Investigating the Effect of Xylitol on ompK36 Overexpression, Increased Meropenem Susceptibility, and Antibiofilm Activity in a Carbapenem‐Resistant Clinical Strain of Klebsiella pneumoniae

Carbapenem‐resistant Klebsiella pneumoniae poses a significant public health threat due to limited therapeutic options. This study investigated the potential of xylitol, a sugar alcohol, to enhance meropenem activity and combat biofilms in a clinical carbapenem‐resistant K. pneumoniae strain (Kp5) and a standard susceptible strain ( K. pneumoniae subsp. pneumoniae ATCC 13883). The synergistic activity between xylitol and meropenem in inhibiting bacterial growth was assessed using a two‐dimensional checkerboard assay. Real‐time PCR was performed to assess the effect of xylitol on the expression of the porin gene ompK36 , a key determinant of carbapenem entry and resistance in K. pneumoniae . Moreover, the microtiter plate assay was used to evaluate its antibiofilm efficacy. Results showed that xylitol exhibited a synergistic effect with meropenem, leading to a significant reduction in the meropenem minimum inhibitory concentration (MIC) in both strains. Notably, the meropenem MIC for the Kp5 strain was reduced by up to 32‐fold in the presence of xylitol. Exposure to xylitol alone induced a significant upregulation of ompK36 expression in both strains, suggesting that increased porin gene expression may enhance meropenem activity. Furthermore, xylitol demonstrated potent, concentration‐dependent antibiofilm activity, both inhibiting biofilm formation and eradicating established biofilms. This approach offers a promising strategy for repurposing a safe and readily available compound to address a critical aspect of antimicrobial resistance.