• Overcoming drug resistance: thymol and ceftazidime synergy against Acinetobacter baumannii and Klebsiella pneumoniae
  • Arman Taran,1 Mina Shirmohammadpour,2 Sajjad Jafari,3 Bahman Mirzaei,4,*
    1. Department of Microbiology and Virology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
    2. Department of Microbiology and Virology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
    3. Department of Microbiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran
    4. Department of Microbiology and Virology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran


  • Introduction: This research evaluates the combined antimicrobial effects of thymol and ceftazidime against Acinetobacter baumannii and Klebsiella pneumoniae.
  • Methods: The antimicrobial effects of thymol and ceftazidime were evaluated individually and in combination against K. pneumoniae ATCC 100031 and A. baumannii ATCC 19906 using the MIC-MBC method. Subsequently, the synergistic antimicrobial effects of these compounds were tested on ten clinical strains employing the MIC-MBC method. Chemical bonds, functional groups, and molecular interactions were analyzed using an FTIR device. Additional experiments included the checkered method, biofilm inhibition assays targeting K. pneumoniae ATCC 100031 and A. baumannii ATCC 19906, as well as cytotoxicity tests on red blood cells (RBCs) through hemolysis and human skin fibroblast cells (Ffk) using the MTT method. Results demonstrated synergistic effects of thymol and ceftazidime, and the outcomes of the tests were compared between the two bacterial species.
  • Results: The results of this study indicated that the antimicrobial effects of thymol/ceftazidime were more effective against K. pneumoniae (4/2 µg/ml) compared to A. baumannii (512/128 µg/ml) in both clinical and ATCC strains. FTIR analysis revealed the presence of bonds such as OH in carbohydrates and proteins, polyphenols, C=O (Amide I band), C-O-C (polysaccharide), and C-N (Amide III band). Additionally, a unique band, C=C conjugated and C≡C, highlighted the interaction between thymol and ceftazidime. The biofilm inhibition efficacy of thymol/ceftazidime was higher for K. pneumoniae ATCC 100031 (59.54%) than for A. baumannii ATCC 19906 (23.41%). The cytotoxicity assessment revealed that the synergistic compounds demonstrated comparable effects on RBCs and human Ffk cells, with lower toxicity compared to Triton X-100.
  • Conclusion: Given the growing antibiotic resistance of ceftazidime in addressing infections caused by K. pneumoniae and A. baumannii, this study found that thymol/ceftazidime demonstrated superior antimicrobial and anti-biofilm effects against K. pneumoniae compared to A. baumannii. With further research, this compound holds potential to be developed into a novel therapeutic option for patients.
  • Keywords: Klebsiella pneumoniae, Acinetobacter baumannii, Thymol, Ceftazidime, Synergistic