q24h) and ceftaroline (CPT) (600 mg q12h) were combined with Intesti13, Sb-1, and Romulus phages (tMOI 1, q12h). Assays were conducted in 168-h biofilm reactor models against DAP non-susceptible (DNS) vancomycin intermediate S. aureus (VISA) MRSA D712 and DAP-susceptible MRSA 8014. Synergistic activity and bactericidal activity were defined as ≥2log Importance: The prevalence of biofilm-associated medical device infections caused by methicillin-resistant Staphylococcus aureus (MRSA) presents a pressing medical challenge. The latest research demonstrates the potential of phage-antibiotic combinations (PACs) as a promising solution, notably in vitro antibiofilm efficacy. By adopting modified checkerboard and 24-h time-kill assays, the study investigated the synergistic action of phages combined with humanized-simulated doses of daptomycin (DAP) and ceftaroline (CPT). The results were promising: a combination of DAP, CPT, and either a 2-phage or 3-phage cocktail effectively exhibited bactericidal activity against both DAP non-susceptible vancomycin intermediate S. aureus MRSA and DAP-susceptible MRSA strains within 168-h biofilm models. Moreover, post-treatment evaluations revealed no discernible rise in antibiotic resistance or complete phage resistance. This pioneering work suggests the potential of PACs in addressing MRSA biofilm infections, setting the stage for further expansive research tailored to diverse bacterial strains and treatment durations. Competing Interests: The authors declare no conflict of interest. |
Databáze: | MEDLINE |
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