Fabrizio Giorgia, Truglio Mauro, Cavallo Ilaria, Sivori Francesca, Francalancia Massimo, Riveros Cabral Rodolfo J, Comar Manola, Trancassini Maria, Compagnino Daniele Emanuele, Diaco Fabiana, Antonelli Guido, Ascenzioni Fiorentina, Cimino Giuseppe, Pimpinelli Fulvia, Di Domenico Enea Gino
Department of Biology and Biotechnology "C. Darwin", Sapienza University of Rome, Rome, Italy.
Microbiology and Virology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy.
J Glob Antimicrob Resist. 2025 Jun;43:111-119. doi: 10.1016/j.jgar.2025.04.010. Epub 2025 Apr 28.
Chronic Pseudomonas aeruginosa infections are a leading cause of acute pulmonary exacerbations in people with cystic fibrosis (pwCF). Intrinsic antibiotic resistance and biofilm formation complicate treatment. This study investigates the genomic diversity and cefiderocol efficacy against planktonic and biofilm-associated forms of P. aeruginosa isolates from pwCF.
Eight P. aeruginosa clinical isolates and three laboratory strains underwent whole genome sequencing (WGS). Biofilm formation was assessed through biomass, cell count, metabolic activity, and extracellular DNA (eDNA). The minimum bactericidal concentration (MBC) and biofilm eradication concentration (MBEC) were also determined.
WGS revealed significant genomic diversity, identifying ten distinct sequence types (STs). Antibiotic susceptibility testing (AST) showed that 10/11 strains were susceptible to cefiderocol, with one isolate (MPA9) displaying resistance linked to the bla gene. Adding the β-lactamase inhibitor avibactam (AVI) restored susceptibility in this resistant strain. Although iron metabolism genes were highly conserved across isolates, MPA9 lacked the fpvA iron receptor, potentially contributing to cefiderocol resistance. Biofilm formation significantly increased tolerance to cefiderocol, with an 8-fold rise in MBEC compared to MBC.
These findings highlight the genomic diversity and adaptive potential of P. aeruginosa in pwCF. Cefiderocol shows promise against planktonic and biofilm-associated P. aeruginosa, and combining it with AVI may counteract β-lactamase-mediated resistance.
慢性铜绿假单胞菌感染是囊性纤维化患者（pwCF）急性肺部加重的主要原因。内在抗生素耐药性和生物膜形成使治疗复杂化。本研究调查了来自pwCF的铜绿假单胞菌分离株的基因组多样性以及头孢地尔对浮游菌和生物膜相关形式的疗效。
对8株铜绿假单胞菌临床分离株和3株实验室菌株进行全基因组测序（WGS）。通过生物量、细胞计数、代谢活性和细胞外DNA（eDNA）评估生物膜形成。还测定了最低杀菌浓度（MBC）和生物膜根除浓度（MBEC）。
WGS显示出显著的基因组多样性，鉴定出10种不同的序列类型（STs）。抗生素敏感性测试（AST）表明，10/11株菌株对头孢地尔敏感，其中1株分离株（MPA9）显示出与bla基因相关的耐药性。添加β-内酰胺酶抑制剂阿维巴坦（AVI）可恢复该耐药菌株的敏感性。尽管铁代谢基因在各分离株中高度保守，但MPA9缺乏fpvA铁受体可能导致对头孢地尔耐药。生物膜形成显著增加了对头孢地尔的耐受性，与MBC相比，MBEC升高了8倍。
这些发现突出了pwCF中铜绿假单胞菌的基因组多样性和适应潜力。头孢地尔对浮游菌和生物膜相关的铜绿假单胞菌显示出前景，将其与AVI联合使用可能抵消β-内酰胺酶介导的耐药性。
