Evaluation of Omadacycline Alone and in Combination with Rifampin against Staphylococcus aureus and Staphylococcus epidermidis in an In Vitro Pharmacokinetic/Pharmacodynamic Biofilm Model.
Evaluation of Omadacycline Alone and in Combination with Rifampin against Staphylococcus aureus and Staphylococcus epidermidis in an In Vitro Pharmacokinetic/Pharmacodynamic Biofilm Model.
复制标题
在体外药代动力学/药效生物膜模型中评估奥马达环素单独使用以及与利福平联合使用对金黄色葡萄球菌和表皮葡萄球菌的作用。
DOI：
10.1128/aac.01317-22
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发表时间：
2023
影响因子：
4.9
通讯作者：
Rybak,MichaelJ
中科院分区：
文献类型：
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作者：
Morrisette,Taylor;Stamper,KyleC;Lev,KatherineL;Kebriaei,Razieh;Holger,DanaJ;Abdul-Mutakabbir,JacindaC;KunzCoyne,AshlanJ;Rybak,MichaelJ
与生物膜相关的感染会导致相当大的发病率。奥马多环素(OMC)是一种新的氨甲基环素类药物，对金黄色葡萄球菌和表皮葡萄球菌具有潜在的体外抗菌活性，但其在生物被膜相关感染中的应用尚缺乏相关资料。我们研究了OMC单独和联合利福平(RIF)对20株临床葡萄球菌的体外生物膜分析的活性，包括体外药代动力学/药效学(PK/PD)CDC生物膜反应器(CBR)模型(模拟人体暴露)。观察到的最低抑菌浓度对被评价菌株有很强的抑制作用(0.125~1 mg/L)，在有生物被膜的情况下，其最低抑菌浓度通常会增加(0.25to>； mg/L)。此外，在90%的菌株中，RIF能降低OMC生物膜MICs(BMICs)，并且在生物膜时间-杀灭分析(TKA)中，OMC和RIF的组合在大多数菌株中显示出协同作用。在PK/PD CBR模型中，OMC单一治疗主要表现出抑菌活性，而RIF单一治疗通常表现出最初的细菌根除，随后可能由于出现RIF耐药而迅速再生(RIF BMIC，>； mg/L)。然而，OMC和RIF的组合在几乎所有的菌株中都产生了快速和持续的杀菌活性(在达到杀菌活性的菌株中，比开始接种的菌株减少了3.76到4.03 log10CFU/cm2)。此外，OMC还可以防止RIF耐药的出现。我们的数据提供了初步证据，表明OMC联合RIF可能是治疗金黄色葡萄球菌和表皮葡萄球菌生物膜相关感染的可行选择。进一步研究OMC在生物膜相关感染中的作用是有必要的。
Biofilm-associated infections lead to substantial morbidity. Omadacycline (OMC) is a novel aminomethylcycline with potentin vitroactivity against Staphylococcus aureus and Staphylococcus epidermidis, but data surrounding its use in biofilm-associated infections are lacking. We investigated the activity of OMC alone and in combination with rifampin (RIF) against 20 clinical strains of staphylococci in multiplein vitrobiofilm analyses, including anin vitropharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor (CBR) model (simulating human exposures). The observed MICs for OMC demonstrated potent activity against the evaluated strains (0.125 to 1 mg/L), with an increase of MICs generally observed in the presence of biofilm (0.25 to >64 mg/L). Furthermore, RIF was shown to reduce OMC biofilm MICs (bMICs) in 90% of strains, and OMC plus RIF combination in biofilm time-kill analyses (TKAs) exhibited synergistic activity in most of the strains. Within the PK/PD CBR model, OMC monotherapy primarily displayed bacteriostatic activity, while RIF monotherapy generally exhibited initial bacterial eradication, followed by rapid regrowth likely due to the emergence of RIF resistance (RIF bMIC, >64 mg/L). However, the combination of OMC plus RIF produced rapid and sustained bactericidal activity in nearly all the strains (3.76 to 4.03 log10CFU/cm2reductions from starting inoculum in strains in which bactericidal activity was reached). Furthermore, OMC was shown to prevent the emergence of RIF resistance. Our data provide preliminary evidence that OMC in combination with RIF could be a viable option for biofilm-associated infections with S. aureus and S. epidermidis. Further research involving OMC in biofilm-associated infections is warranted.