RT Journal Article T1 In-vitro activity of several antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA) isolates expressing aminoglycoside-modifying enzymes: potency of plazomicin alone and in combination with other agents A1 López Díaz, María Carmen A1 Ríos Dueñas, Esther A1 Rodríguez-Avial Infante, Iciar A1 Simaluiza, Rosa Janneth A1 Picazo De La Garza, Juan José A1 Culebras López, Esther AB This study investigated the in-vitro activity of clinically relevant aminoglycosides and new antimicrobial agents—plazomicin, ceftobiprole and dalbavancin—against 55 methicillin-resistant Staphylococcus aureus (MRSA) isolates producing aminoglycoside-modifying enzymes (AMEs). The checkerboard method was used to assess synergism between plazomicin and four antibiotics (fosfomycin, ceftobiprole, cefoxitin and meropenem), and time–kill assays were performed for the most active combinations. Among the aminoglycosides tested, plazomicin was the most active agent against MRSA, with >90% of isolates being inhibited at a minimum inhibitory concentration (MIC) of ≤1 mg/L. MIC50 and MIC90 values for ceftobiprole and dalbavancin were 2 and 4 mg/L, and 0.125 and 0.125 mg/L, respectively. The most prevalent AME gene was aac(6′)Ie-aph(2″)Ia (87.3%), followed by ant(4′)Ia (52.7%) and aph(3′)IIIa (52.7%). Plazomicin activity was not affected by the type or number of enzymes detected. In checkerboard and time–kill assays, indifference was the most common result achieved for the antibiotic combinations. Notably, no antagonism was observed with any combination tested. Overall, plazomicin in combination with meropenem had the highest synergistic effect, demonstrating synergy against seven isolates in the checkerboard assay and three isolates in time–kill curves. In conclusion, plazomicin showed potent activity against aminoglycoside-resistant MRSA isolates, regardless of the number and type of AMEs present. These findings indicate the potential utility of plazomicin in combination with meropenem for the treatment of MRSA infections. PB Elsevier SN 0924-8579 YR 2017 FD 2017-08 LK https://hdl.handle.net/20.500.14352/112716 UL https://hdl.handle.net/20.500.14352/112716 LA eng NO López Díaz, María Carmen, et al. «In-Vitro Activity of Several Antimicrobial Agents against Methicillin-Resistant Staphylococcus Aureus (MRSA) Isolates Expressing Aminoglycoside-Modifying Enzymes: Potency of Plazomicin Alone and in Combination with Other Agents». International Journal of Antimicrobial Agents, vol. 50, n.o 2, agosto de 2017, pp. 191-96. DOI.org (Crossref), https://doi.org/10.1016/j.ijantimicag.2017.01.039. NO Instituto de Salud Carlos III NO Unión Europea DS Docta Complutense RD 9 abr 2025