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 log₁₀ 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.

耐万古霉素的粪肠球菌（VREfm）感染正在增加。当前的抗VREfm选择（利奈唑胺和达托霉素）不是最佳选择。磷霉素对VREfm保持良好疗效，氯霉素对VREfm≥90％具有活性。我们针对从血液中分离出的10种VREfm测试了氯霉素+磷霉素（CAF + FOS）。磷霉素的MICs为64至512 µg / mL，氯霉素的MICs为8至16 µg / mL。该组合降低了两个MIC，在50％的分离物中产生了协同作用，而在其余50％中产生了累加作用。对分数抑制浓度指数≤0.5菌株进行的时间杀灭试验证实了协同作用。最小抑菌浓度（MIC）的¼的抗生素组合导致≥2 log ₁₀与单独使用两种抗生素相比减少了。最后，我们提供了CAF + FOS在加倍菌中的体外功效的概念证明。用该组合物治疗的G. mellonella幼虫的存活率明显更高。组合使用时，磷霉素和氯霉素的抗VREfm活性增加。