We investigated colistin heteroresistance in Citrobacter freundii isolates from Korean hospitals. Using population analysis profiling (PAP), we detected colistin heteroresistance in 31.3% of isolates. Among these, ST217 was the most prevalent clone (58.5%), particularly within colistin-heteroresistant isolates (80.0%). Interestingly, the second most common clone, ST248, was not found in heteroresistant isolates. We identified amino acid changes in PhoQ, PmrA, and PmrB, along with mRNA overexpression in pmrB and arnD. Colistin monotherapy showed no efficacy, but a combination of colistin and ciprofloxacin successfully eradicated all five isolates, even at 0.5 × minimum inhibitory concentrations. This study underscores the high prevalence of colistin heteroresistance in C. freundii isolates, limiting the effectiveness of colistin monotherapy. Combining colistin with ciprofloxacin may offer a viable treatment option for C. freundii infections.

我们调查了韩国医院分离的弗氏柠檬酸杆菌中的粘菌素异质耐药性。使用群体分析谱 (PAP)，我们检测到 31.3% 的分离株存在粘菌素异质抗性。其中，ST217 是最常见的克隆 (58.5%)，特别是在粘菌素异抗性分离株中 (80.0%)。有趣的是，第二个最常见的克隆 ST248 在异质抗性分离株中未发现。我们鉴定了 PhoQ、PmrA 和 PmrB 中的氨基酸变化，以及pmrB和arnD中 mRNA 的过度表达。粘菌素单一疗法没有显示出疗效，但粘菌素和环丙沙星的组合成功地根除所有五种分离株，即使在 0.5 × 最小抑制浓度下也是如此。这项研究强调了弗氏梭菌分离株中粘菌素异质耐药性的高发生率，限制了粘菌素单一疗法的有效性。将粘菌素与环丙沙星联合使用可能为弗氏梭菌感染提供可行的治疗选择。