Molecular docking revealed that celastrol is superior to thymol for binding to KPC and VIM-carbapenemase.

Furthermore, thymol increased CRK cell wall-permeability. Meropenem-MIC did not decrease in presence of celastrol, only 2-fold decrease was observed with thymol, while 4–64 fold decrease was observed when meropenem was combined with both celastrol and thymol. Celastrol showed significant inhibitory effect against carbapenemase-hydrolytic activity. Genotypically, bla NDM1 was detected in 35 isolates, bla VIM in 17 isolates, bla OXA in 18 isolates, and bla KPC was detected only in 6 isolates. Phenotypically, 39 isolates were carbapenemase-producer. Among 85 clinical Klebsiella isolates, 72 were multi-drug-resistant and 43 were meropenem-resistant. Celastrol and thymol-MICs were determined and the carbapenemase-inhibitory effect of sub-MICs was investigated.

Carbapenemase-production was tested phenotypically and genotypically. Antimicrobial susceptibility was determined using disk-diffusion method. Clinical Klebsiella isolates were identified using biochemical and molecular methods. This study aims to restore carbapenem effectiveness against CRK using celastrol and thymol. Currently, treatment options for carbapenem-resistant- Klebsiella (CRK) are very limited. Klebsiella has developed resistance against antimicrobials including the last resort class carbapenem.

Klebsiella pneumoniae is an opportunistic pathogen causing nosocomial and community-acquired infections.

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