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
| Autor: | Esther Culebras, Iciar Rodríguez-Avial, María Carmen López Díaz, Esther Ríos, Rosa Janneth Simaluiza, Juan J. Picazo |
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| Rok vydání: | 2017 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine Microbiology (medical) 030106 microbiology Ceftobiprole Microbial Sensitivity Tests Fosfomycin Biology Pharmacology Plazomicin Meropenem Microbiology 03 medical and health sciences Minimum inhibitory concentration chemistry.chemical_compound Anti-Infective Agents medicine Humans Pharmacology (medical) Cefoxitin Microbial Viability Dalbavancin Drug Synergism General Medicine biochemical phenomena metabolism and nutrition Antimicrobial Aminoglycosides 030104 developmental biology Infectious Diseases chemistry Inactivation Metabolic Sisomicin medicine.drug |
| Zdroj: | International Journal of Antimicrobial Agents. 50:191-196 |
| ISSN: | 0924-8579 |
| Popis: | 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. MIC 50 and MIC 90 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. |
| Databáze: | OpenAIRE |
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