Photodynamic treatment with cationic Ir(III) complexes induces a synergistic antimicrobial effect with imipenem over carbapenem-resistant Klebsiella pneumoniae

Abstract

Background: Bacteria prevalent in the hospital environment have developed multi-drug resistance (MDR), such as the carbapenemase-producing Klebsiella pneumoniae (KPC⁺). Photodynamic therapy (PDT), which uses light-activated photosensitizer compounds (PSs), has emerged as an alternative to antibiotics. Cationic-PSs have a better bactericidal effect by interacting more closely with the bacterial envelope.

Methods: Two PSs based on cationic Ir (III) compounds (PSIR-1 and PSIR-2) were studied in photodynamic therapy against KPC⁺ and KPC^- bacteria, and their PDT activities were compared with a cationic Ru(II) control compound (PS -Ru).

Results: Similar to the behavior of PS-Ru control, the cytotoxicity of PSIR-1 and 2, showing a bacterial inhibition growth of more than 3log₁₀ (>99.9 % inactivation), at light fluency of 17 μW/cm². The minimal dose to accomplish the inhibition in 3log₁₀ was determined for PSIR-1 and PSIR-2 at 4 and 2 μg/mL, respectively and the lethality was 30 min of light exposure for both compounds. Notably, the PSIR-1 and 2 compounds showed a synergistic effect with imipenem by significantly increasing (up to 6 log₁₀) the photodynamic bactericidal effect for KPC⁺ strains. This synergy is specific for PSIR-1 and 2 compounds, since it was not observed with the PS-Ru control. On normal gastric cells GES-1, both PSIR-1 and 2 showed significant cytotoxicity; however, the highest cytotoxicity was found in gastric tumor cells (AGS).

Conclusion: The compounds PSIR-1 and 2 are bactericidal photosensitizers and represent a promising alternative for complementing the treatment of infections by MDR bacteria since they should not be toxic in the dark.

Keywords: Antimicrobial photodynamic therapy; KPC; Klebsiella pneumoniae; MDR; Photodynamic therapy.