Department of Life Sciences, University of Trieste, Trieste, Italy.
Department of Sciences, "Roma Tre" University, Rome, Italy.
Diagn Microbiol Infect Dis. 2021 Feb;99(2):115241. doi: 10.1016/j.diagmicrobio.2020.115241. Epub 2020 Oct 15.
Vancomycin-resistant Enterococcus faecium (VREfm) infections are increasing. Current anti-VREfm options (linezolid and daptomycin) are suboptimal. Fosfomycin maintains good efficacy against VREfm and chloramphenicol is active against ≥ 90% of VREfm. We tested chloramphenicol + fosfomycin (CAF+FOS) against 10 VREfm isolated from blood. MICs were 64 to 512 µg/mL for fosfomycin and 8 to 16 µg/mL for chloramphenicol. The combination decreased both MICs, with a synergic effect in 50% of the isolates and an additive effect in the remaining 50%. Time-kill assays performed on fractional inhibitory concentration index ≤ 0.5 strains confirmed the synergism. The antibiotic combination at ¼ of minimum inhibitory concentrations (MICs) caused a ≥ 2 log reduction compared to the two antibiotics alone. Finally, we provided a proof of concept of the in vitro efficacy of CAF+FOS in G. mellonella. The survival of G. mellonella larvae treated with the combination was significantly higher. The activity of fosfomycin and chloramphenicol against VREfm increases when they are used in combination.
屎肠球菌（VREfm）感染正在增加。目前针对 VREfm 的可选药物（利奈唑胺和达托霉素）并不理想。磷霉素对 VREfm 仍保持良好的疗效，而氯霉素对 90%以上的 VREfm 具有活性。我们检测了氯霉素+磷霉素（CAF+FOS）对从血液中分离出的 10 株 VREfm 的作用。磷霉素的 MIC 值为 64 至 512 µg/mL，氯霉素的 MIC 值为 8 至 16 µg/mL。该组合降低了两种药物的 MIC 值，在 50%的分离株中表现出协同作用，在其余 50%的分离株中表现出相加作用。在分数抑菌浓度指数≤0.5 的菌株上进行的时间杀伤试验证实了协同作用。与两种抗生素单独使用相比，联合使用最低抑菌浓度（MIC）的四分之一浓度可导致 2 个对数减少。最后，我们在 G. mellonella 中提供了 CAF+FOS 体外疗效的概念验证。接受联合治疗的 G. mellonella 幼虫的存活率显著提高。当磷霉素和氯霉素联合使用时，它们对 VREfm 的活性增加。
