Targeting KPC-Producing Klebsiella pneumoniae Biofilms: Genomic Profiles, Clinical Outcomes and Novel Combinations
Chiara Papalini, Giulia Bicchieraro, Luigi Tordelli Ruda, Alicia Yoke Wei Wong, Claudia Battistelli, Giovanni Genga, Andrea Tommasi, Anna Gidari, Daniela Francisci, Giuseppe Vittorio De Socio, Roberta Spaccapelo, Donatella Pietrella, Antonella Mencacci, Claudia Monari, Samuele SabbatiniNew beta-lactam/beta-lactamase inhibitor combinations (BL/BLICs) are licensed for Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) infections. However, data regarding their efficacy against bacterial biofilms and the potential of synergistic combinations remain limited. This study evaluated their efficacy on planktonic and biofilm forms of KPC-Kp isolated from catheter-related bloodstream infections (CRBSIs), correlating findings with genomic and clinical data. Twelve KPC-3-harboring isolates (ST512, n = 7; ST307, n = 3; ST101, n = 2) were characterized via whole-genome sequencing. Ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (MEM/VAB), and imipenem/relebactam (IMI/REL) were tested alone or combined with fosfomycin (FOS), cefepime (FEP), meropenem (MEM), or imipenem (IMI) using checkerboard assays. All BL/BLICs alone showed significant, comparable efficacy against biofilm-producing strains. However, combination testing revealed heterogeneous synergistic profiles. CAZ/AVI combined with MEM, IMI, or FEP achieved 100% synergy in both planktonic and biofilm states. MEM/VAB-based combinations demonstrated consistent synergy (50–100%), whereas IMI/REL showed higher synergistic rates in biofilm than in planktonic forms. Conversely, FOS-based regimens were significantly less effective against biofilms. These findings provide a clinical rationale for selecting optimized dual regimens to eradicate biofilms, offering a critical therapeutic strategy to preserve vascular devices when catheter removal is unfeasible.