Pirlar Rima Fanaei, Halili Nexhmije, Travnik Tina, Trampuz Andrej, Karbysheva Svetlana
Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Berliner Hochschule für Technik (BHT), Berlin, Germany.
Sci Rep. 2025 May 16;15(1):17105. doi: 10.1038/s41598-025-01704-w.
Multi-drug resistant Gram-negative pathogens are increasingly difficult-to-treat perpetrators of infections. New, innovative, and more multifaceted therapies for the treatment of multi-drug resistant strains are thus urgent to hinder further drug resistance and mitigate deadly, untreatable infections. Our study aimed to investigate the efficacy of cefiderocol against Gram-negative aerobic bacteria alone and in combination with phages. The minimum inhibitory concentration (MIC) of cefiderocol was determined using the microdilution broth method, while the minimum biofilm bactericidal concentration was assessed using isothermal microcalorimetry. The combined effect of cefiderocol and phages was evaluated using colony-forming unit counts. Results demonstrated a notable antibacterial effect of cefiderocol, with 83.4% of tested strains exhibiting susceptibility. When combined with phages, the MIC of cefiderocol was reduced by 2-64-fold, indicating a synergistic interaction between the two agents. Furthermore, the combination therapy showed enhanced efficacy against biofilm compared to monotherapy with either cefiderocol or phages alone, leading to complete biofilm elimination in certain cases. This study highlights the potential of combining cefiderocol with phages as a strategy to combat multi-drug resistant Gram-negative bacterial infections. The observed synergy suggests that this combination therapy could improve treatment outcomes and help address the challenges of antibiotic resistance and biofilm-associated infections.
多重耐药革兰氏阴性病原体越来越成为难以治疗的感染源。因此，迫切需要新的、创新的且更具多面性的疗法来治疗多重耐药菌株，以阻止进一步的耐药性并减轻致命的、无法治疗的感染。我们的研究旨在调查头孢地尔单独以及与噬菌体联合使用时对革兰氏阴性需氧菌的疗效。采用微量稀释肉汤法测定头孢地尔的最低抑菌浓度（MIC），同时使用等温微量热法评估最低生物膜杀菌浓度。通过菌落形成单位计数评估头孢地尔和噬菌体的联合效果。结果表明头孢地尔具有显著的抗菌作用，83.4%的受试菌株表现出敏感性。与噬菌体联合使用时，头孢地尔的MIC降低了2至64倍，表明两种药物之间存在协同相互作用。此外，与单独使用头孢地尔或噬菌体的单一疗法相比，联合疗法对生物膜的疗效增强，在某些情况下可导致生物膜完全消除。本研究强调了将头孢地尔与噬菌体联合作为对抗多重耐药革兰氏阴性细菌感染策略的潜力。观察到的协同作用表明，这种联合疗法可以改善治疗效果，并有助于应对抗生素耐药性和生物膜相关感染的挑战。
