Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
Fred Wilson School of Pharmacy, High Point University, High Point, NC, USA.
J Antimicrob Chemother. 2019 Jan 1;74(1):82-86. doi: 10.1093/jac/dky376.
Emergence of reduced susceptibility to vancomycin warrants the development of new antimicrobial agents for the treatment of MRSA. We evaluated the activity of dalbavancin, a novel lipoglycopeptide antibiotic, both alone and combined with β-lactams, in combination MIC testing and time-kill assays against resistant phenotypes of Staphylococcus aureus.
S. aureus isolates included 50 organisms with varying susceptibility patterns. Dalbavancin was tested alone and in combination with five β-lactams: cefazolin, cefepime, ceftaroline, ertapenem and oxacillin. MIC values of the antibiotics were determined for all isolates. After initial MIC testing, dalbavancin MICs were determined in the presence of 0.5 × MIC of each β-lactam to determine the effect of each β-lactam on dalbavancin MIC. Time-kill assays were performed with dalbavancin and β-lactams tested at 0.5 × MIC for randomly selected organisms representing each MRSA phenotype. Time-kill curves were generated by plotting mean colony counts (log10 cfu/mL) versus time.
Dalbavancin MIC50 was 0.0313 mg/L and MIC90 was 0.0625 mg/L. Dalbavancin MICs decreased by zero to greater than five 2-fold dilutions in combination with each β-lactam. In time-kill assays, dalbavancin was synergistic with cefazolin, cefepime and ertapenem against all strains and the combination of dalbavancin and ceftaroline was synergistic against all but one. The combination of dalbavancin and oxacillin was synergistic against 5/8 strains.
Dalbavancin was active against all MRSA strains tested, including heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus, daptomycin-non-susceptible and linezolid-resistant isolates. The synergy demonstrated against these organisms supports the use of dalbavancin in combination with β-lactams against resistant phenotypes of S. aureus. Further evaluation is warranted.
万古霉素敏感性降低的出现，要求开发新的抗菌药物来治疗耐甲氧西林金黄色葡萄球菌（MRSA）。我们评估了新型糖肽类抗生素达巴万星的活性，包括单独使用和与β-内酰胺类药物联合使用，在组合 MIC 检测和时间杀伤试验中，针对金黄色葡萄球菌的耐药表型。
金黄色葡萄球菌分离株包括 50 株具有不同敏感性模式的菌株。单独测试达巴万星，并与五种β-内酰胺类药物（头孢唑林、头孢吡肟、头孢洛林、厄他培南和苯唑西林）联合测试。所有分离株均测定抗生素的 MIC 值。在初始 MIC 测试后，确定达巴万星在 0.5×MIC 每种β-内酰胺类药物存在时的 MIC 值，以确定每种β-内酰胺类药物对达巴万星 MIC 值的影响。随机选择代表每种 MRSA 表型的分离株，用达巴万星和β-内酰胺类药物在 0.5×MIC 下进行时间杀伤试验。通过绘制平均菌落计数（log10 cfu/mL）与时间的关系生成时间杀伤曲线。
达巴万星 MIC50 为 0.0313 mg/L，MIC90 为 0.0625 mg/L。达巴万星与每种β-内酰胺类药物联合使用时，MIC 值降低了零至大于 5 倍 2 倍稀释。在时间杀伤试验中，达巴万星与头孢唑林、头孢吡肟和厄他培南联合使用对所有菌株均具有协同作用，而达巴万星与头孢洛林联合使用对除一株外的所有菌株均具有协同作用。达巴万星与苯唑西林联合使用对 5/8 株具有协同作用。
达巴万星对所有测试的耐甲氧西林金黄色葡萄球菌菌株均具有活性，包括异质性万古霉素中介金黄色葡萄球菌、万古霉素中介金黄色葡萄球菌、达托霉素不敏感和利奈唑胺耐药分离株。对这些菌株表现出的协同作用支持达巴万星与β-内酰胺类药物联合用于治疗金黄色葡萄球菌的耐药表型。需要进一步评估。
